In [1]:
biocause = []
with open('../../../data/wordvec/wordvec_input_biocause_simple.txt', 'r') as rf:
lines = rf.readlines()
for line in lines:
biocause.append(line)
In [2]:
bioscope = []
with open('../../../data/wordvec/wordvec_input_bioscope_abstracts_simple.txt', 'r') as rf:
lines = rf.readlines()
for line in lines:
bioscope.append(line)
with open('../../../data/wordvec/wordvec_input_bioscope_papers_simple.txt', 'r') as rf:
lines = rf.readlines()
for line in lines:
bioscope.append(line)
In [3]:
ncbi = []
with open('../../../data/wordvec/wordvec_input_ncbi_all_simple.txt', 'r') as rf:
lines = rf.readlines()
for line in lines:
ncbi.append(line)
In [4]:
cdr = []
with open('../../../data/wordvec/wordvec_input_cdr_all_simple.txt', 'r') as rf:
lines = rf.readlines()
for line in lines:
cdr.append(line)
In [12]:
scrape = []
with open('../../../data/wordvec/wordvec_input_pubmedScrape_simple_noPunct.txt', 'r') as rf:
lines = rf.readlines()
for line in lines:
scrape.append(line.decode('utf-8'))
---------------------------------------------------------------------------
LookupError Traceback (most recent call last)
<ipython-input-12-dd0ff96810a7> in <module>()
4 lines = rf.readlines()
5 for line in lines:
----> 6 scrape.append(line.decode('utf-8').decode('unicode'))
LookupError: unknown encoding: unicode
In [6]:
combined = []
combined.append(cdr[0] + bioscope[0] + bioscope[1] + biocause[0] + ncbi[0] + scrape[0])
In [14]:
len(combined[0])
Out[14]:
1435062018
In [16]:
with open('../../../data/wordvec/wordvec_input_combined_simple.txt', 'w') as wf:
wf.write(combined[0])
In [8]:
len(scrape[0])
Out[8]:
1428100959
In [11]:
scrape[0][3000000:4000000]
Out[11]:
u'atients who were diagnosed at an immunology department between 1980 and 2013 patient s records were analysed the median diagnostic delay in 77 hae type 1 and 2 patients was seven range 0 42 years the difference observed in diagnostic delay between probands 18 0 42 years and others 1 0 37 year was significant p 0 001 our data show a significant negative correlation between the length of diagnostic delay and the year of diagnosis in our group of patients p 0 024 the median age of first symptoms among all hae patients n 64 was 17 1 40 years the first symptoms of hae in 64 patients were analysed twenty six patients had abdominal seventeen peripheral five facial two urogenital and three had laryngeal oedema as the first manifestation of the disease the last death that was attributed to hae was in 1977 our observations demonstrate improved awareness of hae among physicians as documented by the significant decrease in diagnostic delay it is believed that earlier treatment will improve patient quality of life and life expectancy penile curvature correction with plaque incision and graft pig increases the risk of erectile dysfunction ed and is associated with mechanical and geometric abnormalities the aim of this study was to create and validate a new pig technique using minimum graft area to correct simple or complex penile curvature with or without hourglass deformity while avoiding mechanical and geometric abnormalities using our cotton fabric model we created a mathematic solution for pig with no residual defects this was applied in nine men who had sufficient penile rigidity while penetrating their respective partners they underwent fascia lata patch corporoplasty using the new developed technique ipad apple corp palo alto ca usa app igrafter subjects answered the 5 item version of the international index of erectile function iief 5 questionnaire preoperatively and at the end of follow up the main outcome measures used were patient demographics erectile function residual curvature patient satisfaction graft area and complications after a mean follow up of 17 8 months no significant complication was noted complete penile straightening was achieved in all patients the short side of the penis increased a mean of 3 cm in length and the mean graft area was 12 4 cm 2 at the end of the follow up three patients developed recurrent deformity one patient presented severe fibrosis in the corpora cavernosa and severe ed there was no significant difference between the mean preoperative and postoperative iief 5 scores 20 6 vs 19 4 respectively at the end of follow up all patients were able to have sexual intercourse two with and seven without pharmacological aid eight of the nine patients were satisfied with the surgical result penile curvature surgical correction using the igrafter seems to be an efficient and safe procedure which uses minimum graft area and preserves erectile function after penile rectification without resulting in residual deformities further research is needed to confirm the efficacy of this procedure to address the questions and challenges commonly faced by primary care physicians when ordering serologic tests for celiac disease cd and provide practical clinical tips to help in the interpretation of test results medline was searched from 2000 to 2015 for english language guidelines on the diagnosis and management of cd published by professional gastroenterological organizations to screen patients for cd measurement of the immunoglobulin a iga tissue transglutaminase antibody is the preferred test total serum iga level should be measured to exclude selective iga deficiency and to avoid false negative test results patients with positive serologic test results should be referred to a gastroenterologist for endoscopic small intestinal biopsies to confirm the diagnosis testing for human leukocyte antigens dq2 and dq8 can help exclude the diagnosis a gluten free diet should not be started before confirming the diagnosis of cd serologic testing is very useful for screening patients with suspected cd early diagnosis is essential to prevent complications of cd to summarize the pathophysiology epidemiology screening diagnosis and treatment of familial hypercholesterolemia fh a pubmed search was conducted inception to july 2014 for articles on pathophysiology screening diagnosis and management of fh supplemented with hand searches of bibliographies of guidelines and reviews a supporting level of evidence for each recommendation was categorized as level i randomized controlled trial or systematic review of randomized controlled trials level ii observational study or level iii expert opinion the best available evidence is mostly level ii or iii familial hypercholesterolemia affects 1 in 500 canadians risk of a coronary event is high in these patients and is underestimated by risk calculators eg framingham clinicians should screen patients according to guidelines and suspect fh in any patient with a premature cardiovascular event physical stigmata of hypercholesterolemia or an elevated plasma lipid level physicians should diagnose fh using either the simon broome or dutch lipid network criteria management of heterozygous fh includes reducing low density lipoprotein levels by 50 or more from baseline with high dose statins and other lipid lowering agents clinicians should refer any patient with homozygous fh to a specialized centre familial hypercholesterolemia represents an important cause of premature cardiovascular disease in canadians early identification and aggressive treatment of individuals with fh reduces cardiovascular morbidity and mortality cdc has developed interim guidelines for health care providers in the united states caring for pregnant women during a zika virus outbreak these guidelines include recommendations for pregnant women considering travel to an area with zika virus transmission and recommendations for screening testing and management of pregnant returning travelers updates on areas with ongoing zika virus transmission are available online http wwwnc cdc gov travel notices health care providers should ask all pregnant women about recent travel pregnant women with a history of travel to an area with zika virus transmission and who report two or more symptoms consistent with zika virus disease acute onset of fever maculopapular rash arthralgia or conjunctivitis during or within 2 weeks of travel or who have ultrasound findings of fetal microcephaly or intracranial calcifications should be tested for zika virus infection in consultation with their state or local health department testing is not indicated for women without a travel history to an area with zika virus transmission in pregnant women with laboratory evidence of zika virus infection serial ultrasound examination should be considered to monitor fetal growth and anatomy and referral to a maternal fetal medicine or infectious disease specialist with expertise in pregnancy management is recommended there is no specific antiviral treatment for zika virus supportive care is recommended alzheimer disease ad is a common complex neurodegenerative disorder accounting for nearly 50 to 70 of dementias worldwide yet the current diagnostic options for ad are limited new diagnostic innovation strategies focusing on novel molecules and pathways are sorely needed in this connection micrornas mirnas are conserved small noncoding rnas that regulate posttranscriptional gene expression and are vital for neuronal development and its functional sustainability conceivably biological pathways responsible for the biogenesis of mirnas represent a veritable set of upstream candidate genes that can be potentially associated with the ad pathophysiology notably whereas functional single nucleotide polymorphisms snps in mirna biogenesis pathway genes have been studied in other complex diseases surprisingly virtually no such study has been conducted on their relevance in ad moreover novel diagnostics identified in easily accessible peripheral tissues such as the whole blood samples represent the initial entry or gateway points on the biomarker discovery critical path for ad to the best of our knowledge we report here the first association study of functional snps as measured by real time pcr in 10 upstream candidate genes critically situated on the mirna biogenesis pathway in a large sample of ad patients n 172 and healthy controls n 109 in a hitherto understudied world population from the mersin region of the eastern mediterranean we observed a significant association between 2 candidate genes and ad tarbp2 rs784567 genotype and ad \u03c7 6 292 p 0 043 and a trend for rnasen rs10719 genotype \u03c7 4 528 p 0 104 and allele p 0 035 functional snp variations in the other 8 candidate genes dgcr8 xpo5 ran dicer1 ago1 ago2 gemin3 and gemin4 did not associate with ad in our sample given the putative biological importance of mirna biogenesis pathways these emerging data can provide a new foundation to stimulate future debate and genetic investigations of ad focusing on new molecular mechanisms such as mirna biogenesis particularly in accessible peripheral tissues for novel molecular diagnostics for dementia the aim of this study was to evaluate the effect of postoperative adjuvant therapy on the survival in patients with n1 lymph node metastasis of esophageal squamous cell carcinoma escc 110 patients with positive n1 lymph node metastasis of esophageal squamous carcinoma were included in this study the surgery group included 46 cases and the postoperative adjuvant therapy group included 64 cases 24 cases in the adjuvant chemotherapy subgroup and 40 cases in the adjuvant concurrent chemoradiotherapy the disease free survival dfs and overall survival os of the two groups were compared and the prognostic factors were analyzed by multivariate cox model in the postoperative adjuvant therapy group the dfs 16 8 months and os 21 3 months were significantly prolonged compared with those in the surgery group 10 6 months p 0 007 and 13 7 months p 0 001 respectively postoperative adjuvant chemotherapy significantly extended the os 31 1 months of n1 positive patients compared with 13 7 months p 0 002 in the surgery group but there were no significant differences between the dfs in the two subgroups 16 3 and 16 8 months p 0 346 and between the os 23 4 and 21 3 months p 0 491 postoperative adjuvant therapy was an independent prognostic factor in the escc patients with n1 lymph node metastasis postoperative adjuvant therapy can improve the prognosis and prolong the survival time in escc patients with positive n1 lymph node metastasis in the 1990s china introduced a free tuberculosis tb care policy under the national tb control program recently as a part of a new tb diagnosis and treatment model it has been recommended that the integrated model scale up this paper examines whether or not tb designated hospitals in the selected project sites have provided tb care according to the national and local guidelines and analyzes the actual practices and expenditures involved in completing tb treatment it also explores the reasons why free tb care in china cannot be effectively implemented under the integrated model this study was conducted in three counties of zhenjiang city jiangsu province mixed methods were used which comprised reviewing the national and local tb control guidelines conducting tb patient surveys collecting tb inpatient and outpatient hospital records and conducting qualitative interviews with stakeholders descriptive statistics were used for quantitative data analysis across counties and in order to compare patients who received only outpatient care and those who received both outpatient and inpatient care the chi square test and analysis of variance were performed where necessary qualitative data were analyzed using the framework approach although the national tb care guidelines recommend outpatient care as a basis for tb treatment in china we found high hospital admission rates for tb patients ranging from 39 in yangzhong county to 83 in dantu county almost all outpatient tb patients paid for lab tests and over 80 paid for liver protection drugs and around 70 paid for image examinations these three components accounted for three quarters of the total outpatient expenditure for patients who received only outpatient care the total expenditure upon completion of tb treatment was on average 1 135 chinese yuan for patients who received outpatient and inpatient care the total expenditure upon completion of tb treatment was 11 117 chinese yuan the free tb care policy under the integrated model has not been effectively implemented in china there has been substantial spending on non recommended services examinations and drugs for tb treatment introduction of pneumococcal conjugate vaccines pcvs for infants decreased overall invasive pneumococcal disease ipd while non vaccine serotype ipd increased to fully understand this serotype replacement knowledge about serotype dynamics in the pre vaccine era is needed in addition to ipd surveillance and carriage studies the serotype replacement can be investigated by serosurveillance studies the current study compared the results of two dutch serosurveillance studies conducted in 1995 1996 pienter1 and 2006 2007 pienter2 participants in these studies donated a blood sample and completed a questionnaire pneumococcal antibodies of serotypes included in pcv13 were measured with a fluorescent bead based multiplex immunoassay geometric mean antibody concentrations gmcs and determinants of pneumococcal antibody levels were investigated gmcs were higher in pienter2 for serotypes 1 6a 6b 9v 18c 19f and 23f and lower for 3 and 5 age day care attendance household size vaccination coverage and urbanisation rate were associated with pneumococcal antibodies in children education level ethnicity age low vaccination coverage sample urbanisation rate and asthma copd were associated with pneumococcal antibodies in elderly the determinants significantly associated with pneumococcal igg were slightly different for the elderly in pienter1 compared to the elderly in pienter2 although most of the serotype antibody levels remained stable some of the serotype specific antibody levels varied during the pre vaccine era indicating that exposure of certain serotypes changes without interference of pcvs celiac disease cd may affect healthcare use in children and young adults socio economic factors may act as a confounder or effect modifier we assessed such hypotheses in a population based birth cohort of young celiac subjects and references matched by maternal education the cohort included all newborns recorded in the medical birth register of friuli venezia giulia region italy between 1989 and 2011 cd incident cases were identified through pathology reports hospital discharges and copayment exemptions and matched with up to five references by sex year of birth and maternal education cox regression models were used to estimate hazard ratios hrs for major causes of inpatient diagnosis and drug prescription occurring after diagnosis in cd patients compared to references stratifying by time of first event and maternal education we identified 1294 cd cases and 5681 references cd cases had a higher risk of hospital admission for any cause hr 2 34 95 ci 2 08 2 63 and for all major icd9 cm categories except obstetric complications skin and musculoskeletal diseases and injuries and poisoning prescription of all major atc drug categories except dermatologicals and genito urinary medications was significantly increased in cd subjects for most outcomes hrs were highest in the first year after cd diagnosis but remained significant after five or more years hrs were similar across different categories of maternal education diagnosed cd subjects had a higher risk of hospitalization and medication use compared to the general population even five or more years after diagnosis with no effect modification of maternal education to identify from a patient s perspective difficulties and differences in the comprehension of five global presenteeism measures in patients with inflammatory arthritis and oa across seven countries seventy patients with a diagnosis of inflammatory arthritis or oa in paid employment were recruited from seven countries across europe and canada patients were randomly allocated to be cognitively debriefed on 3 5 global measures work productivity scale rheumatoid arthritis work productivity and activity impairment questionnaire wpai work ability index quality and quantity questionnaire and who health and work performance questionnaire hpq with the wpai debriefed in all patients as a standard measure of comparison between countries and patients nvivo was used to code the data into four themes construct and anchor time recall reference frame and attribution discrepancies were found in the interpretation of the word performance hpq between countries with romania and sweden relating performance to sports rather than work seventy percent of patients considered that a 7 day recall wpai can accurately represent how their disease affects work productivity the compared to normal reference quality and quantity questionnaire was reportedly too ambiguous and the comparison with colleagues hpq made many feel uncomfortable overall 29 of patients said the wpai was the most relevant to them making it the most favoured measure overall patients across countries agree that the construct of work productivity in the last 7 days can accurately reflect the impact of disease while at work some current constructs to assess at work productivity are not interchangeable between languages pheochromocytomas and paragangliomas ppgls are heritable neoplasms that can be classified into gene expression subtypes corresponding to their underlying specific genetic drivers this study aimed to develop a diagnostic and research tool pheo type capable of classifying ppgl tumors into gene expression subtypes that could be used to guide and interpret genetic testing determine surveillance programs and aid in elucidation of ppgl biology a compendium of published microarray data representing 205 ppgl tumors was used for the selection of subtype specific genes that were then translated to the nanostring gene expression platform a support vector machine was trained on the microarray dataset and then tested on an independent nanostring dataset representing 38 familial and sporadic cases of ppgl of known genotype ret nf1 tmem127 max hras vhl and sdhx different classifier models involving between three and six subtypes were compared for their discrimination potential a gene set of 46 genes and six endogenous controls was selected representing six known ppgl subtypes rtk1 3 ret nf1 tmem127 and hras max like vhl and sdhx of 38 test cases 34 90 were correctly predicted to six subtypes based on the known genotype to gene expression subtype association removal of the rtk2 subtype from training characterized by an admixture of tumor and normal adrenal cortex improved the classification accuracy 35 38 consolidation of rtk and pseudohypoxic ppgl subtypes to four and then three class architectures improved the classification accuracy for clinical application the pheo type gene expression assay is a reliable method for predicting ppgl genotype using routine diagnostic tumor samples sickle cell disease scd is the most common cause of stroke in childhood and results primarily from a mismatch of cerebral oxygen supply and demand rather than arterial obstruction however resting cerebral blood flow cbf has not been examined in the general african american population in whom obesity hypertension cerebrovascular disease and diminished cerebrovascular reserve capacity are common to better understand the underlying physiological substrate upon which scd is superimposed we measured cbf in 32 young age 28 10 yr asymptomatic african american subjects with and without sickle cell trait n 14 to characterize the effects of chronic anemia in isolation of sickle hemoglobin we also studied a cohort of 13 subjects with thalassemia major n 10 dyserythropoetic anemia n 1 or spherocytosis n 2 blood was analyzed for complete blood count hemoglobin electrophoresis cell free hemoglobin and lactate dehydrogenase multivariate regression analysis showed that oxygen content was the strongest predictor of cbf r 2 0 33 p 0 001 cbf declined rapidly in the second and third decades of life but this drop was explained by reductions in cerebral gray matter however age effects persisted after correction for brain composition possibly representing microvascular impairment cbf was independent of viscosity hemoglobin s and body mass index hyperoxia resulted in reduced cbf by 12 6 p 0 0002 and cbf changes were proportional to baseline oxygen content r 2 0 16 p 0 02 these data suggest that these hemoglobin subtypes do not alter the normal cbf regulation of the balance of oxygen supply and demand the non classical human leukocyte antigen g hla g molecule and its soluble forms exert multiple immune suppressive regulatory functions in malignancy and in stem cells contributing to immune escape mechanisms hla g can be secreted as free soluble hla g molecules or via extracellular vesicles evs here we evaluated these soluble hla g forms as prognostic marker for prediction of the clinical outcome of neoadjuvant chemotherapy nact treated breast cancer bc patients plasma samples of bc patients procured before n 142 and after n 154 nact were quantified for total soluble hla g shla gtot and hla g levels in exoquick derived ev fractions shla gev by elisa the corresponding increments were specified as free shla g shla gfree total and free shla g were significantly increased in nact treated bc patients compared to healthy controls n 16 high shla gfree levels were exclusively associated to estrogen receptor expression before nact importantly high shla gev levels before nact were related to disease progression and the detection of stem cell like circulating tumor cells but high shla gfree levels indicated an improved clinical outcome thus this study demonstrates for the first time that the different shla g subcomponents represent dissimilar qualitative prognostic impacts on the clinical outcome of nact treated bc patients whereas the total shla g levels without separating into subcomponents are not related to clinical outcome mild traumatic brain injuries can lead to long lasting cognitive and motor deficits increasing the risk of future behavioral neurological and affective disorders our study focused on long term behavioral deficits after repeated injury in which mice received either a single mild chi mchi a repeated mild chi rmchi consisting of one impact to each hemisphere separated by 3 days or a moderate controlled cortical impact injury cci shams received only anesthesia behavioral tests were administered at 1 3 5 7 and 90 days post injury dpi cci animals showed significant motor and sensory deficits in the early 1 7 dpi and long term 90 dpi stages of testing interestingly sensory and subtle motor deficits in rmchi animals were found at 90 dpi most importantly depression like behaviors and social passiveness were observed in rmchi animals at 90 dpi these data suggest that mild concussive injuries lead to motor and sensory deficits and affective disorders that are not observed after moderate tbi this retrospective further analysis of the action database evaluated the relationships between baseline blood pressure bp on treatment bp after 6 weeks and subsequent cardiovascular outcomes analyses were performed using multivariate cox proportional hazard models statistically significant p 0 001 and consistent patterns were noted between the risk of major cardiovascular endpoints and both baseline sbp and on treatment sbp the lowest risk of debilitating stroke was apparent in those patients with baseline sbp 120mmhg with a hazard ratio in this lowest bp group of 0 45 95 confidence interval 0 28 0 72 compared to the referent highest bp group sbp 150mmhg adjusting the model for treatment nifedipine or placebo did not modify the conclusions in any statistical or clinically meaningful way corresponding and similar results were obtained for pulse pressure but diastolic blood pressure dbp was not a consistently useful predictor of outcome these data confirm the predictive importance of on treatment sbp but not dbp and contribute to the debate about treatment related bp targets in this analysis treatment with nifedipine gastrointestinal therapeutic system in high risk patients with coronary artery disease was not associated with any increase in cardiovascular risk even with baseline sbp5120mmhg hepatitis c virus hcv infection is a significant public health problem worldwide however there is still a lack of effective therapeutic drugs which could be used for the interruption of the disease in the present study for the first time we reported that a synthesized peptide which was synthesized by solid phase peptide synthesis and derived from the amino acids 710 to 725 of the hcv e2 functioned as an inhibitor of hcv infection using an mtt assay we found that the e2 710 725 peptide exerted no specific cytotoxicity on huh7 5 cells and primary human hepatocytes phh interestingly e2 710 725 peptide blocked the entry of cell culture \u2011derived hcv hcvcc into hepatocytes moreover it suppressed hcv rna replication and hcv specific protein ns3 and ns5b expression as shown by western blot analysis moreover e2 710 725 markedly attenuated the inhibitory effect of hcvcc on hepatocyte viability additionally a co immunino precipitation assay demonstrated that e2 710 725 abrogated the interaction between cd81 and hcv e2 envelope protein through competitive binding of cd81 overall our results revealed that the synthesized peptide e2 710 725 blocked cd81 \u2011mediated hcv entry and possessed the potential to treat hcv infection thus the present study provided novel insights into the development of new drugs for preventing hcv infection the human cns follows a pattern of development typical of all mammals but certain neurodevelopmental features are highly derived building the human cns requires the precise orchestration and coordination of myriad molecular and cellular processes across a staggering array of cell types and over a long period of time dysregulation of these processes affects the structure and function of the cns and can lead to neurological or psychiatric disorders recent technological advances and increased focus on human neurodevelopment have enabled a more comprehensive characterization of the human cns and its development in both health and disease the aim of this review is to highlight recent advancements in our understanding of the molecular and cellular landscapes of the developing human cns with focus on the cerebral neocortex and the insights these findings provide into human neural evolution function and dysfunction acetylcholinesterase inhibitors acheis are efficacious for the treatment of mild to moderate forms of alzheimer s dementia ad default mode network dmn connectivity is considered to be early impaired in ad long term effects of acheis on the dmn in ad have not yet been investigated twenty eight ad patients and 11 age matched healthy volunteers hc participated in the prospective study ad patients were randomly assigned to either a pharmacotherapy arm galantamine ad g or to a placebo arm ad p g for the period of 6 months followed by open label galantamine therapy from month 7 12 all subjects underwent neuropsychological testing resting state functional and structural mri at baseline and after 12 months ad patients additionally in between after 6 months thirteen ad patients completed the treatment trial and underwent all functional mri follow up sequences of good quality functional connectivity significantly increased within the ad g group in the posterior cingulate cortex and in the precuneus between baseline and 12 months follow up pcorr 0 05 between group analyses demonstrated that functional connectivity in the ad g group significantly increased in the posterior cingulate cortex as well as in the precuneus compared to the hc group and in the anteromedial aspect of the temporal lobes compared to the ad p g group respectively at 12 months follow up pcorr 0 05 cognitive performance remained stable within groups over time indicating that resting state fmri may be sensitive for the detection of pharmacologically induced effects on brain function of ad patients recurrent miscarriage rm is a stressful condition which gives rise to extensive diagnostic evaluation and is seen as a potentially curable maternal disease nevertheless epidemiological data have shown that outcome is related to fertility in addition to maternal age and number of preceding miscarriages further markers derived from the past history may support counselling observational trial comprising 228 couples who were referred between 1996 and 2003 for immunological evaluation at maternal ages 20 39 years after three or more spontaneously conceived primary first trimester miscarriages they were interviewed in 2005 ongoing pregnancies were followed up until birth in 2006 past obstetric history was correlated with 2 year cumulative pregnancy and delivery rates cpr cdr cpr and cdr were 206 228 90 4 and 174 228 76 4 duration of infertility was associated with lower cpr up to 3 3 years p 0 01 whereas age and number of preceding losses inversely correlated with cdr 35 years 35 39 years p 0 002 3 3 miscarriages p 0 002 detection of an embryonic heart beat in 2 3 of the first three miscarriages resulted in favourable outcome cpr p 0 02 cdr p 0 002 prognosis was excellent in younger fertile women after three miscarriages where vital signs had been detected under less favourable conditions not only risks for further miscarriage but also for secondary infertility were elevated secondary infertility is a feature of rm embryonic vital signs in preceding pregnancies are prognostic markers and should be regarded as a strong confounding factor in trials on therapeutic interventions prevention may be more appropriate than treatment in this article we review the biology and physiological importance of transforming growth factor \u03b2 tgf \u03b2 to homeostasis in the respiratory system its importance to innate and adaptive immune responses in the lung and its pathophysiological role in various chronic pulmonary diseases including pulmonary arterial hypertension chronic obstructive pulmonary disease asthma and pulmonary fibrosis the tgf \u03b2 family is responsible for initiation of the intracellular signaling pathways that direct numerous cellular activities including proliferation differentiation extracellular matrix synthesis and apoptosis when tgf \u03b2 signaling is dysregulated or essential control mechanisms are unbalanced the consequences of organ and tissue dysfunction can be profound the complexities and myriad checkpoints built into the tgf \u03b2 signaling pathways provide attractive targets for the treatment of these disease states many of which are currently being investigated this review focuses on those aspects of tgf \u03b2 biology that are most relevant to pulmonary diseases and that hold promise as novel therapeutic targets avian influenza viruses continue to cross the species barrier and if such viruses become transmissible among humans it would pose a great threat to public health since its emergence in china in 2013 h7n9 has caused considerable morbidity and mortality in the absence of a universal influenza vaccine preparedness includes development of subtype specific vaccines in this study we developed and evaluated in ferrets an intranasal live attenuated influenza vaccine laiv against h7n9 based on the a leningrad 134 17 57 h2n2 cold adapted master donor virus we demonstrate that the laiv is attenuated and safe in ferrets and induces high hemagglutination and neuraminidase inhibiting and virus neutralizing titers the antibodies against hemagglutinin were also cross reactive with divergent h7 strains to assess efficacy we used an intratracheal challenge ferret model in which an acute severe viral pneumonia is induced that closely resembles viral pneumonia observed in severe human cases a single and two dose strategy provided complete protection against severe pneumonia and prevented virus replication the protective effect of the two dose strategy appeared better than the single dose only on the microscopic level in the lungs we observed however an increased lymphocytic infiltration after challenge in single vaccinated animals and hypothesize that this a side effect of the model membrane levels of docosahexaenoic acid dha an essential omega 3 polyunsaturated fatty acid \u03c9 3 pufa are decreased in common neuropsychiatric disorders dha modulates key cell membrane properties like fluidity thereby affecting the behaviour of transmembrane proteins like g protein coupled receptors gpcrs these receptors which have special relevance for major neuropsychiatric disorders have recently been shown to form dimers or higher order oligomers and evidence suggests that dha levels affect gpcr function by modulating oligomerisation in this study we assessed the effect of membrane dha content on the formation of a class of protein complexes with particular relevance for brain disease adenosine a2a and dopamine d2 receptor oligomers using extensive multiscale computer modelling we find a marked propensity of dha for interaction with both a2a and d2 receptors which leads to an increased rate of receptor oligomerisation bioluminescence resonance energy transfer bret experiments performed on living cells suggest that this dha effect on the oligomerisation of a2a and d2 receptors is purely kinetic this work reveals for the first time that membrane \u03c9 3 pufas play a key role in gpcr oligomerisation kinetics which may have important implications for neuropsychiatric conditions like schizophrenia or parkinson s disease hypertension htn is a modifiable risk factor for cardiovascular disease cvd renal artery calcium rac may signal the presence of flow limiting atherosclerotic disease that may contribute to changes in the kidney s regulation of blood pressure we hypothesized that rac is independently associated with htn we examined a multiethnic cohort of 1285 participants who underwent abdominal computed tomography scans in five us communities after adjustment for age gender race ethnicity cvd risk factors abdominal aortic calcium score and kidney function the presence of rac was associated with a 50 higher odds of htn odds ratio 1 54 95 confidence interval 1 11 2 13 similarly the presence of rac was associated with a 8 5 mm hg higher systolic blood pressure a 2 1 mm hg higher diastolic blood pressure and a 7 4 mm hg higher pulse pressure in conclusion independent of cvd risk factors abdominal aortic calcium and kidney function the presence of rac is associated with htn prevalence among 1 683 persons in the united states who developed malaria following international travel during 2012 more than half acquired disease in one of 16 countries in west africa since march 2014 west africa has experienced the world s largest epidemic of ebola virus disease ebola primarily affecting guinea sierra leone and liberia in 2014 approximately 20 000 ebola cases were reported both ebola and malaria are often characterized by fever and malaise and can be clinically indistinguishable especially early in the course of disease immediate laboratory testing is critical for diagnosis of both ebola and malaria so that appropriate lifesaving treatment can be initiated cdc recommends prompt malaria testing of patients with fever and history of travel to an area that is endemic for malaria using blood smear microscopy with results available within a few hours empiric treatment of malaria is not recommended by cdc reverse transcription polymerase chain reaction rt pcr testing is recommended to diagnose ebola during the ebola outbreak in west africa cdc received reports of delayed laboratory testing for malaria in travelers returning to the united states because of infection control concerns related to ebola cdc reviewed documented calls to its malaria consultation service and selected three patient cases to present as examples of deficiencies in the evaluation and treatment of malaria among travelers returning from africa during the ebola epidemic the aim of this study was to assess the clinical value of pro gastrin releasing peptide progrp squamous cell carcinoma antigen scc ag cytokeratin 19 fragment antigen 21 1 cyfra21 1 and carcino embryonic antigen cea in the diagnosis and clinical stage of lung cancer in chinese patients patients with lung cancer and benign lesions confirmed by pathology were enrolled in peking union medical college hospital from january 2013 to october 2014 the serum levels of four tumor markers progrp scc ag cyfra21 1 and cea were measured using immunoassays before treatment the sensitivity specificity positive predictive value ppv negative predictive value npv and the areas under the receiver operating characteristic curve aucroc of these four tumor biomarkers were analyzed for the diagnosis of lung cancer a total of 134 patients were finally analyzed including 73 patients with lung cancer and the other 61 patients with benign lung disease the diagnostic sensitivity of serum cyfra21 1 to lung cancer was 67 1 the specificity 45 1 the aucroc 0 658 the diagnostic sensitivity of the panel including progpr cyfra21 1 and cea to lung cancer was 75 3 the specificity 57 4 the aucroc 0 702 in the lung cancer group the aucroc of progrp over 65 ng l to diagnose small cell lung cancer was 0 954 the aucroc of scc ag over 1 5 \u03bcg l to diagnose squamous cell lung cancer was 0 788 the aucroc of cyfra21 1 to diagnose non squamous non small cell lung cancer was 0 716 in small cell lung cancer patients the level of progrp in limited disease small cell lung cancer ld sclc were significantly higher than that in extensive disease small cell lung cancer ed sclc p 0 005 this panel of serum tumor markers including progrp cyfra21 1 and cea improves the diagnostic specificity and sensitivity in patients with high risk lung cancer the serum cea level of advanced lung cancer patients is significantly increased the high level of serum progrp predicts the ed sclc to compare the discrepancy between the new 2012 and the old 1992 atlanta classification criteria for defining severity organ failure and local complications in patients with acute pancreatitis ap demographic clinical and laboratory data of 2 305 consecutive ap patients with onset less than 3 days were collected between january 2005 to december 2013 in the first affiliated hospital of nanchang university severity organ failure and pancreatic local complications were respectively classified by the old atlanta classification and the new revised atlanta classification multi factor scoring system and single serum marker were recorded and calculated using the acute pancreatitis database in 2 305 patients with ap there were 301 cases 13 1 diagnosed with acute respiratory failure 136 cases 5 9 with shock 105 cases 4 6 with acute renal failure 296 cases 12 8 with gastrointestinal bleeding based on the old atlanta classification criteria according to the severity 900 cases 39 0 were classified as mild acute pancreatitis map 1 405 cases 61 0 as severe acute pancreatitis sap however based on the new atlanta classification criteria there were 686 cases 29 8 with acute respiratory failure 129 cases 5 6 with acute renal failure 107 cases 4 6 with circulatory failure consequently 998 cases 43 3 were classified as map 937 cases 40 7 as moderately severe acute pancreatitis msap 370 cases 16 1 as sap the incidence of respiratory failure was lower than that of the old standard in sap patients by new criteria the discharge rate in critical condition and mortality were not only higher than those in msap patients 17 0 vs 4 1 4 1 vs 1 5 respectively all p 0 001 but also higher than those in sap patients by the old classification 17 0 vs 7 2 4 1 vs 2 1 all p 0 001 the diagnostic criteria of organ failure are different between the new and old atlanta classification the sap patients classified by the new standard have worse outcome than those by the old standard more attention needs to be paid to critical patients stratified by the new standard to investigate the correlation between the frequency of dawn phenomenon and obesity in patients with type 2 diabetes this study was conducted in 98 patients with type 2 diabetes admitted to the metabolic disease hospital of tianjin medical university from 2011 to 2014 the subjects were divided into 3 groups according to bmi the normal weight bmi 18 5 23 9 kg m 2 n 30 the overweight bmi 24 27 9 kg m 2 n 33 and the obesity bmi 28 0 kg m 2 n 35 all participants underwent continuous glucose monitoring for 72 h fasting plasma glucose fpg insulin and c peptide were tested frequency of dawn phenomenon among the 3 groups was calculated and the correlations between dawn phenomenon and its related factors were analyzed the frequency of dawn phenomenon in type 2 diabetes increased with the increase of bmi in the 3 groups p 0 05 with 33 3 in the normal weight 78 8 in the overweight and 88 6 in the obesity groups respectively the dawn phenomenon was positively correlated with bmi r 0 424 p 0 05 homeostasis model assessment of insulin resistance homa ir r 0 781 p 0 05 waist circumference r 0 394 p 0 05 fasting c peptide r 0 254 p 0 05 and tg r 0 220 p 0 05 it was negatively correlated with the course of diabetes mellitus r 0 278 p 0 05 and hdl c r 0 268 p 0 05 no correlation could be viewed between the dawn phenomenon and age ldl c glycosylated hemoglobin a1c hba1c tc and fpg p 0 05 the dawn phenomenon is closely associated with obesity and insulin resistance the frequency of dawn phenomenon increases with bmi the mediator complex associated cyclin dependent kinase cdk8 has been implicated in human disease particularly in colorectal cancer where it has been reported as a putative oncogene here we report the discovery of 109 cct251921 a potent selective and orally bioavailable inhibitor of cdk8 with equipotent affinity for cdk19 we describe a structure based design approach leading to the discovery of a 3 4 5 trisubstituted 2 aminopyridine series and present the application of physicochemical property analyses to successfully reduce in vivo metabolic clearance minimize transporter mediated biliary elimination while maintaining acceptable aqueous solubility compound 109 affords the optimal compromise of in vitro biochemical pharmacokinetic and physicochemical properties and is suitable for progression to animal models of cancer there is limited information about the impact of type 1 diabetes on life expectancy in a contemporary population we examined the life expectancy of type 1 diabetic patients and explored the contribution of mortality at different ages and of different causes of death to years of life lost yll compared with the general population we derived mortality rates of australians with type 1 diabetes listed on the national diabetes services scheme ndss between 1997 and 2010 n 85 547 by linking the ndss to the national death index the chiang method was used to estimate life expectancy and arriaga s method was used to estimate the contributions of age specific and cause specific mortality to the yll a total of 5 981 deaths were identified during the 902 136 person years of follow up type 1 diabetic patients had an estimated life expectancy at birth of 68 6 years 95 ci 68 1 69 1 which was 12 2 years 95 ci 11 8 12 7 less than that in the general population the improvement in life expectancy at birth in 2004 2010 compared with 1997 2003 was similar for both type 1 diabetic patients men 1 9 years 95 ci 0 4 3 3 women 1 5 years 95 ci 0 0 3 2 and the general population men 2 2 years women 1 4 years deaths at age 60 years accounted for 60 of the yll from type 1 diabetes for men and 45 for women the major contribution to yll was mortality from endocrine and metabolic disease at age 10 39 years men 39 59 women 35 50 and from circulatory disease at age \u226540 years men 43 75 women 34 75 data from 1997 to 2010 showed that australian type 1 diabetic patients had an estimated loss in life expectancy at birth of 12 2 years compared with the general population a new entity of patients with recurrent prostate cancer limited to a small number of active metastatic lesions is having growing interest the oligometastatic patients patients with oligometastatic disease could eventually be managed by treating all the active lesions with local therapy i e either surgery or ablative stereotactic body radiotherapy this study aims to assess the impact of 18 f choline 18 f fmch pet ct and the use stereotactic body radiotherapy sbrt in patients pts with oligometastatic prostate cancer pca twenty nine pts with oligometastatic pca \u22643 synchronous active lesions detected with 18 f fmchpet ct were treated with repeated salvage sbrt until disease progression development of three active synchronous metastases primary endpoint was systemic therapy free survival measured from the baseline 18 f fmchpet ct a total of 45 lesions were treated with sbrt after a median follow up of 11 5 months range 3 40 months 20 pts were still in the study and did not receive any systemic therapy nine pts started systemic therapy and the median time of the primary endpoint was 39 7 months ci 12 20 62 14 months no grade 3 or 4 toxicity was recorded repeated salvage 18 f fmchpet ct guided sbrt is well tolerated and could defer the beginning of systemic therapy in selected patients with oligometastatic pca oligodendrocyte progenitor cells opcs are the often overlooked fourth glial cell type in the central nervous system cns comprising about 5 of the cns for a long time our vision of opc function was limited to the generation of mature oligodendrocytes however new studies have highlighted the multifaceted nature of opcs during homeostatic and pathological conditions opcs are the most proliferative cell type in the cns a property not consistent with the need to generate new oligodendrocytes indeed opcs modulate neuronal activity and opc depletion in the brain can trigger depressive like behavior more importantly opcs are actively recruited to injury sites where they orchestrate glial scar formation and contribute to the immune response the following is a comprehensive analysis of the literature on opc function beyond myelination in the context of the healthy and diseased adult cns assessment of right ventricular rv function is a challenge especially in patients with congenital heart disease chd the aim of the present study is to assess whether knowledge based rv reconstruction used in the everyday practice of an echo lab for adult chd in a tertiary referral center is accurate when compared to cardiac magnetic resonance cmr examination adult patients who would undergo cmr for assessment of the rv were asked to undergo an echo of the heart for further knowledge based reconstruction kbr echocardiographic images were acquired in standard views using a predefined imaging protocol rv volumes and ejection fraction ef calculated using knowledge based technology were compared with the cmr data of the same patient nineteen consecutive patients with congenital right heart disease were studied median age of the patients was 28 years range 46 years reconstruction was possible in 16 out of 19 patients 85 rv volumes assessed with this new method were smaller than with cmr indexed end diastolic volumes were 114 \xb117 ml vs 121 \xb119 ml p 0 05 and efs were 45 \xb18 vs 47 \xb19 p 0 05 respectively the correlation between the methods was good with an intraclass correlation of 0 84 for edv and 0 89 for ef p value 0 001 in both cases kbr enables reliable measurement of rvs in patients with chds and can be used in clinical practice for analysis of volumes and efs the aim of this study is to compare the hemodynamic effects of neostigmine atropine combination and sugammadex in patients with cardiac problems undergoing noncardiac surgery prospective randomized study in the operating room ninety patients with a class 2 or 3 cardiovascular disease according to the new york heart association classification and aged between 18 and 75 years undergoing noncardiac surgery were randomized group n n 45 received 0 03 mg kg iv neostigmine when t2 appeared as measured with a nerve muscle stimulator when heart rate was 5 beats min \xb110 beats min lower than the heart rate before administration of the medication 0 5 mg iv atropine sulfate was given group s n 45 received 3 mg kg iv sugammadex when t2 appeared as measured with a nerve muscle stimulator heart rate mean systolic and diastolic blood pressures and electrocardiographic alterations including the qtc qt fredericia and qt bazett were recorded there were no significant differences between and within the groups in terms of qtc values sugammadex group had a significant decrease on heart rate 1 minute after the medication when compared to the measurement before the medication p 05 heart rate and systolic blood pressure increased in neostigmine group 3 minutes after the medication and during postoperative measurements p 05 sugammadex group had lower systolic diastolic and mean blood pressures and heart rate when compared to neostigmine group p 05 we suggest that sugammadex might be preferred as it provides more hemodynamic stability compared to neostigmine atropine combination to reverse rocuronium induced neuromuscular blockage in cardiac patients undergoing noncardiac surgery postoperative pulmonary complications ppcs are significant problems in patients undergoing radical head and neck cancer surgery with free flap reconstruction the objective of the study was to identify the incidence outcome and risk factors for ppcs we hypothesized that preoperative pulmonary disease and amount of fluid administered during the surgery would be associated with ppcs a retrospective clinical observational study a large academic institution a total of 110 patients who underwent head and neck cancer surgery with microvascular free flap reconstruction between january 1 2005 and december 31 2011 no study interventions were performed ppcs including pulmonary edema pneumonia and acute respiratory distress syndrome were clinically diagnosed perioperative parameters and outcomes among patients with and without ppcs were compared factors predictive of ppcs were identified with univariate and multiple logistic regression analyses the incidence of ppcs was 32 7 36 patients pulmonary edema in 23 6 26 and pneumonia in 9 1 10 no acute respiratory distress syndrome was found inhospital mortality was 1 8 2 no difference was found in survival between the patients with ppcs and those without 1 year survival was 69 4 vs 78 4 p 85 the patients with ppcs required longer ventilation support median 4 vs 2days p 002 and more frequent intensive care unit readmissions 30 3 vs 5 7 p 001 and stayed longer in the hospital median 17 vs 12days p 014 none of the preoperative parameters or intraoperative parameters including pulmonary comorbidity or the amounts of intraoperative fluid blood administration was found as the factor to predict postoperative pulmonary compilations the incidence of ppcs in patients undergoing radical head and neck surgery was 32 7 in 110 patients preoperative pulmonary disease or the amount of fluid administered during the surgery was not associated with ppcs the clinical importance of the detection of neuroblastoma messenger rna mrna in bone marrow bm of localised neuroblastoma patients at diagnosis remains unclear in this prospective multicentre study bm samples of a large cohort were studied using real time quantitative polymerase chain reaction qpcr bm samples at diagnosis from 160 patients with localised neuroblastoma were prospectively collected at dutch and german centres between 2009 and 2013 qpcr was performed using five neuroblastoma specific markers the association with other biological factors and the prognostic impact of bm positivity and clinical response was assessed in 58 out of 160 patients neuroblastoma mrna was detected in bm in 47 of the 58 positive samples only one marker was found positive bm positivity was significantly associated with mycn amplification p 0 02 and deletion of chromosome 1p p 0 04 in total 31 patients had an event of which only five patients had progression to stage iv bm positivity was not associated with an unfavourable outcome however the detection of more than one marker was associated with an unfavourable outcome systemic or local relapse event free survival 48 versus 85 p 0 03 in the whole cohort and in the observation group bm positivity was associated with unfavourable biological factors and might represent more aggressive tumours patients with qpcr positive bm should not be upstaged because of very few systemic events in the cohort however for patients with more than one marker positive a more careful follow up is advisable these results need to be verified in a very large cohort of localised patients rabies is a neglected viral zoonosis with the highest case fatality of any infectious disease pasteur s historical accomplishments during the late 19 th century began the process of human vaccine development continuing to evolve into the 21 st century over the past 35 years great improvements occurred in the production of potent tissue culture vaccines and the gradual removal from the market of unsafe nerve tissue products timely and appropriate administration of modern biologics virtually assures survivorship even after severe exposures nevertheless in the developing world if not provided for free nationally the cost of a single course of human prophylaxis exceeds the average monthly wage of the common worker beyond traditional approaches recombinant sub unit and other novel methods are underway to improve the availability of safe effective and more affordable rabies biologics although poppers are increasingly popular among msm in china little is known about the patterns of poppers use the objectives of this study were to describe the patterns of poppers use and examine its association with sexual behaviors and hiv infection among msm in beijing china as part of a multi component hiv intervention trial 3588 msm were surveyed between march 2013 and march 2014 in beijing china blood samples were collected and tested for hiv and syphilis the questionnaire collected information about socio demographic and behavioral characteristics univariate and multivariable logistic regression analyses were performed to evaluate the correlates of poppers use over a quarter of men 27 5 reported having used at least one type of drugs in the past three months poppers were the most popular one 26 8 poppers use was correlated with a higher hiv prevalence odds ratio or 1 38 95 confidence interval ci 1 11 1 70 demographic and sexual behavioral factors associated with poppers use included younger age adjusted or aor 1 56 95 ci 1 25 1 94 higher education aor 1 61 95 ci 1 33 1 96 alcohol use aor 1 32 95 ci 1 10 1 60 seeking male partners mainly via the internet aor 1 60 95 ci 1 28 2 00 multiple male sex partnership aor 2 22 95 ci 1 90 2 60 and unprotected receptive anal intercourse aor 1 52 95 ci 1 28 1 81 in this study poppers use was positively associated with hiv infection and unprotected anal intercourse intervention efforts should be devoted to promote safer sex and hiv testing and counseling among msm who use poppers osteoporosis is a systemic metabolic bone disease characterized by a reduction in bone mass bone quality and microarchitectural deterioration an imbalance in bone remodeling that is caused by more osteoclast mediated bone resorption than osteoblast mediated bone formation results in such pathologic bone disorder traditional chinese medicines tcm have long been used to prevent and treat osteoporosis and have received extensive attentions and researches at home and abroad because they have fewer adverse reactions and are more suitable for long term use compared with chemically synthesized medicines here we put the emphasis on osteoblasts summarized the detailed research progress on the active compounds derived from tcm with potential anti osteoporosis effects and their molecular mechanisms on promoting osteoblast mediated bone formation it could be concluded that tcm with kidney tonifying spleen tonifying and stasis removing effects all have the potential effects on treating osteoporosis the active ingredients derived from tcm that possess effects on promoting osteoblasts proliferation and differentiation include flavonoids glycosides coumarins terpenoids sesquiterpenoids monoterpenoids diterpenoids phenolic acids phenols and others tetrameric stilbene anthraquinones diarylheptanoids and it was confirmed that the bone formation effect induced by the above natural products was regulated by the expressions of bone specific matrix proteins alp bsp ocn opn col i transcription factor runx2 cbfa1 osx signal pathways mapk bmp local factors ros no opg rankl system of osteoblasts and estrogen like biological activities all the studies provided theoretical basis for clinical application as well as new drug research and development on treating osteoporosis the link between social practices and representations is now well known but while many studies have focused on the social representation of mental illness in various populations few studies have focused on the notion of disease illness by comparing professionals and non professionals health workers representations indeed the disease is both a reality described explained and treated by medicine for those who are affected by a disease it is an individual experience with psychological social and cultural impacts the social representation is determined by the structure of the social groups in which it develops therefore it is a form of knowledge socially shaped and shared by the members of a social group several theoretical extensions have been elaborated and particularly the structural approach and the central core theory these approaches sustain the arguments of a hierarchical organization of a social representation with a central core surrounded by peripheral zones the central core is common and shared by the majority of the members of a given group whereas the peripheral zones provide space for the individualization of the social knowledge the main goal of our study is to highlight the social representations of disease in health professionals hp and in non health professionals nhp the group of hp has been differentiated into three subgroups medical doctors nurses and pharmacists while that of nhp in two subgroups those submitted to a long period medical treatment and those without treatment our aim is to show that there are different social and professional representations of disease the professional representations are specific social representations related to professional contexts we formulate the following assumptions a that the social representations of hp and nhp will be articulated around a common central core nevertheless we expect to find specific peripheral elements related to professional status based on different knowledge and a differentiated practice b the hp should refer to more descriptive aspects of the disease and monitoring of patients while c nhp should refer more to the experience of illness around emotional aspects our sample is composed of 270 participants 135 hp and 135 hnp representations are measured by a free association task based on the target term disease the data have been submitted to prototypical and categorical analyses in agreement with the central core theory the results confirm that there is a common social representation of disease shared by the two groups which refers essentially to suffering and pain the analysis of each group brings to light two different registers the one of the hp with more descriptive words referring to the nature and the illness s characteristics and the other ones of the hnp with more words connected to emotions and referring to personal real experience of the illness as expected the social representation of the hp is referring to the professional representations of the disease while the one for the hnp is linked to practices of an illness an analysis of intra group differences shows specificities for each of the questioned subgroups in the hp medical doctors focus on the diagnosis and consequences of the disease pharmacists refer to the treatment of the disease and its management while nurses focus on the treatment and on the relation while monitoring patients in the nhp people submitted to a long period medical treatment refer to the emotional aspects and to the consequences of the illness on their live while those without treatment use more descriptive and formal terms these results suggest to the ps to expand exchanges related to the disease in order to facilitate communication centered on taking care of the patient considered in its wholeness and not only as an actual or potential patient this is an important step in improving the health of the patient the main hypothesis of this paper is the presence of malaise in psychiatry the malaise has two sides on one hand the end of psychiatry hegemony that dominated the theoretical field of psychiatry until the 1990s the loss of influence of psychoanalysis is due to its inability to be submitted to any kind of assessment on the other hand the supremacy of neurosciences the idea is not to underestimate the importance of neurosciences but rather to affirm that they occupy the whole theoretical field of psychiatry this is an unusual situation that is specific to our time indeed this monism has succeeded to an epistemological dualism that has existed throughout the history of psychiatry in this article we ll try to draw a history of dualism in psychiatry firstly with pinel we find a tension between a metaphysical philosophical pole and a physiological one pinel s philosophy has something to do with condillac s ideology as pinel applies the analytical method to mental diseases under cabanis s influence the author of the famous rapports du physique et du moral de l homme this ideology is under pressure with physiologism as a materialist he gives an essential part to the brain that distributes pieces of information throughout the body because he thinks that mind influences body secondly dualism lies between the doctrine of localizations defended by gall and the theory of degeneration elaborated by magnan gall in anatomie et physiologie du syst\xe8me nerveux en g\xe9n\xe9ral seeks to know how bumps or hollows that are found on the skull are shaped gall is for the theory of delocalizations he is the counterpart of magnan who wrote a work about les d\xe9g\xe9n\xe9r\xe9s that takes its part in the physiological trend with the famous theory of degeneration for him degeneration means the imperfect state of a subject whose cerebral functions are in a noticeably imperfect state thirdly with henry ey dualism starts to be less important indeed he tends a monist synthesis with its organodynamic model described in des id\xe9es de jackson \xe0 un mod\xe8le organodynamique en psychiatrie indeed he is inspired by the english neurologist jackson to assert that there are levels of conscience structuring where negative symptomatology appears through its dissolution current monism with neuroscience domination sets fundamental epistemological issues perhaps neurosciences were setting an impossible task to achieve while following changeux s intuition in l homme neuronal this latter was developing the idea that to each psychic function one could associate a neuron this is a way to go back to gall who doesn t seem to us to be heuristic indeed let s first introduce the fact that there is no specific cortical area just as the most recent works have shown therefore saying that a cerebral area is correlated to a symptom or a function is no more than relying on parallelism theory thus bergson from whom we took the analysis showed the futility of such a concept and the apporias to which it leads the research of precise cerebral areas implied in mental diseases as important as it is leaves open the question of meaning the meaning of the disease raises many economic cultural psychological and social factors thus we can formulate the hypothesis that psychiatry should be between two complementary poles first the pole of neurosciences whose researches are fundamental for research in disease etiology and the development of a new medicine second there is a pole which is more polymorphous and that would deal with the question of meaning we think that each of these poles should have their own investigation field and their specific methods we defend the idea that creating subjects such as neuropsychoanalysis is an illusion advancing age entails specific treatment modalities for patients with schizophrenia the choice of appropriate antipsychotic therapy ap and the monitoring of treatment is a major challenge however little is known about the real world prescribing practices of psychiatrists for elderly schizophrenia patients the aim of this study was to assess prescribing practices and treatment monitoring in elderly schizophrenia patients and whether socio professional psychiatrists characteristics are related to their practices we contacted by mail 190 psychiatrists to take part in an observational survey of their ap prescribing practices for elderly aged over 65 schizophrenia patients the response rate was 44 2 and of the psychiatrists who replied 75 were treating elderly schizophrenia patients a second generation ap sgap was prescribed as first line of treatment by 87 7 of the psychiatrists the most frequently used sgaps were risperidone and olanzapine respectively preferred by 54 4 and 19 3 of the psychiatrists taking part at the beginning of treatment 91 1 of the psychiatrists prescribed a lower dose than for middle aged patients of the psychiatrists taking part 64 9 prescribed monotherapy and among these psychiatrists 65 cited insufficient control of the disease as the reason for their choice while 48 7 of those who elected not to prescribe combined ap did so in order to limit the side effects of the psychiatrists taking part 54 4 prescribed long acting injectable ap laap better therapeutic compliance and alliance was the main argument in the choice of laap given by the psychiatrists taking part who prescribed the drug whereas the absence of indications and problems of tolerance were arguments against for those who did not personal experience emerged as the governing factor in the choice of ap the ap side effect profile was the main criterion of choice of the ap agent for 3 5 of the psychiatrists taking part and the most frequently chosen secondary criterion 29 8 monitoring of treatment was partly performed according to professional recommendations pre treatment and post prescription assessments of waist circumference and ophthalmological monitoring were very infrequent 8 8 to 18 5 as were pre treatment and early post prescription assessments of prolactinaemia 14 8 to 20 4 long term cardiac monitoring was infrequent 43 9 the psychiatrists taking part whose first line drug was sgap were more familiar with professional recommendations than those who prescribed first generation antipsychotic fga drugs 72 as against 14 3 p 0 006 of the psychiatrists taking part in the study 64 9 reported they commonly use professional recommendations psychiatrists who declared they commonly use professional recommendations measured pulse rate and blood pressure significantly more often over the long term than those who did not 74 3 as against 41 2 p 0 0315 they also measured waist circumference over the long term significantly more often than psychiatrists who did not commonly use professional recommendations 22 9 as against 0 p 0 0420 psychiatrists treating more than ten of these patients yearly measured significantly more often over the long term pulse rate and blood pressure than those treating fewer patients 80 as against 50 p 0 0399 over the long term monitoring psychiatrists with a larger number of elderly schizophrenia patients in their care also performed more often fasting blood glucose test lipid profile and referral for cardiac consultation with ecg respectively 95 5 as against 70 8 p 0 0489 90 9 as against 58 3 p 0 0182 81 8 as against 29 2 p 0 0001 the results of this survey need to be confirmed in a larger population sample the antipsychotic prescribing practices were broadly in agreement with current recommendations except for the tolerance profile which was not the first element taken into account in the choice of the ap agent some clinical and paraclinical medical examinations were carried out infrequently in particular cardiac monitoring over the long term which is essential in this elderly patient population one important element to emerge from our results was that common use of professional recommendations is associated with better monitoring alcohol consumption with its addictive potential may lead to physical and psychological dependence as well as systemic toxicity all of which have serious detrimental health outcomes in terms of morbimortality despite the harmful potential of alcohol use disorders the disease is often not properly managed especially in ambulatory care psychiatric and general practitioners in ambulatory care are first in line to detect and manage patients with excessive alcohol consumption however this is still often regarded as an acute medical condition and its management is generally considered only over the short term on the contrary alcohol dependence has been defined as a primary chronic disease of the brain reward motivation memory and related circuitry involving the signalling pathway of neurotransmitters such as dopamine opioid peptides and gamma aminobutyric acid thus it should be regarded in terms of long term management as are other chronic diseases to propose a standard pathway for the management of alcohol dependence in ambulatory care in terms of duration of treatment and follow up given the lack of official recommendations from health authorities which may help ambulatory care physicians in long term management of patients with alcohol dependence we performed a review and analysis of the most recent literature regarding the long term management of other chronic diseases diabetes bipolar disorders and depression drawing a parallel with alcohol dependence alcohol dependence shares many characteristics with other chronic diseases including a prolonged duration intermittent acute and chronic exacerbations and need for prolonged and often lifelong care in all cases this requires sustained psychosocial changes from the patient patient motivation is also a major issue and should always be taken into consideration by psychiatric and general practitioners in ambulatory care in chronic diseases such as diabetes bipolar disorders or depression psychosocial and motivational interventions have been effective to improve the patient s emotional functioning and to prevent or delay relapses such interventions help patients to accept their disease and to promote long term therapeutic plans based on treatment adherence behavioural changes self management and self efficacy the management of alcohol dependence in ambulatory care should be addressed similarly therapeutic monitoring may be initiated to manage alcohol use disorders including alcohol dependence especially when the patient is unwilling or unready for alcohol withdrawal i e using the strategy of reduction of alcohol consumption which is considered a possible intermediate step toward abstinence alcohol dependence needs long term medical supervision and the therapeutic success depends on the initiation of sustained monitoring at the time of diagnosis initiating phase with several consultations over 2 4 weeks with psychosocial and motivational interventions in order to address all the patient uncertainties to involve him her in a proactive disease management plan and to insure adherence to treatment behavioural changes and new lifestyle a close monitoring once a month during the first 6 months during a consolidation phase is necessary finally a regular monitoring should be maintained overtime after 6 12 months in order to insure that the patient maintains a minimal consumption during the first year to consolidate the patient s motivation to abstain in at risk situations and to maintain a controlled consumption or abstinence to detect salmonella more efficiently and isolate strains more easily a novel and simple detection method that uses an enrichment assay and two chromogenic reactions on a chromatography membrane was developed grade 3 chromatography paper is used as functionalized solid phase support sps which contains specially optimized medium one reaction for screening is based on the sulfate reducing capacity of salmonella hydrogen sulfide h2s generated by salmonella reacts with ammonium ferric citrate to produce black colored ferrous sulfide another reaction is based on salmonella c8 esterase that is unique for enterobacteriaceae except serratia and interacts with 4 methylumbelliferyl caprylate mucap to produce fluorescent umbelliferone which is visible under ultraviolet light a very low detection limit 10 1 cfu ml 1 for salmonella was achieved on the background of 10 5 cfu ml 1 escherichia coli more importantly testing with more than 1 000 anal samples indicated that our method has a high positive detection rate and is relatively low cost compared with the traditional culture based method it took only 1 day for the preliminary screening and 2 days to efficiently isolate the salmonella cells indicating that the new assay is specific rapid and simple for salmonella detection in contrast to the traditional culture based method this method can be easily used to screen and isolate targeted strains with the naked eye the results of quantitative and comparative experiments showed that the visual detection technique is an efficient alternative method for the screening of salmonella spp in many applications of large sized samples related to public health surveillance psoriasis is a multi factorial heritable prototypical immune mediated inflammatory disease characterized by hyperproliferation of keratinocytes in the affected skin there are no studies till date to the best of our knowledge about the association of hla c 06 the risk variant in the psors 1 susceptibility locus that confers the greatest risk for early onset of psoriasis with the disease in south indian tamil patients with psoriasis the present study was performed to determine the association of hla c 06 with psoriasis in the south indian tamil ethnic population three hundred and fifty five cases of psoriasis and 360 healthy controls were included in this case control study severity grading according to psoriasis area severity index pasi scoring was done in patients with psoriasis pcr assays with sequence specific primers pcr ssp were used for specific detection of hla c 06 pcr with analysis of restriction fragment length polymorphism was used to distinguish between patients homozygous and heterozygous for hla c 06 we observed that those with the hla c 06 positive allele had a 3 5 times higher odds of having psoriasis compared to those without p 0 0001 or 3 5 95 ci 2 59 4 79 among cases of psoriasis it was noted that there was a significant association of hla c 06 positivity with female psoriatics p 0 006 or 2 49 1 28 4 87 and early age of onset of psoriasis p 0 002 or 2 04 1 29 3 20 our results suggest that the hla c 06 allele is positively associated with susceptibility to psoriasis female gender and early onset of psoriasis in south indian tamils the role of t helper 17 cells th17 and regulatory t cells tregs in the pathogenesis of alopecia areata aa has not been clearly elucidated b cell activating factor baff being a regulator of t cell activation could be involved in this pathologic process as well the current study evaluated the expression of il 17 il 22 foxp3 and baff in tissue and sera of aa patients forty aa patients and 40 age and sex matched healthy controls were included tissue and serum levels of il 17 il 22 baff as well as serum level of foxp3 were measured by enzyme linked immunosorbent assay elisa immunohistochemical staining was used for assessment of tissue level of foxp3 tissue and serum levels of il 17 tissue levels of il 22 and baff were significantly higher in patients serum levels of il 22 foxp3 and baff were non significantly higher in patients foxp3 immunostaining showed negativity in tissue of patients and controls a significant positive correlation was found between both tissue levels of il 17 and baff r 0 474 p 0 035 and tissue level of il 22 and disease duration r 0 766 p 0 001 in aa patients th17 cells and baff are synergistically involved in the pathogenesis of aa baff represents a promising therapeutic target for such a challenging disease defective tregs number and or function in aa warrants further studies various in vitro animal and limited human adult studies suggest a profound inhibitory effect of inflammation and disease on cytochrome p 450 3a cyp3a mediated drug metabolism studies showing this relationship in critically ill patients are lacking whereas clearance of many cyp3a drug substrates may be decreased potentially leading to toxicity to prospectively study the relationship between inflammation organ failure and midazolam clearance as a validated marker of cyp3a mediated drug metabolism in critically ill children from 83 critically ill children median age 5 1 mo range 0 02 202 mo midazolam plasma n 532 cytokine e g il 6 tumor necrosis factor \u03b1 and c reactive protein crp levels organ dysfunction scores pediatric risk of mortality ii pediatric index of mortality 2 pediatric logistic organ dysfunction and number of failing organs were prospectively collected a population pharmacokinetic model to study the impact of inflammation and organ failure on midazolam pharmacokinetics was developed using nonmem 7 3 in a two compartmental pharmacokinetic model body weight was the most significant covariate for clearance and volume of distribution crp and organ failure were significantly associated with clearance p 0 01 explaining both interindividual and interoccasional variability in simulations a crp of 300 mg l was associated with a 65 lower clearance compared with 10 mg l and three failing organs were associated with a 35 lower clearance compared with one failing organ inflammation and organ failure strongly reduce midazolam clearance a surrogate marker of cyp3a mediated drug metabolism in critically ill children hence critically ill patients receiving cyp3a substrate drugs may be at risk of increased drug levels and associated toxicity we identified a major qtl conferring race nonspecific resistance and revealed its relationships with race specific interactions in the wheat pyrenophora tritici repentis pathosystem tan spot caused by the fungus pyrenophora tritici repentis ptr is a destructive disease of wheat worldwide the disease system is known to include inverse gene for gene race specific interactions involving the recognition of fungal produced necrotrophic effectors nes by corresponding host sensitivity genes however quantitative trait loci qtls conferring race nonspecific resistance have also been identified in this work we identified a major race nonspecific resistance qtl and characterized its genetic relationships with the ne host gene interactions ptr toxa tsn1 and ptr toxc tsc1 in a recombinant inbred wheat population derived from the cross between louise and penawawa both parental lines were sensitive to ptr toxa but penawawa and louise were highly resistant and susceptible respectively to conidial inoculations of all races resistance was predominantly governed by a major race nonspecific qtl on chromosome arm 3bl for resistance to all races another significant qtl was detected at the distal end of chromosome arm 1as for resistance to the ptr toxc producing isolates which corresponded to the known location of the tsc1 locus the effects of the 3b and 1a qtls were largely additive and the 3b resistance qtl was epistatic to the ptr toxa tsn1 interaction resistance to race 2 in f1 plants was completely dominant however race 3 inoculated f1 plants were only moderately resistant because they developed chlorosis presumably due to the ptr toxc tsc1 interaction this work provides further understanding of genetic resistance in the wheat tan spot system as well as important guidance for tan spot resistance breeding gastrointestinal stromal tumors gists are mesenchymal tumors usually driven by the mutational activation of receptor tyrosine kinases kit or pdgfra oncogenic activation of phosphatidylinositide 3 kinase pi3k a downstream effector in the kit signaling pathway has been identified in different types of cancer with the pi3k 110\u03b1 subunit encoded by pik3ca being a common mutational target in this study the mutational hotspot in the pik3ca kinase domain encoded by exon 20 was evaluated in 529 imatinib naive gists using pcr amplification and sanger sequencing eight mutations two co existing in one tumor were identified subsequently the cobas pik3ca mutation test was employed to evaluate mutational hotspots in exons 1 4 7 and 9 in 119 pik3ca exon 20 wild type tumors in two cases mutations in exons 1 and 9 were identified in one gist previously undetected by sanger sequencing the exon 20 mutation was discovered altogether eight primary and two metastatic gists carried pik3ca mutations the size of primary pik3ca mutant gists was \u226514 cm mean size 17 cm and mitotic activity varied from 0 to 72 per 50hpf mean 5 50hpf follow up data showed short survival in 6 of 7 studied cases detection of pik3ca mutations in large or metastatic kit mutant gists may suggest that pik3ca mutant clones have a proliferative advantage during disease progression tyrosine kinase inhibitors have been successfully used in gist treatment however resistance frequently develops due to secondary kit mutations or activation of downstream to kit signaling pathways such as the pi3k akt mtor pathway pik3ca mutations similar to the ones detected in gists have been shown to cause such activation therefore genotyping of pik3ca in gists might help to pinpoint primary and metastatic tumors with the potential to develop resistance to tyrosine kinase inhibitors and guide therapy with pi3k inhibitors spontaneously hypertensive rats shr and normotensive rats w has significant changes in bone metabolism the purpose of this study was to investigate whether the genetic predisposition is sufficient to induce changes in the osteoblast differentiation and osteogenic markers in the bmscs or in the femoral bone for this we use young shr rats without hypertension but with genetic predisposition in compared with young w bmscs were cultured in a proliferation medium mem or osteogenic medium osteogenic differentiation was analyzed by proliferation total protein alkaline phosphatase mineralization and the mrna expression of runx 2 \u03b2 cathenin osterix bone morphogenetic protein 2 bmp 2 osteocalcin ocn bone sialoprotein bsp collagen type i col i and osteopontin opn osteoblast differentiation in shr bmscs shrc had an increased proliferation compared with w bmscs wc after osteogenic induction there was greater reduction in proliferation in shr shrom than in w in the same condition wom on day 7 although no significant difference in the alp activity was observed between shrom and wom poor mineralization and osteoblast differentiation was noted in shrom the osterix and \u03b2 catenin are involved in the reduced osteoblast differentiation in shrom the decreased expression of osteoblast associated proteins such as ocn bsp col i and opn revealed poor quality of extracellular matrix ecm in shrom in the femoral bone the immunostaining of col1 balp opn and ocn in shr was decreased compared with the w trap positive immunoreactions were observed in major extension in the shr femur this study is the first to compare osteoblast differentiation in vitro and femoral bone from shr and w rats our results demonstrated that young shr 4weeks old without hypertension but with genetic predisposition had alterations in osteoblast differentiation of bmscs and in the femoral bone when compared with their progenitor strain w squamoid eccrine ductal carcinoma is a poorly documented skin adnexal carcinoma showing squamous and duct differentiation it is regarded to be of low grade malignant potential but limited follow up information is available to study their clinical behavior and histologic features 30 squamoid eccrine ductal carcinomas were identified from departmental and referral files hematoxylin and eosin stained sections were reviewed and immunohistochemistry for carcinoembryonic antigen and epithelial membrane antigen was examined to confirm duct differentiation clinical follow up was obtained from patient records and referring pathologists the tumors presented as nodules or plaques median size 1 0 cm range 0 5 to 2 5 cm with a predilection for the head and neck 77 the patients were elderly median age 79 5 y range 10 to 96 y with a male predominance histologically these poorly demarcated tumors were characterized by an infiltrative growth pattern within the dermis and additional invasion of subcutis in 70 median tumor thickness was 4 3 mm range 1 5 to 18 mm superficially the tumors resembled well differentiated squamous cell carcinoma in the deeper reaches they were organized in cords and strands showing duct differentiation in a desmoplastic stroma cytologic atypia was moderate to severe ulceration 47 necrosis 23 and perineural and lymphovascular infiltration 27 and 6 respectively were additional features follow up data median 29 mo range 7 to 99 available for 24 patients 80 revealed a local recurrence rate of 25 three patients had lymph node metastasis and 1 patient died of metastatic disease our study outlines the histologic characteristics of squamoid eccrine carcinoma and emphasizes its clinical behavior with risk for local recurrence and potential for more aggressive behavior with metastasis and rare disease related mortality some cases of subcutaneous panniculitis like t cell lymphoma sptcl and lupus erythematosus panniculitis lep demonstrate clinical and histopathologic overlap raising the possibility that they represent opposite ends of a disease spectrum sptcl however is typically associated with greater morbidity and risk for hemophagocytic lymphohistiocytosis hlh therefore diagnostic distinction is clinically important we present the histopathologic immunophenotypic and molecular findings with long term clinical follow up of 13 patients with sptcl median 64 mo follow up and 7 with lep median 50 mo follow up in our multidisciplinary cutaneous oncology clinic six sptcl patients developed hlh including 2 under the age of 21 years in the sptcl group 2 of 13 patients died of disease in contrast we had no mortality or development of hlh in our lep cohort we demonstrate that a limited panel ki 67 cd3 cd4 and cd8 immunostains reveals foci of ki 67 hotspots enriched in cytotoxic atypical cd8 t cells in sptcl ki 67 hotspots were not identified in lep thus aiding the distinction of sptcl from lep lymphocyte atypia combined with adipocyte rimming of cd8 t cells within ki 67 hotspots was also highly specific for the diagnosis of sptcl hyaline lipomembranous change b cell aggregates plasmacytoid dendritic cell clusters and plasma cell aggregates favored the diagnosis of lep but were identified in some cases of sptcl including patients with hlh we confirm that sptcl and lep can show significant histologic overlap suggest a role for high throughput sequencing in confirming neoplastic clones and introduce the concept of sptcl ki 67 hotspots in evolving disease to compare survival data in patients with resected bilateral synchronous pulmonary carcinomas with survival data from patients with lung cancer in pstages i through iv and to evaluate the usefulness of comprehensive histologic evaluation che of tumor histologic patterns to distinguish between synchronous primaries and intrapulmonary metastases ten year overall survival os data from 18 patients with 44 resected synchronous bilateral lung cancers classified as synchronous primaries or metastases using che were compared with survival data of 2 879 patients with lung cancer in pstages i through iv forty and four tumors from 16 and two patients respectively were classified as synchronous primaries and metastases there were no significant differences in survival between these 18 patients and pstage i controls or between the synchronous primaries and the metastases patient groups however there were significant differences in survival between the patients with resected synchronous bilateral tumors and each of the pstage ii through iv control groups p 05 patients with resected synchronous bilateral lung cancers had similar 10 year os to patients with stage i disease regardless of che data most resected tumors were synchronous primaries by che amyloid fibrils are unique fibrous polypeptide aggregates they have been associated with more than 20 serious human diseases including alzheimer s disease and parkinson s disease besides their pathological significance amyloid fibrils are also gaining increasing attention as emerging nanomaterials with novel functions structural characterization of amyloid fibril is no doubt fundamentally important for the development of therapeutics for amyloid related diseases and for the rational design of amyloid based materials in this study we explored to use side chain based infrared ir probe to gain detailed structural insights into the amyloid fibril by a 21 residue model amyloidogenic peptide a\u03b2 8 28 we first proposed an approach to incorporate thiocyanate scn ir probe in a site specific manner into amyloidogenic peptide using 1 cyano 4 dimethylaminopyridinium tetrafluoroborate as cyanylating agent using this approach we obtained three a\u03b2 8 28 variants labeled with scn probe at three different positions we then showed with thioflavin t fluorescence assay congo red assay and atomic force microscopy that the three labeled a\u03b2 8 28 peptides can quickly form amyloid fibrils under high concentration and high salt conditions finally we performed a detailed ir spectral analysis of the a\u03b2 8 28 fibril in both amide i and probe regions and proposed a millipede like structure for the a\u03b2 8 28 fibril the crtc1 maml2 fusion transcript which arises from the crtc1 maml2 translocation is a molecular marker unique to mucoepidermoid carcinoma mec the most common malignant tumor of the salivary gland the extent to which the transcript influences disease features and patient survival is unclear to determine whether the crtc1 maml2 fusion transcript is associated with disease stage tumor grade or survival outcomes in patients with mec a retrospective medical record review was performed at a tertiary care academic medical institution the review included 90 patients with mec who underwent treatment from january 1 1995 to december 31 2011 and for whom archived formalin fixed paraffin embedded tumor specimens were available records were reviewed for clinical demographic and survival data tumor specimens underwent fluorescence in situ hybridization follow up was completed on may 15 2014 and data were analyzed from june 1 to july 1 2014 crtc1 maml2 fusion transcript status statistical analysis determined whether transcript status was associated with disease stage tumor grade and or overall and disease free survival among the 90 eligible patients median range age 55 1 7 8 89 2 years 42 were female and 48 were male fluorescence in situ hybridization revealed a crtc1 maml2 translocation in 50 patients 56 the translocations were more prevalent in intermediate grade tumors 31 of 49 63 than in high grade 11 of 49 22 and low grade 7 of 49 14 tumors 1 tumor sample had no available grading similar proportions of patients with translocation positive disease had t1 13 of 49 26 t2 15 of 49 31 t4a 14 of 49 28 or t0 or tx 8 of 49 16 stages of disease thirty eight of 49 patients with translocation positive mec 78 had n0 stage of disease rates of 5 year overall survival were similar for patients with translocation positive and translocation negative disease 76 8 vs 75 5 respectively p 17 as were rates of disease free survival 65 2 vs 57 4 respectively p 28 detection of the crtc1 maml2 fusion transcript provides useful information for mec diagnosis but is not associated with differences in survival outcomes robust laboratory protocols and stringent quality control qc procedures are essential for meaningful collection of data from multiple sites in large scale population based studies failure to design and implement an effective qc program not only adversely affects the scientific outcome but also affects public confidence in the acceptability of the data a pilot survey was conducted to assess the analytical performance of multicenter plasma glucose measurements in a national surveillance program for diabetes in china quality goals of the imprecision in terms of coefficient of variation cv and total analytical error tea were defined based on the clinical laboratory improvement amendments clia criteria for acceptable performance of proficiency testing pt for plasma glucose using commercial qc preparations a web based internal qc iqc program was established to monitor the analytical performance of the 302 centers participating in the survey the participation rate was 96 289 302 statistical analysis showed that the percentage of centers meeting the acceptable specifications of cv \u22645 0 and tea \u226410 using the clia pt criteria was 91 7 while 76 4 of laboratories achieved the goals for desirable performance of cv \u22642 9 and tea \u22646 9 as proposed by the laboratory medicine practice guidelines for the management of diabetes mellitus based on biological criteria communications and training are important in ensuring the data integrity of multicenter population based studies performance verification and iqc programs should be implemented to help identify centers that can fulfill the eligibility criteria to perform laboratory analyses obstructive sleep apnea hypopnea syndrome osahs is a common disorder that has been identified as a contributor to cardiovascular disease making it a major public health problem continuous positive airway pressure is the standard treatment but compliance is suboptimal mandibular advancement devices and surgery have limited indications inconstant efficiency and potential irreversible side effects stimulation of the hypoglossal nerve that innervates the genioglossus a protrusor muscle of the tongue is now a new treatment option for moderate and severe cases of osahs two types of stimulation are currently available stimulation synchronous with inspiration and continuous stimulation the indication of each type of stimulation and long term effects still need to be assessed but the implantable nerve stimulation is a promising treatment for patients without a therapy solution so far a third alzheimer and related diseases plan ap including a detailed research part has been implemented from 2008 to 2013 the aim of this study was to assess the ap impact on the original articles production concerning alzheimer and related disease ad before 2004 2008 and after its implementation 2009 2013 number and impact factor if based ranking of original articles coming from french university hospitals chu have been assessed using the data provided by the sigaps bibliometric software used so far for calculating allocation of the governmental medical research funding merri scientific production on ad has been compared to four other control pathologies 2 neurologic stroke and parkinson disease and 2 non neurologic diabetes and aids publication trends of the 27 chu and of the 7 interregional grouping of clinical research and innovation girci have been analyzed using specialization indices si the number of ad articles increased from 1277 to 1972 54 4 as well as sigaps score from 18 038 to 29 309 62 5 meanwhile number of articles rated a and b published in the 25 best journals of the specialty increased from 430 to 846 114 1 the figures for these indicators evolved similarly for ad and stroke while quite differently for the 3 other diseases plateauing at a high level for parkinson disease and aids and modestly increasing for diabetes si was 1 for the 3 neurologic diseases including ad in north western and south west girci si of chu on ad did not vary before and after ap implementation 4 chu having both a production and an si at a high level toulouse bordeaux montpellier and lille the number and quality of original articles on ad production by the chu increased after the ap starting of ap initiation in 2008 whether or not this was directly due to the financial support provided by the ap remains to be determined the scientific production on ad was unequally distributed throughout the country the chu being already strongly involved in ad research before the ap reinforced their commitment after this work illustrates the potential implication of sigaps as a strategic tool for research policy to compare dry eye signs and symptoms after femtosecond laser assisted cataract surgery and conventional phacoemulsification eye center of the 2nd affiliated hospital medical college of zhejiang university hangzhou china prospective consecutive nonrandomized comparative cohort study consecutive patients who had femtosecond laser assisted or phacoemulsification cataract surgery were assessed dry eye markers including the ocular surface disease index osdi and subjective symptom questionnaire tear film assessment using keratograph 4 corneal topography schirmer testing i and fluorescein staining were sequentially evaluated preoperatively and postoperatively at 1 day 1 week and 1 month the study recruited 137 eyes 137 patients with similar baseline characteristics most patients developed dry eye postoperatively subjective symptoms and fluorescein staining scores elevated from baseline tear breakup time and schirmer testing i values decreased postoperatively which peaked at 1 week and did not return to baseline within 1 month there were no significant differences between the 2 groups all p 05 except for a higher fluorescein staining score in the femtosecond group at 1 day p 001 1 week p 047 and 1 month p 025 osdi score and subjective symptoms were greater in the laser group at 1 week p 014 and p 016 respectively subgroup analysis showed obvious worsening by fluorescein staining at 1 day p 016 and 1 month p 009 in preoperative dry eye patients both methods worsened dry eye postoperatively femtosecond assisted surgery had a higher risk for staining and dry eye symptoms patients with preexisting dry eye who had femtosecond assisted surgery had more severe ocular surface staining than those having conventional surgery no author has a financial or proprietary interest in any material or method mentioned to study the association between adiponectin plasma levels and gray matter brain volume and cerebral glucose metabolism in a group of type 2 diabetes patients we studied 25 type 2 diabetes patients and 25 age and gender matched healthy control participants biochemical analysis and structural cerebral magnetic resonance imaging including voxel based morphometry and 18 fluorodeoxyglucose positron emission tomography were performed the gray matter volumes and metabolism changes were analyzed using statistical parametric mapping spm8 lower levels of adiponectin correlated with a lower gray matter volume in temporal regions and with reduced cerebral glucose metabolism in temporal regions p 0 001 adjusted for age gender education and the presence of at least one epsilon 4 allele for the apolipoprotein e apoe\u03b54 genotype positive correlations between adiponectin plasma levels and both gray matter volume and cerebral glucose metabolism were found predominantly in temporal regions as in alzheimer s disease adiponectin might be a biomarker for the cognitive decline associated with type 2 diabetic patients using data collected from 2006 to 2014 we applied geographic information system gis mapping and spatial clustering analysis to evaluate prevalence of porcine pasteurellosis in all 31 provinces of mainland china all provinces have been affected but our results show that there is a very high incidence in provinces of the southcentral of mainland china six provinces comprise the area and account for 14082 outbreaks or 74 66 of the total 18862 number guangxi 4574 sichuan 3493 chongqing 2443 guangdong 1584 guizou 1041 and yunnan 947 this study aims to evaluate the relation between meteorological factors and number of cases of porcine pasteurellosis in the southcentral of mainland china local meteorological variables and case data of porcine pasteurellosis were provided by authorities spearman rank correlation analysis and cross correlation analysis were used to control for collinearity and lag effects a zero inflated poisson model was used to estimate the probability of an impact of meteorological factors in the epidemiology of porcine pasteurellosis the results of this model indicated that enso have a positive effect on the occurrence of the disease and there is a positive correlation between mean monthly temperature relative humidity of the current and previous month and the number of cases of the disease in contrast average wind speed of the current month negatively correlated to the number of newly reported cases our findings indicate that there may exist meteorological conditions in the southcentral of mainland china that increase the risk for the appearance of porcine pasteurellosis moreover these meteorological variables may be used to estimate the number of disease cases in this region legislated salmonella control in sweden has been in place since the 1960s the purpose of this study was to investigate presence of salmonella antibodies in dairy cattle herds and to provide a basis for decisions on how surveillance and control can be improved bulk milk samples from all swedish dairy herds n 4 683 were analysed with two different elisas one detecting antibodies against salmonella dublin dublin elisa and one detecting antibodies against several of the serotypes causing bovine salmonellosis including s dublin bovine elisa information about herds i e geographical location local animal density number of test positive herds within 5km animal trade and herd size was based on register data the results confirm a very low prevalence of salmonella in swedish dairy herds throughout the country with the exception of an island in the southeast the test positive herds split into two groups 41 herds 1 positive in the dublin elisa and 101 herds 2 positive in the bovine elisa but negative in the dublin elisa geographical location of positive herds and comparison of the results of the screening with serotypes previously isolated from some of the herds indicated that the first group represents herds presently or previously infected with s dublin while the second group represents herds presently or previously infected with other serotypes differences in serological status between herds in different regions of different size with different animal purchase patterns et cetera were tested using logistic regression presence of positive herds within 5km was significantly associated to testing positive for herds testing positive in the dublin elisa significant associations were also seen with herd size purchase of animals during the last year was not significantly associated with the outcome in the final models we conclude that for future surveillance the bovine elisa can be used to help in identifying infected herds and the dublin elisa can be used to distinguish herds with s dublin infections the geographical clustering of test positive herds could facilitate future surveillance and disease control interventions the results highlight differences between s dublin and other serotypes e g concerning prevalence and degree of geographical clustering further studies on risk factors and potential local spread of salmonella is warranted particularly in the regions with clustering of s dublin infected herds as life expectancy increases oncologic outcome in elderly patients 75 years old or older is a salient topic requiring further investigation we analyzed the records of 13 997 patients who underwent radical prostatectomy from 2006 to 2013 known prognosticators were compared according to age at radical prostatectomy in 13 732 patients younger than 75 years vs 265 patients 75 years old or older univariate and multivariate cox regressions were used to estimate the impact of age on biochemical recurrence free metastasis free cancer specific and overall survival median followup was 47 3 months compared to patients younger than 75 years those 75 years old or older had a higher pathological gleason score p 0 001 and were more likely to harbor a nonorgan confined tumor p 0 001 have a positive surgical margin p 0 004 and positive lymph nodes p 0 028 and receive salvage androgen deprivation therapy p 0 002 five year biochemical recurrence free metastasis free cancer specific and overall survival rates were 64 2 84 7 98 4 and 91 3 in patients 75 years old or older and 76 9 96 2 99 0 and 96 2 respectively in patients younger than 75 years on univariate and multivariate analysis age 75 years or greater was associated with worse biochemical recurrence free and metastasis free survival patients 75 years old or older were more likely to die of other causes than cancer nevertheless noncancer related mortality was low older patients who underwent radical prostatectomy had more advanced disease age itself is an independent predictor of worse biochemical recurrence free and metastasis free survival healthy and highly selected patients 75 years old or older in our sample showed good long term overall survival therefore older age in well selected men should not be a contraindication to radical prostatectomy especially in patients harboring high risk disease we analyze patients with early progression after laparoscopic radical cystectomy in a large cohort by the esut european association of urology section of uro technology more specifically we focus on patients with favorable pathology pt2 n0 r0 or less who experienced an unexpected recurrence and analyze possible causes for such early recurrence discussing the surgical technique including pneumoperitoneum since 2000 the esut has been constructing a large multicenter prospective database of patients undergoing laparoscopic radical cystectomy all procedures were performed via a standard laparoscopic approach without robotic assistance we specifically analyzed patients with favorable pathological characteristics in particular pt2 n0 r0 or less and evaluated those with progression despite these favorable characteristics univariate and multivariate logistic regression was performed to evaluate risk factors for early recurrence a total of 627 patients were available for final analysis with a median followup of 46 months mean 57 of these patients 311 had favorable pathological characteristics of pt2 n0 r0 or less during followup 27 8 7 patients experienced disease progression during the first 24 months surgical negligence was found in only 1 case most of these patients with early recurrence had progression to high tumor volume disseminated metastatic disease on multivariate logistic regression tumor stage was the only factor significantly associated with early recurrence p 0 027 we report early unexpected recurrences after laparoscopic radical cystectomy in nearly 5 of our entire cohort all in patients with favorable pathological characteristics pt2 n0 r0 or less pneumoperitoneum may have had a role in the development of these relapses specifically designed studies are necessary to investigate the possible role of pneumoperitoneum in urothelial cancer recurrence circulating natriuretic peptide measurements have been used extensively over the past 15 years to diagnose and monitor patients with heart failure we are still learning how complex the dynamics of natriuretic peptides can be in the interpretation of test results in individual patients although natriuretic peptide measurements are widely used in practice there are questions regarding why these peptides may not necessarily track with blood volume or invasive hemodynamic measurements in individual patients interpretation of natriuretic peptide measurements will depend on many factors including special patient populations obesity renal function the state of congestion or decongestion and whether patients are receiving specific therapies natriuretic peptide measurements have clearly revolutionized clinical care for patients with heart failure but further research should provide insights to help use these measurements to individualize patient care beyond the current guidelines habitual physical activity and regular exercise training improve cardiovascular health and longevity a physically active lifestyle is therefore a key aspect of primary and secondary prevention strategies an appropriate volume and intensity are essential to maximally benefit from exercise interventions this document summarizes available evidence on the relationship between the exercise volume and risk reductions in cardiovascular morbidity and mortality furthermore the risks and benefits of moderate versus high intensity exercise interventions are compared findings are presented for the general population and cardiac patients eligible for cardiac rehabilitation finally the controversy of excessive volumes of exercise in the athletic population is discussed heart failure hf is characterized by perturbations in energy homeostasis and metabolism the reversibility and prognostic value of circulating markers associated with these changes remain unclear this study sought to describe the metabolomic profiles of patients along the spectrum of systolic hf determine their association with adverse outcomes in a clinical trial of hf and evaluate whether identified metabolites change with treatment for end stage systolic hf to assess association of metabolites with clinical outcomes we evaluated a population of 453 chronic systolic hf patients who had been randomized to exercise training versus usual care to assess change in metabolites with mechanical circulatory support 41 patients with end stage hf who underwent left ventricular assist device lvad placement were studied targeted quantitative profiling of 60 metabolites using tandem flow injection mass spectrometry was performed on frozen plasma samples obtained prior to randomization as well as prior to and \u226590 days post placement in the lvad group principal components analysis was used for data reduction five principal components analysis derived factors were significantly associated with peak vo2 levels at baseline in fully adjusted models of these factor 5 composed of long chain acylcarnitines was associated with increased risk of all 3 pre specified clinical trial outcomes all cause mortality all cause hospitalization all cause hospitalization and cardiovascular death or cardiovascular hospitalization individual components of factor 5 were significantly higher in patients with end stage hf prior to lvad placement and decreased significantly post implantation in chronic hf patients circulating long chain acylcarnitine metabolite levels were independently associated with adverse clinical outcomes and decreased after long term mechanical circulatory support these metabolites may serve as potential targets for new diagnostics or therapeutic interventions exercise training program to improve clinical outcomes in individuals with congestive heart failure nct00047437 in patients with myocardial infarction mi leaflet tethering by displaced papillary muscles induces mitral regurgitation mr which doubles mortality mitral valves mvs are larger in such patients but fibrosis sets in counterproductively the investigators previously reported that experimental tethering alone increases mitral valve area in association with endothelial to mesenchymal transition the aim of this study was to explore the clinically relevant situation of tethering and mi testing the hypothesis that ischemic milieu modifies mitral valve adaptation twenty three adult sheep were examined under cardiopulmonary bypass the papillary muscle tips in 6 sheep were retracted apically to replicate tethering short of producing mr tethered alone papillary muscle retraction was combined with apical mi created by coronary ligation in another 6 sheep tethered plus mi and left ventricular remodeling was limited by external constraint in 5 additional sheep left ventricular constraint six sham operated sheep were control subjects diastolic mitral valve surface area was quantified by 3 dimensional echocardiography at baseline and after 58 5 days followed by histopathology and flow cytometry of excised leaflets tethered plus mi leaflets were markedly thicker than tethered alone valves and sham control subjects leaflet area also increased significantly endothelial to mesenchymal transition detected as \u03b1 smooth muscle actin positive endothelial cells significantly exceeded that in tethered alone and control valves transforming growth factor \u03b2 matrix metalloproteinase expression and cellular proliferation were markedly increased uniquely tethering plus mi showed endothelial activation with vascular adhesion molecule expression neovascularization and cells positive for cd45 considered a hematopoietic cell marker tethered plus mi findings were comparable with external ventricular constraint mi altered leaflet adaptation including a profibrotic increase in valvular cell activation cd45 positive cells and matrix turnover understanding cellular and molecular mechanisms underlying leaflet adaptation and fibrosis could yield new therapeutic opportunities for reducing ischemic mr a lack of clarity exists about the role of complete coronary revascularization in patients presenting with non st segment elevation myocardial infarction the aim of our study was to compare long term outcomes in terms of major adverse cardiovascular and cerebrovascular events of 2 different complete coronary revascularization strategies in patients with non st segment elevation myocardial infarction and multivessel coronary artery disease 1 stage percutaneous coronary intervention 1s pci during the index procedure versus multistage percutaneous coronary intervention ms pci complete coronary revascularization during the index hospitalization in the smile impact of different treatment in multivessel non st elevation myocardial infarction patients one stage versus multistaged percutaneous coronary intervention trial 584 patients were randomly assigned in a 1 1 manner to 1s pci or ms pci the primary study endpoint was the incidence of major adverse cardiovascular and cerebrovascular events which were defined as cardiac death death reinfarction rehospitalization for unstable angina repeat coronary revascularization target vessel revascularization and stroke at 1 year the occurrence of the primary endpoint was significantly lower in the 1 stage group 1s pci n 36 13 63 vs ms pci n 61 23 19 hazard ratio hr 0 549 95 confidence interval ci 0 363 to 0 828 p 0 004 the 1 year rate of target vessel revascularization was significantly higher in the ms pci group 1s pci n 22 8 33 vs ms pci n 40 15 20 hr 0 522 95 ci 0 310 to 0 878 p 0 01 p log rank 0 013 when the analyses were limited to cardiac death 1s pci n 9 3 41 vs ms pci n 14 5 32 hr 0 624 95 ci 0 270 to 1 441 p 0 27 and myocardial infarction 1s pci n 7 2 65 vs ms pci n 10 3 80 hr 0 678 95 ci 0 156 to 2 657 p 0 46 no significant differences were observed between groups in multivessel non st segment elevation myocardial infarction patients complete 1 stage coronary revascularization is superior to multistage pci in terms of major adverse cardiovascular and cerebrovascular events impact of different treatment in multivessel non st elevation myocardial infarction nstemi one stage versus multistaged percutaneous coronary intervention pci smile nct01478984 macro social structural events big events such as wars disasters and large scale changes in policies can affect hiv transmission by making risk behaviors more or less likely or by changing risk contexts the purpose of this study was to develop new measures to investigate hypothesized pathways between macro social changes and hiv transmission we developed novel scales and indexes focused on topics including norms about sex and drug injecting under different conditions involvement with social groups helping others and experiencing denial of dignity we collected data from 300 people who inject drugs in new york city during 2012 2013 most investigational measures showed evidence of validity pearson correlations with criterion variables range 0 12 0 71 and reliability cronbach s alpha range 0 62 0 91 research is needed in different contexts to evaluate whether these measures can be used to better understand hiv outbreaks and help improve social structural hiv prevention intervention programs to externally validate the mskcc nomogram in a uk population and determine if it could be used in our practice here in the uk the colon cancer database from a district general hospital in england was used to extract all patients who had a curative colon cancer resection inclusion criteria were all patients who had curative elective colon cancer resection between 01 01 1998 and 31 12 2003 patients were followed up for up to ten years five and ten year predictions were calculated for each patient and plotted against the actual recurrence using a roc curve and auc was calculated for both the five and ten year nomogram 138 patients were included in the study overall five year recurrence rate was 26 8 with a mean follow up of 60 24 months sd 38 6 118 patients were included in the five year nomogram validation and 102 patients were included in the ten year nomogram validation a roc curve was plotted for both the five and ten year nomogram and auc was calculated for the five year nomogram auc was 0 673 and for the ten year nomogram auc was 0 687 two cut off points were identified for each nomogram and this divided the cohort into low medium and high risk groups for recurrence cox regression showed there was significant difference between all groups for both nomograms the mskcc colon cancer nomogram was validated in our cohort but it is recommended to be used in conjunction with ajcc tnm staging system we evaluate the surgical outcomes and surgical responses of medial rectus muscle mr recession patients with thyroid eye disease ted related esotropia et the surgical dose response curves 1 week postoperatively and at the final visit were analyzed univariable and multivariable linear regression analyses were applied to investigate factors influencing surgical dose response a total of 43 patients with ted related et that underwent mr recession were included the final success rate was 86 0 and the rate of undercorrection was 14 0 the surgical dose response curves of ted related et showed a gentle slope compared with those of standard surgical tables in the univariable model simultaneous vertical rectus muscle recession was the only significant factor influencing surgical dose response of mr recession in ted related et \u03b2 0 397 p 0 044 in a model adjusted for age sex type of surgery and preoperative horizontal angle of deviation simultaneous vertical rectus muscle recession showed marginal significance \u03b2 0 389 p 0 064 the surgical dose response curve of ted related et was unique simultaneous vertical rectus muscle recession was associated with increased surgical dose response in ted related et to confirm gender specific differences in pathologic factors and survival rates of urothelial bladder cancer patients treated with radical cystectomy we conducted a retrospective monocentric study on 701 patients treated with radical cystectomy and pelvic lymphadenectomy for muscle invasive bladder cancer impact of gender on recurrence rate specific and non specific mortality rate were evaluated using cox regression models in univariate and multivariate analysis we collected data on 553 males 78 9 and 148 females 21 1 between 1998 and 2011 both groups were comparable at inclusion regarding age pathologic stage nodal status and lymphovascular invasion mean follow up time was 45 months interquartile 23 73 and by that time 163 patients 23 3 had recurrence of their tumor and 127 18 1 died from their disease in multivariable cox regression analyses female gender was independently associated with disease recurrence rr 1 73 95 ci 1 22 2 47 p 0 02 and cancer specific mortality rr 2 50 95 ci 1 71 3 68 p 0 001 we confirmed female gender to be an independent negative prognosis factor for patients following a radical cystectomy and lymphadenectomy for an invasive muscle bladder cancer the ecm of the intervertebral disc and articular cartilage contains a highly organised network of collagens and proteoglycans which resist compressive forces applied to these tissues a pathological hallmark of the intervertebral disc is the imbalance between production of anabolic and catabolic factors by the resident cells this process is thought to be mediated by pro inflammatory cytokines predominantly tnf \u03b1 and il 1\u03b2 which upregulate expression of matrix degrading enzymes such as mmps and adamtss this imbalance ultimately results in tissue degeneration causing failure of the biomechanical function of the tissues a similar cascade of events is thought to occur in articular cartilage during development of osteoarthritis within these skeletal tissues a small cell surface heparan sulphate proteoglycan syndecan 4 sdc4 has been implicated in maintaining physiological functions however in the degenerating niche of the intervertebral disc and cartilage dysregulated activities of this molecule may exacerbate pathological changes studies in recent years have elucidated a role for sdc4 in mediating matrix degradation in both intervertebral discs and cartilage by controlling adamts 5 function and mmp3 expression discourse presented in this review highlights the potential of sdc4 as a possible therapeutic target in slowing the progression of ecm degradation in both degenerative disc disease and osteoarthritis critical limb ischemia cli is the most severe form of peripheral artery occlusive disease and is characterized by high amputation morbidity and mortality rates therefore revascularization is the essential step in therapy for retention of the affected limb although for a long time bypass surgery represented the gold standard in the treatment of cli in recent years there has been a disproportionate increase of endovascular treatment despite the lack of level data in this review the indications and results of endovascular therapy of cli are presented on the basis of published data a literature search was carried out to identify publications that compared the results of endovascular and surgical therapy as well as observational studies about different endovascular techniques the basil study provided the highest quality data comparing endovascular and surgical treatment of cli the long term data of the basil trial showed that apart from patients with a suitable vein and a life expectancy of more than 2 years first line endovascular therapy is equivalent to surgical treatment the equivalence could also be demonstrated in a meta analysis comparing operative and endovascular treatment of cli the cli is a disease with high mortality and morbidity risks due to the comparable amputation free survival times with lower complication rates in the published data in most patients an endovascular first strategy in experienced centers can be justified igg4 related disease is a recently recognized systemic disease characterized by storiform fibrosis with infiltration of igg4 positive plasma cells in rare incidences igg4 related renal disease can present as a solitary mass lesion at renal pelvis and can pose a diagnostic challenge since these lesions mimic malignancy herein we present a rare case of igg4 related disease presenting as inflammatory pseudotumor lesion involving the renal pelvis and also neighboring renal parenchyma a 75 year old man with no history of igg4 related disease underwent computed tomography ct scan for evaluation of prostatic cancer the ct scan incidentally revealed a mass lesion located at the right renal pelvis radiologic findings were highly suggestive of malignancy therefore the patient underwent right nephroureterectomy microscopically the mass lesion showed storiform fibrosis with diffuse and intense inflammatory cell infiltration infiltrating cells were mainly histiocytes and plasma cells tubulointerstitium adjacent to the lesion also showed fibrosis with abundant plasmacytic infiltration immunohistochemical staining revealed the presence of igg4 positive plasma cells in both the mass lesion and tubulointerstitium mean of 94 hpf per field considering these findings we diagnosed the mass lesion as igg4 related inflammatory pseudotumor of the renal pelvis in patients with renal pelvic masses igg4 related inflammatory pesudotumor should be considered in the differential diagnosis to avoid unnecessary surgical intervention to identify the origins of the name of the disease glaucoma ancient greek medical literature homeric poems and ancient greek religion and art were examined the roots of the name glaucoma could be traced back to homeric times ancient greek physicians following the hippocratic tradition preferred the use of the terms hypochysis or hypochyma for the same disease this fact indicates that the older term glaucoma did not fulfill strict medical criteria but had a long history connected to superstition which the rational ancient greek physician tried to overcome using terms derived from their fundamental principal of humoral pathology in ancient greek medical literature glaucoma had a significant place among ocular diseases the origin of its name could be traced back to homeric times and could be connected to the ancient belief of a primitive folk about the apotropaic role of animals against diseases which in this case is represented by the superstitious role of the owl to report a case of secondary pulmonary arterial hypertension pah and the relationship of intraocular pressure iop change with right ventricular diameter rvd and brain natriuretic peptide bnp case report a 22 year old woman with dilated and congested conjunctival and episcleral veins was diagnosed with high iop she was previously diagnosed with sj\xf6gren syndrome and suffered from secondary pah the rvd and bnp level improved and the iop decreased with routine treatment for pah during self cessation of treatment for pah the rvd bnp level and iop deteriorated however they improved after treatment was reinitiated there was a synchronizing change in the parameters representing high pulmonary arterial pressure and iop during treatment of pah malaria a deadly infectious parasitic disease is a major issue of public health in the world today and already produces serious economic constraints in the endemic countries most of the malarial infections and deaths are due to plasmodium falciparum and plasmodium vivax species the recent emergence of resistance necessitates the search for new antimalarial drugs which overcome the resistance and act through new mechanisms although much effort has been directed towards the discovery of novel antimalarial drugs 4 anilino quinolone triazines as potent antimalarial agents their in silico modelling and bioevaluation as plasmodium falciparum transketolase and \u03b2 hematin inhibitors has been reported this review is primarily focused on the drug discovery of the recent advances in the development of antimalarial agents and their mechanism of action the aim of the present study is to describe the purification and identification of methyl 2 3 dihydroxybenzoate m2 3db isolated for the first time from paenibacillus elgii hoa73 and to subsequently investigate its antifungal activity against important plant pathogens the results show that m2 3db can be purified by many different chromatographic techniques and is identified as methyl 2 3 dihydroxybenzoate based on nuclear magnetic resonance nmr and liquid chromatography mass spectrometry lc ms spectra analyses m2 3db was firstly evaluated for its antifungal activity where the growth of botrytis cinerea and rhizoctonia solani was almost completely inhibited at an m2 3db concentration of 50 \u03bcg ml growth inhibition of phytophthora capsici and fusarium oxysporum f sp lycopersici was found at the same m2 3db concentration by 48 8 and 36 6 respectively minimum inhibitory concentrations mics of m2 3db that inhibited any visible mycelial growth of b cinerea r solani and f oxysporum f sp lycopersici were defined as 32 32 and 64 \u03bcg ml respectively the broad antifungal activity of m2 3db against various plant pathogens suggests its scope as a biofungicide in the management of plant disease type ii endoleaks are common after endovascular aneurysm repair evar but their clinical significance remains undefined and their management controversial we determined risk factors for type ii endoleaks and associations with adverse outcomes we identified all evar patients in the vascular study group of new england abdominal aortic aneurysm database patients were subdivided into two groups 1 those with no endoleak or transient type ii endoleak and 2 persistent type ii endoleak or new type ii endoleak no endoleak at completion of case patients with other endoleak types and follow up shorter than 6 months were excluded multivariable analysis was used to evaluate predictors of persistent or new type ii endoleaks kaplan meier and cox regression analysis were used to evaluate predictors of reintervention and survival two thousand three hundred sixty seven evar patients had information on endoleaks 1977 84 were in group 1 of which 79 had no endoleaks at all and 21 had transient endoleaks that resolved at follow up the other 390 16 were in group 2 of which 31 had a persistent leak and 69 had a new leak at follow up that was not seen at the time of surgery group 2 was older mean age 75 vs 73 years p 001 and less likely to have chronic obstructive pulmonary disease copd 24 vs 34 p 001 or elevated creatinine levels 2 6 vs 5 3 p 027 coil embolization of one or both hypogastric arteries was associated with a higher rate of persistent type ii endoleaks 12 vs 8 p 024 as was distal graft extension 12 vs 8 p 008 in multivariable analysis copd odds ratio or 0 7 95 confidence interval ci 0 5 0 9 p 017 was protective against persistent type ii endoleak while hypogastric artery coil embolization or 1 5 95 ci 1 0 2 2 p 044 distal graft extension or 1 6 95 ci 1 1 2 3 p 025 and age 80 or 2 7 95 ci 1 4 5 3 p 004 were predictive graft type was also associated with endoleak development persistent type ii endoleaks were predictive of postdischarge reintervention or 15 3 95 ci 9 7 24 3 p 001 however they were not predictive of long term survival or 1 1 95 ci 0 9 1 6 p 477 persistent type ii endoleak is associated with hypogastric artery coil embolization distal graft extension older age the absence of copd and graft type but not with aneurysm size persistent type ii endoleaks are associated with an increased risk of reinterventions but not rupture or survival this reinforces the need for continued surveillance of patients with persistent type ii endoleaks and the importance of follow up to detect new type ii endoleaks over time exposure to bloodborne pathogens is the most serious occupational health risk encountered within the healthcare profession worldwide the world health organization estimates that 3 million healthcare workers experience percutaneous injuries each year the objectives of this study were to 1 examine the frequency of sharps injuries and 2 assess the adequacy understanding and use of post exposure protocols within a sample of the nursing staff at a busy tertiary care emergency department in the ashanti region of ghana a mixed methods descriptive study design was used including key informant interviews to develop the survey a structured survey of emergency department nursing staff and document review overall the emergency department staff was well informed regarding the risks of sharps injury and the immediate steps to take in the event of a sharps injury however few staff could list essential post exposure follow up steps over one quarter 28 9 of emergency nurses reported a sharps injury during a one year period according to hospital records the high incidence of sharps injuries indicates an urgent and pressing need for policy and educational interventions to address the infectious disease risk to this group of emergency department staff to investigate the role of ccl5 secreted by tumor associated macrophages tams in gastric cancer and to explore how ccl5 ccr5 axis modulates phenotypes of gastric cancer cells expression of ccl5 and tam surface marker cd68 in gastric cancer tissues was examined using sp immunohistochemistry serum ccl5 levels of patients were assessed using elisa cross analyses of ccl5 and cd68 expression with clinicopathological data were done correlation between ccl5 and cd68 in gastric cancer tissues was also studied in vitro functional characterization of ccl5 in gastric cancer was done in co culture of ags and thp 1 derived macrophages using mts assay plate clone formation assay and transwell experiment expression of chemokines and its receptors were detected by rt pcr while stat3 phosphorylation and downstream target proteins were studied using western blot ccl5 and cd68 were both highly expressed in tissues gastric cancer of which the expressions were positively correlated with each other and of clinical importance were associated with the depth of invasion lymph node metastasis tnm staging and tumor differentiation serum ccl5 was also elevated in patients with gastric cancer comparing to healthy volunteers co culture of ags cells with thp 1 derived macrophages increased cell proliferation clone forming ability as well as migration of ags cells migration of ags cells across transwell membrane was also enhanced by increasing exogenous ccl5 meanwhile mrna expression of ccl5 mmp2 mmp9 and ccr5 was also highly expressed in the cells stat3 signaling as reflected by its phosphorylation was also increased in ags cells upon co culture with thp 1 derived macrophages ccl5 secreted by tams may promote the proliferation invasion and metastasis of gastric cancer cells in which stat3 signaling pathway is likely to play an important role the correlation of ccl5 with clinicopathological parameters suggested ccl5 holds promise as important molecular marker of gastric cancer staging and disease progression although many studies have implicated the crosstalk between the wnt and pkc signaling pathways in tumor initiation and progression the molecular roles of pkc isoforms in the wnt signaling pathway remain poorly understood in this study we explored the contribution of pkc isoforms to canonical and noncanonical wnt signaling pathway in mediating cell migration and an epithelial mesenchymal transition emt when mcf 7 cells were treated with 12 o tetradecanoylphorbol 13 acetate tpa for up to 3 weeks the effect of tpa on wnt signaling pathway was dramatically different depending on the exposure time the short term exposure 3 days of mcf 7 cells to tpa exhibited significant induction of wnt5a expression along with the enhanced expression of pkc \u03b1 to promote cell migration which suggested that activation of noncanonical wnt signaling pathway is associated with pkc \u03b1 however the chronic exposure 3 weeks of cells to tpa completely suppressed wnt5a expression and the expression of pkc \u03b7 and pkc \u03b4 whereas the expression of wnt3a and pkc \u03b8 were up regulated to activate the canonical wnt signaling pathway moreover the loss of epithelial markers including e cadherin and gata 3 suggested that chronic exposure of tpa stimulates emt taken together our data suggest that pkc \u03b8 positively regulates the canonical wnt signaling pathway and that pkc \u03b7 and pkc \u03b4 negatively modulate this signaling pathway cellular adhesion molecules might be used as markers in diagnosis and prognosis in some types of malignant tumors the purpose of this study was to determine the clinical significance of the serum levels of activated leukocyte cell adhesion molecule 1 alcam and intercellular adhesion molecule 1 icam 1 in gastric cancer gc patients fifty eight gc patients and 20 age and sex matched healthy controls were enrolled into this study pretreatment serum markers were determined by the solid phase sandwich enzyme linked immunosorbent assay elisa the median age at diagnosis was 59 5 years range 32 82 years tumor localizations of the majority of the patients were antrum n 42 72 4 and tumor histopathologies of the majority of the patients were diffuse n 43 74 1 the majority of the patients had stage iv disease n 41 70 7 thirty six 62 1 patients had lymph node involvement the median follow up time was 66 months range 1 97 2 months at the end of the observation period 26 patients 44 8 were dead the median survival for all patients was 21 4 \xb15 months 95 ci 11 5 31 3 the 1 year survival rates were 66 2 the baseline serum alcam levels of the patients were significantly higher than those of the controls p 0 001 there was no significant difference in the serum levels of icam 1 between the patients and controls p 0 232 no significant correlation was detected between the levels of the serum markers and other clinical parameters p 0 05 tumor localization p 0 03 histopathology p 0 05 and response to chemotherapy p 0 003 had prognostic factors on survival neither serum alcam levels nor serum icam 1 levels were identified to have a prognostic role on overall survival icam 1 p 0 6 alcam p 0 25 in conclusion serum levels of alcam were found to have diagnostic value in gc patients 3 nitropropionic acid 3 np causes severe neurotoxicity in animals which depicts huntington s disease hd in humans embelin the main active constituent of embelia ribes has been reported to possess various pharmacological actions mainly anti inflammatory antioxidant anticonvulsant and neuroprotective the aim of the present study was to evaluate the neuroprotective effect of embelin against 3 np induced experimental hd in rats adult wistar rats were pretreated with vehicle embelin 10 and 20mg kg p o for 7 days from 8th day onwards embelin was co treated with 3 np 15mg kg i p for 7 days at the end of the treatment schedule animals were evaluated for behavioral alterations and brain homogenates were used for estimation of oxidative stress parameters lipid peroxidation reduced glutathione catalase and glutathione s transferase 2 3 5 triphenyl tetrazolium chloride ttc stained brain slices were used for lesion size measurement administration of 3 np significantly altered the behavioral and neuronal antioxidant status and caused significant neuronal damage in striatal region embelin at both the tested doses caused a significant reversal of behavioral and antioxidant status alterations and reversed the striatal neuronal damage induced by 3 np these findings suggest the neuroprotective effect of embelin against hd the observed protective effect might be attributed to the antioxidant properties of embelin chronic chagas cardiomyopathy in humans is characterized by segmental left ventricular wall motion abnormalities wma mainly in the early stages of disease this study aimed at investigating the detection of wma and its correlation with the underlying histopathological changes in a chronic chagas cardiomyopathy model in hamsters female syrian hamsters n 34 infected with 3 5 \xd710 4 or 10 5 blood trypomastigote trypanosoma cruzi y strain forms and an uninfected control group n 7 were investigated after 6 or 10 months after the infection the animals were submitted to in vivo evaluation of global and segmental left ventricular systolic function by echocardiography followed by euthanasia and histological analysis for quantitative assessment of fibrosis and inflammation with tissue sampling in locations coinciding with the left ventricular wall segmentation employed at the in vivo echocardiographic evaluation ten of the 34 infected animals 29 showed reduced left ventricular ejection fraction 73 left ventricular ejection fraction was more negatively correlated with the intensity of inflammation r 0 63 p 0 0001 than with the extent of fibrosis r 0 36 p 0 036 among the 24 animals with preserved left ventricular ejection fraction 82 9 \xb15 5 8 33 showed segmental wma predominating in the apical inferior and posterolateral segments the segments exhibiting wma in comparison to those with normal wall motion showed a greater extent of fibrosis 9 3 \xb15 7 and 7 \xb16 3 p 0 0001 and an even greater intensity of inflammation 218 0 \xb1111 6 and 124 5 \xb184 8 nuclei mm \xb2, p 0 0001 isolated wma with preserved global systolic left ventricular function is frequently found in syrian hamsters with experimental chronic chagas cardiomyopathy whose underlying histopathological features are mainly inflammatory paeoniflorin the main active component of the peony plant exerts various pharmacological effects recently research on the effect of paeoniflorin on the nervous system has gained more attention the aim of the present study was to determine whether paeoniflorin exerts a protective effect that improves alzheimer s disease ad via inflammation and apoptosis in the cerebral cortex of a transgenic mouse model of ad transgenic mice were used to construct the model of ad and were treated with paeoniflorin the morris water maze test was used to analyze cognitive function in ad mice the protein expression levels of nuclear factor \u2011\u03bab tumor necrosis factor \u2011\u03b1 interleukin il \u20111\u03b2 il \u20116 and caspase \u20113 were examined with commercial kits expression levels of b \u2011cell lymphoma 2 bcl \u20112 bcl \u20112 \u2011associated x protein bax phosphorylated p \u2011akt and p \u2011p38 mitogen \u2011activated protein kinase p \u2011p38 mapk in ad were evaluated by western blotting the neuroprotective effects of paeoniflorin significantly improved cognitive function and ameliorated patterns of escape distance and escape latency in ad mice furthermore the effects of paeoniflorin decreased inflammation and caspase \u20113 activity and inhibited cell death via increasing the bcl \u20112 bax ratio and p \u2011akt expression levels and downregulating p \u2011p38 mapk expression in ad mice intensification of food production has the potential to drive increased disease prevalence in food plants and animals microsporidia are diversely distributed opportunistic and density dependent parasites infecting hosts from almost all known animal taxa they are frequent in highly managed aquatic and terrestrial hosts many of which are vulnerable to epizootics and all of which are crucial for the stability of the animal human food chain mass rearing and changes in global climate may exacerbate disease and more efficient transmission of parasites in stressed or immune deficient hosts further human microsporidiosis appears to be adventitious and primarily associated with an increasing community of immune deficient individuals taken together strong evidence exists for an increasing prevalence of microsporidiosis in animals and humans and for sharing of pathogens across hosts and biomes epidemic fade out refers to infection elimination in the trough between the first and second waves of an outbreak the number of infectious individuals drops to a relatively low level between these waves of infection and if elimination does not occur at this stage then the disease is likely to become endemic for this reason it appears to be an ideal target for control efforts despite this obvious public health importance the probability of epidemic fade out is not well understood here we present new algorithms for approximating the probability of epidemic fade out for the markovian sir model with demography these algorithms are more accurate than previously published formulae and one of them scales well to large population sizes this method allows us to investigate the probability of epidemic fade out as a function of the effective transmission rate recovery rate population turnover rate and population size we identify an interesting feature the probability of epidemic fade out is very often greatest when the basic reproduction number r0 is approximately 2 restricting consideration to cases where a major outbreak is possible i e r0 1 the public health implication is that there may be instances where a non lethal infection should be allowed to spread or antiviral usage should be moderated to maximise the chance of the infection being eliminated before it becomes endemic a two sex deterministic ordinary differential equations model for human papillomavirus hpv is constructed and analyzed for optimal control strategies in a vaccination program administering three types of vaccines in the female population a bivalent vaccine that targets two hpv types and provides longer duration of protection and cross protection against some non target types a quadrivalent vaccine which targets an additional two hpv types and a nonavalent vaccine which targets nine hpv types including those covered by the quadrivalent vaccine but with lesser type specific efficacy considering constant vaccination controls the disease free equilibrium and the effective reproduction number rv for the autonomous model are computed in terms of the model parameters local asymptotic stability of the disease free equilibrium is established in terms of rv uncertainty and sensitivity analyses are carried out to study the influence of various important model parameters on the hpv infection prevalence assuming the hpv infection prevalence in the population under the constant control optimal control theory is used to devise optimal vaccination strategies for the associated non autonomous model when the vaccination rates are functions of time the impact of these strategies on the number of infected individuals and the accumulated cost is assessed and compared with the constant control case switch times from one vaccine combination to a different combination including the nonavalent vaccine are assessed during an optimally designed hpv immunization program the hydrostatic pressure stimulation of an appropriately cell seeded porous scaffold within a bioreactor is a promising method for engineering bone tissue external to the body we propose a mathematical model and employ a suite of candidate constitutive laws to qualitatively describe the effect of applied hydrostatic pressure on the quantity of minerals deposited in such an experimental setup by comparing data from numerical simulations with experimental observations under a number of stimulation protocols we suggest that the response of bone cells to an applied pressure requires consideration of two components i a component describing the cell memory of the applied stimulation and ii a recovery component capturing the time cells require to recover from high rates of mineralisation we consider a model for an epidemic in a population that occupies geographically distinct locations the disease is spread within subpopulations by contacts between infective and susceptible individuals and is spread between subpopulations by the migration of infected individuals we show how susceptible individuals can act collectively to limit the spread of disease during the initial phase of an epidemic by specifying the distribution that minimises the growth rate of the epidemic when the infectives are migrating so as to maximise the growth rate we also give an explicit strategy that minimises the basic reproduction number which is also shown be optimal in terms of the probability of extinction and total size of the epidemic the novel concept of modifying and enhancing the properties of existing functional micelles through self complementary interactions has significant potential in this study a practical approach to living polymerization of functionalized thermoresponsive monomers enabled the incorporation of self constituted multiple hydrogen bonded groups into micelles that have potential as supramolecular drug delivery systems phase transitions and morphological studies in aqueous solution showed that the microstructure can be controlled to achieve well defined vesicle like micelles with respect to the strength of the hydrogen bond segment thus the resulting micelles have a very low critical micellization concentration and very high loading capacity 16 1 making the loading process extremely stable and efficient incorporation of the anticancer drug doxorubicin dox affected the micellization process in aqueous solution and enabled fine tuning of drug loading and precise control of drug release rate with excellent sensitivity release studies in vitro showed that dox loaded micelles exerted dose dependent cytotoxicity against human liver carcinoma hepg2 cells at the physiological temperature of 37 \xb0c in addition dox loaded micelles were efficiently endocytosed by the cancer cells which may enable the micelles to serve as suitable vehicles for effective delivery of anticancer drugs to primary tumors and metastatic disease this newly developed material may provide a potential route towards next generation drug delivery vehicles a breakthrough innovation in water based thermo responsive polymers has enabled significant progress in developing smart stimuli responsive nanocarriers by generating novel supramolecular polymeric micelles via self complementary hydrogen bonding interactions these newly developed micelles exhibit extremely high micellar stability and drug loading capacity up to 16 excellent thermo responsive behavior and precise control of drug release rate due to hydrogen bond induced physical cross linking in addition doxorubicin loaded micelles were efficiently endocytosed by the cancer cells which allows them to serve as suitable vehicles for effective delivery of anticancer drugs to primary tumors and metastatic disease thus this work provides a potential route for the development of next generation multifunctional nanocarriers that have improved safety and to increase the therapeutic efficacy of anticancer therapy club clara cells are nonciliated secretory epithelial cells present in bronchioles of distal pulmonary airways so far no information is available on the postnatal differentiation of club cells by a combination of molecular biological biochemical and stereological approaches in the murine lung therefore the present study was designed to investigate the changes in the club cell secretory proteins cc10 surfactant proteins a b and d and club cell abundance within the epithelium of bronchioles of distal airways during the postnatal development of the mouse lung perfusion fixed murine lungs of three developmental stages newborn 15 day old and adult were used frozen unfixed lungs were used for cryosectioning and subsequent laser assisted microdissection of bronchiolar epithelial cells and rt pcr analyses high resolution analyses of the three dimensional structures and composition of lung airways were obtained by scanning electron microscopy finally using design based stereology the total and average club cell volume and the volume of secretory granules were quantified by light and transmission electron microscopy our results reveal that murine club cells are immature at birth and differentiate postnatally further increase of the club cell volume and number of intracellular granules are closely correlated to the total lung volume enlargement however secretory granule density was only increased within the first 15 days of postnatal development the differentiation is accompanied by a decrease in glycogen content and a close positive relationship between cc10 expression and secretory granule abundance taken together our data are consistent with the concept that the morphological and functional differentiation of club cells is a postnatal phenomenon diabetes mellitus is a worldwide metabolic disease which constitutes a major threat to human health stem cells with the ability to differentiate into insulin producing cells ipcs could provide unlimited sources of transplanted cells and solve allogeneic rejection problems the decellularized scaffolds could provide ipcs with tissue microarchitecture and intact vascular systems the goal of this study was to engineer intact whole rat liver scaffolds and repopulate the stem cell derived ipcs into the scaffolds to discover whether the decellularized scaffolds could facilitate the growth and development of ipcs decellularized liver scaffolds were obtained using 1 triton x 100 with 0 1 ammonium hydroxide architecture and composition of the original extracellular matrix were confirmed by morphologic histological and immunolabeling examinations islet like clusters were differentiated from wharton s jelly mesenchymal stem cells wjmscs by a three step induction procedure the differentiation was evaluated by morphology rt pcr immunofluorescence and glucose stimulation experiments the islet like clusters were recellularized into the decellularized scaffolds by the portal vein infusion method and cultured by the dynamic circulation perfusion device after cultivation hematoxylin eosin staining immunofluorescence and rt pcr were conducted our results demonstrated that the decellularized rat liver scaffolds have favorable biochemical properties and could support the survival of wjmsc derived ipcs in addition the three dimensional decellularized scaffolds could enhance the expression of the insulin gene compared with two dimensional plate culture in conclusion these findings suggested that the decellularized scaffolds could provide a suitable platform for cellular activities of ipcs such as survival differentiation proliferation and insulin secretion this study provides fundamental support for regenerating insulin secreting organs from the decellularized scaffolds combined with stem cell derived ipcs as a potential clinical application huntington s disease hd is a neurodegenerative disorder characterized by a progressive decline of motor and cognitive functions it is caused by a polyglutamine expansion in the huntingtin htt protein which then leads to neurodegeneration that span both the central and peripheral nervous system previous works have shown that htt interacts with several proteins from the neurotransmitter release machinery causing synaptic dysfunction in this work we looked for alterations in diaphragm neuromuscular junctions nmjs from 3 to 4 months old bachd mouse model for hd this model represents a new and robust in vivo paradigm for studying the pathogenesis of hd for optical analysis nmjs were stained with fm1 43fx and \u03b1 bungarotoxin to visualize both pre and postsynaptic elements respectively confocal microscopy optical analysis showed a decrease in the number of synaptic elements and fluorescence intensity in nmjs from bachd diaphragms compared to wt we next analyzed presynaptic activity and we observed that synaptic vesicle exocytosis was impaired in nmjs from bachd diaphragms ultrastructural analysis revealed significant changes in the form and sizes of the synaptic vesicles in bachd diaphragm nmjs that could contribute to impaired exocytosis additionally electrophysiology recordings revealed a decrease in the amplitude of miniature endplate potentials mepps from bachd diaphragm nmjs our data suggest a dysfunction in bachd diaphragm nmjs that might occur in other muscles and may aggravate the motor defects seen in hd these results may contribute to a better understanding of peripheral cholinergic dysfunction in this neurodegenerative disease this study was designed to determine the long term safety and efficacy of using modified double disk occluders for perimembranous ventricular septal defect pmvsd closure in adults from january 2004 to december 2014 337 adults with pmvsds were treated through transcatheter intervention using 2 types of double disk occluders 302 patients received a symmetrical concentric pmvsd occluder and 35 patients received an asymmetrical concentric pmvsd occluder all patients were followed up through electrocardiography and transthoracic echocardiography until june 2015 the success rate was 100 for both procedures during the median 71 month follow up period no cases of infective endocarditis cerebrovascular accidents heart failure or death occurred two major adverse events 0 6 were recorded complete atrioventricular block requiring surgical treatment in one patient and severe tricuspid valvular regurgitation requiring surgical repair in another patient cardiac conduction block was the most common minor adverse event the mean left ventricular lv end diastolic volume decreased from 96 6 23 2 ml before intervention to 86 0 22 0 ml p 0 05 at the 6 month follow up visit previously enlarged lv chambers decreased to normal sizes during the follow up period in conclusion transcatheter closure of pmvsds using modified double disk occluders was both safe and effective and yielded excellent long term results in adults the potential benefits of this intervention included remodeling of the heart a reduced incidence of infective endocarditis and prevention of lv volume overload guidelines do not recommend an implantable cardioverter defibrillator icd for prevention of sudden death in patients who develop ventricular arrhythmia va within 48 hours of acute myocardial infarction ami if they are successfully revascularized we aimed to determine long term survival in a cohort of early va survivors treated with percutaneous coronary intervention pci and to determine whether certain high risk characteristics predicted worse outcomes this retrospective study included all patients with early va after ami treated with pci at our institution from 2002 to 2012 who survived to hospital discharge patients who had an icd before their index ami and those who received icd before hospital discharge were excluded overall survival in the early va survivors was analyzed based on post mi left ventricular ejection fraction lvef \u226550 vs 50 mi type st segment elevation myocardial infarction stemi vs non st segment elevation myocardial infarction nstemi and single vessel versus multivessel disease baseline presenting clinical and pci characteristics plus outcomes were compared with matched controls with pci treated ami but no early va of the 79 early va survivors treated with pci there were no significant differences in long term overall survival between ami type stemi vs nstemi single vessel versus multivessel disease and lvef at time of mi 50 vs 50 despite having lower presenting lvef 46 vs 55 p 0 001 and higher rates of cardiogenic shock 28 vs 4 p 0 001 survivors of early va had similar overall survival compared with pci treated controls whose post ami hospital course was not complicated by early va p 0 61 in conclusion patients with early va treated with pci who survive to discharge were more likely to have stemi lower lvef and cardiogenic shock type of ami or the presence of systolic dysfunction or multivessel disease did not predict long term mortality with early pci early va survivors have similar long term prognosis compared with those without early va polymer coatings on drug eluting stents des serve as a vehicle for delivery of antirestenotic drugs whether they influence outcomes for contemporary des is unknown the evolution of polymer coatings for zotarolimus eluting stents zes provides a natural experiment that facilitates such analysis the resolute zes r zes uses the same antirestenotic drug as the endeavor zes e zes but has a more biocompatible polymer with enhanced drug release kinetics however there are limited data on the real world comparative efficacy of r zes and the preceding e zes thus we analyzed 17 643 patients who received either e zes or r zes from 2008 to 2014 from the british columbia cardiac registry a total of 9 869 patients 56 received e zes and 7 774 patients 44 received r zes compared with e zes r zes was associated with lower 2 year mortality 4 1 vs 6 4 p 0 001 and 2 year target vessel revascularization tvr 6 8 vs 10 7 p 0 001 r zes use was an independent predictor of lower mortality rate and tvr this was confirmed in propensity matched analyses for 2 year mortality hazard ratio hr 0 59 95 ci 0 49 to 0 71 p 0 001 and 2 year tvr hr 0 86 95 ci 0 75 to 0 98 p 0 032 instrumental variable analyses demonstrated r zes to be associated with lower 2 year mortality \u03b4 2 2 95 ci 4 3 to 0 2 p 0 032 and 2 year tvr \u03b4 3 3 to 95 ci 6 1 to 0 7 p 0 015 acknowledging the limitations of observational analyses this study has shown that r zes was associated with lower long term tvr and mortality these data are reassuring for the newer r zes and demonstrate how polymer coatings may influence the clinical performance of des with wider implications for future des development and design preterm delivery ptd remains a serious challenge in perinatology intrauterine infection and or inflammation followed by increased inflammatory cytokines represented by il 6 are involved in this pathology our aim was to identify il 6 producing cells in the placenta and to analyze the potential of targeting i\u03bab kinase \u03b2 ikk\u03b2 signaling to suppress il 6 production for the treatment of ptd immunohistochemical analyses using placentas complicated with severe chorioamnionitis revealed that il 6 is mainly expressed in human amniotic mesenchymal stromal cells hamscs primary hamscs were collected and strong il 6 expression was confirmed in hamscs the treatment of tumor necrosis factor \u03b1 or il 1\u03b2 drastically induced il 6 production followed by the phosphorylation of ikks a novel ikk\u03b2 inhibitor imd 0560 almost completely inhibited il 6 production from hamscs using an experimental lipopolysaccharide induced ptd mouse model the therapeutic potential of imd 0560 was examined imd 0560 was delivered vaginally 4 hours before lipopolysaccharide administration mice in the imd 0560 30 mg kg twice a day group had a significantly lower rate of ptd 10 of 22 45 without any apparent adverse events on the mice and their pups in uteri collected from mice imd 0560 inhibited not only il 6 production but also production of related cytokines such as keratinocyte derived protein chemokine cxcl1 macrophage inflammatory protein 2 cxcl2 and monocyte chemoattractant protein 1 chemokine ligand 2 targeting ikk\u03b2 signaling shows promising effects through the suppression of these cytokines and can be explored as a future option for the prevention of ptd a major aim of systems pharmacology is to understand clinically relevant mechanisms of action moa of drugs and to use this knowledge in order to optimize therapy to enable this mission it is necessary to obtain knowledge on how in vitro testable insights translate into clinical efficacy mathematical modeling and data integration are essential components to achieve this goal two modeling philosophies are prevalent each of which in isolation is not sufficient to achieve the above described in a top down approach a minimal pharmacokinetic pharmacodynamic pk pd model is derived from and fitted to available clinical data this model may lack interpretability in terms of mechanisms and may only be predictive for scenarios already covered by the data used to derive it a bottom up approach builds on mechanistic insights derived from in vitro ex vivo experiments which can be conducted under controlled conditions but may not be fully representative for the in vivo clinical situation in this work we employ both approaches side by side to predict the clinical potency ic50 values of the nucleoside reverse transcriptase inhibitors nrtis lamivudine emtricitabine and tenofovir in the top down approach this requires to establish the dynamic link between the intracellularly active nrti triphosphates which exert the effect and plasma prodrug pk and to subsequently link this composite pk model to viral kinetics the bottom up approach assesses inhibition of reverse transcriptase mediated viral dna polymerization by the intracellular active nrti triphosphates which has to be brought into the context of target cell infection by using entirely disparate sets of data to derive and parameterize the respective models our approach serves as a means to assess the clinical relevance of the bottom up approach we obtain very good qualitative and quantitative agreement between top down vs bottom up predicted ic50 values arguing for the validity of the bottom up approach we noted however that the top down approach is strongly dependent on the sparse and noisy intracellular pharmacokinetic data all in all our work provides confidence that we can translate in vitro parameters into measures of clinical efficacy using the bottom up approach this may allow to infer the potency of various nrtis in inhibiting e g mutant viruses to distinguish sources of interaction of nrti combinations and to assess the efficacy of different nrtis for repurposing e g for pre exposure prophylaxis caseous lymphadenitis cla is a contagious infectious chronic disease caused by corynebacterium pseudotuberculosis which affects mainly sheep and goats the clinical prevalence of cla in brazil is 30 resulting in decreased milk production weight loss and unusable meat and leather prophylaxis is based on vaccination however current vaccinations do not offer effective protection against the infection which makes the development of a new vaccine essential to control this disease here we developed a recombinant vaccine based on cp40 protein rcp40 combined with an adjuvant freund s complete adjuvant or saponin and evaluated its efficacy in a murine model of cla female balb c mice were used in an immunization assay rcp40 induced high levels of igg2a and igg2b antibodies after challenge with a virulent strain of c pseudotuberculosis c57 10 4 cfu ml the levels of igg2a and igg2b were sustained indicating a th1 response the groups immunized with rcp40 protein ges and gef groups showed 100 protection and was statistically significant in the ges and gef groups p 0 037 and p 0 0952 respectively the results indicated the recombinant protein cp40 induced an specific immune response in mice that was able to afford protection after challenge regardless the adjuvant used in the formulation chronic obstructive pulmonary disease copd is independently and positively associated with abdominal aortic aneurysm aaa presence the aim of the present article was to determine whether copd is associated with aaa growth we reviewed currently available studies with a systematic literature search and meta analytic estimate databases including medline and embase were searched through july 2015 using web based search engines pubmed and ovid studies considered for inclusion met the following criteria the study population was aaa patients with and without copd and outcomes included data regarding aaa growth for each study growth rates in both the copd and non copd groups were used to generate standardized mean differences smds and 95 confidence intervals cis of 614 potentially relevant publications screened initially we identified 10 eligible studies including data on a total of 2663 aaa patients none of them demonstrated a statistically significant positive or negative association of copd with aaa growth rates a pooled analysis demonstrated that copd is not associated with aaa growth rates smd 0 04 95 ci 0 07 to 0 15 p 0 50 there was no evidence of significant publication bias in conclusion we found that copd is not associated with aaa growth further investigations would be required to elucidate why copd is not associated with aaa growth despite its positive association with aaa presence immunoglobulin g4 igg4 related disease is an emerging new clinicopathological disorder that is characterized by elevation of serum igg4 levels and histological findings of igg4 positive plasmacytic infiltration igg4 related disease may appear synchronously or metachronously in a wide variety of organs the current patient was found to have pericardial effusion and retroperitoneal fibrosis he was subsequently diagnosed with coronary artery stenosis 18 f fdg positron emission tomography showed enhanced fdg uptake in lymph nodes as well as pericardial and peri aortic tissue histopathology of the mediastinal lymph node showed the infiltration of numerous igg4 positive cells leading to the diagnosis of igg4 related lymphadenopathy with pericardial and periarterial involvement pigmentary variation in animals has been studied because of its application in genetics evolution and developmental biology the large number of known color loci provides rich resource to elucidate the functional pigmentary system nonetheless more color loci remain to be identified in our previous study we revealed that two different strains namely agh rats and leh rats but which had the same null mutation of the ednrb gene ednrb sl showed markedly different pigmented coat ratio this result strongly suggested that the severity of pigment abnormality was modified by genetic factor s in each strain to elucidate the modifier locus of pigment disorder we carried out whole genome scanning for quantitative trait loci qtls on 149 f2 agh ednrb sl leh ednrb sl rats a highly significant qtl constituting 26 of the total pigmentation phenotype variance was identified in a region around d7got23 on chromosome chr 7 in addition investigation on epistatic interaction revealed significant interactions between d7got23 and d3rat78 and between d7got23 and d14mit4 results suggested that a modified locus on chr 7 was mainly responsible for the variance of pigmentary disorder between agh ednrb sl rats and leh ednrb sl rats and two modifier loci showing epistatic interaction may in part influence pigment phenotype the prevalence of hypertension in chinese mainland has increased rapidly in the recent decades this study aimed to determine the prevalence of hypertension and sodium intake in an economically booming area in china 9600 adults aged from 18 to 69 years old in jiangsu province of china were recruited using a complex multistage sampling method blood pressure was measured and a face to face interview was conducted among all participants 24 hours 24 h urine sample was collected from each participant and then measured for sodium and potassium hypertension was determined by blood pressure and use of anti hypertension medications all of the analyses were weighted according to the population distribution in the province overall the weighted means of systolic blood pressure sbp and diastolic blood pressure dbp were 128 8 mm hg 95 confidence interval ci 128 3 129 3 and 82 2 mm hg 95 ci 81 4 83 1 the weighted hypertension prevalence of jiangsu residents was 33 0 95 ci 29 4 36 7 among those with hypertension 31 4 95 ci 24 6 38 1 were aware of their blood pressure condition in total 88 4 95 ci 83 5 93 3 of those with known hypertension took anti hypertension medications only 23 7 95 ci 13 3 34 2 of those under anti hypertension medications had their blood pressure controlled the mean of 24 h urinary sodium excretion was 188 2 mmol standard deviation sd 69 5 representing that the mean intake of salt was 11 0 g sd 4 1 through conversion hypertension and excessive sodium intake in adults are prevalent in jiangsu province china these observations suggest that a public health approach is necessary to prevent hypertension and manage hypertensive patients peste des petits ruminants virus pprv causes an economically important disease of sheep and goats primarily in developing countries it is becoming the object of intensive international control efforts current vaccines do not allow vaccinated and infected animals to be distinguished no diva capability we have previously shown that recombinant replication defective adenovirus expressing the pprv h glycoprotein adh gives full protection against wild type pprv challenge we have now tested lower doses of the vaccine as well as adh in combination with a similar construct expressing the pprv f glycoprotein adf we show here that in a local breed of goat in a country where ppr disease is common kenya as little as 10 7 pfu of adh gives significant protection against pprv challenge while a vaccine consisting of 10 8 pfu of each of adh and adf gives apparently sterile protection these findings underline the utility of these constructs as diva vaccines for use in ppr control patients with clostridium difficile infection cdi can experience long term symptoms and poor quality of life due to the disease despite this a health related quality of life hrqol instrument specific for patients with cdi does not exist the aim of this study was to develop and validate a disease specific instrument to assess hrqol in patients with cdi a systematic literature review was conducted to identify hrqol instruments and questions related to general health n 3 or gastrointestinal disease n 12 potentially related to cdi hrqol removing duplicate questions and using direct patient or clinician interviews a 36 item survey was developed the survey was then tested using 98 patients with cdi and compared with the rand short form 36 sf 36 health survey psychometric analysis techniques were used to identify domains and remove redundant items exploratory factor analysis identified 3 major domains physical mental and social with 4 associated subdomains survey overall and domain scores displayed good internal consistency cronbach \u03b1 coefficient 0 87 and concurrent validity evidenced by significant correlation with sf 36 scores the c difficile survey scores were better able than the sf 36 to discriminate quality of life score differences in patients with primary versus recurrent cdi and increasing time since last episode of cdi the final version contained 32 items related to the physical mental and social health of cdi patients the properties of the newly developed cdiff32 should make it appropriate to assess changes over time in hrqol in patients with cdi cardiac erosion related to transcatheter atrial septal defect closure devices is of increasing concern erosion is reported to have occurred with most of currently available occluder devices perhaps due to the very large number of implants worldwide the amplatzer st jude occluder is associated with the majority of cardiac erosion events reported in the literature best current estimates of the incidence of erosion with the st jude device are between one and three cases per 1000 implants most events occur early after implantation and it is rare although not unheard of for events to occur after a year following device insertion it is important that those involved with closure programmes are vigilant for the problem because device related erosion is associated with a significant mortality risk despite considerable debate the risk factors either patient or device for erosion remain unclear and require further investigation currently available data sets have focussed largely on erosion cohorts and are unable to place these cases in appropriate context with non erosion closure cases what is certain is that programmes implanting these devices must take care to implant appropriately sized devices and have in place plans to ensure that patients are both well informed and can access help and advice in the event of developing symptoms our objective is to assess the impact of varying risk profiles in men and women on the clinical picture of ischemic stroke the study involved 185 patients 100 women and 85 men we assessed the patients neurological status upon admission 1 and 2 weeks following stroke onset using the scandinavian stroke scale and the barthel index stroke syndromes according to the oxfordshire classification their etiology and pathogenesis according to the trial of org 10172 in acute stroke treatment and the prevalence of vascular risk factors we used cranial magnetic resonance imaging to locate infarcts women had more total anterior circulation infarct subtype strokes whereas men had more posterior circulation infarct and lacunar infarct on neuroimaging women had more infarcts in the middle cerebral artery circulation whereas men had more in the brain stem and or cerebellum women had a higher prevalence of atrial fibrillation af and coronary artery disease whereas men were more likely to smoke and abuse alcohol women had more cases of cardioembolism whereas men had more strokes caused by atherosclerosis of large vessels in the present study heart diseases such as coronary artery disease and af were more prevalent among women it seems that af is a risk factor with significant impact on the epidemiological differences regarding ischemic stroke in men and women ischemic stroke patients subtyped as of undetermined cause suc usually outnumber those with determined cause subtypes etiological stroke classifications may lead to neglect of parallel noncausative findings atherosclerosis progresses over decades and is associated with high morbidity and mortality in young stroke patients in long term follow up studies we compared the prevalence of carotid atherosclerosis in all toast subtypes among young patients with acute ischemic stroke we investigated 150 patients aged 15 60 years with documented acute ischemic stroke and 84 controls free of cardiovascular disease stroke etiology was classified according to toast criteria carotid intima media thickness cimt measurements were obtained from 12 standardized multiangle measurements in the common carotid artery carotid bifurcation and internal carotid artery the causes of stroke were 5 3 large artery atherosclerosis laa 26 7 cardioembolism 21 3 small artery occlusion sao 10 stroke of other determined cause and 36 7 stroke of undetermined cause suc cimt was increased in patients with laa 1 56 mm p 002 sao 1 11 mm p 006 and suc 1 10 mm p 004 compared to controls cimt 0 86 mm segmental cimt distribution differed across stroke subtypes age groups and sexes atherosclerotic disease is prevalent in the majority of young and middle aged ischemic stroke patients requiring determined investigation and aggressive treatment of modifiable risk factors rna regulation participates in many aspects of brain development there is substantial evidence that rna dysregulation is critical in the pathogenesis of neurodevelopmental disorders neurological diseases and cancer several gene families encode rna binding proteins rnabps that bind directly to rna and orchestrate the post transcriptional regulation of gene expression including pre mrna splicing stability and poly a site usage among neural rnabps the elavl and msi families are the focus of neuronal development research owing to their hierarchical expression pattern msi1 is expressed in neural progenitor stem cells elavl2 is expressed in early neuronal progenitors to mature neurons and elavl3 4 expression begins slightly later during cortical neuron development traditional biochemical analyses provide mechanistic insight into rna regulation by these rnabps and drosophila and mouse genetic studies support a relationship between these rnabps and several neurodevelopmental disorders in addition a recent cohort analysis of the human genome shows that genetic mutations and snps in these rnabps are associated with various neurological disorders newly emerged technologies assess transcriptome wide rna protein interactions in vivo these technologies combined with classical genetics methods provide new insight into elavl and msi not only with respect to their neurodevelopmental functions but also their roles in several diseases we review recent discoveries related to the two rnabp families in brain development and disease mitochondrial fission and fusion control the shape size number and function of mitochondria in the cells of organisms from yeast to mammals the disruption of mitochondrial fission and fusion is involved in severe human diseases such as parkinson s disease alzheimer s disease metabolic diseases and cancers agents that can real time track the mitochondrial dynamics are of great importance however the short excitation wavelengths and rapidly photo bleaching properties of commercial mitochondrial dyes render them unsuitable for tracking mitochondrial dynamics thus mitochondrial targeting agents that exhibit superior photo stability under continual light irradiation deep tissue penetration and at intrinsically high three dimensional resolutions are urgently needed two photon excited compounds employ low energy near infrared light and have emerged as a non invasive tool for real time cell imaging here cyclometalated ir iii complexes ir1 ir5 are demonstrated as one and two photon phosphorescent probes for the real time imaging and tracking of mitochondrial fission and fusion the results indicate that ir2 is well suited for two photon phosphorescent tracking of mitochondrial fission and fusion in living cells and in caenorhabditis elegans c elegans this study provides a practical use for mitochondrial targeting two photon phosphorescent ir iii complexes many surgical interventions for cardiovascular disease are limited by the availability of autologous vessels or suboptimal performance of prosthetic materials tissue engineered vascular grafts show significant promise but have yet to achieve clinical efficacy in small caliber 5 mm arterial applications we previously designed cell free elastomeric grafts containing solvent casted particulate leached poly glycerol sebacate pgs that degraded rapidly and promoted neoartery development in a rat model over 3 months building on this success but motivated by the need to improve fabrication scale up potential we developed a novel method for electrospinning smaller grafts composed of a pgs microfibrous core enveloped by a thin poly \u03b5 caprolactone pcl outer sheath electrospun pgs pcl composites were implanted as infrarenal aortic interposition grafts in mice and remained patent up to the 12 month endpoint without thrombosis or stenosis many grafts experienced a progressive luminal enlargement up to 6 months however due largely to degradation of pgs without interstitial replacement by neotissue lack of rupture over 12 months confirmed sufficient long term strength due primarily to the persistent pcl sheath immunohistochemistry further revealed organized contractile smooth muscle cells and neotissue in the inner region of the graft but a macrophage driven inflammatory response to the residual polymer in the outer region of the graft that persisted up to 12 months overall the improved surgical handling long term functional efficacy and strength of this new graft strategy are promising and straightforward modifications of the pgs core should hasten cellular infiltration and associated neotissue development and thereby lead to improved small vessel replacements to document the electrocardiographic findings of vagally induced paroxysmal atrial fibrillation following a presumed reflex syncopal episode in the dog seven dogs with a syncopal episode followed by a paroxysm of atrial fibrillation recorded on a 24 hour holter twenty four hour holter monitors were retrospectively reviewed analysing the cardiac rhythm associated with syncopal events each recording was analysed from 10 min before the syncopal episode to until 10 min after a normal sinus rhythm had returned nine episodes were recorded in seven dogs with one patient experiencing three events during one holter recording five of the seven dogs presented with underlying structural heart disease in two the syncopal episodes occurred following exercise two associated with coughing and three were during a period of rest all dogs had documented on the holter recording a rhythm abnormality during syncope the most common finding leading up to the syncopal event was development of a progressive sinus bradycardia followed by sinus arrest interrupted by a ventricular escape rhythm and then ventricular arrest this was then followed by an atrial fibrillation the atrial fibrillation was paroxysmal in seven recordings and persistent in two in two dogs the atrial fibrillation reorganised into self limiting runs of atypical atrial flutter this combination of electrocardiographic arrhythmias are probably caused by an inappropriate parasympathetic stimulation initiating a reflex or neurally mediated syncope with abnormal automaticity of the sinus node and of the subsidiary pacemaker cells and changes in the electrophysiological properties of the atrial muscle which promoted the paroxysmal atrial fibrillation the aim of this study was to determine the prevalence and clinical characteristics of voice disorders in a large group of patients seeking voice therapy this is a prospective prevalence study a total of 821 patients were enrolled each patient was evaluated following a multidimensional protocol including videolaryngostroboscopy perception acoustics aerodynamics and self rating by the patient data regarding age gender tobacco use gastroesophageal reflux disease gerd and professional voice use were collected and analyzed based on videolaryngoscopic findings the sample group was divided into patients with functional dysphonia n 155 patients with organic dysphonia n 359 and patients with dysphonia due to movement disorders n 307 the most frequently detected pathologies were vocal fold paralysis muscle tension dysphonia and vocal fold edema children n 41 and adolescents n 43 represented a minority of the sample group dysphonia was significantly more common in women organic dysphonia was more common in children and adolescents gerd was suspected in 382 patients and confirmed in 83 of them 164 patients were smokers professional voice users composed the large majority of the working population and were more frequently affected by organic dysphonia patients with dysphonia due to movement disorders presented a worse voice quality and voice related quality of life in patients seeking voice therapy there are more females than males children and adolescents represent a minority of the sample professional voice users more commonly present organic dysphonia and patients with dysphonia due to movement disorders show significantly worse voice quality crohn s disease cd is characterized by chronic transmural inflammation the symptom of the mice model induced by 2 4 6 trinitrobenzenesulfonic acid tnbs is closed to human under cd condition so this kind of animal is widely used in the related researches although the dysbiosis of the fecal microbiota has been proved to play an important role in the patients with cd the composition of the gastrointestinal microbiota in the mouse model under disease condition is still unclear in the current study male 7 week balb c mice were anesthetized and intrarectal administrated by ethanol et group tnbs in ethanol tn group and phosphate buffered saline pbs ck group as control the symptoms of individuals under the cd condition were observed and the changes of the bacterial taxonomic structure and functional composition were revealed by next generation sequencing ngs 16s sequencing the balb c mice in tn group demonstrated cd like symptoms and the damages in the intestinal tract the ngs 16s results exhibited that the diversity and microbial composition under cd condition are significantly different with those in et group the kegg orthology ko profile were generated from picrust and function modules such as methanogenesis m00347 and microcin c transport system m00349 were found enriched in the individuals in the tn group this study proved that mouse model induced by tnbs could develop the similar symptom to cd patient and we firstly showed the significant intestinal microbe changes on both taxonomic structure and functional composition in this mouse model tissue remodeling of sub epithelial mesenchymal cells is a major pathology occurring in chronic obstructive pulmonary disease copd and asthma fibroblasts as a major source of interstitial connective tissue extracellular matrix contribute to the fibrotic and inflammatory changes in these airways diseases previously we described that protein arginine methyltransferase 1 prmt1 participates in airway remodeling in a rat model of pulmonary inflammation in this study we investigated the mechanism by which pdgf bb regulates prmt1 in primary lung fibroblasts isolated from human lung biopsies fibroblasts were stimulated with pdgf bb for up to 48h and the regulatory and activation of signaling pathways controlling prmt1 expression were determined prmt1 was localized by immuno histochemistry in human lung tissue sections and by immunofluorescence in isolated fibroblasts prmt1 activity was suppressed by the pan prmt inhibitor ami1 erk1 2 mitogen activated protein kinase mapk was blocked by pd98059 p38 mapk by sb203580 and stat1 by small interference si rna treatment the results showed that pdgf bb significantly increased prmt1 expression after 1h lasting over 48h through erk1 2 mapk and stat1 signaling the inhibition of erk1 2 mapk or of prmt1 activity decreased pdgf bb induced fibroblast proliferation cox2 production collagen 1a1 secretion and fibronectin production these findings suggest that prmt1 is a central regulator of tissue remodeling and that the signaling sequence controlling its expression in primary human lung fibroblast is pdgf erk stat1 therefore prmt1 presents a novel therapeutic and diagnostic target for the control of airway wall remodeling in chronic lung diseases myocarditis is defined as an inflammatory disease of the heart muscle and is an important cause of acute heart failure sudden death and dilated cardiomyopathy viruses account for most cases of myocarditis or inflammatory cardiomyopathy which could induce an immune response causing inflammation even when the pathogen has been cleared other etiologic agents responsible for myocarditis include drugs toxic substances or autoimmune conditions in the last few years advances in noninvasive techniques such as cardiac magnetic resonance have been very useful in supporting diagnosis of myocarditis but toxic infectious inflammatory infiltrative or autoimmune processes occur at a cellular level and only endomyocardial biopsy can establish the nature of the etiological agent furthermore after the generalization of immunohistochemical and viral genome detection techniques endomyocardial biopsy provides a definitive etiological diagnosis that can lead to specific treatments such as antiviral or immunosuppressive therapy endomyocardial biopsy is not commonly performed for the diagnosis of myocarditis due to safety reasons but both right and left endomyocardial biopsies have very low complication rates when performed by experienced operators this document provides a state of the art review of myocarditis and inflammatory cardiomyopathy with special focus on the role of endomyocardial biopsy to establish specific treatments we present 2 patients with moyamoya disease undergoing revascularization surgery who developed transient intraoperative central diabetes insipidus with spontaneous resolution in the immediate postoperative period we speculate that patients with moyamoya disease may be predisposed to a transient acute on chronic insult to the arginine vasopressin producing portion of their hypothalamus mediated by anesthetic agents we describe our management discuss pertinent literature and offer possible mechanisms of this transient insult we hope to improve patient safety by raising awareness of this potentially catastrophic complication familial hypercholesterolemia is an uncommon disease that may be associated with atherosclerosis affecting coronary arteries and the ascending aorta coarctation of the aorta is rarely involved in this disease the ideal surgical approach for management of coexisting coronary artery disease and coarctation of the aorta in a child with familial hypercholesterolemia is unclear we report the case of a 14 year old girl with familial hypercholesterolemia who underwent double coronary artery bypass grafting due to proximal lesions of both the left anterior descending artery and the right coronary artery with advancing technology the sensitivity of computed tomography ct for the detection of subdural hematoma sdh continues to improve in some cases the finding is limited to one or 2 images of the ct examination at our institution all patients with an sdh require intensive care unit icu admission regardless of size in this report we tested the hypothesis that patients with a small traumatic sdh on their presenting ct examination do not require the intensive monitoring offered in the icu and can instead be managed on a hospital unit with a lower level of monitoring this is a retrospective study of patients evaluated and treated at a level i trauma center for acute traumatic intracranial hemorrhage between 2011 and 2014 the clinical and imaging profile of 87 patients with traumatic sdh were studied patients with small isolated traumatic subdural hemorrhage tsdh 10 cm 3 blood volume spent less time in the icu demonstrated neurologic and medical stability during hospitalization and did not require any neurosurgical intervention it is our recommendation that patients with isolated tsdh 10 cm 3 do not require icu monitoring patients with small tsdh and additional intracranial hemorrhages overall show low rates of medical decline 4 and neurologic decline 4 but may still benefit from icu observation patients with tsdh greater than 10 cm 3 overall demonstrated poor clinical courses and outcome and would benefit icu monitoring small bowel obstruction sbo is a common cause of admission to the surgical service on rare occasions a diagnosed sbo is actually due to large bowel pathology combined with an incompetent ileocecal valve the purpose of this study was to investigate this phenomenon we performed a retrospective medical record review of patients that were admitted with a diagnosis of sbo at university of louisville hospital and the veterans affairs hospitals in louisville ky from 2006 until 2014 a total of 498 patients were admitted with sbo during this time period forty one patients were found to have an underlying large bowel disease the most common large bowel pathologies included malignancy 51 inflammation 15 and infection 15 fifteen 43 of these patients died during admission 93 of these were due to either their bowel obstruction or the underlying disease state this was significantly higher than the general population 9 4 mortality 6 due to underlying disease patients that present with sbo due to a large bowel source have a much higher mortality rate than those that present with other causes rapid identification of these patients will allow for more timely and appropriate treatment stress echocardiography is recommended for the assessment of asymptomatic patients with severe valvular heart disease vhd when there is discrepancy between symptoms and resting markers of severity the aim of this study is to determine the prognostic value of exercise stress echocardiography in patients with common valve lesions one hundred and fifteen patients with vhd aortic stenosis n 28 aortic regurgitation n 35 mitral regurgitation n 26 mitral stenosis n 26 and age and sex matched controls n 39 with normal ejection fraction underwent exercise stress echocardiography the primary endpoint was a composite of death or hospitalization for heart failure asymptomatic vhd patients had lower exercise capacity than controls and 37 of patients achieved 85 of their predicted metabolic equivalents mets there were three deaths and four hospital admissions and 24 patients underwent surgery during follow up an abnormal stress echocardiogram mets 5 blood pressure rise 20 mmhg or pulmonary artery pressure post exercise 60 mmhg was associated with an increased risk of death or hospital admission 14 vs 1 p 0 0001 the assessment of contractile reserve did not offer additional predictive value in conclusion an abnormal stress echocardiogram is associated with death and hospitalization with heart failure at 2 years stress echocardiography should be considered as part of the routine follow up of all asymptomatic patients with vhd falls are a frequent and serious complication of parkinson s disease and are related partly to an underlying cholinergic deficit that contributes to gait and cognitive dysfunction in these patients gait dysfunction can lead to an increased variability of gait from one step to another raising the likelihood of falls in the respond trial we aimed to assess whether ameliorating this cholinergic deficit with the acetylcholinesterase inhibitor rivastigmine would reduce gait variability we did this randomised double blind placebo controlled phase 2 trial at the north bristol nhs trust hospital bristol uk in patients with parkinson s disease recruited from community and hospital settings in the uk we included patients who had fallen at least once in the year before enrolment were able to walk 18 m without an aid had no previous exposure to an acetylcholinesterase inhibitor and did not have dementia our clinical trials unit randomly assigned 1 1 patients to oral rivastigmine or placebo capsules both taken twice a day using a computer generated randomisation sequence and web based allocation rivastigmine was uptitrated from 3 mg per day to the target dose of 12 mg per day over 12 weeks both the trial team and patients were masked to treatment allocation masking was achieved with matched placebo capsules and a dummy uptitration schedule the primary endpoint was difference in step time variability between the two groups at 32 weeks adjusted for baseline age cognition step time variability and number of falls in the previous year we measured step time variability with a triaxial accelerometer during an 18 m walking task in three conditions normal walking simple dual task with phonemic verbal fluency walking while naming words beginning with a single letter and complex dual task switching with phonemic verbal fluency walking while naming words alternating between two letters of the alphabet analysis was by modified intention to treat we excluded from the primary analysis patients who withdrew died or did not attend the 32 week assessment this trial is registered with isrctn number 19880883 between oct 4 2012 and march 28 2013 we enrolled 130 patients and randomly assigned 65 to the rivastigmine group and 65 to the placebo group at week 32 compared with patients assigned to placebo 59 assessed those assigned to rivastigmine 55 assessed had improved step time variability for normal walking ratio of geometric means 0 72 95 ci 0 58 0 88 p 0 002 and the simple dual task 0 79 0 62 0 99 p 0 045 improvements in step time variability for the complex dual task did not differ between groups 0 81 0 60 1 09 p 0 17 gastrointestinal side effects were more common in the rivastigmine group than in the placebo group p 0 0001 20 31 patients in the rivastigmine group versus three 5 in the placebo group had nausea and 15 17 versus three 5 had vomiting rivastigmine can improve gait stability and might reduce the frequency of falls a phase 3 study is needed to confirm these findings and show cost effectiveness of rivastigmine treatment parkinson s uk graft versus host disease gvhd after liver transplant although a rare disease has a very high mortality rate gvhd occurs due to immunoreactions caused by donor t lymphocytes and host cell surface antigens resulting in proliferation and clonal expansion of t lymphocyte migration of effector cells including macrophages nk cells and cytotoxic t lymphocyte to the target organs such as skin intestine and bone marrow results in skin rashes diarrhea and bone marrow depression gvhd is diagnosed by clinical symptoms histopathological findings and by the presence of chimerism the delayed diagnosis opportunistic infections and lack of definitive treatment of post orthotopic liver transplant olt gvhd results in sepsis and multi organ failure leading to very low survival rates in this review we have focused on early diagnosis and critically discuss novel treatment modalities to decrease the incidence of gvhd strangles characterised by pyrexia followed by abscessation of the lymph nodes of the head and neck was first described in 1251 rufus 1251 and the causative agent streptococcus equi was identified in 1888 schutz 1888 however despite more than a century of research into this disease strangles remains the most frequently diagnosed infection of horses with over 600 outbreaks being identified in the uk alone each year parkinson and others 2011 here andrew waller reviews some of the recent advances in the understanding of the evolution of s equi and puts this into the context of preventing and resolving outbreaks of infection west nile virus in europe and the usa evidence that the spread of vesicular stomatitis in the usa is beginning to slow summary of uk surveillance testing july to september 2015 these are among matters discussed in the most recent quarterly equine disease surveillance report prepared by defra the animal health trust and the british equine veterinary association a conference organised by the world health organization who and the world organisation for animal health oie in collaboration with the food and agriculture organization of the united nations fao and the global alliance for rabies control garc in geneva on december 10 to 11 2015 saw delegates from nearly 100 countries meet to discuss the who s goal of eliminating dog mediated human rabies by 2030 and work on a new framework to focus efforts towards achieving this goal suzanne jarvis reports increasing concern about antimicrobial resistance and moves to restrict the use of antibiotics in food producing animals mean that farmers will need new ways of preventing and controlling disease in their animals with its focus on addressing the needs of the farming industry the moredun research institute sees this as an opportunity to be at the forefront of developing new solutions kristy ebanks reports from an event organised to showcase some of the institute s latest research palonosetron has shown efficacy in the prevention of chemotherapy induced nausea and vomiting in adults undergoing moderately or highly emetogenic chemotherapy we assessed the efficacy and safety of palonosetron versus ondansetron in the prevention of chemotherapy induced nausea and vomiting in paediatric patients in this multicentre multinational double blind double dummy phase 3 study paediatric patients aged between 0 and younger than 17 years who were naive or non naive to chemotherapy and scheduled to undergo moderately or highly emetogenic chemotherapy for the treatment of malignant disease were randomised centrally 1 1 1 to receive up to four cycles of 10 \u03bcg kg or 20 \u03bcg kg palonosetron on day 1 or three 150 \u03bcg kg doses of ondansetron on day 1 scheduled 4 h apart according to a static central permuted block randomisation scheme by an interactive web response system randomisation was stratified according to age and emetogenicity treatment allocation was masked to project team members involved in data collection and analysis and members of the investigator s team the primary endpoint was complete response no vomiting retching or use of rescue drugs during the acute phase 0 24 h post chemotherapy of the first on study chemotherapy cycle as assessed in the population of randomly assigned patients who received moderately or highly emetogenic chemotherapy and an active study drug the primary efficacy objective was to show the non inferiority of palonosetron versus ondansetron during the acute phase 0 24 h post chemotherapy of the first on study chemotherapy cycle through comparison of the difference in the proportions of patients who achieved a complete response with palonosetron \u03c0t minus ondansetron \u03c0r versus a preset non inferiority margin \u03b4 15 to be considered as non inferior to ondansetron for at least one of the doses of palonosetron the lower limit of the 97 \xb75 ci for the weighted sum of the differences in complete response rates had to be superior to 15 safety was assessed according to treatment received this study is registered with clinicaltrials gov number nct01442376 and has been completed between sept 12 2011 and oct 26 2012 we randomly assigned 502 patients 169 were assigned to receive 10 \u03bcg kg palonosetron 169 to receive 20 \u03bcg kg palonosetron and 164 to receive 3 150 \u03bcg kg ondansetron of whom 166 165 and 162 respectively were included in the efficacy analysis in the acute phase complete responses were recorded in 90 54 patients in the 10 \u03bcg kg palonosetron group 98 59 in the 20 \u03bcg kg palonosetron group and 95 59 in the ondansetron group non inferiority versus ondansetron was shown for 20 \u03bcg kg palonosetron in the acute phase weighted sum of the differences in complete response rates 0 \xb736 97 \xb75 ci 11 \xb77 to 12 \xb74 p 0 \xb70022 non inferiority versus ondansetron was not shown for 10 \u03bcg kg palonosetron in the acute phase weighted sum of the differences in complete response rates 4 \xb741 97 \xb75 ci 16 \xb74 to 7 \xb76 in the first on study treatment cycle treatment emergent adverse events were reported in 134 80 of 167 patients who received 10 \u03bcg kg palonosetron 113 69 of 163 who received 20 \u03bcg kg palonosetron and 134 82 of 164 who received ondansetron the most common drug related treatment emergent adverse events were nervous system disorders mainly headache which occurred in three 2 patients who received 10 \u03bcg kg palonosetron one 1 patient who received 20 \u03bcg kg palonosetron and two 1 patients who received ondansetron the incidence of serious adverse events in the first on study treatment cycle was lower in the 20 \u03bcg kg palonosetron group 43 26 than in the 10 \u03bcg kg palonosetron group 52 31 and the ondansetron group 55 34 non inferiority was shown for 20 \u03bcg kg palonosetron during the acute phase of the first on study chemotherapy cycle 20 \u03bcg kg palonosetron is now indicated by the european medicines agency and the us food and drug administration for the prevention of chemotherapy induced nausea and vomiting in paediatric patients aged 1 month to younger than 17 years helsinn healthcare predicting survival in decompensated cirrhosis dc is important in decision making for liver transplantation and resource allocation we investigated whether high resolution metabolic profiling can determine a metabolic phenotype associated with 90 day survival two hundred and forty eight subjects underwent plasma metabotyping by 1 h nuclear magnetic resonance nmr spectroscopy and reversed phase ultra performance liquid chromatography coupled to time of flight mass spectrometry uplc tof ms dc 80 derivation set 101 validation stable cirrhosis cld 20 and 47 healthy controls hc 1 h nmr metabotyping accurately discriminated between surviving and non surviving patients with dc the nmr plasma profiles of non survivors were attributed to reduced phosphatidylcholines and lipid resonances with increased lactate tyrosine methionine and phenylalanine signal intensities this was confirmed on external validation area under the receiver operating curve auroc 0 96 95 ci 0 90 1 00 sensitivity 98 specificity 89 uplc tof ms confirmed that lysophosphatidylcholines and phosphatidylcholines lpc pc were downregulated in non survivors uplc tof ms profiles auroc of 0 94 95 ci 0 89 0 98 sensitivity 100 specificity 85 positive ion detection lpc concentrations negatively correlated with circulating markers of cell death m30 and m65 levels in dc histological examination of liver tissue from dc patients confirmed increased hepatocyte cell death compared to controls cross liver sampling at time of liver transplantation demonstrated that hepatic endothelial beds are a source of increased circulating total cytokeratin 18 in dc plasma metabotyping accurately predicts mortality in dc lpc and amino acid dysregulation is associated with increased mortality and severity of disease reflecting hepatocyte cell death to study kidney injury molecule 1 kim 1 biomarker levels indicating renal tubular damage in patients with kidney stones and in those who underwent minimally invasive method stone treatment sixty patients with renal stones between 10 and 20 mm were included into the present study patients who were divided into three cohorts underwent micropercutaneous nephrolithotomy microperc retrograde intrarenal stone surgery rirs and percutaneous nephrolithotomy pnl urine samples were obtained from all participants before 4 h and 14 days after the procedure in all the samples obtained urinary kim 1 and creatinine cr levels were measured and kim 1 cr ratios ng mg creatinine were calculated preoperative urine kim 1 cr ratio was higher than postoperative 14th day the bigger the renal stone size the higher was the ratio correlation coefficient 0 353 p 0 006 according to preferred treatment procedure there was a statistically significant decrease in preoperative and postoperative 4th hour and 14th day urine kim 1 cr rates in the rirs and pnl yet none in the microperc group p 0 010 p 0 001 p 0 212 respectively in renal stone patients the elevated urine kim 1 cr ratio levels increase further according to stone size kim 1 cr ratio is a promising marker might be helpful in monitoring the damage created by stone disease clopidogrel use as single antiplatelet therapy sapt has never been evaluated in stable coronary artery disease cad outpatients either as compared to placebo or aspirin we therefore studied 2 823 outpatients included in a prospective registry the patients were divided into 2 groups according to their antiplatelet therapy regimen patients treated with clopidogrel were compared with those treated with aspirin alone the mean time since cad diagnosis was 7 9 years altogether 776 27 5 patients received clopidogrel as sapt factors independently associated with clopidogrel use were prior aortic or peripheral intervention drug eluting stent implantation stroke carotid endarterectomy and time since cad diagnosis clopidogrel tended to be used in higher risk patients composite of cardiovascular death myocardial infarction or stroke at 5 8 versus 4 2 p 0 056 however after propensity score matching similar event rates were observed between the groups 5 9 when treated with clopidogrel versus 4 4 with aspirin p 0 207 the rate of bleeding was also similar between the groups our study shows that a significant proportion of stable cad patients are treated with clopidogrel as sapt in modern practice several correlates of such an attitude were identified our results suggest that this strategy is not beneficial as compared to aspirin alone in terms of ischaemic or bleeding events fingolimod fty720 was the first per os administered disease modifying agent approved for the treatment of relapsing remitting multiple sclerosis it is thought that fingolimod modulates the immune response by activating sphingosine 1 phosphate receptor type 1 s1p1 on lymphocytes following its in vivo phosphorylation in addition to its immune related effects there is evidence that fingolimod exerts several other effects in the central nervous system including regulation of the proliferation survival and differentiation of various cell types and their precursors in the present study we have investigated the effect of fingolimod on the production of new neurons in the adult mouse hippocampus and the association of this effect with the ability for pattern separation an established adult neurogenesis dependent memory function immunofluorescence analysis after chronic administration of a physiologic dose of fingolimod 0 3 mg kg 1 revealed a significant increase in both the proliferation and the survival of neural progenitors in the area of dentate gyrus of hippocampus compared with control animals these effects were replicated in vitro in cultures of murine hippocampal neural stem precursor cells that express s1p1 receptor suggesting cell autonomous actions the effects of fingolimod on neurogenesis were correlated to enhanced ability for context discrimination after fear conditioning since impairment of adult hippocampal neurogenesis and memory is a common feature of many neuropsychiatric conditions fingolimod treatment may be beneficial in therapeutic armamentarium of these disorders the extracorporeal treatments in poisoning extrip workgroup was formed to provide recommendations on the use of extracorporeal treatments ectr in poisoning here we present our results for digoxin after a systematic literature search clinical and toxicokinetic data were extracted and summarized following a predetermined format the entire workgroup voted through a two round modified delphi method to reach a consensus on voting statements a rand ucla appropriateness method was used to quantify disagreement and anonymous votes were compiled and discussed in person a second vote was conducted to determine the final workgroup recommendations out of 435 articles screened 77 met inclusion criteria only in vitro animal studies case reports and case series were identified yielding a very low quality of evidence for all recommendations based on data from 84 patients including six fatalities it was concluded that digoxin is slightly dialyzable level of evidence b and that ectr is unlikely to improve the outcome of digoxin toxic patients whether or not digoxin immune fab fab is administered despite the lack of robust clinical evidence the workgroup recommended against the use of ectr in cases of severe digoxin poisoning when fab was available 1d and also suggested against the use of ectr when fab was unavailable 2d ectr in any form is not indicated for either suspected or proven digoxin toxicity regardless of the clinical context and is not indicated for removal of digoxin fab complex multiple myeloma mm is characterized by an accumulation of abnormal clonal plasma cells in the bone marrow despite recent advancements in anti myeloma therapies mm remains an incurable disease antioxidant molecules are upregulated in many cancers correlating with tumor proliferation survival and chemoresistance and therefore have been suggested as potential therapeutic targets this study investigated the cross talk between two antioxidant molecules thioredoxin reductase trxr and heme oxygenase 1 ho 1 and their therapeutic implications in mm we found that although auranofin a trxr inhibitor significantly inhibited trxr activity by more than 50 at lower concentrations myeloma cell proliferation was only inhibited at higher concentrations of auranofin inhibition of trxr using lower auranofin concentrations induced ho 1 protein expression in myeloma cells using a sub lethal concentration of auranofin to inhibit trxr activity in conjunction with ho 1 inhibition significantly decreased myeloma cell growth and induced apoptosis trxr was shown to regulate ho 1 via the nrf2 signaling pathway in a ros dependent manner increased ho 1 mrna levels were observed in bortezomib resistant myeloma cells compared to parent cells and ho 1 inhibition restored the sensitivity to bortezomib in bortezomib resistant myeloma cells these findings indicate that concurrent inhibition of ho 1 with either a trxr inhibitor or with bortezomib would improve therapeutic outcomes in mm patients hence our findings further support the need to target multiple antioxidant systems alone or in combination with other therapeutics to improve therapeutic outcomes in mm patients stroke is a worldwide cause of morbidity and mortality that affects health related quality of life in this study our objective was to identify determinants of disease specific health related quality of life in turkish stroke survivors a total of 114 consecutive patients who experienced a stroke at least 6 months earlier were studied health related quality of life was measured using stroke specific quality of life ss qol consisting of 12 domains demographic and clinical data were collected including age sex marital status years of education time since stroke whether the patient received rehabilitation before enrollment stroke etiology whether the dominant hand was affected or not presence of vision defect neglect aphasia and dysarthria the patients were assessed by the functional independence measure fim and the mini mental state examination a multiple linear regression analysis was carried out using a stepwise method to determine the predictors of 12 domains and the total score of the ss qol the domains of work social roles mobility and self care had the lowest ss qol scores whereas the highest scores were for the domains of personality thinking language and vision the total ss qol score was explained by the total fim and mini mental state examination among the 12 domains the mobility domain was explained the best r 0 50 by motor fim previously received rehabilitation and age followed by the language domain r 0 37 explained by the presence of aphasia and dysarthria and previously received rehabilitation the domains of mood r 0 13 and upper extremity r 0 19 were explained the worst the results indicated that functional independence age cognitive status and receiving a rehabilitation program were the primary determinants of the ss qol the mini balance evaluation systems test mini bestest has been identified as the most comprehensive balance measure for community dwelling adults and elderly individuals it can be used to assess balance impairments in several other conditions mainly parkinson s disease and stroke despite increasing use of the mini bestest since it was first published 5 years ago no systematic review synthesizing its psychometric properties is available the aim of this study was to provide a comprehensive review of the psychometric properties of the mini bestest when administered to patients with balance deficits because of different diseases a literature search was performed on articles published before july 2015 in journals indexed by medline and scopus databases the search produced 98 papers 24 of which fulfilled the inclusion criteria for this review most papers n 19 focused on patients affected by neurological diseases mainly parkinson s disease in 21 papers the psychometric characteristics were analyzed using classical test theory methods and in only three papers was rasch analysis carried out this review shows the interest of researchers in the mini bestest despite the short time frame since its first publication the mini bestest is used widely in both clinical practice and research the results support the reliability validity and responsiveness of this instrument and it can be considered a standard balance measure however it would be valuable to learn more about how this scale performs in different diseases causing balance deficits and to better define the minimal clinically important difference for each disease we report a method for blocking interactions between 129 xe and cucurbit 6 uril cb6 until activation by a specific chemical event we synthesized a cb6 rotaxane that allowed no 129 xe interaction with the cb6 macrocycle component until a cleavage event released the cb6 which then produced a 129 xe cb6 nmr signal this contrast upon activation 129 xe nmr platform allows for modular synthesis and can be expanded to applications in detection and disease imaging sensory ganglionopathy sg is characterised by asymmetrical sensory fibre degeneration with the primary pathology occurring at the level of the dorsal root ganglion it is seen in the context of autoimmune paraneoplastic and degenerative disorders there is limited literature examining the electrophysiological correlate of the trigeminal ganglion and associated pathways the blink reflex br in cases of sg previous work has suggested that the br is preserved in cases of sg associated with paraneoplasia the local clinical neurophysiology database was searched for patients diagnosed with sg from peripheral nerve conduction studies in whom the br was performed twenty six patients were included in the final analysis sj\xf6gren s syndrome constituted the most common sg aetiology 8 26 followed by idiopathic cases 7 26 and paraneoplasia 5 26 br abnormalities were seen in 9 of the 26 patients 34 6 across all aetiologies no patients reported sensory disturbance in the distribution of the trigeminal nerve indicating that the changes noted are subclinical three patients showed abnormality of the r1 response in the remaining six patients only r2 responses were affected subclinical abnormalities of both r1 and r2 can be seen in the context of sg of varying aetiologies including paraneoplasia performing the br in patients with suspected of having sg may be helpful in providing additional evidence of patchy sensory fibre involvement that is characteristic of the disease the purpose of the study was to examine whether birth characteristics affect the risk of rhabdomyosarcoma rms in children and adolescents younger than 19 years a total of 722 rms cases diagnosed at the age of 0 19 years during 1988 2011 were identified from the california cancer registry and matched by birth date sex and race to 2 888 controls using california birth records conditional logistic regression was used to estimate the risk of rms associated with birth weight gestational age and size for gestational age high birth weight odds ratio or 1 00 95 confidence interval ci 0 78 1 29 and large for gestational age lga or 0 94 95 ci 0 72 1 23 were not associated with rms risk overall among non hispanic whites the ors were 1 33 for high birth weight 95 ci 0 94 1 89 and 1 17 for lga 95 ci 0 78 1 75 no indications of association were observed for other racial or ethnic groups p interaction 10 compared with normal gestational age preterm 37 weeks and post term 40 weeks babies had 16 18 lower risks of rms overall after adjusting for birth weight in the largest study to date there was an indication of association between high birth weight lga and increased rms risk among non hispanic white children and adolescents but not in other racial or ethnic groups to investigate the prevalence of pseudoexfoliation syndrome pex among turkish patients with senile cataract records of 352 eyes of 352 patients who underwent cataract surgery were analyzed in this retrospective study the presence of pex type of cataract intraocular pressure iop glaucoma age related macular degeneration and systemic diseases coronary artery disease hypertension diabetes mellitus were recorded the overall prevalence of pex syndrome was detected to be 11 the mean age of pex patients was significantly higher than without pex 74 4 7 2 years and 69 3 11 4 years respectively p 0 004 the most common cataract type in the pex patients was mixed type cataract determined in 51 2 of patients iop was significantly higher in eyes with pex than in eyes without it 16 1 4 5 mmhg and 14 7 3 8 mmhg respectively p 0 03 moreover the prevalence of age related macular degeneration was found to be significantly higher and prevalence of glaucoma slightly higher in pex patients than without pex pseudoexfoliation syndrome is a common condition in turkish people pex is associated with mixed type of cataract age related macular degeneration and elevated iop therefore pex patients should be checked for concomitant diseases the present study aimed to investigate the molecular mechanisms underlying non \u2011syndromic cleft lip with or without cleft palate nscl p and the association between this disease and cancer the gse42589 data set was downloaded from the gene expression omnibus database and contained seven dental pulp stem cell samples from children with nscl p in the exfoliation period and six controls differentially expressed genes degs were screened using the rankprod method and their potential functions were revealed by pathway enrichment analysis and construction of a pathway interaction network subsequently cancer genes were obtained from six cancer databases and the cancer \u2011associated protein \u2011protein interaction network for the degs was visualized using cytoscape in total 452 upregulated and 1 288 downregulated degs were screened the upregulated degs were significantly enriched in the arachidonic acid metabolism pathway including ptgds cyp4f2 and pla2g16 and transforming growth factor tgf \u2011\u03b2 signaling pathway including smad3 and tgfb2 the downregulated degs were distinctly involved in the pathways of dna replication including mcm2 and pola1 cell cycle including cdk1 and stag1 and viral carcinogenesis including pik3ca and hist1h2bf furthermore the pathways of cell cycle and viral carcinogenesis with higher degrees of interaction were found to interact with other pathways including dna replication transcriptional misregulation in cancer and the tgf \u2011\u03b2 signaling pathway additionally tp53 cdk1 smad3 pik3r1 and casp3 with higher degrees interacted with the cancer genes in conclusion the degs for nscl p were implicated predominantly in the tgf \u2011\u03b2 signaling pathway the cell cycle and in viral carcinogenesis the tp53 cdk1 smad3 pik3r1 and casp3 genes were found to be associated not only with nscl p but also with cancer these results may contribute to a better understanding of the molecular mechanisms of nscl p this study evaluated 3rd generation human immunodeficiency virus hiv test patterns and hiv infection rates in the united states air force usaf retrospective database study hiv enzyme linked immunoassay elisa and western blot tests were analysed for all usaf personnel from 2008 to 2012 for new hiv cases unadjusted and adjusted annual rates were calculated per 100 000 persons in total 1 608 665 tests were performed in 626 298 individuals with a reactive elisa observed in 809 0 001 persons western blot n 1949 results included 378 19 4 positive 1283 65 8 negative and 288 15 0 indeterminate wbi unadjusted annual hiv rates were between 16 7 and 20 6 per 100 000 persons during the study period the overall age adjusted rate was 14 8 cases per 100 000 persons tested blacks african americans had the highest risk of hiv risk ratio 7 9 95 confidence interval 5 78 9 95 compared to whites wbi results which can cause delays in determining hiv status were relatively common with the 3rd generation assay however this will be mitigated by a planned transition to a 4th generation assay although the overall rate of hiv in the usaf is lower than us civilian adults hiv prevention efforts targeting young blacks african americans may help to reduce hiv incidence in the usaf human papillomavirus hpv vaccines were licensed by demonstrating prevention of anogenital disease caused by specific hpv types in clinical studies measuring the impact of hpv vaccination on the overall burden of anogenital disease irrespective of hpv is an important public health question which is ideally addressed in post licensure epidemiological studies attempts were made to use clinical trial data for that purpose however the interpretation of vaccine efficacy on the endpoint of disease irrespective of hpv is not widely understood we used the 9 valent hpv vaccine clinical program as a case study to determine the value of measuring vaccine efficacy in such endpoint this assessment was rigorously performed by heuristic reasoning and through probability calculations the measure of vaccine efficacy in the irrespective of hpv endpoint is driven simultaneously in opposite directions by the high estimate of prophylactic efficacy and a numerically negative estimate of risk reduction that is also a reflection of high prophylactic efficacy and no cross protection the vaccine efficacy estimate in the irrespective of hpv endpoint is ambiguous and difficult to interpret comparing this estimate across different hpv vaccine studies requires an understanding of the contributions of vaccine hpv type efficacy and the incidence of disease not related to vaccine hpv types for each study without such understanding comparing studies and drawing conclusions from such comparison are highly misleading approaches are proposed to divide this endpoint in components that are easier to interpret heart failure is a complex disease process with various aetiologies and is a significant cause of morbidity and death world wide post translational modifications ptms alter protein structure and provide functional diversity in terms of physiological functions of the heart in addition alterations in protein ptms have been implicated in human disease pathogenesis small ubiquitin like modifier mediated modification sumoylation pathway was found to play essential roles in cardiac development and function abnormal sumoylation has emerged as a new feature of heart failure pathology in this review we will highlight the importance of sumoylation as a regulatory mechanism of serca2a function and its therapeutic potential for the treatment of heart failure disrupted organ growth leads to disease development hypertrophy underlies postnatal heart growth and is triggered after stress but the molecular mechanisms involved in these processes are largely unknown here we show that cardiac activation of p38\u03b3 and p38\u03b4 increases during postnatal development and by hypertrophy inducing stimuli p38\u03b3 \u03b4 promote cardiac hypertrophy by phosphorylating the mtorc1 and mtorc2 inhibitor deptor which leads to its degradation and mtor activation hearts from mice lacking one or both kinases are below normal size have high levels of deptor low activity of the mtor pathway and reduced protein synthesis the phenotype of p38\u03b3 \u03b4 mice is reverted by overactivation of mtor with amino acids shrna mediated knockdown of deptor or cardiomyocyte overexpression of active p38\u03b3 and p38\u03b4 moreover in wt mice heart weight is reduced by cardiac overexpression of deptor our results demonstrate that p38\u03b3 \u03b4 control heart growth by modulating mtor pathway through deptor phosphorylation and subsequent degradation x linked nephrogenic diabetes insipidus ndi omim 304800 is caused by mutations in the arginine vasopressin avp omim 192340 receptor type 2 avpr2 omim 300538 gene a 20 month old boy and his 8 year old brother presented with polyuria polydipsia and failure to thrive both boys demonstrated partial ddavp 1 desamino 8 d avp or desmopressin responses thus ndi diagnosis was delayed while routine sequencing of avpr2 showed a potential splice site variant it was not until exome sequencing confirmed the avpr2 splice site variant and did not reveal any more likely candidates that the patients diagnosis was made and proper treatment was instituted both patients were hemizygous for two avpr2 variants predicted in silico to affect avpr2 messenger rna mrna splicing a minigene assay revealed that the novel avpr2 c 276a g mutation creates a novel splice acceptor site leading to 5 truncation of avpr2 exon 2 in hek293 human kidney cells both patients have been treated with high dose ddavp with a remarkable improvement of their symptoms and accelerated linear growth and weight gain we present here a unique case of partial x linked ndi due to an avpr2 splice site mutation patients with diabetes insipidus of unknown etiology may harbor splice site mutations that are initially underestimated in their pathogenicity on sequence analysis x linked nephrogenic diabetes insipidus is caused by avpr2 mutations and disease severity can vary depending on the functional effect of the mutation what is new we demonstrate here that a splice site mutation in avpr2 leads to partial x linked ndi in two brothers treatment with high dose ddavp led to improvement of polyuria and polydipsia weight gain and growth to investigate the utility of eccentricity index ei using cardiac cine mri for the assessment of right ventricular rv hemodynamics in congenital heart disease chd fifty five patients with chd 32 women mean age 40 7 20 9 years underwent both cardiac mri and right heart catheterization ei was defined as the ratio of the distance between the anterior posterior wall and the septal lateral wall measured in the short axis of mid ventricular cine mri correlations between eis and rv hemodynamic parameters were analyzed eis were compared between patients with and without late gadolinium enhancement lge a strong correlation between mean pulmonary artery pressure pap and systolic ei r 0 81 p 0 0001 and a moderate negative correlation between diastolic ei and rv ejection fraction ef r 0 62 p 0 0001 were observed receiver operating characteristic analysis revealed optimal ei thresholds for detecting patients with mean pap \u226540 mmhg with c statistics of 0 90 and patients with rvef 40 with c statistics of 0 78 systolic eis were significantly greater for patients with lge 1 45 0 05 than for those without lge 1 15 0 07 p 0 001 ei offers a simple comprehensive index that can predict pulmonary hypertension and rv dysfunction in chd ei offers a simple and comprehensive index of rv hemodynamics ei could predict pulmonary hypertension and rv dysfunction left ventricular deformation expressed as high ei is related to myocardial fibrosis the presence of circulating tumor cells ctcs is an established marker for prognosis in men with castration resistant prostate cancer a cutoff of \u22655 ctcs 7 5ml blood in the cellsearch epithelial cell test has been shown to stratify prognostic groups and predict outcome of abiraterone treatment in contrast the value of ctc detection in men with localized prostrate cancer before radical prostatectomy rp is unknown a total of 152 patients treated with rp between 06 2009 and 09 2009 were included peripheral venous blood drawn the day before rp was evaluated for ctcs by the cellsearch system the detection of ctcs was correlated with prostate specific antigen psa and the histopathological outcome of the rp specimen a cutoff of 0 vs \u22651 ctc 7 5ml blood was defined as the threshold for positive vs negative ctc status median age was 62 years and median psa was 6 7ng dl staging revealed 62 5 pt2 26 3 pt3a and 11 2 pt3b tumors and high grade disease \u2265gleason 4 3 was determined in 25 6 of patients ctcs were detected in 17 patients 11 with a median ctc count 7 5ml of 1 range 1 clusters with 100 epithelial cells without significant correlations to psa levels pt stage or gleason scores postoperative pt stage was a significant predictor of biochemical recurrence bcr in univariable logistic regression models and as a composite measure together with positive ctc counts p 0 0001 ctc positivity alone tended to have a higher hazard ratio for bcr but this was not statistically significant p 0 1 after a median follow up of 48 months there was no significant difference in bcr free survival between patients with or without ctcs p 0 7 using the cellsearch system we infrequently detected ctcs in patients with localized tumors before rp the detection of ctcs did not correlate significantly with psa disease characteristics or the development of bcr however larger cohorts with extended follow up are needed to validate our findings delaying nephrectomy 3 months does not adversely affect treatment outcome of renal tumors whether surgical waiting time swt time from diagnosis to surgery 3 months affects treatment outcome for large renal masses has not been well studied we aimed to evaluate if swt is associated with treatment outcome of renal masses 4cm and identify patients who are more likely to experience prolonged swt data from 1 484 patients undergoing radical or partial nephrectomy at a single institution for a nonmetastatic renal mass 4cm between 1995 and 2013 were reviewed patients with benign tumors and incomplete preoperative data were excluded the association between swt and disease upstaging at the time of surgery and recurrence at 2 and 5 years was assessed using logistic regression cancer specific survival css and overall survival were assessed with landmark survival analyses and multivariable cox proportional hazards models all analyses were adjusted for patient and tumor characteristics of the final cohort of 1 278 patients 267 21 had swt 3 months patients with larger symptomatic tumors had shorter swt median follow up for survivors was 3 8 years interquartile range 1 5 7 4 on multivariable analysis swt was not associated with disease upstaging recurrence or css longer swt was associated with decreased overall survival hazard ratio 1 17 95 ci 1 08 1 27 p 0 0002 sex and tumor size histology and presentation were associated with disease upstaging recurrence and css the most common cause for surgical delay 3 months was evaluation and treatment of comorbidities patient and tumor characteristics rather than swt were associated with disease upstaging recurrence and css and should guide the decision to delay surgery when treating nonmetastatic renal tumors 4cm very little is known about the burden and determinants of stillbirths in china we used data from a national surveillance system for health facility births to compute a stillbirth rate representative of all facility births in china and to explore sociodemographic and obstetric factors associated with variation in the stillbirth rate we used data from china s national maternal near miss surveillance system between jan 1 2012 and dec 31 2014 which covers 441 hospitals in 326 urban districts and rural counties the surveillance aimed to enumerate all maternal deaths and near misses in health facilities and collected data prospectively for all pregnant or post partum women admitted to the obstetric department we restricted the analysis to births of 28 or more completed weeks of gestation or 1000 g or heavier birthweight we examined the strength of association between sociodemographic characteristics gestational age and obstetric complications and stillbirths using logistic regression taking account of the sampling strategy and clustering of births within hospitals and in cases of more than one birth per woman there were 3 956 836 births and 37 855 stillbirths giving a stillbirth rate of 8 \xb78 per 1000 births 95 ci 8 \xb78 8 \xb79 the stillbirth rate was particularly high for women younger than 15 years of age 59 \xb79 stillbirths per 1000 births those who had not sought antenatal care 38 \xb73 per 1000 the unmarried 32 \xb75 per 1000 those with no education 26 \xb79 per 1000 or those who had had four or more births 23 \xb72 per 1000 a high proportion 29 319 78 \xb72 of 37 514 of stillbirths occurred at gestational ages of younger than 37 weeks and about two thirds 24 787 66 \xb71 of 37 514 were in women without any maternal complication at the time of birth of babies born at normal gestations 37 41 weeks maternal complications substantially increased the risk of stillbirth odds ratio comparing antepartum or intrapartum complications with no complication 3 \xb796 95 ci 3 \xb766 4 \xb729 but only a small proportion 1638 4 \xb74 of 37 514 of stillbirths fell into this group our analysis of nearly 4 million births in 441 health facilities in china suggests a stillbirth rate of 8 \xb78 per 1000 births between 2012 and 2014 stillbirths do not feature in the chinese government s 5 year plans and most information systems do not include stillbirths the government need to start paying attention to stillbirths and invest strategically in antenatal care particularly for the most disadvantaged women including the very young unmarried and illiterate and those at high parity national health and family planning commission of the people s republic of china national natural science foundation of china china medical board who and unicef familial cerebral cavernous malformation type 1 ccm1 is an autosomal dominant disease caused by mutations in the krev interaction trapped 1 krit1 ccm1 gene and characterized by multiple brain lesions ccm lesions manifest across a range of different phenotypes including wide differences in lesion number size and susceptibility to intracerebral hemorrhage ich oxidative stress plays an important role in cerebrovascular disease pathogenesis raising the possibility that inter individual variability in genes related to oxidative stress may contribute to the phenotypic differences observed in ccm1 disease here we investigated whether candidate oxidative stress related cytochrome p450 cyp and matrix metalloproteinase mmp genetic markers grouped by superfamilies families or genes or analyzed individually influence the severity of ccm1 disease clinical assessment and cerebral susceptibility weighted magnetic resonance imaging swi were performed to determine total and large \u22655mm in diameter lesion counts as well as ich in 188 hispanic ccm1 patients harboring the founder krit1 ccm1 common hispanic mutation ccm1 chm samples were genotyped on the affymetrix axiom genome wide lat1 human array we analyzed 1 122 genetic markers both single nucleotide polymorphisms snps and insertion deletions grouped by cyp and mmp superfamily family or gene for association with total or large lesion count and ich adjusted for age at enrollment and gender genetic markers bearing the associations were then analyzed individually the cyp superfamily showed a trend toward association with total lesion count p 0 057 and large lesion count p 0 088 in contrast to the mmp superfamily the cyp4 and cyp8 families were associated with either large lesion count or total lesion count p 0 014 and two other families cyp46 and the mmp stromelysins were associated with ich p 0 011 and 0 007 respectively cyp4f12 rs11085971 cyp8a1 rs5628 cyp46a1 rs10151332 and mmp3 rs117153070 single snps mainly bearing the above mentioned associations were also individually associated with ccm1 disease severity overall our candidate oxidative stress related genetic markers set approach outlined cyp and mmp families and identified suggestive snps that may impact the severity of ccm1 disease including the development of numerous and large ccm lesions and ich these novel genetic risk factors of prognostic value could serve as early objective predictors of disease outcome and might ultimately provide better options for disease prevention and treatment the present study explored the apoptosis pathways in hydroxyl radicals \u2219) oh induced carp erythrocytes carp erythrocytes were treated with the caspase inhibitors in physiological carp saline pcs or ca 2 free pcs in the presence of 40\u03bcm feso4 20\u03bcm h2o2 the results showed that the generation of reactive oxygen species ros the release of cytochrome c and dna fragmentation were caspase dependent and ca 2 was involved in calpain activation and phosphatidylserine ps exposure in \u2219) oh induced carp erythrocytes moreover the results suggested that caspases were involved in ps exposure and ca 2 was involved in dna fragmentation in \u2219) oh induced fish erythrocytes these results demonstrated that there might be two apoptosis pathways in fish erythrocytes one is the caspase and cytochrome c dependent apoptosis that is similar to that in mammal nucleated cells the other is the ca 2 involved apoptosis that was similar to that in mammal non nucleated erythrocytes so fish erythrocytes may be used as a model for studying oxidative stress and apoptosis in mammal cells furthermore the present study investigated the effects of glutamine gln s metabolites alanine ala citrulline cit proline pro and their combination ala10pro4cit1 on the pathways of apoptosis in fish erythrocytes the results displayed that ala cit pro and ala10pro4cit1 effectively suppressed ros generation cytochrome c release activation of caspase 3 caspase 8 and caspase 9 at the physiological concentrations prevented ca 2 influx calpain activation ps exposure dna fragmentation and the degradation of the cytoskeleton and oxidation of membrane and hemoglobin hb and increased activity of anti hydroxyl radical ahr in \u2219) oh induced carp erythrocytes ala10pro4cit1 produced a synergistic effect of inhibited oxidative stress and apoptosis in fish erythrocytes these results demonstrated that ala cit pro and their combination can protect mammal erythrocytes and nucleated cells against oxidative stress and apoptosis the studies supported the use of gln ala cit and pro as oxidative stress and apoptosis inhibitors in mammal cells and the hypothesis that the inhibited effects of gln on oxidative stress and apoptosis are at least partly dependent on that of its metabolites in mammalian to assess the yield of diagnostic exome sequencing des and to characterize the molecular findings in characterized and novel disease genes in patients with epilepsy in an unselected sample of 1 131 patients referred for des overall results were compared between patients with and without epilepsy des results were examined based on age of onset and epilepsy diagnosis positive likely positive results were identified in 112 293 38 2 epilepsy patients compared with 210 732 28 7 patients without epilepsy p 0 004 the diagnostic yield in characterized disease genes among patients with epilepsy was 33 4 105 314 kcnq2 mecp2 foxg1 iqsec2 kmt2a and stxbp1 were most commonly affected by de novo alterations patients with epileptic encephalopathies had the highest rate of positive findings 43 4 a likely positive novel genetic etiology was proposed in 14 200 7 patients with epilepsy this frequency was highest in patients with epileptic encephalopathies 17 three genes coq4 dnm1 and pura were initially reported as likely positive novel disease genes and were subsequently corroborated in independent peer reviewed publications des with analysis and interpretation of both characterized and novel genetic etiologies is a useful diagnostic tool in epilepsy particularly in severe early onset epilepsy the reporting on novel genetic etiologies may further increase the diagnostic yield genet med advance online publication 21 january 2016genetics in medicine 2016 doi 10 1038 gim 2015 186 krabbe disease kd results from galactocerebrosidase galc deficiency infantile kd symptoms include irritability progressive stiffness developmental delay and death the only potential treatment is hematopoietic stem cell transplantation new york state nys implemented newborn screening for kd in 2006 dried blood spots from newborns were assayed for galc enzyme activity using mass spectrometry followed by molecular analysis for those with low activity \u226412 of the daily mean infants with low enzyme activity and one or more mutations were referred for follow up diagnostic testing and neurological examination of 1 9 million screened 620 infants were subjected to molecular analysis and 348 were referred for diagnostic testing five had enzyme activities and mutations consistent with infantile kd and manifested clinical neurodiagnostic abnormalities four underwent transplantation two are surviving with moderate to severe handicaps and two died from transplant related complications the significance of many sequence variants identified is unknown forty six asymptomatic infants were found to be at moderate to high risk for disease the positive predictive value of kd screening in nys is 1 4 5 346 considering confirmed infantile cases the incidence of infantile kd in nys is approximately 1 in 394 000 but it may be higher for later onset forms micrornas mirnas have been shown to play a critical role in the development and progression of nasopharyngeal carcinoma npc although accumulating studies have been performed on the molecular mechanisms of npc the mirna regulatory networks in cancer progression remain largely unknown laser capture microdissection lcm and deep sequencing are powerful tools that can help us to detect the integrated view of mirna target network illumina hiseq2000 deep sequencing was used to screen differentially expressed mirnas in laser microdessected biopsies between 12 npc and 8 chronic nasopharyngitis patients the result was validated by real time pcr on 201 npc and 25 chronic nasopharyngitis patients the potential candidate target genes of the mirnas were predicted using published target prediction softwares rnahybrid targetscan miranda pita and the overlay part was analyzed in gene ontology go and kyoto encyclopedia of genes and genomes kegg biological process the mirna regulatory network analysis was performed using the ingenuity pathway analysis ipa software eight differentially expressed mirnas were identified between npc and chronic nasopharyngitis patients by deep sequencing further qrt pcr assays confirmed 3 down regulated mirnas mir 34c 5p mir 375 and mir 449c 5p 4 up regulated mirnas mir 205 5p mir 92a 3p mir 193b 3p and mir 27a 5p additionally the low level of mir 34c 5p mir 34c was significantly correlated with advanced tnm stage go and kegg enrichment analyses showed that 914 target genes were involved in cell cycle cytokine secretion and tumor immunology and so on ipa revealed that cancer was the top disease associated with those dysregulated mirnas and the genes regulated by mir 34c were in the center of mirna mrna regulatory network including tp53 ccnd1 cdk6 met and bcl2 and the pi3k akt mtor signaling was regarded as a significant function pathway in this network our study presents the current knowledge of mirna regulatory network in npc with combination of bioinformatics analysis and literature research the hypothesis of mir 34c regulatory pathway may be beneficial in guiding further studies on the molecular mechanism of npc tumorigenesis evidence based management of patients with hepatocellular carcinoma hcc is key to their optimal care for individuals at risk for hcc surveillance usually involves ultrasonography there is controversy over use of biomarkers a diagnosis of hcc is made based on findings from biopsy or imaging analyses molecular markers are not used in diagnosis or determination of prognosis and treatment for patients the barcelona clinic liver cancer algorithm is the most widely used staging system patients with single liver tumors or as many as 3 nodules \u22643 cm are classified as having very early or early stage cancer and benefit from resection transplantation or ablation those with a greater tumor burden confined to the liver and who are free of symptoms are considered to have intermediate stage cancer and can benefit from chemoembolization if they still have preserved liver function those with symptoms of hcc and or vascular invasion and or extrahepatic cancer are considered to have advanced stage cancer and could benefit from treatment with the kinase inhibitor sorafenib patients with end stage hcc have advanced liver disease that is not suitable for transplantation and or have intense symptoms studies now aim to identify molecular markers and imaging techniques that can detect patients with hcc at earlier stages and better predict their survival time and response to treatment duchenne muscular dystrophy dmd cardiomyopathy is a progressive disease for which there is no cure disease specific therapies are needed that can be initiated before irreversible myocardial damage ensues in order to evaluate therapeutic efficacy surrogate endpoints other than ejection fraction must be found the hypothesis of this study is that t1 and extracellular volume fraction ecv mapping using cardiovascular magnetic resonance cmr can detect diffuse extracellular matrix expansion in dmd patients with normal left ventricular ejection fraction lvef and without myocardial late gadolinium enhancement lge thirty one dmd and 11 healthy control participants were prospectively enrolled cmr using a modified look locker molli sequence was performed in all participants before and after contrast administration t1 and ecv maps of the mid left ventricular myocardium were generated and regions of interest were contoured using the standard 6 segment aha model global and segmental values were compared between dmd and controls using a wilcoxon rank sum test the dmd participants had significantly higher mean native t1 compared with controls 1045 ms vs 988 ms p 0 001 dmd participants with normal lvef and without evidence of lge also demonstrated elevated mean native t1 1039 ms vs 988 ms p 0 002 and 1038 ms vs 988 ms p 0 011 dmd participants had a significantly greater mean ecv than controls 0 31 vs 0 24 p 0 001 even in the settings of normal lvef 0 28 vs 0 24 p 0 001 and negative lge 0 29 vs 0 24 p 0 001 dmd participants have elevated lv myocardial native t1 and ecv even in the setting of normal lvef and in the absence of lge t1 and ecv mapping in dmd have potential to serve as surrogate cardiomyopathy outcome measures for clinical trials bone metastasis is one of the most common causes of skeletal morbidity in patients with advanced cancer and is manifested as osteoblastic and osteolytic lesions bone metastasis occurs as an organized and multistep process involving tumor intravasation and the survived tumor cells in circulation extravasation into the secondary site initiation of tumorgenesis and angiogenesis are also included in developing the bone metastasis several studies demonstrated that zoledronic acid which belongs to the second generation of bp nitrogen containing bps class agents is an important and well established drug in the treatment of wide range of cancer patients such as breast cancer prostate cancer and multiple myeloma associated with bone metastases this study investigated the preventive effects of vinegar and acetic acid the active component of vinegar on ulcerative colitis uc in mice vinegar 5 v v or acetic acid 0 3 w v treatment significantly reduced the disease activity index and histopathological scores attenuated body weight loss and shortened the colon length in a murine experimental colitis model induced by dextran sulfate sodium dss further mechanistic analysis showed that vinegar inhibited inflammation through suppressing th1 and th17 responses the nlrp3 inflammasome and mapk signaling activation vinegar also inhibited endoplasmic reticulum er stress mediated apoptosis in the colitis mouse model surprisingly pretreatment with vinegar for 28 days before dss induction increased levels of the commensal lactic acid producing or acetic acid producing bacteria including lactobacillus bifidobacteria and enterococcus faecalis whereas decreased escherichia coli levels were found in the feces of mice these results suggest that vinegar supplementation might provide a new dietary strategy for the prevention of uc kounis syndrome is defined as the co incidental occurrence of an acute coronary syndrome with hypersensitivity reactions following an allergenic event and was first described by kounis and zavras in 1991 as an allergic angina syndrome multiple causes have been described and most of the data in the literature are derived from the description of clinical cases mostly in adult patients and the pathophysiology remains only partly explained three different variants of kounis syndrome have been defined type i without coronary disease is defined as chest pain during an acute allergic reaction in patients without risk factors or coronary lesions in which the allergic event induces coronary spasm that electrocardiographic changes secondary to ischemia type ii with coronary disease includes patients with pre existing atheromatous disease either previously quiescent or symptomatic in whom acute hypersensitive reactions cause plaque erosion or rupture culminating in acute myocardial infarction more recently a type iii variant of kounis syndrome has been defined in patients with preexisting coronary disease and drug eluting coronary stent thrombosis the pathogenesis of the syndrome is discussed and a therapeutic algorithm is proposed exposure to secondhand smoke occurs primarily in the home due to passage of smoke free legislation creation of a total household smoking ban can reduce associated health conditions such as asthma lung cancer heart disease and stroke this paper describes the results of a randomized control trial of a minimal intervention to create smoke free homes 2 1 1 callers were invited to participate in the trial and were randomized to an intervention mailings and a coaching call or a control group no intervention we assessed reach dose fidelity and receptivity to the intervention through program records and a 3 month follow up survey with intervention participants for the intervention materials materials were mailed to 244 participants 99 2 and 227 participants 92 3 received the coaching call intervention 92 3 received all intervention components participants who had full household bans at 3 months were more likely to conduct behaviors leading to a smoke free home i e making a list of reasons having a family talk posting a pledge than were those with no partial ban the intervention materials also were rated higher in relevance and usefulness by non smokers than smokers results demonstrate that this minimal intervention had high fidelity to the delivery of components and relatively high receptivity creatine is of paramount importance for maintaining and managing cellular atp stores in both physiological and pathological states besides these ergogenic actions it has a number of additional pleiotropic effects e g antioxidant activity neurotransmitter like behavior prevention of opening of mitochondrial permeability pore and others creatine supplementation has been proposed for a number of conditions including neurodegenerative diseases however it is likely that creatine s largest therapeutic potential is in those diseases caused by energy shortage or by increased energy demand for example ischemic stroke and other cerebrovascular diseases surprisingly despite a large preclinical body of evidence little or no clinical research has been carried out in these fields however recent work showed that high dose creatine supplementation causes an 8 9 increase in cerebral creatine content and that this is capable of improving in humans neuropsychological performances that are hampered by hypoxia in addition animal work suggests that creatine supplementation may be protective in stroke by increasing not only the neuronal but also the endothelial creatine content creatine should be administered before brain ischemia occurs and thus should be given for prevention purposes to patients at high risk of stroke in myocardial ischemia phosphocreatine has been used clinically with positive results e g showing prevention of arrhythmia and improvement in cardiac parameters nevertheless large clinical trials are needed to confirm these results in the context of modern reperfusion interventions so far the most compelling evidence for creatine and or phosphocreatine use in cardiology is as an addition to cardioplegic solutions where positive effects have been repeatedly reported stroke comprises the leading cause of death in greece and more than 40 of the overall lifetime cost for stroke care represents the acute phase hospitalization the aim of the present study was to assess the resource utilization and estimate the costs for treatment of stroke patients in an acute stroke unit asu patients with first ever stroke treated in the asu of an academic hospital in athens during 2003 2009 were included in the analysis the national institutes of health stroke scale nihss and the modified rankin scale mrs were employed to assess the neurological impairment on admission and the handicap at discharge respectively the cost categories measured were diagnostic investigations medications medical and nursing staff and overhead costs a generalized linear model was used to predict the mean cost per patient based on the clinical characteristics of the patients on admission and during their hospitalization in total 784 patients were included in the analysis with mean age of 72 2 11 2 and mean length of hospital stay of 12 3 9 5 days the mean cost per patient was estimated at \u20ac2 864 2 198 and the mean cost per day at \u20ac244 54 the relevant cost for the mildly handicapped patients was \u20ac1 573 625 while for the severely handicapped patients it was \u20ac4 136 2 538 delayed discharge was associated with a mean cost of \u20ac362 634 per patient while the cost for the acute phase management of the patients was \u20ac2 445 2 471 the neurological impairment on admission nihss score and the delayed discharge were strong predictors of the mean cost per patient the costs for treatment of stroke patients in an asu comprise a significant burden in greece further research should be performed to explore the long term costs for the treatment of the disease at a nation wide level drosophila melanogaster is a useful organism for determining protein function and modeling human disease drosophila offers a rapid generation time and an abundance of genomic resources and genetic tools conservation in protein structure signaling pathways and developmental processes make studies performed in drosophila relevant to other species including humans drosophila models have been generated for neurodegenerative diseases muscular dystrophy cancer and many other disorders recently intermediate filament protein diseases have been modeled in drosophila these models have revealed novel mechanisms of pathology illuminated potential new routes of therapy and make whole organism compound screens feasible the goal of this chapter is to outline steps to study intermediate filament function and model intermediate filament associated diseases in drosophila the steps are general and can be applied to study the function of almost any protein the protocols outlined here are for both the novice and experienced drosophila researcher allowing the rich developmental and cell biology that drosophila offers to be applied to studies of intermediate filaments the most frequently occurring mutations in the gene encoding nuclear lamin a and nuclear lamin c cause striated muscle diseases virtually always involving the heart in this review we describe the approaches and methods used to discover that cardiomyopathy causing lamin a c gene mutations increase map kinase signaling in the heart and that this plays a role in disease pathogenesis we review different mouse models of cardiomyopathy caused by lamin a c gene mutations and how transcriptomic analysis of one model identified increased cardiac activity of the erk1 2 jnk and p38\u03b1 map kinases we describe methods used to measure the activity of these map kinases in mouse hearts and then discuss preclinical treatment protocols using pharmacological inhibitors to demonstrate their role in pathogenesis several of these kinase inhibitors are in clinical development and could potentially be used to treat human subjects with cardiomyopathy caused by lamin a c gene mutations current research utilizes the specific expression pattern of intermediate filaments if for identifying cellular state and origin as well as for the purpose of disease diagnosis nestin is commonly utilized as a specific marker and driver for cns progenitor cell types but in addition nestin can be found in several mesenchymal progenitor cells and it is constitutively expressed in a few restricted locations such as muscle neuromuscular junctions and kidney podocytes alike most other members of the if protein family nestin filaments are dynamic constantly being remodeled through posttranslational modifications which alter the solubility protein levels and signaling capacity of the nestin filaments through its interactions with kinases and other signaling executors resulting in a complex and bidirectional regulation of cell signaling events nestin has the potential to determine whether cells divide differentiate migrate or stay in place in this review the broad and similar roles of ifs as dynamic signaling scaffolds is exemplified by observations of nestin functions and its interaction with the cyclin dependent kinase 5 the atypical kinase in the family of cyclin dependent kinases \u03b1 internexin and peripherin are neuronal specific intermediate filament if proteins \u03b1 internexin is a type iv if protein like the neurofilament triplet proteins nftps which include neurofilament light chain neurofilament medium chain and neurofilament high chain that are generally considered to be the primary components of the neuronal ifs however \u03b1 internexin is often expressed together with the nftps and has been proposed as the fourth subunit of the neurofilaments in the central nervous system \u03b1 internexin is also expressed earlier in the development than the nftps and is a maker for neuronal if inclusion disease \u03b1 internexin can self polymerize in vitro and in transfected cells and it is present in the absence of the nftp in development and in granule cells in the cerebellum in contrast peripherin is a type iii if protein like \u03b1 internexin peripherin is specific to the nervous system but it is expressed predominantly in the peripheral nervous system pns peripherin can also self assemble both in vitro and in transfected cells it is as abundant as the nftps in the sciatic nerve and can be considered a fourth subunit of the neurofilaments in the pns peripherin has multiple isoforms that arise from intron retention cryptic intron receptor site or alternative translation initiation the functional significance of these isoforms is not clear peripherin is a major component found in inclusions of patients with amyotrophic lateral sclerosis als and peripherin expression is upregulated in als patients intermediate filament if cytoskeleton comprises the fine tuning cellular machinery regulating critical homeostatic mechanisms in skeletal and cardiac muscle deficiency or disturbance of the if network leads to severe pathology particularly in the latter the three dimensional scaffold of the muscle specific if protein desmin interconnects key features of the cardiac muscle cells including the z disks intercalated disks plasma membrane nucleus mitochondria lysosomes and potentially sarcoplasmic reticulum this is crucial for the highly organized striated muscle in which effective energy production and transmission as well as mechanochemical signaling are tightly coordinated among the organelles and the contractile apparatus the role of desmin and desmin associated proteins in the biogenesis trafficking and organelle function as well as the development differentiation and survival of the cardiac muscle begins to be enlightened but the precise mechanisms remain elusive we propose a set of experimental tools that can be used in vivo and in vitro to unravel crucial new pathways by which the if cytoskeleton facilitates proper organelle function homeostasis and cytoprotection and further understand how its disturbance and deficiency lead to disease simple epithelial keratins seks are the cytoplasmic intermediate filament proteins of single layered and glandular epithelial cells as found in the liver pancreas intestine and lung seks have broad cytoprotective functions which are facilitated by dynamic posttranslational modifications and interaction with associated proteins sek filaments are composed of obligate heteropolymers of type ii k7 k8 and type i k18 k20 k23 keratins the multifaceted roles of seks are increasingly appreciated due to findings obtained from transgenic mouse models and human studies that identified sek variants in several digestive diseases reorganization of the sek network into aggregates called mallory denk bodies mdbs is characteristic for specific liver disorders such as alcoholic and nonalcoholic steatohepatitis to spur further research on seks we here review the methods and potential caveats of their isolation as well as possibilities to study them in cell culture the existing transgenic sek mouse models their advantages and potential drawbacks are discussed the tools to induce mdbs ways of their visualization and quantification as well as the possibilities to detect sek variants in humans are summarized keratins comprise the type i and type ii intermediate filament forming proteins and occur primarily in epithelial cells they are encoded by 54 evolutionarily conserved genes 28 type i 26 type ii and regulated in a pairwise and tissue type differentiation and context dependent manner keratins serve multiple homeostatic and stress enhanced mechanical and nonmechanical functions in epithelia including the maintenance of cellular integrity regulation of cell growth and migration and protection from apoptosis these functions are tightly regulated by posttranslational modifications as well as keratin associated proteins genetically determined alterations in keratin coding sequences underlie highly penetrant and rare disorders whose pathophysiology reflects cell fragility and or altered tissue homeostasis moreover keratin mutation or misregulation represents risk factors or genetic modifiers for several acute and chronic diseases this chapter focuses on keratins that are expressed in skin epithelia and details a number of basic protocols and assays that have proven useful for analyses being carried out in skin the discovery of the causative link between keratin mutations and a growing number of human diseases opened the way for a better understanding of the function of the whole intermediate filament families of cytoskeleton proteins this chapter describes analytical approaches to identification and interpretation of the consequences of keratin mutations from the clinical and diagnostic level to cells in tissue culture intermediate filament pathologies can be accurately diagnosed from skin biopsies and dna samples the human intermediate filament database collates reported mutations in intermediate filament genes and their diseases and can help clinicians to establish accurate diagnoses leading to disease stratification for genetic counseling optimal care delivery and future mutation aligned new therapies looking at the best studied keratinopathy epidermolysis bullosa simplex the generation of cell lines mimicking keratinopathies is described in which tagged mutant keratins facilitate live cell imaging to make use of today s powerful enhanced light microscopy modalities cell stress assays such as cell spreading and cell migration in scratch wound assays can interrogate the consequences of the compromised cytoskeletal network application of extrinsic stresses such as heat osmotic or mechanical stress can enhance the differentiation of mutant keratin cells from wild type cells to bring the experiments to the next level 3d organotypic human cultures can be generated and even grafted onto the backs of immunodeficient mice for greater in vivo relevance while development of these assays has focused on mutant k5 k14 cells the approaches are often applicable to mutations in other intermediate filaments reinforcing fundamental commonalities in spite of diverse clinical pathologies intermediate filament if proteins have unique and complex cell and tissue distribution importantly if gene mutations cause or predispose to more than 80 human tissue specific diseases if pathies with the most severe disease phenotypes being due to mutations at conserved residues that result in a disrupted if network a critical need for the entire if pathy field is the identification of drugs that can ameliorate or cure these diseases particularly since all current therapies target the if pathy complication such as diabetes or cardiovascular disease rather than the mutant if protein or gene we describe a high throughput approach to identify drugs that can normalize disrupted if proteins this approach utilizes transduction of lentivirus that expresses green fluorescent protein tagged keratin 18 k18 r90c in a549 cells the readout is drug hits that convert the dot like keratin filament distribution due to the r90c mutation to a wild type like filamentous array a similar strategy can be used to screen thousands of compounds and can be utilized for practically any if protein with a filament disrupting mutation and could therefore potentially target many if pathies hits of interest require validation in cell culture then using in vivo experimental models approaches to study the mechanism of mutant if normalization by potential drugs of interest are also described the ultimate goal of this drug screening approach is to identify effective and safe compounds that can potentially be tested for clinical efficacy in patients studies of the intermediate filament if structure are a prerequisite of understanding their function in addition the structural information is indispensable if one wishes to gain a mechanistic view on the disease related mutations in the ifs over the years considerable progress has been made on the atomic structure of the elementary building block of all ifs the coiled coil dimer here we discuss the approaches methods and practices that have contributed to this advance with abundant genetic information on hand bioinformatics approaches give important insights into the dimer structure including the head and tail regions poorly assessable experimentally at the same time the most important contribution has been provided by x ray crystallography following the divide and conquer approach many fragments from several if proteins could be crystallized and resolved to atomic resolution we will systematically cover the main procedures of these crystallographic studies suggest ways to maximize their efficiency and also discuss the possible pitfalls and limitations in addition electron paramagnetic resonance with site directed spin labeling was another method providing a major impact toward the understanding of the if structure upon placing the spin labels into specific positions within the full length protein one can evaluate the proximity of the labels and their mobility this makes it possible to make conclusions about the dimer structure in the coiled coil region and beyond as well as to explore the dimer dimer contacts bovine tuberculosis tb impacts livestock farming in new zealand where the introduced marsupial brushtail possum trichosurus vulpecula is the wildlife maintenance host for mycobacterium bovis new zealand has implemented a campaign to control tb using a co ordinated programme of livestock diagnostic testing and large scale culling of possums with the long term aim of tb eradication for management of the disease in wildlife methods that can optimise the balance between control and surveillance effort will facilitate the objective of eradication on a fixed or limited budget we modelled and compared management options to optimise the balance between the two activities necessary to achieve and verify eradication of tb from new zealand wildlife the number of lethal population control operations required to halt the m bovis infection cycle in possums and the subsequent surveillance effort needed to confidently declare tb freedom post control the approach considered the costs of control and surveillance as well as the potential costs of re control resulting from false declaration of tb freedom the required years of surveillance decreased with increasing numbers of possum lethal control operations but the overall time to declare tb freedom depended on additional factors such as the probability of freedom from disease after control and the probability of success of mop up control i e retroactive culling following detection of persistent disease in the residual possum population the total expected cost was also dependent on a number of factors many of which had wide cost ranges suggesting that an optimal strategy is unlikely to be singular and fixed but will likely vary for each different area being considered our approach provides a simple framework that considers the known and potential costs of possum control and tb surveillance enabling managers to optimise the balance between these two activities to achieve and prove eradication of a wildlife disease or the pest species that transmits it in the most expedient and economic way this cost and risk evaluation approach may be applicable to other wildlife disease problems where limited management funds exist clopidogrel reduces the risk of non cardioembolic ischemic stroke but it is unclear whether it affects the severity and outcome of stroke we aimed at evaluating the effect of prior treatment with clopidogrel on acute non cardioembolic ischemic stroke severity and in hospital outcome we prospectively studied 608 consecutive patients 39 5 males age 79 1 6 6 years who were admitted with acute ischemic stroke the severity of stroke was assessed at admission with the national institutes of health stroke scale nihss severe stroke was defined as nihss \u226521 the outcome was assessed using the dependency rates that prevailed at the time of discharge i e modified rankin scale between 2 and 5 and with in hospital mortality at admission 397 patients did not have atrial fibrillation or heart valve disease among these 397 patients 69 were receiving monotherapy with clopidogrel prior to stroke 69 were receiving monotherapy with aspirin and 236 patients were not on any antiplatelet treatment the prevalence of severe stroke was lower in patients who were receiving clopidogrel than in patients who were receiving aspirin and patients who were not on antiplatelets 1 4 13 0 and 11 0 respectively p 0 05 independent predictors of severe stroke at admission were male gender relative risk rr 0 31 95 ci 0 12 0 78 p 0 05 and treatment with clopidogrel prior to stroke compared with no antiplatelet treatment rr 0 13 95 ci 0 02 0 97 p 0 05 treatment with aspirin prior to stroke did not predict severe stroke compared with no antiplatelet treatment rr 1 24 95 ci 0 51 2 98 p ns the rate of dependency at discharge did not differ between patients who were receiving clopidogrel patients who were receiving aspirin and those who were not on antiplatelets 57 9 47 8 and 59 7 respectively p ns independent predictors of dependency at discharge were age rr 1 12 95 ci 1 05 1 19 p 0 001 and nihss at admission rr 1 67 95 ci 1 46 1 92 p 0 001 in hospital mortality rate also did not differ between patients who were receiving clopidogrel patients who were receiving aspirin and those who were not on antiplatelets 4 3 4 3 and 5 0 respectively p ns the only independent predictor of in hospital mortality was nihss at admission rr 1 22 95 ci 1 14 1 30 p 0 001 treatment with clopidogrel prior to acute non cardioembolic ischemic stroke attenuates the severity of stroke at admission but does not appear to affect the functional outcome at discharge or the in hospital mortality of these patients for numerous patients allogeneic stem cell transplantation sct is the only therapeutic option that could potentially cure their disease despite significant progress made in clinical management of allogeneic sct acute graft versus host disease agvhd remains the second cause of death after disease recurrence agvhd is highly immunosuppressive and the adverse effect of allogeneic sct on t cell regeneration is typically more important than the levels of immunosuppression normally seen after autologous sct in these patients immune reconstitution often takes several years to occur and restoring immunocompetence after allogeneic sct represents an important challenge principally because clinical options are limited and current methods used to accelerate immune reconstitution are associated with increased gvhd interleukin 7 and il 15 are both under clinical investigation and demonstrate the greatest potential on peripheral t cells regeneration in mice and humans however awareness has been raised about the use of il 7 and il 15 after allogeneic sct with regards to potential adverse effects on agvhd in this review we will discuss about recent progress made in lymphocyte regeneration the critical role played by il 7 and il 15 in t cell homeostasis and how these cytokines could be used to improve immune reconstitution after allogeneic sct to determine the efficiency of noninvasive mechanical ventilation niv both in protection from intubation and in preventing reintubation of postextubation in patients in the pediatric intensive care unit picu a prospective observational study was conducted in a multidisciplinary 10 bed tertiary picu of a university hospital all patients were admitted to our unit from june 2012 to may 2014 and deemed to be candidates to receive continuous positive airway pressure or bilevel positive airway pressure we performed 160 niv episodes in 137 patients their median age was 9 months range 1 240 months and their median weight was 7 5 kg range 2 5 65 kg fifty seven percent of patients were male noninvasive mechanical ventilation was successful in 70 112 episodes of patients there was an underlying illness in 83 8 134 episodes of the patients bilevel positive airway pressure support was given to 57 5 92 episodes of the patients whereas the remaining 42 5 68 episodes received continuous positive airway pressure support among the causes of respiratory failure in our patients the most frequent were postextubation pneumonia bronchiolitis atelectasia and cardiogenic pulmonary edema sedation was applied in 43 1 of the episodes complications were detected in 29 episodes 18 1 the niv failure group showed higher pediatric risk of mortality iii 24 score shorter niv duration more frequent underlying disease lower number fed longer length of picu stay and hospital stay and mortality was higher noninvasive mechanical ventilation effectively and reliably reduced endotracheal intubation in the treatment of respiratory failure due to different clinical situations our results suggest that niv can play an important role in picus in helping to avoid intubation and prevent reintubation although there were serious underlying diseases in most of our patients such as immunosuppression 70 avoided intubation with use of niv the domestic dog is becoming an increasingly valuable model species in medical genetics showing particular promise to advance our understanding of cancer and orthopaedic disease here we undertake the largest canine genome wide association study to date with a panel of over 4 200 dogs genotyped at 180 000 markers to accelerate mapping efforts for complex diseases we identify loci significantly associated with hip dysplasia elbow dysplasia idiopathic epilepsy lymphoma mast cell tumour and granulomatous colitis for morphological traits we report three novel quantitative trait loci that influence body size and one that influences fur length and shedding using simulation studies we show that modestly larger sample sizes and denser marker sets will be sufficient to identify most moderate to large effect complex disease loci this proposed design will enable efficient mapping of canine complex diseases most of which have human homologues using far fewer samples than required in human studies perinatal growth restriction gr is associated with heightened sympathetic tone and hypertension we have previously shown that naturally occurring neonatal gr programmes hypertension in male but not female mice we therefore hypothesized that intact ovarian function or post ovariectomy ovx oestrogen administration protects gr female mice from hypertension utilizing a non interventional model that categorizes mice with weanling weights below the tenth percentile as gr control and gr adult mice were studied at three distinct time points baseline post ovx and post ovx with oral oestrogen replacement ovx elicited hypertension in gr mice that was significantly exacerbated by psychomotor arousal systolic blood pressure at light to dark transition control 122 2 gr 119 2 control ovx 116 3 gr ovx 126 3 mmhg oestrogen partially normalized the rising blood pressure surge seen in gr ovx mice 23 7 reduction gr mice had left ventricular hypertrophy and gr ovx mice in particular had exaggerated bradycardic responses to sympathetic blockade for gr mice a baseline increase in baroreceptor reflex sensitivity and high frequency spectral power support a vagal compensatory mechanism and that compensation was lost following ovx for gr mice the ovx induced parasympathetic withdrawal was partially restored by oestrogen 40 25 increase in high frequency spectral power p 0 05 in conclusion gr alters cardiac morphology and cardiovascular regulation the haemodynamic consequences of gr are attenuated in ovarian sufficient or oestrogen replete females further investigations are needed to define the role of hormone replacement therapy targeted towards young women with oestrogen deficiency and additional cardiovascular risk factors including perinatal gr cardiac hypertrophy and morning surge hypertension mutations in the gene encoding the bone morphogenetic protein receptor type ii bmpr2 are the commonest genetic cause of pulmonary arterial hypertension pah however the effect of bmpr2 mutations on clinical phenotype and outcomes remains uncertain we analysed individual participant data of 1550 patients with idiopathic heritable and anorexigen associated pah from eight cohorts that had been systematically tested for bmpr2 mutations the primary outcome was the composite of death or lung transplantation all cause mortality was the secondary outcome hazard ratios hrs for death or transplantation and all cause mortality associated with the presence of bmpr2 mutation were calculated using cox proportional hazards models stratified by cohort overall 448 29 of 1550 patients had a bmpr2 mutation mutation carriers were younger at diagnosis mean age 35 \xb74 sd 14 \xb78 vs 42 \xb70 17 \xb78 years had a higher mean pulmonary artery pressure 60 \xb75 13 \xb78 vs 56 \xb74 15 \xb73 mm hg and pulmonary vascular resistance 16 \xb76 8 \xb73 vs 12 \xb79 8 \xb73 wood units and lower cardiac index 2 \xb711 0 \xb769 vs 2 \xb751 0 \xb792 l min per m 2 all p 0 \xb70001 patients with bmpr2 mutations were less likely to respond to acute vasodilator testing 3 10 of 380 vs 16 147 of 907 p 0 \xb70001 among the 1164 individuals with available survival data age adjusted and sex adjusted hrs comparing bmpr2 mutation carriers with non carriers were 1 \xb742 95 ci 1 \xb715 1 \xb775 p 0 \xb70011 for the composite of death or lung transplantation and 1 \xb727 1 \xb700 1 \xb760 p 0 \xb7046 for all cause mortality these hrs were attenuated after adjustment for potential mediators including pulmonary vascular resistance cardiac index and vasoreactivity hrs for death or transplantation and all cause mortality associated with bmpr2 mutation were similar in men and women but higher in patients with a younger age at diagnosis p 0 \xb70030 for death or transplantation p 0 \xb7011 for all cause mortality patients with pah and bmpr2 mutations present at a younger age with more severe disease and are at increased risk of death and death or transplantation compared with those without bmpr2 mutations cambridge nihr biomedical research centre medical research council british heart foundation assistance publique h\xf4pitaux de paris inserm universit\xe9 paris sud intermountain research and medical foundation vanderbilt university national center for advancing translational sciences national institutes of health national natural science foundation of china and beijing natural science foundation the relative contribution of demographic lifestyle and medication factors to the association between affective disorders and cardiometabolic diseases is poorly understood to assess the relationship between cardiometabolic disease and features of depresion and bipolar disorder within a large population sample cross sectional study of 145 991 uk biobank participants multivariate analyses of associations between features of depression or bipolar disorder and five cardiometabolic outcomes adjusting for confounding factors there were significant associations between mood disorder features and any cardiovascular disease depression odds ratio or 1 15 95 ci 1 12 1 19 bipolar or 1 28 95 ci 1 14 1 43 and with hypertension depression or 1 15 95 ci 1 13 1 18 bipolar or 1 26 95 ci 1 12 1 42 individuals with features of mood disorder taking psychotropic medication were significantly more likely than controls not on psychotropics to report myocardial infarction depression or 1 47 95 ci 1 24 1 73 bipolar or 2 23 95 ci 1 53 3 57 and stroke depression or 2 46 95 ci 2 10 2 80 bipolar or 2 31 95 ci 1 39 3 85 associations between features of depression or bipolar disorder and cardiovascular disease outcomes were statistically independent of demographic lifestyle and medication confounders psychotropic medication may also be a risk factor for cardiometabolic disease in individuals without a clear history of mood disorder the effects of chronic low dose radiation on human health have not been well established recent studies have revealed that neural progenitor cells are present not only in the fetal brain but also in the adult brain since immature cells are generally more radiosensitive here we investigated the effects of chronic low dose radiation on cultured human neural progenitor cells hnpcs derived from embryonic stem cells radiation at low doses of 31 124 and 496 mgy per 72 h was administered to hnpcs the effects were estimated by gene expression profiling with microarray analysis as well as morphological analysis gene expression was dose dependently changed by radiation by thirty one mgy of radiation inflammatory pathways involving interferon signaling and cell junctions were altered dna repair and cell adhesion molecules were affected by 124 mgy of radiation while dna synthesis apoptosis metabolism and neural differentiation were all affected by 496 mgy of radiation these in vitro results suggest that 496 mgy radiation affects the development of neuronal progenitor cells while altered gene expression was observed at a radiation dose lower than 100 mgy this study would contribute to the elucidation of the clinical and subclinical phenotypes of impaired neuronal development induced by chronic low dose radiation purposeto evaluate the long term outcomes after femtosecond laser fsl assisted mushroom configuration keratoplasty in advanced keratoconus patients and methodsthirteen eyes with amsler krumeich stage iv keratoconus underwent fsl assisted mushroom configuration penetrating keratoplasty pkp and deep anterior lamellar keratoplasty dalk at a tertiary referral centre preoperative risk factors included low orneal thickness high keratometry measurements previous hydrops and central stromal scarring main outcome measures were visual acuity and refractive outcome resultsthe median follow up was 33 months range 4 43 preoperatively the mean corrected distance visual acuity cdva was 1 22 \xb10 47 logmar range 0 5 1 9 logmar mean minimum corneal thickness was 282 \xb1100 8 \u03bcm range 147 478 \u03bcm and mean average keratometric k value was 63 4 \xb17 63 dioptre d range 57 0 75 7 d four patients underwent pkp and nine underwent dalk two converted to pkp five patients subsequently underwent a modified arcuate mushroom interface dissection amid procedure for astigmatic correction at the final follow up the mean cdva was 0 05 \xb10 13 logmar range 0 10 to 0 20 logmar mean spherical equivalent was 3 21 \xb13 21d mean cylindrical refractive error was 3 23 \xb12 20 d and mean average k was 43 1 \xb11 53 d complications included early graft dehiscence corneal vascularisation stromal rejection and sclerokeratitis sutures were completely removed at the mean 18 4 months for pkp and 9 1 months for dalk postoperatively conclusionfsl assisted mushroom configuration keratoplasty is feasible and safe in patients with stage iv keratoconus amid could further enhance the refractive outcome safely the 14th 18th century pandemic of yersinia pestis caused devastating disease outbreaks in europe for almost 400 years the reasons for plague s persistence and abrupt disappearance in europe are poorly understood but could have been due to either the presence of now extinct plague foci in europe itself or successive disease introductions from other locations here we present five y pestis genomes from one of the last european outbreaks of plague from 1722 in marseille france the lineage identified has not been found in any extant y pestis foci sampled to date and has its ancestry in strains obtained from victims of the 14th century black death these data suggest the existence of a previously uncharacterized historical plague focus that persisted for at least three centuries we propose that this disease source may have been responsible for the many resurgences of plague in europe following the black death adverse effects associated with synthetic cannabinoid use include agitation psychosis seizures and cardiovascular effects all which may result in a lethal outcome we report the collection of data from 25 medical examiner and coroner cases where the presence of synthetic cannabinoids was analytically determined participating offices provided case history investigative and relevant autopsy findings and toxicology results along with the cause and manner of death determination this information with the agency and cause and manner of death determinations blinded was sent to participants participants offered their opinions regarding the likely contribution of the toxicology findings to cause and manner of death the results show that some deaths are being attributed to synthetic cannabinoids with the highest risk areas being behavioral toxicity resulting in excited delirium trauma or accidents and as contributing factors in subjects with pre existing cardiopulmonary disease while insufficient information exists to correlate blood synthetic cannabinoid concentrations to effect in the absence of other reasonable causes the drugs should be considered as a cause or contributory cause of death based on history and circumstances with supporting toxicological data pediatric onset multiple sclerosis ms negatively affects cognitive function mood and health related quality of life hrqol we aimed to explore the cognitive psychological and hrqol impacts of pediatric ms on young adults and to explore the relationships between disability disease duration cognition mood and hrqol in this hypotheses generating study thirty four young adults with pediatric onset ms at st michael s hospital in toronto were included in this cross sectional study mean age 21 3 years 56 female participants completed assessments of physical disability expanded disability status scale edss cognitive function symbol digit modalities test sdmt mood beck depression inventory ii bdi ii and hrqol short form health survey sf 36v2 findings were compared to age and gender matched normative data individuals with pediatric ms performed worse on the sdmt compared to normative data with 53 demonstrating cognitive impairment there was no difference in bdi ii scores from normative data but 21 showed at least mild depression there was a non significant impairment in physical hrqol compared to normative data decreased physical hrqol was related to disability edss while mental hrqol was related to depression bdi ii young adults with pediatric ms have reduced cognitive function non significant reductions in hrqol may be partly attributed to physical disability and depression these factors should be addressed in the care of adults with pediatric ms further studies including control groups and longitudinal design are needed to confirm these findings influenza vaccine effectiveness ve is increasingly estimated using the case test negative study design cases have a symptom complex consistent with influenza and test positive for influenza while non cases have the same symptom complex but test negative we aimed to determine a parsimonious logistic regression model for this study design when applied to patients in the community to determine the minimum covariate set required we used a previously published systematic review to find covariates and restriction criteria commonly included in case test negative logistic regression models covariates were assessed for inclusion using a directed acyclic graph we used data from the victorian influenza sentinel practice network from 2007 to 2013 excluding the pandemic year of 2009 to test the model ve was estimated as 1 adjusted or 100 changes in model fit from addition of specified covariates were examined restriction criteria were examined using change in ve estimate ve was estimated for each year all years aggregated and for influenza type and sub type using publicly available software the directed acyclic graph indicated that covariates specifying age time within the influenza season immunocompromising comorbid conditions and year or study site where applicable were required for closure the inclusion of sex was not required inclusions and exclusions were validated when testing the variables when collected with our data restriction by time between onset and swab was supported by the data ve for all years aggregated was estimated as 53 95 ci 38 64 ve was estimated as 42 95 ci 19 59 for h3n2 75 95 ci 51 88 for h1n1pdm09 and 63 95 ci 38 79 for influenza b theoretical covariates specified by the directed acyclic graph were validated when tested against surveillance data a parsimonious model using the case test negative design allows regular estimates of ve and aggregated estimates by year although recombinant glucocerebrosidase gcase is the standard therapy for the inherited lysosomal storage disease gaucher s disease gd enzyme replacement is not effective when the central nervous system is affected we created a series of recombinant genes proteins where gcase was linked to different membrane binding peptides including the tat peptide the rabies glycoprotein derived peptide rdp the binding domain from tetanus toxin ttc and a tetanus like peptide tet1 the majority of these proteins were well expressed in a mammalian producer cell line hek 293f purified recombinant tat gcase and rdp gcase showed similar gcase protein delivery to a neuronal cell line that genetically lacks the functional enzyme and greater delivery than control gcase cerezyme genzyme this initial result was unexpected based on observations of superior protein delivery to neurons with rdp as a vector a recombinant protein where a fragment of the flexible hinge region from iga igah was introduced between rdp and gcase showed substantially enhanced gcase neuronal delivery 2 5 times over tat gcase suggesting that the original construct resulted in interference with the capacity of rdp to bind neuronal membranes extended treatment of these knockout neuronal cells with either tat gcase or rdp igah gcase resulted in an 90 reduction in the lipid substrate glucosylsphingosine approaching normal levels further in vivo studies of rdp igah gcase as well as tat gcase are warranted to assess their potential as treatments for neuronopathic forms of gd these peptide vectors are especially attractive as they have the potential to carry a protein across the blood brain barrier avoiding invasive direct brain delivery porcine circovirus type 2 pcv2 capsid cap protein has been successfully used as a vaccine to control porcine circovirus associated disease pcvad most pcv2 subunit vaccines are recombinant cap protein expressed in baculovirus insect cell expression system but using this eukaryotic system is laborious and expensive in our previous study full length of pcv2cap protein expressed in escherichia coli formed virus like particles vlps this expression system has the advantages of being relatively simple and inexpensive in this study we constructed a recombinant plasmid containing the full length codon optimized cap orf2 gene to improve high level expression of recombinant cap protein rcap with no changed amino acids the highly water soluble rcap protein was purified by a single column high throughput fractionation procedure based on size exclusion chromatography yield was 10mg per 200ml bacterial culture the rcap protein self assembled into vlps of diameter 25 30nm that contained exogenous nucleic acids the immunogenicity of pcv2 vlps was analyzed by immunizing mice vlp immunized mice mounted specific immune responses to pcv2 thus expression of rcap in e coli was feasible for large scale production of pcv2 vlps which could potentially be used for a vlp based pcv2 vaccine prostate cancer metastasis is the main cause of disease related mortality elucidating the mechanisms underlying prostate cancer metastasis is critical for effective therapeutic intervention in this study we performed gene expression profiling of prostate cancer stem like cells pcsc derived from du145 human prostate cancer cells to identify factors involved in metastatic progression our studies revealed contactin 1 cntn1 a neural cell adhesion protein to be a prostate cancer promoting factor cntn1 knockdown reduced pcsc mediated tumor initiation whereas cntn1 overexpression enhanced prostate cancer cell invasion in vitro and promoted xenograft tumor formation and lung metastasis in vivo in addition cntn1 overexpression in du145 cells and corresponding xenograft tumors resulted in elevated akt activation and reduced e cadherin cdh1 expression cntn1 expression was not readily detected in normal prostate glands but was clearly evident on prostate cancer cells in primary tumors and lymph node and bone metastases tumors from 637 patients expressing cntn1 were associated with prostate cancer progression and worse biochemical recurrence free survival following radical prostatectomy p 0 05 collectively our findings demonstrate that cntn1 promotes prostate cancer progression and metastasis prompting further investigation into the mechanisms that enable neural proteins to become aberrantly expressed in non neural malignancies the findings from genome wide association studies hold enormous potential for novel insight into disease mechanisms a major challenge in the field is to map these low risk association signals to their underlying functional sequence variants fsv simple sequence study designs are insufficient as the vast numbers of statistically comparable variants and a limited knowledge of noncoding regulatory elements complicate prioritization furthermore large sample sizes are typically required for adequate power to identify the initial association signals one important question is whether similar sample sizes need to be sequenced to identify the fsvs here we present a proof of principle example of an extreme discordant design to map fsvs within the 2q33 low risk breast cancer locus our approach employed dna sequencing of a small number of discordant haplotypes to efficiently identify candidate fsvs our results were consistent with those from a 2 000 fold larger traditional imputation based fine mapping study to prioritize further we used expression quantitative trait locus analysis of rna sequencing from breast tissues gene regulation annotations from the encode consortium and functional assays for differential enhancer activities notably we implicate three regulatory variants at 2q33 that target casp8 rs3769823 rs3769821 in casp8 and rs10197246 in als2cr12 as functionally relevant we conclude that nested discordant haplotype sequencing is a promising approach to aid mapping of low risk association loci the ability to include more efficient sequencing designs into mapping efforts presents an opportunity for the field to capitalize on the potential of association loci and accelerate translation of association signals to their underlying fsvs cancer res 76 7 1916 25 \xa92016 aacr c repeat binding factor dehydration responsive element binding factor 1c cbf2 dreb1c gene encodes a small family of transcriptional activator that has been described as playing an important role in freezing tolerance and cold acclimation of plants we here report that cbf2 gene also plays an important role in the early response to the pathogen infection of grapevine downy mildew disease the expression level of cbf2 increased dramatically and reached a peak at 7 h after infection in immune grapevine muscadinia rotundifolia noble which was much faster than moderate resistant vitis amurensis pi1288 and susceptible vitis vinifera cabernet sauvignon muscadinia rotundifolia mrcbf2 exhibited amino acid domains characteristic of vitis cbf2 proteins with unique features including rich serine repeats and slight differences in nls dsawrl and ap2 domains the mrcbf2 gene was introduced to arabidopsis col0 which are susceptible to downy mildew pathogen the transgenic lines showed an increased resistance to downy mildew disease and more accumulation of sa as well as higher expression of pathogenesis related pr genes atpr1 atpr4 and atpr5 as a consequence of mrcbf2 overexpression besides constitutive expression of mrcbf2 enhanced phytohormone abscisic acid aba independent drought tolerance of transgenic plants freezing tolerance of transgenic lines was also enhanced accompanied with an increase in the expression of the cold regulated genes atcor atcor15a atkin1 atrd29a and atsusy in addition the development of mrcbf2 overexpressing plants was seen to be altered and resulted in growth retardation dwarfism late flowering and prone rosette leaves which may be because of an increase in the gene expression of partial della proteins and ddf1 the 5 untranslated region 5 utr of foot and mouth disease virus fmdv contains an internal ribosome entry site ires that facilitates translation initiation of the viral orf in a 5 m7gpppn cap independent manner ires elements are responsible for the virulence phenotypes of several enteroviruses here we constructed a chimeric virus in which the ires of fmdv was completely replaced with that of bovine rhinitis b virus brbv in an infectious clone of serotype o fmdv the resulting ires replaced virus fmdv brbv replicated as efficiently as wt fmdv in hamster derived bhk 21 cells but was restricted for growth in porcine derived ibrs 2 pk 15 and sk 6 cells which are susceptible to wt fmdv to identify the genetic determinants of fmdv underlying this altered cell tropism a series of ires chimeric viruses were constructed in which each domain of the fmdv ires was replaced with its counterpart from the brbv ires the replication kinetics of these chimeric viruses in different cell lines revealed that the growth restriction phenotype in porcine derived cells was produced after the replacement of domain 3 or 4 in the fmdv ires furthermore the change in fmdv cell tropism due to ires replacement in porcine derived cells was mainly attributed to a decline in cell specific ires translation initiation efficiency these findings demonstrate that ires domains 3 and 4 of fmdv are novel cell specific cis elements for viral replication in vitro and suggest that ires mediated translation determines the species specificity of fmdv infection in vivo the aim of this study was to evaluate serum paraoxonase 1 pon1 activity and its association with oxidative stress in autoimmune thyroid disease aitd a total of 50 patients with aitd including 25 with hashimoto s thyroiditis and 25 with graves disease were enrolled the control group comprised 27 healthy subjects blood samples were obtained in the euthyroid period and 3 months after initiation of medical treatment serum samples from patients with aitd and the healthy control group were analyzed for basal pon1 salt stimulated pon1 and arylesterase are activities along with lipid hydroperoxide looh and total free sulfhydryl sh levels serum pon1 activities and sh levels were significantly lower p 0 001 for each whereas looh levels were significantly higher p 0 001 for each in patients with aitd compared to the control group we observed no significant differences in are levels between the patient and healthy control groups p 0 05 pon1 activity was positively correlated with sh r 0 522 p 0 001 and negatively correlated with looh r 0 487 p 0 001 pon1 phenotype distribution of the subjects was not significantly different among the three groups p 0 961 serum pon1 activity is decreased in patients with aitd and correlated positively with sh a well known antioxidant and negatively with looh an index of lipid oxidation interventions that lead to reductions in soil transmitted helminths sths include chemotherapy with anthelmintic drugs and improvements in water sanitation and hygiene wash in this opinion article we aim to determine the evidence for optimal approaches for sth control first we explore the evidence for the above interventions we then appraise two integration strategies current chemotherapy oriented integrated neglected tropical disease ntd control and expanded multicomponent integration which includes integrated chemotherapy wash and other intervention strategies while multicomponent integrated control may be an effective approach to sustainably reduce sth transmission there is a need for evidence to prove the feasibility of this approach this prospective pilot study evaluated the ability of na 18 f pet ct to detect and monitor bone metastases over time and its correlation with clinical outcomes and survival in advanced prostate cancer sixty prostate cancer patients including 30 with and 30 without known bone metastases by conventional imaging underwent na 18 f pet ct at baseline 6 mo and 12 mo positive lesions were verified on follow up scans changes in suvs and lesion number were correlated with prostate specific antigen change clinical impression and overall survival significant associations included the following suv and prostate specific antigen percentage change at 6 mo p 0 014 and 12 mo p 0 0005 suv maximal percentage change from baseline and clinical impression at 6 mo p 0 0147 and 6 12 mo p 0 0053 suv change at 6 mo and overall survival p 0 018 number of lesions on na 18 f pet ct and clinical impression at baseline p 0 0001 6 mo p 0 0078 and 12 mo p 0 0029 and number of lesions on na 18 f pet ct per patient at baseline and overall survival p 0 017 in an exploratory analysis paired 99m tc methylene diphosphonate bone scans 99m tc bs were available for 35 patients at baseline 19 at 6 mo and 14 at 12 mo 68 scans malignant lesions on na 18 f pet ct n 57 were classified on 99m tc bs as malignant 65 of the time indeterminate 25 of the time and negative 10 of the time additionally 69 of paired scans showed more lesions on na 18 f pet ct than on 99m tc bs the baseline number of malignant lesions and changes in suv on follow up na 18 f pet ct significantly correlate with clinical impression and overall survival na 18 f pet ct detects more bone metastases earlier than 99m tc bs and enhances detection of new bone disease in high risk patients because a correlation between tau pathology and the clinical symptoms of alzheimer disease ad has been hypothesized there is increasing interest in developing pet tracers that bind specifically to tau protein the aim of this study was to evaluate tracer kinetic models for quantitative analysis and generation of parametric images for the novel tau ligand s 18 f thk5117 nine subjects 5 with ad 4 with mild cognitive impairment received a 90 min dynamic s 18 f thk5117 pet scan arterial blood was sampled for measurement of blood radioactivity and metabolite analysis volume of interest voi based analysis was performed using plasma input models single tissue and 2 tissue 2tcm compartment models and plasma input logan and reference tissue models and simplified reference tissue model srtm reference logan and suv ratio suvr cerebellum gray matter was used as the reference region voxel level analysis was performed using basis function implementations of srtm reference logan and suvr regionally averaged voxel values were compared with voi based values from the optimal reference tissue model and simulations were made to assess accuracy and precision in addition to 90 min initial 40 and 60 min data were analyzed plasma input logan distribution volume ratio dvr 1 values agreed well with 2tcm dvr 1 values r 2 0 99 slope 0 96 srtm binding potential bp nd and reference logan dvr 1 values were highly correlated with plasma input logan dvr 1 r 2 1 00 slope 1 00 whereas suvr 70 90 1 values correlated less well and overestimated binding agreement between parametric methods and srtm was best for reference logan r 2 0 99 slope 1 03 suvr 70 90 1 values were almost 3 times higher than bp nd values in white matter and 1 5 times higher in gray matter simulations showed poorer accuracy and precision for suvr 70 90 1 values than for the other reference methods srtm bp nd and reference logan dvr 1 values were not affected by a shorter scan duration of 60 min srtm bp nd and reference logan dvr 1 values were highly correlated with plasma input logan dvr 1 values voi based data analyses indicated robust results for scan durations of 60 min reference logan generated quantitative s 18 f thk5117 dvr 1 parametric images with the greatest accuracy and precision and with a much lower white matter signal than seen with suvr 70 90 1 images the aim of this study was to assess the prognostic and predictive value of early quantitative 18 f fdg pet to monitor therapy with an antibody to the insulinlike growth factor 1 receptor igf 1r antibody in patients with ewing sarcoma family of tumors esft 18 f fdg pet images at baseline and approximately 9 d after initiation of igf 1r antibody therapy in 115 patients with refractory or relapsed esft were prospectively obtained as part of the sarcoma alliance for research through collaboration trial responses were centrally evaluated by percist 1 0 in 93 patients the 9 d pet responses were correlated to overall survival os progression free survival pfs and clinical benefit after 6 wk of therapy based on clinical observation and ct response by world health organization anatomic criteria the median os was 8 1 mo 95 confidence interval 6 4 10 0 mo when percist was used patients with progressive metabolic disease showed shorter os median 4 7 mo than patients without progression median 10 0 mo p 0 001 progressive metabolic disease on day 9 pet was associated with a significantly higher risk of death hazard ratio 2 8 95 confidence interval 1 5 5 5 changes in 18 f fdg uptake after 9 d of therapy had an area under the curve of receiver operating characteristic of 0 71 to predict 1 y os the area under the curve was 0 63 to predict progression at 3 mo and 0 79 to predict clinical benefit after 6 wk of therapy treatment response by quantitative 18 f fdg pet assessed by percist 1 0 as early as 9 d into igf 1r antibody therapy in patients with esft can predict the os pfs and clinical response to therapy the objective of this study was to analyze the safety and efficacy of the 177 lu labeled dotaga based prostate specific membrane antigen psma ligand 177 lu dotaga i y fk sub kue 177 lu psma in patients with metastatic castration resistant prostate cancer mcrpc fifty six mcrpc patients underwent psma radioligand therapy rlt with 177 lu psma 68 ga psma n n bis 2 hydroxy 5 carboxyethyl benzyl ethylenediamine n n diacetic acid 68 ga psma pet ct was used for patient selection and follow up after psma rlt hematologic status renal function and serum prostate specific antigen levels were documented before and after therapy dosimetry was performed in 30 patients 177 lu psma demonstrated high absorbed tumor doses median 3 3 mgy mbq compared with the levels in normal organs parotid glands received higher doses 1 3 mgy mbq than kidneys 0 8 mgy mbq all patients tolerated the therapy without any acute adverse effects except for mild reversible xerostomia in 2 patients no long term side effects were observed there was a small but statistically significant reduction in erythrocyte and leukocyte counts only the reduction in erythrocyte counts decreased slightly below the reference range no thrombocytopenia occurred the severity of pain was significantly reduced in 2 of 6 patients 33 3 a decrease in prostate specific antigen levels was noted in 45 of 56 patients 80 4 of 25 patients monitored for at least 6 mo after 2 or more psma rlt cycles a molecular response evaluation 68 ga psma pet ct revealed partial remission in 14 stable disease in 2 and progressive disease in 9 patients contrast enhanced ct revealed partial remission in 5 stable disease in 13 and progressive disease in 7 patients the median progression free survival was 13 7 mo and the median overall survival was not reached during follow up for 28 mo psma rlt with 177 lu psma is feasible safe and effective in end stage progressive mcrpc with appropriate selection and follow up of patients by 68 ga psma pet ct through application of the concept of theranostics atherosclerosis is inherently an inflammatory process that is strongly affected by the chemokine chemokine receptor axes regulating the trafficking of inflammatory cells at all stages of the disease of the chemokine receptor family some specifically upregulated on macrophages play a critical role in plaque development and may have the potential to track plaque progression however the diagnostic potential of these chemokine receptors has not been fully realized on the basis of our previous work using a broad spectrum peptide antagonist imaging 8 chemokine receptors together the purpose of this study was to develop a targeted nanoparticle for sensitive and specific detection of these chemokine receptors in both a mouse vascular injury model and a spontaneously developed mouse atherosclerosis model the viral macrophage inflammatory protein ii vmip ii was conjugated to a biocompatible poly methyl methacrylate core polyethylene glycol shell amphiphilic comblike nanoparticle through controlled conjugation and polymerization before radiolabeling with 64 cu for pet imaging in an apolipoprotein e deficient apoe mouse vascular injury model and a spontaneous apoe mouse atherosclerosis model histology immunohistochemistry and real time reverse transcription polymerase chain reaction were performed to assess the plaque progression and upregulation of chemokine receptors the chemokine receptor targeted 64 cu vmip ii comb showed extended blood retention and improved biodistribution pet imaging showed specific tracer accumulation at plaques in apoe mice confirmed by competitive receptor blocking studies and assessment in wild type mice histopathologic characterization showed the progression of plaque including size and macrophage population corresponding to the elevated concentration of chemokine receptors and more importantly increased pet signals this work provides a useful nanoplatform for sensitive and specific detection of chemokine receptors to assess plaque progression in mouse atherosclerosis models preclinical data suggest a negative correlation between brown adipose tissue bat and the degree of coronary atherosclerosis we sought to evaluate the relationship between 18 f fdg uptake in supraclavicular bat in relation to arterial inflammation and subsequent cardiovascular disease cvd events in humans individuals who underwent 18 f fdg pet ct for clinical indications but who did not have either cancer or known atherosclerotic disease at the time of imaging were included a radiologist masked to clinical data measured 18 f fdg uptake within bat in the supraclavicular region as well as in subcutaneous adipose tissues tissue density was evaluated using ct hounsfield units arterial inflammation was assessed by measuring arterial 18 f fdg uptake and calculating target to background ratio cvd events were independently adjudicated by masked cardiologists thereafter the relationship between bat activity and cvd events was evaluated a total of 443 patients age 55 y 44 66 y 44 men body mass index bmi 26 range 23 31 were included and 30 patients experienced a cardiovascular event during a median follow up of 4 y bat activity negatively correlated with arterial inflammation r 0 178 p 0 01 a relationship that persisted after correcting for age and bmi r 0 147 p 0 01 when either high sensitivity or high accuracy thresholds from receiver operating curve analyses were used to define elevated bat high bat was associated with a reduced risk of cvd events p 0 048 even after correcting for age p 0 037 our results suggest that increased supraclavicular bat activity is inversely associated with arterial inflammation independently of age and bmi additionally increased bat may be associated with fewer cardiovascular events the aim of this study was to test the hypothesis that inhibiting mammalian target of rapamycin and insulin like growth factor 1 receptor would be efficacious in metastatic uveal melanoma this was a phase 2 trial of everolimus 10 mg daily plus pasireotide long acting release 60 mg every 28 days enrolling patients with progressive metastatic uveal melanoma to treatment until progression by response evaluation criteria in solid tumors 1 1 recist 1 1 or unacceptable toxicity the primary endpoint was clinical benefit rate defined as any objective response or recist 1 1 stable disease at 16 weeks a subset of patients underwent baseline indium 111 octreotide scans a total of 14 patients were enrolled of which 13 were evaluable for the primary endpoint before the study was terminated due to poor accrual three of 13 26 patients obtained clinical benefit seven of 13 54 had stable disease lasting for a median of 8 weeks range 8 16 weeks grade 3 adverse events deemed at least possibly related to study drugs were hyperglycemia n 7 oral mucositis n 2 diarrhea n 1 hypophosphatemia n 1 and anemia n 1 seven of 14 50 patients required at least one dose reduction due to toxicity seven of eight 88 patients with baseline indium 111 octreotide scans had at least one avid lesion with significant intrapatient heterogeneity there was a trend toward an association between octreotide avidity and cytostatic response to therapy p 0 078 the combination of everolimus and pasireotide has limited clinical benefit in this small metastatic uveal melanoma cohort dose reductions for side effects were common further investigation into the relationship between somatostatin receptor expression and cytostatic activity of somatostatin analogues is warranted this small exploratory study was designed to test the hypothesis that thin melanoma lesions contain nuclei of two similar phenotypes in different proportions in lesions likely to progress to metastatic disease one of these phenotypes predominates histopathological sections from 18 cases of thin melanomas which did not progress to metastasis and from 10 cases which did progress were imaged and digitized at high resolution with a total of 2084 and 1148 nuclei respectively recorded five karyometric features were used to discriminate between nuclei from indolent and from potentially metastatic lesions for each case the percentage of nuclei classified by the discriminant function as having come from a potentially metastatic lesion was determined and termed as case classification criterion standard histopathological criteria such as ulceration and high mitotic index indicated in this material the need for intensive therapy for only one of the 10 participants as compared with 7 10 identified correctly by the karyometric measure using a case classification criterion threshold of 40 the overall accuracy was 86 in the test set the proportion of nuclei of an aggressive phenotype may lend itself as an effective prognostic clue for thin melanoma lesions the algorithm developed in this training set appears to identify those patients at high risk for metastatic disease and demonstrates a basis for a further study to assess the utility of prognostic clues for thin melanomas nasal polyps np are a chronic inflammatory disease of the nasal mucosa their etiology is suspected to involve oxidative stress growth differentiation factor 15 gdf 15 brain natriuretic peptide bnp and ischemia modified albumin ima are biomarkers used especially in the early diagnosis and follow up of cardiovascular diseases the aim of this study was to assess levels of serum gdf 15 bnp and ima in patients with np and to compare them with those of healthy subjects this was a prospective study enrolling 41 patients with np and 48 healthy controls all aged 18 65 years and referred to the department of otorhinolaryngology head and neck surgery between january 2014 and february 2015 after a 12 h fast venous blood 3ml was drawn and centrifuged 3000rpm 10min to collect serum blood samples were drawn before endoscopic sinus surgery in the np group serum gdf 15 bnp and ima levels were measured gdf 15 bnp and ima levels of patients with np were statistically significantly higher than in controls and gdf 15 values were higher than the normal upper limit gdf 15 bnp and ima levels were significantly correlated in both groups as gdf 15 is a marker of chronic inflammation and oxidative stress our finding of increased serum gdf 15 in patients with np supports the hypothesis that its pathogenesis involves chronic inflammation and oxidative stress leishmaniasis is an overlooked tropical disease affecting approximately 1 million people in several countries clinical manifestation depends on the interaction between leishmania and the host s immune response currently available treatment options for leishmaniasis are limited and induce severe side effects in this research we tested nitro heterocyclic compounds bsf series as a new alternative against leishmania its activity was measured in leishmania leishmania infantum promastigotes and intracellular amastigotes using mtt colorimetric assay additionally we assessed the phosphatidylserine exposure by promastigotes measured by flow cytometry as well as nitric oxide production measured by griess method the nitro heterocyclic compounds bsf series showed activity against l l infantum promastigotes inducting the phosphatidylserine exposition by promastigotes decreasing intracellular amastigotes and increasing oxide nitric production the selectivity index was more prominent to leishmania than to macrophages compared to amphotericin b our compounds presented higher ic50 however the selectivity index was more specific to parasite than to amphotericin b in conclusion these nitro heterocyclic compounds showed to be promising as an anti leishmania drug in in vitro studies systematic childhood vaccination against meningococcus c has had a considerable impact on meningococcal invasive disease mid the aim of this study is to perform an analysis on the epidemiology the clinical features and the factors associated with a worse prognosis of mid in the era of a meningococcal c vaccine the study included confirmed cases of mid in children less than 15 years of age in navarra spain between 2008 and 2014 the risk of death or permanent sequelae was evaluated according to the presence of clinical features and analytical parameters at diagnosis the average annual incidence was 7 9 cases per 100 000 children with the highest attack rate in children 1 year of 53 cases analysed 87 were due to meningococcus b fever 100 rash 91 and elevation of procalcitonin 94 were the most frequent findings at diagnosis some sign of shock was observed in 70 upon arrival at the hospital the case fatality rate was 3 8 and 10 survived with permanent sequelae glasgow coma scale 15 odds ratio or 9 2 seizure or 8 3 sepsis without meningitis or 9 1 thrombocytopenia or 30 5 and disseminated intravascular coagulation or 10 9 showed a greater association with a worse prognosis the mid continues to be a significant cause of morbidity and mortality in children therefore new advances are needed in the prevention early diagnosis and detection of the factors associated with poor prognosis gene expression profiling has become a mainstay in immunology but subtle changes in gene networks related to biological processes are hard to discern when comparing various datasets for instance conservation of the transcriptional response to sepsis in mouse models and human disease remains controversial to improve transcriptional analysis in immunology we created immunesigdb a manually annotated compendium of \u223c5 000 gene sets from diverse cell states experimental manipulations and genetic perturbations in immunology analysis using immunesigdb identified signatures induced in activated myeloid cells and differentiating lymphocytes that were highly conserved between humans and mice sepsis triggered conserved patterns of gene expression in humans and mouse models however we also identified species specific biological processes in the sepsis transcriptional response although both species upregulated phagocytosis related genes a mitosis signature was specific to humans immunesigdb enables granular analysis of transcriptomic data to improve biological understanding of immune processes of the human and mouse immune systems allogeneic hematopoietic stem cell transplantation allo hsct a curative treatment for hematologic malignancies relies on donor cytotoxic t lymphocyte ctl mediated graft versus leukemia gvl effect major complications of hsct are graft versus host disease gvhd that targets specific tissues and tumor relapses however the mechanisms dictating the anatomical features of gvhd and gvl remain unclear here we show that after hsct ctls exhibited different killing activity in distinct tissues being highest in the liver and lowest in lymph nodes differences were imposed by the microenvironment partly through differential pd 1 ligand expression which was strongly elevated in lymph nodes two photon imaging revealed that pd 1 blockade restored ctl sensitivity to antigen and killing in lymph nodes weak ctl activity in lymph nodes promoted local tumor escape but could be reversed by anti pd 1 treatment our results uncover a mechanism generating an anatomical segregation of ctl activity that might dictate sites of gvhd and create niches for tumor escape excessive retention of neutral lipids in cardiac lipid droplets lds is a common observation in cardiomyopathy thus the systematic investigation of the cardiac ld proteome will help to dissect the underlying mechanisms linking cardiac steatosis and myocardial dysfunction here after isolation of lds from normal and dysfunctional sprague dawley rat hearts we identified 752 heart associated ld proteins using itraq quantitative proteomic method including 451 proteins previously unreported on lds the most noteworthy finding was the identification of the membrane resealing protein dysferlin an analysis of dysferlin truncation mutants indicated that its c2 domain was responsible for its ld localization quantitative proteomic results further determined that 27 proteins were increased and 16 proteins were decreased in lds from post pressure overload induced dysfunctional hearts compared with normal hearts notably adipose triacylglycerol lipase atgl was dramatically decreased and dysferlin was substantially increased on dysfunctional cardiac lds this study for the first time reveals the dataset of the heart ld proteome in healthy tissue and the variation of it under cardiac dysfunction these findings highlight an association between the altered ld protein localization of dysferlin and atgl and myocardial dysfunction tick borne encephalitis tbe has been a growing public health problem in europe and other parts of the world for the past 20 years in 1999 in order to encourage the control of tbe international experts created a new body the international scientific working group on tick borne encephalitis isw tbe this working group has been composed of internationally recognized scientific experts from tick borne encephalitis virus tbev endemic and non endemic regions with extensive personal expertise in the field and a high level of commitment to improve the knowledge of tbe and to increase the public awareness of tbe since the foundation of the working group isw tbe members meet annually every meeting is dedicated to a specific topic and since 2004 a yearly conference report has been published to inform the scientific community about the latest developments among the specific issues that have been extensively discussed over the years were the following clinical aspects of the disease tbe in children and golden agers epidemiology possible causes for the increase in tbe incidence in europe tbe and awareness tbe and travel low vaccination rates and the cooperation with the european centre for disease prevention and control ecdc this paper gives an overview of the most important activities and achievements of the isw tbe over the past 17 years the mumps outbreak in the plze\u0148 region in 2011 was analysed retrospectively using the epidemiological clinical and laboratory data vaccine efficacy analysis was also conducted in various population groups the routine procedure and standard form were used by the epidemiologists to collect data on the age sex place of residence presence in collectivities date of disease onset type of complications and date of their onset hospital admission vaccination and results of laboratory analyses based on the records of general practitioners for children and adolescents data on the vaccination of children born in the previous three years have been provided to the epidemic control departments every year by 30 june since 1989 to estimate the vaccination coverage rate the numbers of single dose or two dose recipients are related to the number of children registered in a given year the first year of vaccine recipients were children born in 1986 who were aged 25 in 2011 the data collected on the population of the plze\u0148 region were used for the primary analyses to estimate the efficacy of the mumps vaccine age and vaccine coverage cohort analysis was performed using the screening method to analyse categories the chi square test with yates correction was applied at a significance level of p 0 05 epiinfo version 6 04d in 2011 721 mumps cases were reported in the plze\u0148 region incidence 126 1 cases per 100 000 population the average patient age was 19 4 years with a median of 18 years age range 1 77 years four hundred and seventeen 57 8 patients were males biological specimens from 375 52 0 patients were investigated serologically in the virology laboratory and mumps were laboratory confirmed in 316 43 8 of them in 222 patients one blood specimen was analysed the most afflicted area was the klatovy district with the incidence of 449 3 100 000 population the most affected age group were 15 19 year olds with the incidence of 1008 2 100 000 population forty two 5 8 patients were diagnosed with complications and 68 9 4 patients were admitted to the hospital no statistically significant difference was found in the incidence of complications between the vaccinated and non vaccinated patients the assessment of hospitalisation risk showed a statistically significant difference between the vaccinated and non vaccinated persons in both the whole study cohort and subcohort of patients who received the mumps vaccine within the childhood immunization schedule p 0 000 and p 0 004 respectively the average age of the vaccinated patients was 16 1 years median of 17 and that of the non vaccinated patients was 29 3 years median of 27 at the six to ten month interval as laid down by the legislation the second dose of the vaccine was only given to 83 6 of the patients the screening method showed a high efficacy of the vaccine in the age group 20 25 years 97 6 in two dose recipients declining to 29 6 in the most affected age group of 15 19 years mumps outbreak may has been a result of the accumulation of high numbers of susceptible individuals in the population the most affected area was the klatovy district where the last epidemic outbreak occurred 23 years ago to make the favourable epidemiological situation with occasional local outbreaks continue the high two dose vaccine coverage rate needs to be maintained analysis of the course of benign acute childhood myosistis during the influenza epidemic of 2012 2013 with a focus on the clinical specificities laboratory findings diagnostic and therapeutic approaches and prognosis a retrospective study was conducted of 10 patients with myositis during influenza infection the haematological and biochemistry parameters were analysed a direct real time pcr assay was used to detect the virus from nasopharyngeal swabs eight of 10 patients were males of an average age of 7 1 years muscle disorders emerged during recovery from influenza they were characterized by a sudden onset of severe pain in the calf muscles with the consequent inability to walk in nine patients toe walking was reported in six children and wide base gait in one patient the full blood count showed leukopenia eight cases and thrombocytopenia five cases blood biochemistry typically detected elevated muscle enzymes creatine kinase and aspartate aminotransferase and elevated myoglobin in all patients influenza b was confirmed in all study patients they all recovered spontaneously within two to four days benign acute childhood myositis presents with the clinical picture of transient muscle disorders resulting in difficulty walking and very rarely can be complicated by rhabdomyolysis and kidney failure it is most often associated with influenza b and affects school age children mostly males good awareness of the condition facilitates the differential diagnosis and enables to rule out other more serious causes of difficulty walking symptomatic therapy is an adequate option and the patient recovers spontaneously within a couple of days early recognition of the disease avoids unnecessary diagnostic and therapeutic interventions the study aim was to implement a molecular real time polymerase chain reaction pcr assay recommended by the cdc centers for disease control and prevention for the detection of neisseria meningitidis haemophilus influenzae and streptococcus pneumoniae in clinical culture negative specimens from patients with suspected invasive bacterial disease clinical specimens are referred to the national reference laboratory nrl for meningococcal infections unit for airborne bacterial infections centre for epidemiology and microbiology national institute of public health from various regions of the czech republic clinical specimens are in particular cerebrospinal fluid anti coagulated blood or serum and exceptionally post mortem specimens the nrl has implemented molecular diagnosis of these bacterial pathogens involved in meningitis and sepsis from clinical specimens since 1999 the first diagnostic method was semi nested pcr followed by electrophoretic analysis in 2014 a molecular qualitative real time pcr assay was implemented the authors present an up to date review of toxic shock syndrome tss a life threatening condition where toxins of the gram positive bacteria staphyloccocus aureus and streptococcus pyogenes play a key role in the pathogenesis the authors provide insight into the epidemiology and pathogenesis of the disease and point out the relevant patient history data and clinical signs and symptoms that may indicate progression of tss last but not least the state of the art diagnostic and therapeutic approaches to early and full blown tss are summarized case reports are presented to illustrate two different etiological forms of this relatively rare nosological entity hantavirus disease is the most common rodent borne viral infection in the czech republic with a mean annual incidence of 0 02 cases per 100 000 population and specific antibodies detected in 1 of the human population four hantaviruses puumala dobrava belgrade tula and seewis circulate in this country of which puumala virus responsible for a mild form of hemorrhagic fever with renal syndrome called nephropathia epidemica and dobrava belgrade virus causing haemorrhagic fever with renal syndrome have been proven to cause human disease the aim of this study is to provide a comprehensive review of the hantaviruses occurring in the czech republic based on the literature published during the past three decades including their geographical distribution and clinical symptoms the recent detection of tula virus in an immunocompromised person as well as reports of seoul virus infections in europe highlight the possible emergence of neglected hantavirus infections in the foreseeable future ct p13 remsima \xae, inflectra \xae) is a biosimilar of the infliximab reference product rp remicade \xae) and is approved in europe and elsewhere mostly for the same indications as rp the aim of this study was to compare the 54 week efficacy immunogenicity pharmacokinetics pk and safety of ct p13 with rp in patients with ankylosing spondylitis as with a focus on patient reported outcomes pros this was a multinational double blind parallel group study in patients with active as participants were randomized 1 1 to receive ct p13 5 mg kg or rp 5 mg kg at weeks 0 2 6 and then every 8 weeks up to week 54 to assess responses standardized assessment tools were used with an intention to treat analysis of observed data anti drug antibodies adas pk parameters and safety outcomes were also assessed of 250 randomized patients n 125 per group 210 84 0 completed 54 weeks of treatment with similar completion rates between groups at week 54 assessment of spondylo arthritis international society asas 20 response asas40 response and asas partial remission were comparable between treatment groups changes from baseline in pros such as mean bath ankylosing spondylitis disease activity index basdai ct p13 3 1 versus rp 2 8 bath ankylosing spondylitis functional index basfi 2 9 versus 2 7 and short form health survey sf 36 scores 9 26 versus 10 13 for physical component summary 7 30 versus 6 54 for mental component summary were similar between treatment groups at 54 weeks 19 5 and 23 0 of patients receiving ct p13 and rp respectively had adas all observed pk parameters of ct p13 and rp including maximum and minimum serum concentrations were similar through 54 weeks the influence of adas on pk was similar in the two treatment groups most adverse events were mild or moderate in severity there was no notable difference between treatment groups in the incidence of adverse events serious adverse events infections and infusion related reactions ct p13 and rp have highly comparable efficacy including pros and pk up to week 54 over a 1 year period ct p13 was well tolerated and displayed a safety profile comparable to rp no differences in immunogenicity were observed clinicaltrials gov identifier nct01220518 registered 4 october 2010 alzheimer disease ad has become an epidemic within the growing elderly population and effective therapies of ad have not been discovered genetic factors accounted for over 70 of the incidence of ad and the disease related polymorphisms are located on chromosome 19 which is one of several prominent chromosomes related to the development of ad many inconsistent associations between polymorphisms in abca7 cd33 and tomm40 genes and the susceptibility to ad have been suggested by several independent studies a comprehensive literature search for studies involving the association between gene polymorphisms and ad was performed and we finally selected 3 genes 4 polymorphisms for the meta analysis abca7 rs3764650 cd33 rs3865444 and tomm40 rs157580 rs2075650 a total of 25 articles investigating 3 genes 4 polymorphisms were included in the meta analysis the pooled results of 4 polymorphisms were all significantly associated with the susceptibility to ad the pooled effect of abca7 rs3764605 allele g was significantly associated with an increased the risk of ad or 1 20 95 ci 1 14 1 26 p value 0 001 similarly our evidence suggested that allele a of tomm40 rs2075650 polymorphism was a risk factor for ad or 2 87 95 ci 2 46 3 34 p value 0 001 alleles a of cd33 rs3865444 and a of tomm40 rs157580 were both protective factors for ad onset or 0 94 95 ci 0 90 0 98 p value 0 003 or 0 62 95 ci 0 57 0 66 p value 0 001 conclusions results from the meta analysis revealed that the pooled abca7 rs376465 cd33 rs3865444 tomm40 rs157580 and rs2075650 variants were significantly associated with the susceptibility to ad however the association differed significantly between asian and caucasian groups for snps of cd33 rs3865444 tomm40 rs157580 and rs2075650 polyunsaturated fatty acids pufas are crucial for our health and wellbeing therefore they have been widely investigated for their roles in maintaining human health and in disease treatment most western diets include significant amount of saturated and omega 6 fatty acids and insufficient quantity of omega 3 however the balance between omega 6 and omega 3 pufa in particular is essential for the formation of pro and anti inflammatory lipids to promote health and prevent disease as our daily diet affects our health this paper draws attention to unique representatives of the omega 3 fatty acid group alpha linolenic acid and its derivatives recently this has been shown to be effective in treating and preventing various diseases it has been confirmed that omega 3 pufas may act as therapeutic agents as well and their significant role against inflammatory diseases such as cardiovascular and neurodegenerative diseases has been described some of nutritional factors have been described as a significant modifiers which can influence brain elasticity and thus effect on central nervous system functioning therefore appropriate dietary management appears to be a non invasive and effective approach to counteract neurological and cognitive disorders astrocytes are the most abundant neuron supporting glial cells in the central nervous system the neuroprotective role of astrocytes has been demonstrated in various neurological disorders such as amyotrophic lateral sclerosis spinal cord injury stroke and parkinson s disease pd astrocyte dysfunction or loss of astrocytes increases the susceptibility of neurons to cell death while astrocyte transplantation in animal studies has therapeutic advantage we reported recently that stimulation of serotonin 1a 5 ht1a receptors on astrocytes promoted astrocyte proliferation and upregulated antioxidative molecules to act as a neuroprotectant in parkinsonian mice pd is a progressive neurodegenerative disease with motor symptoms such as tremor bradykinesia rigidity and postural instability that are based on selective loss of nigrostriatal dopaminergic neurons and with non motor symptoms such as orthostatic hypotension and constipation based on peripheral neurodegeneration although dopaminergic therapy for managing the motor disability associated with pd is being assessed at present the main challenge remains the development of neuroprotective or disease modifying treatments therefore it is desirable to find treatments that can reduce the progression of dopaminergic cell death in this article we summarize first the neuroprotective properties of astrocytes targeting certain molecules related to pd next we review neuroprotective effects induced by stimulation of 5 ht1a receptors on astrocytes the review discusses new promising therapeutic strategies based on neuroprotection against oxidative stress and prevention of dopaminergic neurodegeneration transgenic nicotiana benthamiana lines with constitutive expression of an arabidopsis lectin receptor kinase gene lecrk i 9 or lecrk ix 1 show enhanced resistance to phytophthora pathogens demonstrating conserved gene functionality after interfamily transfer in plants cell surface receptors mediate the first layer of innate immunity against pathogenic microbes in arabidopsis several l type lectin receptor kinases lecrks were previously found to function as phytophthora resistance components in this study we determined the functionality of arabidopsis lecrk i 9 or lecrk ix 1 in phytophthora resistance when transferred into the solanaceous plant nicotiana benthamiana multiple transgenic lines were generated for each lecrk gene and molecular analyses revealed variation in transgene copy number transgene expression levels and lecrk protein accumulation infection assays showed that transgenic n benthamiana plants expressing either arabidopsis lecrk i 9 or lecrk ix 1 are more resistant to phytophthora capsici and to phytophthora infestans these results demonstrate that arabidopsis lecrk i 9 and lecrk ix 1 retained their phytophthora resistance function when transferred into n benthamiana therefore these lecrks have the potential to function as a complementary phytophthora resistance resource in distantly related plant species next to the canonical phytophthora resistance genes encoding nucleotide binding leucine rich repeat proteins paraoxonase 1 pon1 is a high density lipoprotein associated enzyme implicated in the pathogenesis of atherosclerosis by protecting lipoproteins against peroxidation pon1 has two genetic polymorphisms both due to amino acid substitution one involving glutamine and arginine at position 192 and the other leucine and methionine at position 55 recent reports suggest that nephrolithiasis and atherosclerosis share a number of risk factors our study aimed to compare the effects of pon1 192 pon1 55 polymorphisms and pon1 activity in patients with urolithiasis and controls pon1 s arylesterase paraoxonase activities and phenotype were determined in 158 stone forming cases group 1 and 138 non stone forming controls group 2 the pon1 192 and pon1 55 polymorphisms were studied by polymerase chain reaction restriction fragment length polymorphism paraoxonase activity was significantly lower in group 1 than group 2 112 31 8 vs 208 53 1 iu l p 0 001 the pon1 l55m polymorphism was significantly higher in group 1 the m allele coding for pon1 was higher in group 1 p 0 001 pon1 192 rr homozygotes had significantly higher pon1 activity than qr and qq genotypes among all the patients p 0 001 the results of our study demonstrate that the pon1 55 gene m allele is associated with renal stone disease individuals possessing the m allele have a higher incidence of urolithiasis the results of this study provide genetic evidence that the pon1 gene may play a role in stone formation pon1 genotype determination may provide a tool to identify individuals who are at risk of urolithiasis for the past decade emergency preparedness campaigns have encouraged households to meet preparedness metrics such as having a household evacuation plan and emergency supplies of food water and medication to estimate current household preparedness levels and to enhance disaster response planning the virginia department of health with remote technical assistance from the centers for disease control and prevention conducted a community health assessment in 2013 in portsmouth virginia using the community assessment for public health emergency response casper methodology with 2 stage cluster sampling we randomly selected 210 households for in person interviews households were questioned about emergency planning and supplies information sources during emergencies and chronic health conditions interview teams completed 180 interviews 86 interviews revealed that 70 of households had an emergency evacuation plan 67 had a 3 day supply of water for each member and 77 had a first aid kit most households 65 reported that the television was the primary source of information during an emergency heart disease 54 and obesity 40 were the most frequently reported chronic conditions the virginia department of health identified important gaps in local household preparedness data from the assessment have been used to inform community health partners enhance disaster response planning set community health priorities and influence portsmouth s community health improvement plan in africa studies primarily devoted to chronic leg ulcer due to sickle cell disease are rare the objectives of the study were to determine the epidemiology diagnosis and progression of chronic leg ulcers in sickle cell disease a 5 year multicentre retrospective study was conducted in three university hospitals in dakar we included all patients with chronic leg ulcers occurring in a setting of sickle cell disease we identified 40 cases of chronic leg ulcers associated with sickle cell disease representing 3 4 of the current population of sickle cell patients in our institutions the average patient age was 25 9 years and the sex ratio was 2 33 chronic leg ulcer was the presenting feature enabling diagnosis of sickle cell disease in one third of the cases the average time to consultation from onset was 5 4 years pain was reported in 22 cases 48 ulcers were isolated in 76 and multiple in 24 of cases the most common site was the medial malleolus 39 a cbc allowed identification of anaemia in 35 cases haemoglobin electrophoresis was performed and homozygous sickle cell ss disease was identified in 39 cases and heterozygous sc disease in 1 case local treatments included physiologic serum topical antibiotics and skin grafting systemic treatment included supplementation with folic acid in all patients blood transfusion in 16 cases vasodilators in 11 cases and antibiotics in 25 cases the outcome was favourable in 61 8 of cases in dakar sickle cell disease is a common cause of chronic leg ulcer and is frequently revealed by chronic leg ulcer recent studies have leveraged mhc tetramer and tcr sequencing approaches towards a more precise characterization of the peripheral t cell repertoire providing important insight into both the contribution of self reactive t cells to the overall repertoire and their function the peripheral t cell repertoire of healthy individuals contains a high frequency of diverse self reactive t cells furthermore self reactive t cells can perform essential beneficial physiological functions we review these recent findings here and discuss their implications to the current understanding of peripheral tolerance and the role of self reactive t cells in autoimmune disease we outline gaps in understanding and argue that an important step forward is to revise the definition of self reactive t cells to incorporate new concepts regarding the nature and physiological functions of different populations of t cells capable of recognizing self antigens most west nile virus wnv infections are asymptomatic but some lead to neuroinvasive disease with symptoms ranging from disorientation to paralysis and death evidence from animal models suggests that neuroinvasive infections may arise as a consequence of impaired immune protection however other data suggest that neurologic symptoms may arise as a consequence of immune mediated damage we demonstrate that elevated immune responses are present in neuroinvasive disease by directly characterizing wnv specific t cells in subjects with laboratory documented infections using human histocompatibility leukocyte antigen hla class ii tetramers subjects with neuroinvasive infections had higher overall numbers of wnv specific t cells than those with asymptomatic infections independent of this we also observed age related increases in wnv specific t cell responses further analysis revealed that wnv specific t cell responses included a population of atypically polarized cxcr3 ccr4 ccr6 t cells whose presence was highly correlated with neuroinvasive disease moreover a higher proportion of wnv specific t cells in these subjects co produced interferon \u03b3 and interleukin 4 than those from asymptomatic subjects more globally subjects with neuroinvasive infections had reduced numbers of cd4 foxp3 tregs that were ctla4 positive and exhibited a distinct upregulated transcript profile that was absent in subjects with asymptomatic infections thus subjects with neuroinvasive wnv infections exhibited elevated dysregulated and atypically polarized responses suggesting that immune mediated damage may indeed contribute to pathogenic outcomes reperfusion after stroke is critical for improved patient survival and recovery and can be achieved clinically through pharmacological recombinant tissue plasminogen activator or physical endovascular intervention means yet these approaches remain confined to a small percentage of stroke patients often with incomplete reperfusion and therefore there is an urgent need to learn more about the mechanisms underlying the no reflow phenomenon that prevents restoration of adequate microvascular perfusion recent evidence suggests systemic inflammation as an important contributor to no reflow and to further investigate this here we inject interleukin 1 il 1 i p 30 min prior to an ischaemic challenge using a remote filament to occlude the middle cerebral artery mca in mice before during and after the injection of il 1 and occlusion we use two dimensional optical imaging spectroscopy to record the spatial and temporal dynamics of oxyhaemoglobin concentration in the cortical areas supplied by the mca our results reveal that systemic inflammation significantly reduces oxyhaemoglobin reperfusion as early as 3h after filament removal compared to vehicle injected animals cd41 immunohistochemistry shows a significant increase of hyper coagulated platelets within the microvessels in the stroked cortex of the il 1 group compared to vehicle we also observed an increase of pathophysiological biomarkers of ischaemic damage including elevated microglial activation co localized with interleukin 1\u03b1 il 1\u03b1 increased blood brain barrier breakdown as shown by igg infiltration and increased pyknotic morphological changes of cresyl violet stained neurons these data confirm systemic inflammation as an underlying cause of no reflow in the post ischaemic brain and that appropriate anti inflammatory approaches could be beneficial in treating ischaemic stroke central nervous system cns regeneration is restricted by both the lack of neurotrophic responses and the presence of inhibitory factors as of yet a common mediator of these two pathways has not been identified microtubule dynamics is responsible for several key processes after cns injuries intracellular trafficking of receptors for neurotrophic factors axonal retraction by inhibitory factors and secondary tissue damages by inflammation and scarring kinases regulating microtubule organization such as cdk5 or gsk3\u03b2 may play pivotal roles during cns recovery but the molecular mechanisms remain to be elucidated collapsin response mediator protein 2 crmp2 stabilizes cytoskeletal polymerization while crmp2 phosphorylation by cdk5 and gsk3\u03b2 loses its affinity for cytoskeleton proteins leading to the inhibition of axonal growth here we characterized crmp2 phosphorylation as the first crucial factor regulating neurotrophic and inhibitory responses after spinal cord injury sci we found that pharmacological inhibition of gsk3\u03b2 enhanced brain derived neurotrophic factor bdnf induced axonal growth response in cultured dorsal root ganglion drg neurons drg neurons from crmp2 knock in crmp2ki ki mice where crmp2 phosphorylation was eliminated showed elevated sensitivity to bdnf as well additionally cultured crmp2ki ki neurons exhibited suppressed axonal growth inhibition by chondroitin sulfate proteoglycan cspg these data suggest a couple of new molecular insights the bdnf gsk3\u03b2 crmp2 and cspg gsk3\u03b2 crmp2 pathways next we tested the significance of crmp2 phosphorylation after cns injury in vivo the phosphorylation level of crmp2 was enhanced in the injured spinal cord crmp2ki ki mice exhibited prominent recovery of locomotive and nociceptive functions after sci which correlated with the enhanced axonal growth of the motor and sensory neurons neuroprotective effects against sci such as microtubule stabilization reduced inflammation and suppressed scarring were also observed by inhibiting crmp2 phosphorylation therefore inhibition of crmp2 phosphorylation demonstrates the unique potential to repair sci by both enhancing sensitivity to bdnf and reducing inhibitory responses plasmablastic lymphoma pbl is an aggressive variant of diffuse large b cell lymphoma we sought to assess the treatment outcomes after combined modality therapy for early stage pbl we retrospectively reviewed the outcomes of 10 consecutive patients diagnosed with stage i ii pbl from february 2001 to december 2013 at a single institution the baseline clinical characteristics treatment modalities overall outcomes and treatment related toxicity were assessed the median age at diagnosis was 50 5 years all patients had extranodal disease 2 were positive for human immunodeficiency virus seven patients received hyper cvad cyclophosphamide vincristine doxorubicin dexamethasone based chemotherapy 2 received chop cyclophosphamide doxorubicin vincristine prednisone and 1 received dose adjusted epoch etoposide prednisone vincristine cyclophosphamide doxorubicin radiotherapy rt was administered after a complete response to chemotherapy in 7 patients and a partial response in 1 patient at a median follow up period of 42 months the estimated 2 year progression free and overall survival rates were 90 and 100 respectively pbl can be successfully treated with aggressive chemotherapy followed by rt the treatment was well tolerated and can result in long term survival for patients with limited stage disease the present study evaluated the pharmacokinetics and safety of elotuzumab a humanized igg1 monoclonal antibody against signaling lymphocyte activation molecule f7 combined with lenalidomide and dexamethasone in patients with multiple myeloma mm and renal impairment patients with mm and normal renal function nrf creatinine clearance crcl 90 ml min severe renal impairment sri crcl 30 ml min not requiring dialysis or end stage renal disease esrd requiring dialysis were enrolled in this open label phase ib study elotuzumab 10 mg kg lenalidomide 5 25 mg and dexamethasone 40 mg were administered in 28 day cycles until disease progression or unacceptable toxicity developed the primary endpoint was single dose elotuzumab pharmacokinetics a total of 26 patients median age 63 years were treated nrf n 8 sri n 9 esrd n 9 the median baseline crcl was 105 ml min range 84 146 ml min for those with nrf and 26 ml min range 15 33 ml min for those with sri twenty three patients 89 had received previous therapy median 2 regimens range 1 7 treatment was discontinued in 6 patients with nrf 4 with sri and 5 with esrd primarily because of disease progression the mean elotuzumab serum concentrations were comparable across groups n 23 no statistically significant differences were observed in the maximum observed serum concentration area under the concentration time curve from time 0 to the last quantifiable serum concentration or area under the concentration time curve from time 0 to infinity when the sri and esrd groups were compared with the nrf group p 05 all patients had 1 adverse event ae of the 8 patients with nrf 9 with sri and 9 with esrd 7 8 and 7 experienced grade 3 to 4 aes the overall response rates were 75 in the nrf 67 in the sri and 56 in the esrd groups the results of the present study support the use of elotuzumab for the treatment of patients with mm and renal dysfunction without dose adjustment alcoholism is one of the most devastating diseases with high incidence but knowledge of its pathology and treatment is still plagued with gaps mostly because of the inherent limitations of research with patients we developed an animal model for studying liver histopathology hsp heat shock protein chaperones involvement and response to treatment the system was standardized using mice to which ethanol was orally administered alone or in combination with lactobacillus fermentum following a precise schedule over time and applying at predetermined intervals a battery of techniques histology immunohistochemistry western blotting real time pcr immunoprecipitation 3 nitrotyrosine labeling to assess liver pathology e g steatosis fibrosis and hsp60 and inos inducible form of nitric oxide synthase gene expression and protein levels and post translational modifications typical ethanol induced liver pathology occurred and the effect of the probiotic could be reliably monitored steatosis score inos levels and nitrated proteins e g hsp60 decreased after probiotic intake we describe a mouse model useful for studying liver disease induced by chronic ethanol intake and for testing pertinent therapeutic agents e g probiotics we tested l fermentum which reduced considerably ethanol induced tissue damage and deleterious post translational modifications of the chaperone hsp60 the model is available to test other agents and probiotics with therapeutic potential in alcoholic liver disease given the growing use and great potential of mobile apps this project aimed to develop and implement a user friendly app to increase laypeople s knowledge and awareness of invasive pneumococcal disease ipd despite the heavy burden of ipd the documented low awareness of ipd among both laypeople and healthcare professionals and far from optimal pneumococcal vaccination coverage no app specifically targeting ipd has been developed so far the app was designed to be maximally functional and conceived in accordance with user centered design its content layout and usability were discussed and formally tested during several workshops that involved the principal stakeholders including experts in ipd and information technology and potential end users following several workshops it was decided that in order to make the app more interactive its core should be a personal checker of the risk of contracting ipd and a user friendly risk communication strategy the checker was populated with risk factors identified through both italian and international official guidelines formal evaluation of the app revealed its good readability and usability properties a sister web site with the same content was created to achieve higher population exposure seven months after being launched in a price and registration free modality the app named pneumo rischio averaged 20 9 new users day and 1 3 sessions user the first in field results suggest that pneumo rischio is a promising tool for increasing the population s awareness of ipd and its prevention through a user friendly risk checker universal screening of children for dyslipidemia and other cardiovascular risk factors has been recommended given the clustering of cardiovascular risk factors within families one benefit of screening adolescents may be to identify at risk families in which adult members might also be at elevated risk and potentially benefit from medical evaluation cross sectional study of grade 9 students evaluating adiposity lipids and blood pressure data collected by heart niagara inc through the healthy heart schools program parents completed questionnaires evaluating family history of dyslipidemia hypertension diabetes and early cardiovascular disease events in parents and siblings first degree relatives and grandparents second degree relatives associations between positive risk factor findings in adolescents and presence of a positive family history were assessed in logistic regression models n 4014 adolescents ages 14 15 years were screened 3467 86 provided family medical history amongst adolescents 4 7 had dyslipidemia 9 5 had obesity and 3 5 had elevated blood pressure central adiposity waist to height ratio \u22650 5 in the adolescent was associated with increased odds of diabetes in first or 2 0 1 6 2 6 p 0 001 and second degree relatives or 1 3 1 1 1 6 p 0 002 dyslipidemia was associated with increased odds of diabetes or 1 6 1 1 2 3 p 0 001 hypertension or 2 2 1 5 3 2 p 0 001 and dyslipidemia or 2 2 1 5 3 2 p 0 001 in first degree relatives elevated blood pressure did not identify increased odds of a positive family history presence of obesity and or dyslipidemia in adolescents identified through a universal school based screening program is associated with risk factor clustering within families universal pediatric cardiometabolic screening may be an effective entry into reverse cascade screening mutations in the fused in sarcoma fus gene have been linked to amyotrophic lateral sclerosis als als patients with fus mutations exhibit neuronal cytoplasmic mislocalization of the mutant fus protein als patients fibroblasts or induced pluripotent stem cell ipsc derived neurons have been developed as models for understanding als associated fus als fus pathology however pathological neuronal signatures are not sufficiently present in the fibroblasts of patients whereas the generation of ipsc derived neurons from als patients requires relatively intricate procedures here we report the generation of disease specific induced neurons ineurons from the fibroblasts of patients who carry three different fus mutations that were recently identified by direct sequencing and multi gene panel analysis the mutations are located at the c terminal nuclear localization signal nls region of the protein p g504wfs 12 p r495 p q519e two de novo mutations in sporadic als and one in familial als case aberrant cytoplasmic mislocalization with nuclear clearance was detected in all patient derived ineurons and oxidative stress further induced the accumulation of cytoplasmic fus in cytoplasmic granules thereby recapitulating neuronal pathological features identified in mutant fus p g504wfs 12 autopsied als patient importantly such fus pathological hallmarks of the patient with the p q519e mutation were only detected in patient derived ineurons which contrasts to predominant fus p q519e in the nucleus of both the transfected cells and patient derived fibroblasts thus ineurons may provide a more reliable model for investigating fus mutations with disrupted nls for understanding fus associated proteinopathies in als the aim of this study was to evaluate the outcomes of loco regional hyperthermia ht with radiotherapy rt and or chemotherapy ct in elderly patients with muscle invasive bladder cancers mibc twenty consecutive mibc patients were treated with htrt n 8 or htctrt n 12 following transurethral resection of their bladder tumours weekly ht was administered prior to rt to a mean temperature of 40 6 42 7 \xb0c for 60 min a mean rt dose of 54 6 gy sd 4 2 was delivered single agent cisplatin n 2 or carboplatin n 10 was used in htctrt patients the median age was 81 years htrt patients received a mean rt dose of 51 0 gy compared to 57 1 gy with htctrt p 0 001 in a shorter overall treatment time ott 30 8 6 9 versus 43 9 4 0 days p 0 001 all htrt patients had long term local disease control while 41 6 of htctrt recurred during follow up none of the htrt patients experienced grade iii iv acute and late toxicities while these were evident in two and one htctrt patients respectively taken together the 3 year bladder preservation local disease free survival cause specific survival and overall survival were 86 6 60 7 55 and 39 5 respectively even though the mean biological effective dose bed for both groups was similar 57 8 gy15 the thermo radiobiological bed estimated from ht induced reduction of \u03b1 \u03b2 was significantly higher for htrt patients 91 4 4 versus 85 8 4 3 gy3 p 0 018 thermal radiosensitisation with consequent reduction in \u03b1 \u03b2 results in a higher thermo radiobiological bed with a relatively higher rt dose fraction and shorter ott this translates into a favourable outcome in elderly mibc patients any benefit of ct in these patients needs further investigation during pregnancy many patients with rheumatoid arthritis ra experience disease improvement whereas patients with ankylosing spondylitis often suffer from persistent active disease here we investigated whether pregnancy related changes in disease activity were associated with changes in the proportion and function of \u03b3\u03b4t cells the study population comprised 55 patients with ra 31 patients with ankylosing spondylitis and 35 healthy controls among these participants 28 ra patients 21 ankylosing spondylitis patients and 23 healthy controls were investigated once before conception when possible at each trimester of pregnancy and at 8 weeks postpartum data were compared with age matched non pregnant patients to obtain disease related background in all subjects peripheral v\u03b41 and v\u03b42 t cells were analyzed for cell frequencies the activation marker cd69 the cytotoxicity markers nkg2d and nkg2a and the intracellular cytokines tumor necrosis factor tnf \u03b1 interferon ifn \u03b3 interleukin il 17 and il 10 pregnant patients showed a decreased v\u03b42 v\u03b41 ratio in the third trimester which resulted from a slightly reduced proportion of v\u03b42 cells changes in ra disease activity during pregnancy and postpartum were not associated with numerical proportions of \u03b3\u03b4t cells but with changes of the cell activation marker cd69 on v\u03b41 and v\u03b42 cells only ra patients showed reduced proportions of tnf\u03b1 positive v\u03b41and v\u03b42 cells and ifn\u03b3 positive v\u03b42 cells at the third trimester of pregnancy a finding that was not apparent in the entire population of cd3 t cells the proportions of il 17 positive \u03b3\u03b4t cells and il 10 positive \u03b3\u03b4t cells did not differ between pregnant and non pregnant women of the different groups changes of disease activity in pregnant ra patients were associated with functional changes in both \u03b3\u03b4t cell subsets this reduced pro inflammatory profile of \u03b3\u03b4t cells might contribute to the immunomodulation resulting in pregnancy induced improvement of ra a novel strip array was developed for a nine spacer spoligotyping scheme of mycobacterium tuberculosis complex mtbc the new method was evaluated using 211 mtbc isolates and the results were fully concordant with the traditional spoligotyping approach the strip array proved to be rapid and convenient for spoligotyping of mtbc elicitation of e grandis plants with streptomyces pm9 reduced the gray mold disease through increasing the levels of enzymes directly related to the induction of plant defense responses and accumulation of specific phenolic compounds members of eucalyptus are economically important woody species especially as a raw material in many industrial sectors species of this genus are susceptible to pathogens such as botrytis cinerea gray mold biological control of plant diseases using rhizobacteria is one alternative to reduce the use of pesticides and pathogen attack this study evaluated the metabolic and phenotypic responses of eucalyptus grandis and e globulus plants treated with streptomyces sp pm9 and challenged with the pathogenic fungus b cinerea metabolic responses were evaluated by assessing the activities of the enzymes polyphenol oxidase and peroxidase as well as the levels of phenolic compounds and flavonoids the incidence and progression of the fungal disease in pm9 treated plants and challenged with b cinerea were evaluated treatment with streptomyces sp pm9 and challenge with b cinerea led to changes in the activities of polyphenol oxidase and peroxidase as well as in the levels of phenolic compounds in the plants at different time points alterations in enzymes of pm9 treated plants were related to early defense responses in e grandis gallic and chlorogenic acids were on average more abundant although caffeic acid benzoic acid and catechin were induced at specific time points during the culture period treatment with streptomyces sp pm9 significantly delayed the establishment of gray mold in e grandis plants these results demonstrate the action of streptomyces sp pm9 in inducing plant responses against b cinerea making this organism a potential candidate for biological control in eucalyptus mitochondrial dysfunction in kidney cells has been implicated in the pathogenesis of ckd mitochondrial dna mtdna copy number is a surrogate measure of mitochondrial function and higher mtdna copy number in peripheral blood has been associated with lower risk of two important risk factors for ckd progression diabetes and microalbuminuria we evaluated whether mtdna copy number in peripheral blood associates with incident ckd in a population based cohort of middle aged adults we estimated mtdna copy number using 25 high quality mitochondrial single nucleotide polymorphisms from the affymetrix 6 0 array among 9058 participants those with higher mtdna copy number had a lower rate of prevalent diabetes and lower c reactive protein levels and white blood cell counts baseline egfr did not differ significantly by mtdna copy number over a median follow up of 19 6 years 1490 participants developed ckd higher mtdna copy number associated with lower risk of incident ckd highest versus lowest quartile hazard ratio 0 65 95 confidence interval 0 56 to 0 75 p 0 001 after adjusting for age sex and race after adjusting for additional risk factors of ckd including prevalent diabetes hypertension c reactive protein level and white blood cell count this association remained significant highest versus lowest quartile hazard ratio 0 75 95 confidence interval 0 64 to 0 87 p 0 001 in conclusion higher mtdna copy number associated with lower incidence of ckd independent of traditional risk factors and inflammation biomarker levels in this cohort further research on modifiable factors influencing mtdna copy number may lead to improvement in the prevention and treatment of ckd a fucoidan sargassum fusiforme polysaccharide 65 sfps65 a was isolated from a brown alga s fusiforme sfps65a had an estimated molecular weight of 90kda and showed \u03b1d 20 74 3288 c 0 05 h2o sfps65a is composed of fucose galactose xylose glucose glucuronic acid and mannose in the ratio of 19 23 9 58 6 64 1 6 52 2 57 the structural features of sfps65a were investigated using composition analysis methylation analysis infrared spectrum nuclear magnetic resonance spectroscopy and electrospray ionization quadruple time of flight tandem mass spectroscopy results showed that sfps65a has a main chain composed of \u21923 \u03b2 l fucp 1 \u21923 4 \u03b2 l fucp 1 \u21923 4 \u03b2 l fucp 1 and connected with \u21923 4 \u03b1 d glcap 1 \u2192, \u21924 \u03b2 d xylp 1 \u2192, \u21924 \u03b1 d galp 1 \u2192, \u21923 6 \u03b1 d manp 1 alternately the branches at o 3 of the fucosyl residue and o 3 of the hexosyl residues may include sulfate \u21924 \u03b2 l fucp 1 \u2192, \u03b2 d xylp 1 \u2192, and \u03b2 d xylp 1 \u2192. sfps65a exhibited an activity on alzheimer s disease in vivo in the pharmacological experiments by increasing the cognitive abilities of scopolamine ethanol and sodium nitrite treated mice against memory deficits currently we still lack effective measures to modify disease progression in neurodegenerative diseases iron containing proteins play an essential role in many fundamental biological processes in the central nervous system in addition iron is a redox active ion and can induce oxidative stress in the cell although the causes and pathology hallmarks of different neurodegenerative diseases vary iron dyshomeostasis oxidative stress and mitochondrial injury constitute a common pathway to cell death in several neurodegenerative diseases mri is capable of depicting iron content in the brain and serves as a potential biomarker for early and differential diagnosis tracking disease progression and evaluating the effectiveness of neuroprotective therapy iron chelators have shown their efficacy against neurodegeneration in a series of animal models and been applied in several clinical trials in this review we summarize recent developments on iron dyshomeostasis in parkinson s disease alzheimer s disease friedreich ataxia and huntington s disease non clear cell renal cell carcinomas are histologically and genetically diverse kidney cancers with variable prognoses and their optimum initial treatment is unknown we aimed to compare the mtor inhibitor everolimus and the vegf receptor inhibitor sunitinib in patients with non clear cell renal cell carcinoma we enrolled patients with metastatic papillary chromophobe or unclassified non clear cell renal cell carcinoma with no history of previous systemic treatment patients were randomly assigned 1 1 to receive everolimus 10 mg day or sunitinib 50 mg day 6 week cycles of 4 weeks with treatment followed by 2 weeks without treatment administered orally until disease progression or unacceptable toxicity randomisation was stratified by memorial sloan kettering cancer center risk group and papillary histology the primary endpoint was progression free survival in the intention to treat population using the recist 1 1 criteria safety was assessed in all patients who were randomly assigned to treatment this study is registered with clinicaltrials gov number nct01108445 between sept 23 2010 and oct 28 2013 108 patients were randomly assigned to receive either sunitinib n 51 or everolimus n 57 as of december 2014 87 progression free survival events had occurred with two remaining active patients and the trial was closed for the primary analysis sunitinib significantly increased progression free survival compared with everolimus 8 \xb73 months 80 ci 5 \xb78 11 \xb74 vs 5 \xb76 months 5 \xb75 6 \xb70 hazard ratio 1 \xb741 80 ci 1 \xb703 1 \xb792 p 0 \xb716 although heterogeneity of the treatment effect was noted on the basis of histological subtypes and prognostic risk groups no unexpected toxic effects were reported and the most common grade 3 4 adverse events were hypertension 12 24 of 51 patients in the sunitinib group vs one 2 of 57 patients in the everolimus group infection six 12 vs four 7 diarrhoea five 10 vs one 2 pneumonitis none vs five 9 stomatitis none vs five 9 and hand foot syndrome four 8 vs none in patients with metastatic non clear cell renal cell carcinoma sunitinib improved progression free survival compared with everolimus future trials of novel agents should account for heterogeneity in disease outcomes based on genetic histological and prognostic factors novartis and pfizer bilateral internal mammary artery bima grafting is associated with improved survival however many surgeons are reluctant to use this technique owing to the potentially increased risk of sternal infection the composite t graft with radial artery ra attached end to side to the left internal mammary artery ima provides complete arterial revascularization without increased risk of sternal infection the purpose of this study is to compare outcomes of these 2 strategies patients who underwent bima grafting using the composite t graft technique between 1996 and 2010 n 1329 were compared with 389 patients who underwent composite grafting with a single ima ra during the same time period patients undergoing single ima grafting were older more often women and more likely to have diabetes peripheral vascular disease and copd and to need an emergency operation congestive heart failure left main disease and recent myocardial infarction were more prevalent with bilateral grafting propensity score matching was used to account for differences between groups in preoperative patient characteristics the 268 matched pairs had similar characteristics the median follow up time was 14 19 95 confidence interval 13 43 14 95 years operative mortality and kaplan meier 10 year survival of the 2 matched groups were similar 3 4 vs 3 7 and 61 6 vs 64 for the groups treated with bima and single ima respectively cox adjusted survival was similar p 514 age chronic renal failure and performance of 3 bypass grafts were independent predictors of decreased survival this study suggests that long term outcomes of arterial revascularization with a composite t graft constructed using left ima and ra are not inferior to outcomes after bima grafting cd48 a member of the signaling lymphocyte activation molecule family participates in adhesion and activation of immune cells although constitutively expressed on most hematopoietic cells cd48 is upregulated on subsets of activated cells cd48 can have activating roles on t cells antigen presenting cells and granulocytes by binding to cd2 or bacterial fimh and through cell intrinsic effects interactions between cd48 and its high affinity ligand cd244 are more complex with both stimulatory and inhibitory outcomes cd244 cd48 interactions regulate target cell lysis by nk cells and ctls which are important for viral clearance and regulation of effector memory t cell generation and survival here we review roles of cd48 in infection tolerance autoimmunity and allergy as well as the tools used to investigate this receptor we discuss stimulatory and regulatory roles for cd48 its potential as a therapeutic target in human disease and current challenges to investigation of this immunoregulatory receptor we set out to present the late 3 year performance of total endovascular treatment of juxtarenal aortic aneurysms in octogenarians by the chimney snorkel technique at one center between january 2009 and december 2014 chimney snorkel technique endovascular aortic aneurysm repair was performed in 35 high risk unfit for open repair octogenarian patients with juxtarenal aortic aneurysms twenty five patients were asymptomatic 71 4 and 10 patients were treated in an urgent care setting the median follow up was 36 months range 1 69 the primary endpoint was the survival rate technical success was 100 a single chimney graft placement was performed in 22 patients 62 9 double chimneys in 10 patients 28 6 and triple chimneys were performed in 3 8 5 patients overall 51 renovisceral vessels 22 right renal arteries 23 left renal arteries and 6 superior mesenteric arteries were involved the thirty day mortality rate was 2 9 n 1 early morbidity was 14 3 predominantly due to access related complications major adverse events were observed in 5 7 n 2 of the present cohort no early reinterventions for endoleaks were registered the midterm reintervention rate was 12 1 due to type ib endoleak n 1 type ii endoleak n 1 and high grade chimney graft stenosis n 2 estimated survival was 91 9 at 1 year and 72 8 at 3 years freedom from reintervention at 1 and 3 years was 94 and 91 respectively juxtarenal aortic aneurysm treatment with chimney snorkel technique endovascular aortic aneurysm repair in octogenarians is associated with low perioperative mortality and morbidity as well as acceptable midterm survival and secondary procedures data from clinical trials suggest that changes in the glucose avidity of the primary site of lung cancer during induction therapy measured by changes in 18 f fluorodeoxyglucose positron emission tomography correlate with tumor response little information about the utility of changes in positron emission tomography imaging of involved lymph nodes during induction chemotherapy is available the utility of positron emission tomography imaging of either the primary site or nodal metastases obtained during routine clinical care outside of a clinical trial setting to predict response has also not been examined a retrospective review of all surgical patients with non small cell lung cancer at a single institution imaged between 2000 and 2006 with 18 f fluorodeoxyglucose positron emission tomography before or after induction therapy was performed an increase in standardized uptake value in the primary site of disease during induction therapy was associated with reduced overall survival after resection neither pretreatment standardized uptake value nor percentage change in the primary site was associated with overall survival after resection a decrease in standardized uptake value of greater than 60 in the involved n2 mediastinal nodes was the best predictor of overall survival better than changes seen in the primary site of disease an increase in glucose avidity of non small cell lung cancers during induction therapy was associated with a worse prognosis compared with stable or any decrease in standardized uptake value changes in the glucose avidity of mediastinal nodal metastases may be a stronger predictor of survival than changes in the primary site of disease coronary artery disease cad among patients with diabetes and chronic kidney disease ckd is not well studied and the best treatment for this condition is not established our aim was to compare three therapeutic strategies for cad in diabetic patients stratified by renal function patients with multivessel cad that underwent coronary artery bypass graft cabg angioplasty percutaneous coronary intervention pci or medical therapy alone mt were included data were analyzed according to glomerular filtration rate in three strata normal 90 ml min mild ckd 60 to 89 ml min and moderate ckd 30 to 59 ml min end points comprised overall rate of mortality acute myocardial infarction and need for additional revascularization among patients with normal renal function n 270 122 underwent cabg 72 pci and 76 mt among patients with mild ckd n 367 167 underwent cabg 92 pci and 108 mt and among patients with moderate ckd n 126 46 underwent cabg 40 pci and 40 mt event free survival was 80 4 75 7 67 5 for strata 1 2 and 3 respectively p 0 037 survival rates among patients with no mild and moderate ckd are 91 1 89 6 and 76 2 respectively p 0 001 hazard ratio 0 69 95 confidence interval 0 51 to 0 95 p 0 024 for stratum 1 versus 3 we found no differences for overall number of deaths or acute myocardial infarctions irrespective of strata the need of new revascularization was different in all strata favoring cabg p 0 001 p 0 001 and p 0 029 for no mild and moderate ckd respectively mortality rates were higher in patients with mild and moderate ckd higher event free survival was observed in the cabg group among patients with no and mild ckd besides cabg was associated with less need for new revascularization compared with pci and mt in all renal function strata this trial was registered at http www controlled trials com as isrctn66068876 programmed death ligand 1 pd l1 has been reported to be expressed in various malignancies and is considered to be a prognostic factor and an immunotherapeutic target the aim of this study was to characterize pd l1 expression in thymoma and determine statistical associations between this expression and clinical features we reviewed formalin fixed paraffin embedded tissue specimens from 82 thymoma cases accumulated at kurume university the majority of which achieved surgical complete resection expression of pd l1 was evaluated by immunohistochemistry statistical associations between pd l1 expression and clinicopathologic features were evaluated by using \u03c7 2 test and fisher s exact test disease free survival and overall survival curves were established by the kaplan meier method and compared using a log rank test predictive factors for disease free survival after complete resection were analyzed by using a cox proportional hazards model in univariate and multivariate analysis overall 44 thymoma cases 54 revealed high pd l1 expression high pd l1 expression was statistically associated with masaoka stage iii iv disease p 0 043 and world health organization type b2 or b3 thymoma p 0 044 disease free survival after complete resection in high pd l1 expression was significantly worse than that in low pd l1 expression p 0 021 although there was no significant difference in overall survival p 0 957 multivariate analysis also revealed high pd l1 expression as an independent risk factor for recurrence p 0 008 characterization of pd l1 expression in thymoma should enable more effective clinical approaches including prognostic stratification of patients and potential use of anti pd l1 antibody immunotherapy the indication for limited resection of radiologically pure solid non small cell lung cancer nsclc is controversial owing to its invasive pathologic characteristics this study was performed to compare the outcomes after lobectomy and segmentectomy in these nsclc patients we retrospectively reviewed 251 patients with radiologically pure solid ct1a n0 m0 nsclc who underwent lobectomy or segmentectomy and the preoperative characteristics of the patients treated with the two operative techniques were matched using propensity score methods overall survival os and disease free survival dfs curves were compared using the log rank test and differences in survival were also evaluated by the mcnemar test the preoperative factors and surgical procedure were analyzed with the multivariate cox proportional hazards regression model to identify independent predictors of poor os and dfs in the propensity score matched lobectomy and segmentectomy groups 87 patients per group the 5 year and 10 year os rates were 85 versus 84 and 66 versus 63 respectively and the 5 year and 10 year dfs rates were 80 versus 77 and 64 versus 58 respectively there were no significant differences between the two groups in os or dfs by the log rank test and also no significant differences in 3 year 5 year or 7 year os or dfs by the mcnemar test although age smoking status pulmonary function and carcinoembryonic antigen were identified as significant predictors of both os and dfs the surgical procedure was not identified similar oncologic outcomes after lobectomy and segmentectomy were indicated among patients with radiologically pure solid small sized nsclc it is unclear whether three dimensional 3d video assisted thoracic surgery vats pulmonary resections are comparable to two dimensional 2d vats pulmonary resections in patients with potentially operable benign pulmonary diseases we analyzed the clinical data of patients who underwent 2d and 3d vats pulmonary resections for benign diseases in our hospital from november 2013 to august 2014 perioperative factors estimated blood loss and operative time and postoperative factors postoperative hospital length of stay postoperative complications and duration of chest tube drainage were evaluated vats was performed in 278 patients during the 10 month study period the 2d vats system was used in 142 patients 51 08 and the 3d vats system was used in 136 48 92 operative time was significantly different between the two groups p 0 007 however no significant differences were found in estimated blood loss p 0 75 chest drainage tube placement time p 0 852 rate of postoperative complications p 0 566 or postoperative hospital length of stay p 0 951 the use of 3d vats appears to facilitate precise execution of surgical techniques in specific operative tasks and as a result reduces lung resection performance time in patients with benign pulmonary diseases careful patient selection is the prerequisite to raise transplant benefit in lung transplant lt candidates the effect of body mass index bmi on postoperative outcome remains controversial possibly due to the inaccuracy of bmi in discriminating between fat and muscle mass we therefore hypothesized that assessment of body composition by muscle mass measures is more accurate than by bmi regarding postoperative outcome all lt recipients from 2011 to 2014 were included and retrospectively analyzed lean psoas area lpa was assessed from pretransplant computed tomography scans and associations with postoperative outcomes were investigated included were 103 consecutive lt recipients with a mean pre lt bmi of 22 0 4 0 kg m 2 and a mean lpa of 22 3 8 3 cm 2 lpa was inversely associated with length of mechanical ventilation p 0 03 requirement of tracheostomy p 0 035 and length of stay in the intensive care unit p 0 02 while controlling for underlying disease bmi sex age and procedure in contrast bmi was not p 0 25 p 0 54 and p 0 42 respectively multiple regression analysis revealed that the 6 minute walk distance at the end of pulmonary rehabilitation was significantly associated with lpa p 0 02 lpa can easily be assessed in lt candidates as part of pretransplant evaluation and was significantly associated with short term outcome whereas bmi was not assessment of lpa may provide additional information on body composition beyond bmi however the clinical utility has to be further evaluated this study evaluated preoperative predictors of in hospital death for the surgical treatment of patients with acute type a aortic dissection type a and created an easy to use scorecard to predict in hospital death we reviewed retrospectively all consecutive patients who underwent operations for acute type a between 1996 and 2011 at 2 tertiary care institutions a logistic regression model was created to identify independent preoperative predictors of in hospital death the results were used to create a scorecard predicting operative risk emergency operations were performed in 534 consecutive patients for acute type a mean age was 61 14 years and 36 3 were women critical preoperative state was present in 31 of patients and malperfusion of one or more end organs in 36 unadjusted in hospital mortality was 18 7 and not significantly different between institutions independent predictors of in hospital death were age 50 to 70 years odds ratio or 3 8 p 0 001 age older than 70 years or 2 8 p 0 03 critical preoperative state or 3 2 p 0 001 visceral malperfusion or 3 0 p 0 003 and coronary artery disease or 2 2 p 0 006 age younger than 50 years or 0 3 p 0 01 was protective for early survival using this information we created an easily usable mortality risk score based on these variables the patients were stratified into four risk categories predicting in hospital death less than 10 10 to 25 25 to 50 and more than 50 this represents one of the largest series of patients with type a in which a risk model was created using our approach we have shown that age critical preoperative state and malperfusion syndrome were strong independent risk factors for early death and could be used for the preoperative risk assessment to study the performance of the chimney technique in the treatment of aortic arch pathologic conditions we retrospectively evaluated the clinical and procedural outcome data of patients undergoing endovascular treatment in the aortic arch by use of the chimney technique at four european centers between june 2002 and december 2014 the primary endpoint was technical success the secondary endpoints were type i endoleak 30 day mortality stroke primary patency of the chimney graft and freedom from reintervention ninety five patients were included in the study the underlying pathologic conditions were degenerative aneurysm n 45 47 4 type b aortic dissection n 30 31 6 dissecting aneurysm n 6 6 5 penetrating atherosclerotic ulcer n 5 5 3 type i endoleak after previous thoracic endovascular aortic repair n 6 6 3 and aortic embolic disease n 3 3 2 twenty one patients 22 underwent arch branch debranching before chimney graft implantation the majority of patients were treated electively n 49 51 6 forty six patients 48 4 underwent urgent placement of chimney grafts because of their symptoms n 25 or rupture n 21 technical success was 89 5 the 30 day mortality was 9 5 9 patients no aorta related death was observed a type ia endoleak occurred in 10 patients 10 5 intraoperatively resolving spontaneously within the first 30 days in 50 of these cases major stroke was diagnosed in 2 patients 2 primary patency of the chimney grafts was 98 and 5 patients 5 2 required a reintervention the chimney technique in the aortic arch proved highly and predictably successful with a low rate of reinterventions the purpose of this systematic review and meta analysis was to compare the prognosis of patients with p16 expressing oropharyngeal squamous cell cancers to patients with p16 non expressing cancers clinical outcomes that were evaluated included overall survival local recurrence disease free survival disease specific survival and event free survival the following electronic databases were searched cochrane library medline via pubmed and web of science publications were restricted to english language studies were limited to controlled clinical trials on the survival rates of patients with oropharyngeal tumors that were p16 expressing compared to patients with p16 non expressing tumors and at least one clinical endpoint reported by trial authors hazard ratios specific ascertainment criteria were applied for inclusion and exclusion of eligible studies data was independently extracted in duplicate this systematic review adhered to the preferred reporting items for systematic reviews and meta analysis prisma checklist risk of bias was assessed for all included studies and disagreements between review authors were discussed until an agreement was reached eighteen studies were included for final review and meta analysis the subgroup meta analyses which included survival and recurrence data showed significantly favorable outcomes for patients with p16 expressing tumors there is strong evidence to support that patients with p16 expressing oropharyngeal squamous cell cancers have favorable clinical outcomes and prognosis despite several randomized trials the optimal chemotherapy paradigm for locally advanced oropharyngeal carcinoma opscc is controversial this population based analysis assessed the overall survival os benefit of induction chemotherapy ic for patients with stage iii ivb opscc patients in the national cancer database with stage iii iva b opscc treated with curative dose radiotherapy and ic or concurrent chemotherapy crt between 2003 and 2011 were eligible the primary outcome was os and secondary endpoints included os for high risk t4 and or n3 disease and human papillomavirus hpv subsets of the 14 856 analyzed patients 78 and 22 received crt and ic respectively with a median follow up for surviving patients of 44 months the 5 year os probability for the entire cohort was 66 66 crt vs 64 ic p 0 022 multivariable survival analysis showed no significant difference between crt and ic hazard ratio hr 0 95 for ic p 0 255 and sensitivity analyses to adjust for immortal time bias brought the hr to 1 0 p 0 859 there was also no os difference for high risk patients there was a trend in favor of crt for hpv positive opscc hr 1 63 with ic p 0 064 with a significant os benefit for hpv negative high risk opscc hr 0 63 p 0 048 for the vast majority of patients including hpv positive individuals there was no difference in os with ic arguing for crt to remain as the standard therapy subset analysis revealed a small cohort of aggressive cancer t4 n3 hpv negative which may benefit from from ic although selection bias could not be ruled out micrornas mirnas are critical regulators of gene expression and exert extensive impacts on development physiology and disease of eukaryotes a high degree of parallelism is found in the molecular basis of mirna biogenesis and action in plants and animals recent studies interestingly suggest a potential cross kingdom action of plant derived mirnas through dietary intake in regulating mammalian gene expression although the source and scope of plant mirnas detected in mammalian specimens remain controversial these initial studies inspired us to determine whether plant mirnas can be detected in western human sera and whether these plant mirnas are able to influence gene expression and cellular processes related to human diseases such as cancer here we found that western donor sera contained the plant mirna mir159 whose abundance in the serum was inversely correlated with breast cancer incidence and progression in patients in human sera mir159 was predominantly detected in the extracellular vesicles and was resistant to sodium periodate oxidation suggesting the plant originated 2 o methylation on the 3 terminal ribose in breast cancer cells but not non cancerous mammary epithelial cells a synthetic mimic of mir159 was capable of inhibiting proliferation by targeting tcf7 that encodes a wnt signaling transcription factor leading to a decrease in myc protein levels oral administration of mir159 mimic significantly suppressed the growth of xenograft breast tumors in mice these results demonstrate for the first time that a plant mirna can inhibit cancer growth in mammals the use of cardiac computed tomography ct for quantification of ventricular function is limited by relatively high radiation dose the goal of this study was to describe the radiation exposure and image quality of 70 kvp functional cardiac ct in patients with congenital heart disease chd a retrospective review of 70 kvp ecg gated functional ct scans using tube current modulation was performed in chd patients at a single institution quantitative and qualitative assessed by myocardial segment 1 4 1 optimal image quality was determined per segment image quality was compared between thin 1 5 mm and thick 8 mm reconstructions and by patient age and size scan dlp was used to estimate radiation dose 72 scans were performed during the time of review 7 2013 6 2015 median patient age was 19 5 years 8 0 27 1 and bmi was 20 1 16 6 24 5 kg m 2 median functional scan dlp was 78 8 45 5 98 and unadjusted and adjusted procedural msv were 1 10 0 64 1 37 and 1 13 0 90 1 37 image quality of 1 was achieved in all myocardial segments in 75 of scans patients with a weight \u226575 kg were more likely to have a scan achieve optimal image when using thick reconstructions compared to thin 81 3 vs 43 8 p 0 028 imaging of ventricular function with 70 kvp in chd patients can be done with low radiation doses and provides diagnostic image quality particularly for patients 75 kg in larger patients thicker slice reconstruction improved image quality as an initial step in the development of a local therapeutic to treat osteoarthritis oa a number of agents were tested for their ability to block activation of inflammation through nuclear factor \u03ba light chain enhancer of activated b cells nf \u03bab subchondral bone changes through receptor activator of nuclear factor \u03bab ligand rankl mediated osteoclastogenesis and proteolytic degradation through matrix metalloproteinase mmp 13 activity candidates with low toxicity and predicted efficacy were further examined using either of two widely accepted models of oa joint degeneration in the rat the monoiodoacetic acid mia model or the medial meniscal tear medial collateral ligament tear mmt mclt model potential therapeutics were assessed for their effects on the activation of nuclear factor nf \u03bab rankl mediated osteoclastogenesis and mmp 13 activity in vitro using previously established assays toxicity was measured using hela cells a synovial cell line or primary human chondrocytes drugs predicted to perform well in vivo were tested either systemically or via intraarticular injection in the mia or the mmt mclt model of oa pain behavior was measured by mechanical hyperalgesia using the digital randall selitto test drs or by incapacitance with weight bearing wb joint degeneration was evaluated using micro computed tomography and a comprehensive semiquantitative scoring of cartilage subchondral bone and synovial histopathology several agents were effective both in vitro and in vivo with regard to pain behavior systemically delivered clonidine was superior in treating mia induced changes in wb or drs while systemic clonidine curcumin tacrolimus and fluocinolone were all somewhat effective in modifying mmt mclt induced changes in wb systemic tacrolimus was the most effective in slowing disease progression as measured by histopathology in the mmt mclt model all of the agents that demonstrated highest benefit in vivo excepting clonidine were found to inhibit mmp 13 nf \u03bab and bone matrix remodeling in vitro the mia and mmt mclt models of oa previously shown to possess inflammatory characteristics and to display associated pain behavior were affected to different degrees by the same drugs although no therapeutic was remarkable across all measures the several which showed the most promise in either model merit continued study with alternative dosing and therapeutic strategies light chain deposition disease lcdd is a model of glomerulosclerosis the mature lesion of lcdd mimics nodular glomerulosclerosis in diabetic nephropathy the pathogenetic mechanisms involved are similar in both disorders though the causative factors are entirely different this fact highlights the generic response of the mesangium to varied stimuli in vitro work has provided much insight into the pathogenesis of glomerulosclerosis in lcdd where the mesangium is the main target for initiation and progression of the disease the lack of animal models has prevented the development of further therapeutic approaches to be tested in platforms such as ex vivo and in vivo preparing the way for human studies light chains lcs obtained from the urine of patients with renal biopsy proven lcdd were delivered to glomeruli using ex vivo and in vivo approaches to address whether in vitro information could be validated in vivo selected in vitro studies were conducted to address specific issues dealing with mesangial cell mc differentiation and composition of extracellular matrix to add additional data to the existing vast literature using light electron and scanning microscopy together with immunohistochemistry and ultrastructural immunolabeling mcs incubated in matrigel with lcdd lcs as well as delivery of such lcs by perfusion via renal artery ex vivo and penile dorsal vein in vivo to the kidneys validation of pathogenetic pathways previously suggested in in vitro experiments were tested and confirmed the animal models described in this manuscript provide validation for the in vitro data that have been previously published and expand our appreciation of the important role that caveolin 1 plays in signaling events essential for the downstream sequence of events that eventually leads to the pathological alterations centered in the mesangium characterized by an increase in matrix production and formation of mesangial nodules the same findings observed in renal biopsies of patients with lcdd mesangial expansion with increased matrix were documented in the ex vivo and in vivo platforms in vivo understanding of the pathogenesis of mesangial glomerulosclerosis as accomplished in the reported research is crucial for the design of novel therapeutic approaches to treat a number of glomerulopathies with similar pathogenetic mechanisms inhibiting interactions between glomerulopathic lcs and mcs or interrupting the protein production secretion pathways are potentially effective therapeutic maneuvers the results obtained with caveolin 1 knockout mice emphasized the importance of caveolin 1 in signaling events essential to effect downstream mesangial alterations pinpointing causal genes for spermatogenic failure spf on the y chromosome has been an ever daunting challenge with setbacks during the past decade since complex diseases result from the interaction of multiple genes and also display considerable missing heritability network analysis is more likely to explicate an etiological molecular basis we therefore took a network medicine approach by integrating interactome protein protein interaction ppi and transcriptome data to reconstruct a y centric spf network two sets of seed genes y genes and spf implicated genes sigs were used for network reconstruction since no ppi was observed among y genes we identified their common immediate interactors interestingly 81 n 175 of these interactors not only interacted directly with sigs but also they were enriched for differentially expressed genes 89 6 n 43 the spf network formed mainly by the dys regulated interactors and the two seed gene sets comprised three modules enriched for ribosomal proteins and nuclear receptors for sex hormones ribosomal proteins generally showed significant dys regulation with rpl39l thought to be expressed at the onset of spermatogenesis strongly down regulated this network is the first global ppi network pertaining to severe spf and if experimentally validated on independent data sets can lead to more accurate diagnosis and potential fertility recovery of patients phosphorus is an essential mineral in the regulation of many metabolic processes however is known as alterations in serum phosphate levels compared to the normal range have clinical relevance many studies about phosphorus and cardiovascular risk have shown that high serum phosphate levels are associated with clinical and subclinical cardiovascular disease in ckd and non ckd patients in recent years serum phosphate level within the upper limits of normal range is also identified as a stealthier killer and has emerged as a risk factor of cardiovascular mortality and progression of ckd this mounting evidence suggests the possibility that lowering serum phosphate levels may be a future target of cardiovascular disease management also through the use of early biomarkers of phosphate overload such as fgf23 klotho or the urinary fractional excretion of phosphate the goal must be an early diagnosis and treatment of disordered phosphorus metabolism before end organ damage occurs since the western diet is rich in phosphate a dietary restriction associated with the use of phosphate binders as well as the use of intervention such as calcitriol supplementation certainly will have a positive influence on the phosphate regulatory axis inflammatory myopathies are a heterogeneous group of diseases with unknown etiology characterized by inflammation of the skeletal muscles and proximal muscle weakness dermatomyositis dm is an idiopathic inflammatory myopathy with characteristic cutaneous findings such as heliotrope rash gottron s sign gottron s papules shawl sign and machinist hand amyopathic dermatomyositis adm is a rare but well recognized clinical subtype of dm constituting aproximately 10 20 of patients with this disease it generally manifests only pathognomonic skin findings without clinical and laboratory evidence of muscle involvement in this report we present a rare case of adm associated with interstitial pulmonary disease progressive multifocal leukoencephalopathy is a demyelinating disease of the central nervous system characterized by aggressive deterioration of white matter pathways throughout the subcortical brain parenchyma this disease leads the patient to a total dependence in all activities of daily adls living in few months the literature on rehabilitation of progressive multifocal leukoencephalopathy is scanty and at present it is unknown whether rehabilitation may modify the course of disability in this disease this paper describes the functional course of a patients with progressive multifocal leukoencephalopathy who incurred in a severe functional impairment of adls after an unintentional fall and prolonged bed rest the multidisciplinary in hospital rehabilitation program and integrated homecare approach allowed the patient to improve her functional capacities and go on with living at home psychological disorders are often associated with diseases of the upper digestive tract although emotions can influence gastrointestinal function in healthy individuals psychological setting in upper gastrointestinal patients are unclear we evaluate the psychological alterations prevalence in outpatients submitted to upper endoscopy a total of 130 patients 50 males and 80 females mean age 54 \xb117 years submitted to upper gastrointestinal endoscopy were enrolled over the period may 2009 september 2010 subjects were asked to complete questionnaires before endoscopic examination alexithymia anxiety depression and coping style were assessed using the toronto alexithymia scale spielberger trait anxiety inventory beck depression inventory and coping inventory for stressful situations respectively coping impairment alexithymia anxiety and depression were found respectively in 80 3 25 4 24 6 and 17 2 often in association task oriented emotion oriented and avoidance oriented alterations were found in 41 8 40 and 30 6 respectively no correlations were demonstrated between diagnosis of upper gastrointestinal disease and psychometric results in our study a high prevalence of psychometric alterations in gastrointestinal outpatients was unconnected with endoscopic findings especially considering coping style alterations this aspect should be taken into account in patients management and a long term follow up should clarify a possible role of these factors in patients prognosis and compliance there are several genetic diseases with a wide spectrum of congenital bone stigmata in association to cutaneous and visceral benign and malignant neoplasms gorlin goltz syndrome also named nevoid basal cell carcinoma syndrome is an autosomal dominant systemic disease with almost complete penetrance and high intra familial phenotypic variability caused by germline mutations of the gene ptch1 the syndrome is characterized by unusual skeletal changes and high predisposition to the development of multiple basal cell carcinomas odontogenic keratocysts tumors and other visceral tumors the gorlin syndrome clinically defined as distinct syndrome in 1963 existed during dynastic egyptian times as revealed by a costellation of skeletal findings compatible with the syndrome in mummies dating back to 3000years ago and most likely in the ancient population of pompeii these paleogenetic and historical evidences together with the clinical and biomolecular modern evidences confirm the quite benign behavior of the syndrome and the critical value of the multiple and synchronous skeletal anomalies in the recognition of these rare and complex genetic disease exosomes a key component of cell paracrine secretion can exert protective effects in various disease models however application of exosomes in vascular repair and regeneration has rarely been reported in this study we tested whether endothelial progenitor cell epc derived exosomes possessed therapeutic effects in rat models of balloon induced vascular injury by accelerating reendothelialization exosomes were obtained from the conditioned media of epcs isolated from human umbilical cord blood induction of the endothelial injury was performed in the rats carotid artery and the pro re endothelialization capacity of epc derived exosomes was measured the in vitro effects of exosomes on the proliferation and migration of endothelial cells were investigated we found that the epc derived exosomes accelerated the re endothelialization in the early phase after endothelial damage in the rat carotid artery we also demonstrated that these exosomes enhanced the proliferation and migration of endothelial cells in vitro moreover endothelial cells stimulated with these exosomes showed increased expression of angiogenesis related molecules taken together our results indicate that exosomes are an active component of the paracrine secretion of human epcs and can promote vascular repair in rat models of balloon injury by up regulating endothelial cells function mesenchymal stromal cells mscs modulate the immune response and represent a potential treatment for inflammatory and autoimmune diseases we hypothesized that this feature could be potentiated by co administering anti inflammatory cytokines in this article we asked whether engineering of wharton jelly derived human mscs wj hmscs to express an anti inflammatory cytokine increases cell immunomodulatory properties without altering their native features we used epstein barr virus derived interleukin 10 vil 10 which shares some immunosuppressive properties with human il 10 but lacks immunostimulatory activity engineering was accomplished by transducing wj hmscs with a self inactivating feline immunodeficiency virus derived vector co expressing vil 10 and herpes simplex virus type 1 thymidine kinase tk tk was added to allow future tracking of wj hmsc in vivo by positron electron tomography pet the results show that i expression of tk and or vil 10 does not change wj hmsc phenotypic and functional properties ii vil 10 is secreted biologically active and enhances the immunosuppressing functions of wj hmscs iii v il10 and tk can be produced simultaneously by the same cells and do not interfere with each other wj hmscs engineered to secrete vil 10 could be a powerful tool for adoptive cell therapy of immune mediated diseases and therefore additional studies are warranted to confirm their efficacy in suitable animal disease models allogeneic hematopoietic stem cell transplantation hsct is a potentially curative treatment option for patients with hematological malignancies co transplantation of multipotent mesenchymal stromal cells mscs during allogeneic hsct has been explored to enhance engraftment and decrease the risk of graft versus host disease gvhd we aimed to identify evaluate and summarize the findings of all relevant controlled clinical studies to determine the potential benefits of msc infusion during allogeneic hsct with regard to the outcomes engraftment gvhd post transplant relapse and survival we conducted a systematic search of electronic databases for relevant controlled clinical studies studies included patients of all ages with hematological malignancies receiving allogeneic hsct with or without infusion of mscs within a 24 h time frame of transplantation nine studies met our inclusion criteria including three randomized one non randomized and five historically controlled trials representing a total of 309 patients our meta analyses did not reveal any statistically significant differences in donor engraftment or gvhd a review of data regarding relapse and overall survival may result in a positive attitude toward intervention with mscs but due to heterogeneous reporting it is difficult to draw any strict conclusions none of the studies had overall serious risks of bias but the quality of the evidence is low meta analysis did not reveal any statistically significant effects of msc co transplantation but the results must be interpreted with caution because of the weak study design and small study populations we discuss further needs to explore the potential effects of mscs in a hsct setting cases of posterior pharyngeal masses are quite rare and are typically derived from schwannoma or encephalocele or are of vascular or infectious origin they are clinically significant due to their tendency to cause airway obstruction the aim of this study was to present a rare atypical marginal hyperplasia case of a posterior pharyngeal wall mass a 10 year old male was admitted to our clinic with dyspnea a plane surfaced 4 3 3 cm mass was observed on the posterior pharyngeal wall upon physical examination the patient underwent magnetic resonance imaging and surgical treatment following excision of material from the patient s mass a pathologic diagnosis of atypical marginal zone hyperplasia was made atypical marginal zone hyperplasia of the posterior pharyngeal wall has not yet been reported in the literature marginal zone hyperplasia associated with a lymphoproliferative disease should be considered when making differential diagnoses of posterior pharyngeal wall masses metorchis spp are flukes platyhelminthes digenea that infect vertebrates including humans dogs cats poultry and wild game with cyprinid freshwater fish serving as typical second intermediate hosts in their definitive hosts the metorchis spp are difficult to identify to species we provide and analyze sequences of two nuclear 18s rdna and its2 and two mitochondrial co1 and nd1 dna loci of four morphologically identified european species of the metorchis namely metorchis albidus metorchis bilis metorchis crassiusculus and metorchis xanthosomus and of another opisthorchiid euamphimerus pancreaticus dna analysis suggests that the metorchis specimens identified morphologically as m albidus from lutra lutra m bilis from phalacrocorax carbo and m crassiusculus from aquila heliaca and buteo rufinus represent a single species thus m albidus braun 1893 loos 1899 and m crassiusculus rudolphi 1809 looss 1899 are recognized as junior subjective synonyms of m bilis braun 1790 odening 1962 we also provide comparative measurements of the central european metorchis spp and address their tissue specificity and prevalence based on the examination of extensive bird cohort from 1962 to 2015 m bilis and m xanthosomus can be morphologically diagnosed by measuring the extent of genitalia relative to body length and by the size ratio of their suckers they also differ in their core definitive hosts with ducks anas aythya and coots fulica hosting m xanthosomus and cormorants phalacrocorax the birds of prey buteo aquila etc piscivorous mammals lutra vulpes ursus etc and humans hosting m bilis previous reports on the metorchis spp contain numerous suspected misidentifications in an accident later known as the l\xfcbeck disaster 251 neonates were orally given three doses of the new bacille calmette gu\xe9rin bcg antituberculosis tb vaccine contaminated with mycobacterium tuberculosis a total of 173 infants developed clinical or radiological signs of tb but survived the infection while 72 died from tb while some blamed the accident on bcg itself by postulating reversion to full virulence such a possibility was conclusively disproven rather by combining clinical microbiological and epidemiological data the chief public health investigator dr a moegling concluded that the bcg vaccine had been contaminated with variable amounts of fully virulent m tuberculosis here we summarize the conclusions drawn by moegling and point out three lessons that can be learned first while mortality was high approximately 29 the majority of neonates inoculated with m tuberculosis eventually overcame tb disease this shows the high constitutional resistance of humans to the bacillus second four semiquantitative levels of contamination were deduced by moegling from the available data while at low levels of m tuberculosis there was a large spread of clinical phenotypes reflecting a good degree of innate resistance to tb at the highest dose the majority of neonates were highly susceptible to tb this shows the dominating role of dose for innate resistance to tb third two infants inoculated with the lowest dose nevertheless died of tb and their median time from inoculation to death was substantially shorter than for those who died after inoculation with higher doses this suggests that infants who developed disease after low dose inoculation are those who are most susceptible to the disease we discuss some implications of these lessons for current study of genetic susceptibility to tb the unique immunomodulatory properties of mesenchymal stem cells mscs make them an invaluable cell type for the repair of tissue organ damage caused by chronic inflammation or autoimmune disorders although they hold great promise in the treatment of immune disorders such as graft versus host disease gvhd and allergic disorders there remain many challenges to overcome before their widespread clinical application an understanding of the biological properties of mscs will clarify the mechanisms of msc based transplantation for immunomodulation in this review we summarize the preclinical and clinical studies of mscs from different adult tissues discuss the current hurdles to their use and propose the future development of pluripotent stem cell derived mscs as an approach to immunomodulation therapy age is the most powerful of risk factors and is related continuously to systolic bp and cardiovascular disease risk yet current guidelines have dichotomized age groups around a cutoff value of 55 60 years and some guidelines now suggest that age should affect diagnostic thresholds and drug choices these choices are not supported directly by scientific evidence but are based on expert opinion the value of which is uncertain this initial topic of the new controversies in hypertension series highlights important differences among current u s european and canadian practice guidelines then moves on to editorial commentaries with different perspectives renal hyperfiltration is observed prior to the development of diabetic kidney disease dkd in patients with type 1 diabetes t1dm however its significance remains uncertain longitudinal data were used to investigate the association between measured baseline glomerular filtration rate gfr and renal function decline in patients with t1dm this study included 142 adult patients with t1dm and \u22652 measurements of glomerular filtration rate mgfr determined by diethylene triamine penta acetic acid plasma clearance median follow up was 19 years patients were stratified by baseline mgfr quartile the relationship between baseline mgfr and rate of renal function decline was assessed using random effect generalized least squares regression adjusted for age duration of diabetes hba1c blood pressure renin angiotensin aldosterone system inhibitor therapy ldl and bmi the average rates of decline in renal function for the 2nd baseline mgfr 96 4 112 6 ml min 1 1 73 m 2 3 rd baseline mgfr 112 6 125 5 ml min 1 1 73 m 2 and 4th quartiles baseline mgfr 125 5 ml min 1 1 73 m 2 were significantly faster than the first quartile baseline mgfr 60 9 96 4 ml min 1 1 73 m 2 in further detail the average rates of decline in the 2nd rate of decline 1 25 ml min 1 1 73 m 2 per year 95 ci 0 97 1 52 p 0 008 3rd rate of decline 1 35 ml min 1 1 73 m 2 per year 95 ci 1 08 1 62 p 0 001 and 4th quartiles rate of decline 1 6 ml min 1 1 73 m 2 per year 95 ci 1 34 1 88 0 0001 were significantly faster when compared to the first quartile rate of decline 0 67 ml min 1 1 73 m 2 per year 95 ci 0 37 0 96 sub analysis of quartile 4 revealed higher hba1c measurements throughout follow up in those with rapid mgfr decline 3 0 ml min 1 1 73 m 2 year in patients with t1dm higher baseline mgfr is associate ed with more rapid mgfr decline patients with high baseline mgfr who developed rapid mgfr decline had higher hba1c measurements throughout the study these findings are consistent with the concept that poor glycaemic control over time may be a determining factor for the rapid renal function decline observed in some hyperfiltering patients to determine the reliability and validity of a quality of life survey for patients with nonmuscle invasive bladder cancer a total of 180 patients were included in the study we developed a survey with 21 questions grouped into 5 areas the patients filled in this survey and the functional assessment of cancer therapy bladder cancer fact bl survey to assess reliability we calculated cronbach s alpha coefficient and the kappa index to determine criterion validity we studied the association between the scores obtained from our survey and those from the fact bl survey using the pearson correlation coefficient to determine the construct validity factorial and discriminatory we performed a factor analysis comparing it with student s t test for the scores obtained according to the tumour characteristics of reduced quality of life e g malignancies located at the trigone of the bladder cronbach s alpha reliability coefficient was 83 and the kappa index varied between 7 and 1 for the association study between the new survey and the fact bl survey we measured an r 82 for the overall score and between r 68 disease and r 97 sex life in the various measures in the factor analysis we measured a kaiser meyer olkin index of 77 and performed the barlett test p 001 the comparison between the scores in the presence or absence of certain tumour characteristics has shown a reduced quality of life when those characteristics are present which was statistically significant p 05 in the majority of cases our survey to measure the quality of life of patients with nonmuscle invasive bladder cancer is reliable and valid the treatment of high risk prostate cancer requires a multimodal approach to improve control of the disease there is still no consensus as to the initial strategy of choice the aim of this study is to review the results of radical prostatectomy as first step in management of patients with high risk disease a search was conducted on pubmed of english and spanish texts we included those studies that reported the results of radical prostatectomy in patients with high risk prostate cancer as well as those that compared radical prostatectomy with other treatment alternatives the last search was conducted in november 2015 the advantages of radical prostatectomy include a better pathological analysis more accurate staging better local control of the disease and better follow up and adjuvant therapy strategies when compared with external radiation therapy plus hormonal blockade the patients who underwent prostatectomy had greater chances of healing and longer cancer specific survival the patients who most benefit from this approach are younger have fewer comorbidities and no evidence of organ metastases the available scientific evidence to date is not without bias and confounders however they appear to favour radical prostatectomy as the initial approach of choice for high risk prostate cancer elucidate the mechanism of action of the small molecule inhibitor of protein binding to glycosaminoglycans rx 111 and assay its anti inflammatory activity in animal models of inflammatory disease the glycosaminoglycan heparin was used in the mechanism of action study of rx 111 human t lymphocytes and umbilical vein endothelial cells were used to assay the in vitro activity of rx 111 mouse and rat models of disease were used to assay the anti inflammatory activity of rx 111 in vivo circular dichroism and uv vis absorption spectroscopy were used to study the binding of rx 111 to the glycosaminoglycan heparin t lymphocyte rolling on endothelial cells under shear flow was used to assay rx 111 activity in vitro delayed type hypersensitivity dth and tri nitrobenzene sulfonic acid tnbs induced colitis in mice and experimental autoimmune encephalomyelitis eae in rats were used to assay anti inflammatory activity of rx 111 in vivo rx 111 was shown to bind directly to heparin it inhibited leukocyte rolling on endothelial cells under shear flow and reduced inflammation in the mouse model of dth rx 111 was efficacious in the mouse model of inflammatory bowel disease tnbs induced colitis and the rat model of multiple sclerosis eae rx 111 exercises its broad spectrum anti inflammatory activity by a singular mechanism of action inhibition of protein binding to the cell surface gag heparan sulfate rx 111 and related thieno 2 3 c pyridine derivatives are potential therapeutics for the treatment of inflammatory and autoimmune diseases the regional and temporal variation in patterns of fruit and vegetable intake contributes to differences in the impact on gastric cancer burden across regions and over the years we aimed to estimate the proportion and absolute number of gastric cancer cases that could have been prevented in 2012 with an increase in fruit and vegetable intake up to the levels defined by the global burden of disease as the theoretical minimum risk exposure distribution 300 and 400 g d respectively as well as the corresponding figures expected for 2025 preventable fractions pf were computed for 161 countries using data on fruit and vegetable availability in 1997 and 2010 and published estimates of the magnitude of the association between fruit and vegetable intake and gastric cancer assuming a time lag of approximately 15 years countries classified as very high human development index hdi presented median pf in 2012 much lower than low hdi countries for both fruits 3 \xb70 v 10 \xb72 p 0 \xb7001 and vegetables 6 \xb70 v 11 \xb79 p 0 \xb7001 for vegetables only pf significantly decreased until 2025 in most settings however this corresponded to a reduction in the absolute number of preventable gastric cancer cases in less than half of the countries increasing fruit and vegetable intake would allow preventing a relatively high proportion of gastric cancer cases mostly in developing countries although declines in pf are predicted in the near future changes in order to achieve healthier lifestyles may be insufficient to overcome the load of demographic variation to further reduce the gastric cancer burden early suppression of disease activity in rheumatoid arthritis ra patients may result in drug free remission and prevent damage we assessed 2 year clinical and radiological outcomes of two disease activity score das remission steered treatment strategies in early arthritis patients patients n 610 with early ra or undifferentiated arthritis ua were treated with methotrexate mtx and tapered high dose of prednisone patients in early remission 44 53 joints das 1 6 after 4 months tapered and stopped medication patients who did not achieve early das remission were randomized to either mtx plus hydroxychloroquine plus sulphasalazine plus low dose prednisone arm 1 or to mtx adalimumab arm 2 at four monthly intervals medication was tapered and stopped if das was 1 6 but restarted increased or switched if das was \u22651 6 proportions of drug free das remission dfr after 2 years and sharp van der heijde scores shs were analyzed separately for the treatment strategies and patients with ra and ua after 2 years 301 610 49 patients were in das remission and 131 610 21 in dfr in the early remission group 241 387 patients 62 were in das remission and 111 387 29 dfr in arm 1 22 83 27 and in arm 2 24 78 31 were in das remission and 6 83 7 and 7 78 9 respectively were in dfr ra and ua patients achieved das remission in comparable percentages ra 234 479 49 ua 64 122 52 p 0 25 more ua patients achieved dfr 41 122 34 compared to ra patients 89 479 19 p 0 001 mean sd das over time was 1 74 0 58 across all patients and median iqr shs progression was 0 0 0 after 2 years remission steered treatment in early ra and ua patients das remission and dfr percentages were relatively low patients who achieved early remission more often achieved drug free remission after 2 years than patients who needed additional treatment steps in the randomization arms and more ua than ra patients achieved dfr overall disease activity and radiologic damage progression in all patients were well suppressed http www controlled trials com isrctn11916566 registered 07 11 2006 and eudract number 2006 06186 16 registered 16 07 2007 pathophysiological and atrophic changes in the cerebellum are documented in parkinson s disease without compensatory activity such abnormalities could potentially have more widespread effects on both motor and non motor symptoms we examined how atrophic change in the cerebellum impacts functional connectivity patterns within the cerebellum and between cerebellar cortical networks in 42 patients with parkinson s disease and 29 control subjects voxel based morphometry confirmed grey matter loss across the motor and cognitive cerebellar territories in the patient cohort the extent of cerebellar atrophy correlated with decreased resting state connectivity between the cerebellum and large scale cortical networks including the sensorimotor dorsal attention and default networks but with increased connectivity between the cerebellum and frontoparietal networks the severity of patients motor impairment was predicted by a combination of cerebellar atrophy and decreased cerebellar sensorimotor connectivity these findings demonstrate that cerebellar atrophy is related to both increases and decreases in cerebellar cortical connectivity in parkinson s disease identifying potential cerebellar driven functional changes associated with sensorimotor deficits a post hoc analysis exploring the effect of atrophy in the subthalamic nucleus a cerebellar input source confirmed that a significant negative relationship between grey matter volume and intrinsic cerebellar connectivity seen in controls was absent in the patients this suggests that the modulatory relationship of the subthalamic nucleus on intracerebellar connectivity is lost in parkinson s disease which may contribute to pathological activation within the cerebellum the results confirm significant changes in cerebellar network activity in parkinson s disease and reveal that such changes occur in association with atrophy of the cerebellum enhancement of central availability of the second messenger camp is a promising approach to improve cognitive function pharmacological inhibition of phosphodiesterase type 4 pde4 a group of camp hydrolyzing enzymes in the brain has been shown to improve cognitive performances in rodents and monkeys however inhibition of pde4 is generally associated with severe emetic side effects roflumilast an fda approved pde4 inhibitor for treatment of chronic obstructive pulmonary disease copd is yielding only mild emetic side effects in the present study we investigate the potential of roflumilast as a cognition enhancer and to determine the potential coinciding emetic response in comparison to rolipram a classic pde4 inhibitor with pronounced emetic effects cognition enhancement was evaluated in mice and it was found that both roflumilast and rolipram enhanced memory in an object location task 0 03mg kg whereas only roflumilast was effective in a spatial y maze 0 1mg kg emetic potential was measured using competition of pde4 inhibition for \u03b12 adrenergic receptor antagonism in which recovery from xylazine ketamine mediated anesthesia is used as a surrogate marker while rolipram displayed emetic properties at a dose 10 times the memory enhancing dose roflumilast only showed increased emetic like properties at a dose 100 times the memory enhancing dose moreover combining sub efficacious doses of the approved cognition enhancer donepezil and roflumilast which did not improve memory when given alone fully restored object recognition memory deficit in rats induced by the muscarinic receptor antagonist scopolamine these findings suggest that roflumilast offers a more favorable window for treatment of cognitive deficits compared to rolipram cognitive and sensorimotor processes are both needed for successful planning of footsteps during complex gait situations but the interaction between these factors during motor planning as well as their response to dopaminergic treatment is poorly understood in parkinson s disease pd in the current study we evaluated walking and gaze behaviors of individuals with pd while planning an approach toward an obstacle to be stepped over the obstacle clearance task was completed both on and off dopaminergic medication by individuals with parkinson s disease n 20 and compared to healthy age matched control participants n 19 as well as with and without an auditory digit monitoring dual task in this novel protocol of synchronized gaze and gait data collection each trial was split into an early and late phase prior to the obstacle providing a unique opportunity to examine dopamine dependent planning deficits in pd interestingly only patients in the off medication state showed greater deceleration in the late phase i e just before the obstacle f 1 37 45 42 p 0 001 as well as an increase in step time variability also in this late phase with the additional demands of a dual task f 2 74 3 49 p 0 035 only gait deceleration between approaching phases improved with dopaminergic treatment f 1 18 59 20 p 0 001 although groups showed different walking behaviors gaze behaviors were the same for all participants in that they planned for the obstacle more so in the early phase p 0 05 and fixations were reduced across participants with the presence of the dual task p 0 001 surprisingly the gaze behavior of the pd off group showed no interactions with phase or condition suggesting that the deceleration and increased variability when approaching an obstacle is the result of a greater demand for online sensory feedback that cannot be compensated for with visual strategies we conclude that dopamine influences planning by limiting sensorimotor processing capacity especially in the presence of increased cognitive demand in pd we describe a strategy for fluorescent imaging of organelle transport in primary hippocampal neurons treated with amyloid \u03b2 a\u03b2 peptides that cause alzheimer s disease ad this method enables careful rigorous analyses of axonal transport defects which are implicated in ad and other neurodegenerative diseases moreover we present and emphasize guidelines for investigating a\u03b2 induced mechanisms of axonal transport disruption in the absence of nonspecific irreversible cellular toxicity this approach should be accessible to most laboratories equipped with cell culture facilities and a standard fluorescent microscope and may be adapted to other cell types axonal transport is important for neuronal development and the maintenance of effective neuronal function in mature cells observing the active transport of organelles and vesicles along the axons of living neurons has emerged as a valuable tool for probing the health of the neuron and assessing changes associated with stress and neurodegenerative disease transport relies on two families of motor proteins kinesins and dynein using these motors a diverse set of cargos are transported toward the axon tip the cell body or anywhere in between of particular interest are organelles and cargos associated with disease and the changes in motility that these cargos undergo during pathogenesis here we describe the factors that should be considered when studying different cargos and the imaging parameters associated with optimal tracking of various organelles and proteins ultimately the ideal cargo to investigate depends on the question being asked and the limitations of individual microscopes available for imaging development of the cerebral cortex is a very dynamic process involving a series of complex morphogenetic events following division of progenitor cells in the ventricular zone neurons undergo a series of morphological changes and migrate outward toward the cortical plate where they differentiate and integrate into functional circuits errors at several of stages during neurogenesis and migration cause a variety of severe cortical malformations a number of disease genes encode factors associated with the cytoskeleton which plays a crucial role throughout cortical development methods for regulating gene expression coupled with imaging of subcellular structures have provided important insight into the mechanisms governing normal and abnormal brain development we describe here a series of protocols for imaging motor protein dependent processes in real time in the developing rat brain intracellular transport of proteins and organelles in neurons plays an essential role in nervous system development and maintenance axon outgrowth synapse formation and synapse function among other physiological processes require active transport of these cargos between the neuronal soma and axon terminals abnormalities in this axonal transport are associated with a number of neurodevelopmental and neurodegenerative disorders such as charcot marie tooth disease alzheimer disease and amyotrophic lateral sclerosis despite its importance for nervous system development and health methods for visualizing axonal transport in an intact vertebrate have been lacking using the advantages of the zebrafish system we have developed a straightforward approach to visualize axonal transport of various cargos and motor proteins in intact zebrafish embryos and larvae here we describe this approach in detail and discuss how it can be applied to address questions related to cargo specific transport regulation and its effects on axon morphology and function in the developing and mature nervous system proper neuronal function critically depends on efficient intracellular transport and disruption of transport leads to neurodegeneration molecular pathways that support or regulate neuronal transport are not fully understood a greater understanding of these pathways will help reveal the pathological mechanisms underlying disease drosophila melanogaster is the premier model system for performing large scale genetic functional screens here we describe methods to carry out primary and secondary genetic screens in drosophila aimed at identifying novel gene products and pathways that impact neuronal intracellular transport these screens are performed using whole animal or live cell imaging of intact neural tissue to ensure integrity of neurons and their cellular environment the primary screen is used to identify gross defects in neuronal function indicative of a disruption in microtubule based transport the secondary screens conducted in both motoneurons and dendritic arborization neurons will confirm the function of candidate gene products in intracellular transport together the methodologies described here will support labs interested in identifying and characterizing gene products that alter intracellular transport in drosophila axonal transport is an essential function in neurons as mutations in either motor proteins or their adaptors cause neurodegeneration while some mutations cause a complete block in axonal transport other mutations affect transport more subtly this is especially true of mutations identified in human patients many of which impair but do not block motor function in the cell dissecting the pathogenic mechanisms of these more subtle mutations requires assays that can tease apart the distinct phases of axonal transport including transport initiation sustained regulated motility and cargo specific sorting or delivery here we describe a live cell photobleaching assay to assess retrograde flux from the distal axon tip a measure for distal transport initiation we have previously used this method to show that the cap gly domain of dctn1 is required for efficient retrograde transport initiation in the distal axon but it is not required to maintain retrograde flux along the mid axon moughamian holzbaur 2012 this approach has allowed us to examine the effects of disease causing mutations in the axonal transport machinery and in combination with other assays will be useful in determining the mechanisms and regulation of axonal transport in normal and diseased conditions appropriate functionality of nodes of ranvier presynaptic terminals and other axonal subdomains depends on efficient and timely delivery of proteins synthesized and packaged into membrane bound organelles mbos within the neuronal cell body mbos are transported and delivered to their final sites of utilization within axons by a cellular process known as fast axonal transport fat conventional kinesin the most abundant multisubunit motor protein expressed in mature neurons is responsible for fat of a large variety of mbos and plays a major role in the maintenance of appropriate axonal connectivity consistent with the variety and large number of discrete subdomains within axons experimental evidence revealed the identity of several protein kinases that modulate specific functional activities of conventional kinesin thus methods for the analysis of kinase activity and conventional kinesin phosphorylation facilitate the study of fat regulation in health and disease conditions axonal degeneration abnormal patterns of protein phosphorylation and deficits in fat represent early pathological features characteristic of neurological diseases caused by unrelated neuropathogenic proteins interestingly some of these proteins were shown to produce deficits in fat by modulating the activity of specific protein kinases involved in conventional kinesin phosphorylation however experimental systems that facilitate an evaluation of molecular events within axons remain scarce using the isolated squid axoplasm preparation we describe methods for evaluating axon autonomous effects of neuropathogenic proteins on the activity of protein kinases protocols are also provided to evaluate the effect of such proteins on the phosphorylation of endogenous axonal substrates including conventional kinesin and neurofilaments in the current study the ex vivo permeation of ropinirole hydrochloride rh across porcine buccal mucosa in the presence of three permeation enhancers namely n trimethyl chitosan tmc positively charged a chitosan derivative sulfobutyl ether \u03b2 cyclodextrin sbe \u03b2 cd negatively charged and hydroxypropyl \u03b2 cyclodextrin hp \u03b2 cd neutral was investigated buccal permeation studies were conducted using franz diffusion cells cumulative amounts of rh were plotted versus time the presence of the permeation enhancers significantly increased the transport of the drug across the porcine buccal epithelium compared to its plain congener rh solution the rank order effect of the permeation enhancers for the transport of rh across buccal epithelium was tmc sbe \u03b2 cd hp \u03b2 cd rh solution the presence of tmc increased 1 34 fold the transport of rh across buccal epithelium whereas an increase of 1 23 and 1 28 fold was reported in the presence of hp \u03b2 cd and sbe \u03b2 cd respectively infrared spectroscopy ir was employed to investigate the interaction of permeation enhancers with the epithelial lipids of porcine buccal mucosa corroborating the permeation results finally light microscopy was performed to assess the histological changes in the porcine epithelium formation of vacuoles spongiosis and acantholysis linear detachment and destruction of the epithelium resulted from the presence of the permeation enhancers the data suggest that all enhancers tested and particularly tmc increase the transport of rh across buccal epithelium natalizumab is a therapeutic option for treating multiple sclerosis ms and is particularly efficacious for patients with highly active disease a long washout period has been recommended between withdrawal of natalizumab and start of fingolimod another option for treating ms this long washout period has been associated with a significant increase in ms activity in the present study a group of 96 patients who were switched from natalizumab to fingolimod had short washout periods between drugs or monthly corticosteroid pulse therapy if longer washout periods were recommended this therapeutic approach led to the lowest reported relapse rate so far among patients with ms switching from natalizumab to fingolimod 8 3 no complications from short withdrawal were observed in this group of patients gastroesophageal reflux is common but remains a controversial disease to diagnose and treat and little is known about the role of reflux testing in predicting clinical outcomes particularly in children at risk for extraesophageal reflux complications the aim of this study was to determine if rates of hospitalization were affected by reflux burden even after adjusting for aspiration risk we prospectively recruited between 2009 and 2014 a cohort of pediatric patients with suspected extraesophageal reflux disease who were referred for reflux testing and underwent both multichannel intraluminal impedance with ph ph mii and modified barium swallow studies a subset of patients also underwent bronchoalveolar lavage with pepsin analysis we determined their rates of hospitalization for a minimum of 1 year following ph mii testing we prospectively enrolled 116 pediatric patients who presented for care at boston children s hospital and underwent both ph mii and modified barium swallow studies there was no statistically significant relationship between reflux burden measured by ph mii or bronchoalveolar pepsin and total number of admissions or number of admission nights even after adjusting for aspiration status p 0 2 there were no statistically significant relationships between reflux burden by any method and the number or nights of urgent pulmonary admissions before or after adjusting for aspiration risk p 0 08 even in aspirating children reflux burden did not increase the risk of hospitalization based on these results routine reflux testing cannot be recommended even in aspirating children because the results do not impact clinically significant outcomes catch up growth in preterm born children occurs in the first months of life but in some cases growth recovery takes place in adolescence the objective of this study was to study the growth and development of preterm born adolescents from a cohort of preterm infants born between 1995 and 1996 who resided in the cities of chill\xe1n and san carlos in the biob\xedo region chile the results were then compared with term born adolescents a sample of 91 children from the cohort was studied and compared with 91 term born adolescents matched for gender age and attendance at the same educational institution the nutritional status was assessed by bmi for age height for age body composition by skinfold cardiovascular risk due to blood pressure and waist circumference there was 23 0 and 24 1 overweight and obesity in preterm born and term born adolescents respectively with 25 5 of preterm born and small for gestational age adolescents vs 14 5 of those born adequate for gestational age were overweight lower height was observed in 16 5 and 5 5 of the preterm born and term born adolescents respectively and with a higher proportion of girls p 04 preterm born adolescents had a more fat mass than the controls particularly in the suprailiac skinfold no significant differences were found in blood pressure and waist circumference the results indicate that there is a group of preterm born children who do not recover height during adolescence especially girls recent clinical trials have demonstrated that targeting chromatin remodeling factors is as a promising strategy for the treatment of glioblastoma gbm we and others have shown constitutive activation of dna damage response ddr pathways in gliomas and suggested that targeting the ddr may improve the currently grim prognosis for patients based on our previous findings that inhibition of poly adp ribose polymerase parp increases radio sensitivity of the notoriously radio resistant gbm cells we hypothesized that epigenetic down regulation of the ddr responses and induction of oxidative stress via hdac inhibition would contribute to more efficient targeting of this deadly disease our data show that saha an hdac class i ii inhibitor in combination with olaparib parp inhibitor i enhanced inhibition of gbm cell survival ii induced apoptosis and iii impaired cell cycle progression these results provide a pre clinical rationale for combined administration of saha and olaparib which are already individually in clinical trials lysosomal integral membrane protein 2 limp 2 is an important protein in lysosomal biogenesis and function and also plays a role in the tissue inflammatory response it is known that lysosomes play a central role in acute pancreatitis with inflammatory cell infiltration triggering the disease early on in this study we report increases in pancreatic limp 2 protein and mrna levels as early events that occur during the development of cerulein cer induced acute pancreatitis ap in rats gdcl3 a macrophage inhibitor but not fk506 a t lymphocyte inhibitor was able to reverse the increase in limp 2 expression after cer treatment although such reversion was abolished if the animals were depleted of neutrophils due to a vinblastine sulfate pre treatment immunostaining revealed that the cellular source of limp 2 was mainly acinar cells additionally pre treatments with the mapks inhibitors sp600125 and pd98059 inhibitors of jnk and erk activation respectively but not of rolipram a type iv phosphodiesterase inhibitor suppressed the increase in the expression of limp 2 after cer administration together these results indicate that neutrophils are able to drive a macrophage activation that would regulate the increase in limp 2 expression during the early phase of cer induced ap with the stress kinases jnk and erk also playing a coordinated role in the increase of limp 2 expression due to cer kawasaki disease kd is an autoimmune disease in which the medium sized blood vessels throughout the body become inflamed the increased evidences showed that tnf \u03b1 was association with vascular inflammation in kd patients however the detailed mechanism was still unclear recent studies indicated abnormal expressed long non coding rnas lncrnas involved in many diseases thus the purpose of this study is to explore the role of lncrnas in kd and find out the new target for kd treatment in this study firstly we verified the overexpressed tnf \u03b1 in kd patients and found tnf \u03b1 was able to induce huvecs apoptosis and inhibit huvecs proliferation after this we screened out pregnancy induced noncoding rna pinc was significantly overexpression in tnf \u03b1 treated huvecs we also found pinc overexpressed in kd patients for further study we designed two sirna of pinc after silenced the expression of pinc in huvecs we found the knockdown of pinc enhanced the viability of huvecs treated with tnf \u03b1 and increased the expression of anti apoptotic and reduced the expression of apoptotic gene these results suggest pinc involves in the process of tnf \u03b1 induces vascular endothelial cell apoptosis it may become a new target for kd treatment the transcription factor foxp3 and nf \u03bab regulates the expression of various genes that play an important role in the regulation of renal inflammation we investigated the association of foxp3 rs2232365 rs3761548 rs5902434 and rs2294021 and nf \u03bab1 rs28362491 and rs696 gene variants in susceptibility and prognosis of end stage renal disease esrd and renal allograft outcome we genotyped four common polymorphisms of foxp3 and two tag snps of nf \u03bab1 genes in 350 esrd cases and 350 controls single marker analysis and snp snp interaction model one to six way combinations was used for determination of clinical outcome of esrd and acute rejection episode are we observed significantly higher occurrence of mutant genotypes of tag snps of foxp3 namely rs2232365 and rs3761548 along with nf kb1 namely rs28362491 and rs696 in esrd and are cases suggested a risk association for esrd and are interestingly multifactor dimension reduction analysis suggested an increased risks of nearly 6 folds for esrd and 23 folds for are cases under the six factors model which consists of tag snps of foxp3 rs2232365 rs3761548 rs5902434 and rs2294021 and nf kb1 rs28362491 and rs696 kaplan meier survival analysis showed the lowest overall survival for mutant genotypes compared with wild and heterozygous genotypes of rs2232365 and rs3761548 tag snps of foxp3 as well as nf kb1 tag snps rs28362491 and rs696 in renal allograft recipients the crude and adjusted hazard ratios in univariate and multivariate cox regression models showed almost 2 folds to 3 folds risk for overall survival against mutant genotypes of tag snps of foxp3 rs2232365 and rs3761548 and nf kb1 rs28362491 and rs696 genes these results suggest that variants of transcription factor foxp3 and nf kb1 might be associated with increased risk to the clinical outcome of esrd and renal allograft survival ferroptosis is a recently recognized form of regulated cell death it is characterized morphologically by the presence of smaller than normal mitochondria with condensed mitochondrial membrane densities reduction or vanishing of mitochondria crista and outer mitochondrial membrane rupture it can be induced by experimental compounds e g erastin ras selective lethal small molecule 3 and buthionine sulfoximine or clinical drugs e g sulfasalazine sorafenib and artesunate in cancer cells and certain normal cells e g kidney tubule cells neurons fibroblasts and t cells activation of mitochondrial voltage dependent anion channels and mitogen activated protein kinases upregulation of endoplasmic reticulum stress and inhibition of cystine glutamate antiporter is involved in the induction of ferroptosis this process is characterized by the accumulation of lipid peroxidation products and lethal reactive oxygen species ros derived from iron metabolism and can be pharmacologically inhibited by iron chelators e g deferoxamine and desferrioxamine mesylate and lipid peroxidation inhibitors e g ferrostatin liproxstatin and zileuton glutathione peroxidase 4 heat shock protein beta 1 and nuclear factor erythroid 2 related factor 2 function as negative regulators of ferroptosis by limiting ros production and reducing cellular iron uptake respectively in contrast nadph oxidase and p53 especially acetylation defective mutant p53 act as positive regulators of ferroptosis by promotion of ros production and inhibition of expression of slc7a11 a specific light chain subunit of the cystine glutamate antiporter respectively misregulated ferroptosis has been implicated in multiple physiological and pathological processes including cancer cell death neurotoxicity neurodegenerative diseases acute renal failure drug induced hepatotoxicity hepatic and heart ischemia reperfusion injury and t cell immunity in this review we summarize the regulation mechanisms and signaling pathways of ferroptosis and discuss the role of ferroptosis in disease retinitis pigmentosa rp is a genetically highly heterogeneous retinal disease and one of the leading causes of blindness in the world next generation sequencing technology has enormous potential for determining the genetic etiology of rp we sought to identify the underlying genetic defect in a 35 year old male from an autosomal dominant rp family with 14 affected individuals by capturing next generation sequencing cngs of 144 genes associated with retinal diseases we identified eight novel dna variants however none of them cosegregated for all the members of the family further analysis of the cngs data led to identification of a recurrent missense mutation c 403c t p r135w in the rhodopsin rho gene which cosegregated with all affected individuals in the family and was not observed in any of the unaffected family members the p r135w mutation has a reference single nucleotide polymorphism snp id rs104893775 and it appears to be responsible for the disease in this large family this study highlights the importance of examining ngs data with reference snp ids thus our study is important for data analysis of ngs based clinical genetic diagnoses porokeratosis is recognized as a heterogenously inherited epidermal keratinization disorder disseminated superficial actinic porokeratosis dsap is considered to be the most common form of porokeratosis and is characterized by multiple small keratotic lesions on sun exposed areas of body mvk has been reported to be the main candidate gene associated with dsap in this study six sporadic cases of dsap were clinically characterized direct dna sequencing analysis of the whole coding regions of mvk detected three mvk missense mutations and two were novel for dsap c 31c t p11s and c 1004g a g335d the three mutant mvk proteins were less stable than the wild type protein in different degrees mutation g335d also resulted in the misfolding of the atp binding domain this study extends the mutation spectrum of mvk mvk protein stability and correct folding might be the molecular mechanism causing dasp a 50 probability of detecting a mvk mutation in six dsap sporadic cases indicated that the mvk gene was useful for clinical characterization genetic counseling and prenatal diagnosis of dsap the rheumatoid arthritis impact of disease raid score was developed as a european league against rheumatism initiative to obtain a patient reported outcome score for clinical trials in patients with rheumatoid arthritis ra based on patients perception of the impact of the disease on several domains of health the objective of this study was to assess the content validity of this score in dutch ra patients during three focus group discussions n 23 patients with ra reflected on comprehensiveness of the raid to measure impact of ra on their life relevance of the raid domains and formulation of questions also the domains of the raid score were compared to the comprehensive international classification of functioning disability and health core set for ra patients confirmed that ra had impact on five domains already incorporated in the raid score emotional well being pain performing daily activities fatigue and coping there was variation in interpretation of some of the items of the raid score suggesting problems in comprehension patients indicated that the domains work relationships with others such as family and friends and spare time hobbies were missed in the raid and could be added to obtain a more complete picture of the impact of the disease the raid score has fairly good content validity if confirmed as important in other patient groups items in the above mentioned areas should be considered in a future upgrade dengue virus a positive sense rna virus is one of the major human pathogens transmitted by mosquitoes however no fully effective licensed dengue vaccines or therapeutics are currently available several potent neutralizing antibodies against denv have been isolated from mice and humans and the characterization of their properties by biochemical and biophysical methods have revealed important insights for development of therapeutic antibodies in this review we summarize recently reported antibody antigen complex structures their likely neutralization mechanisms and enhancement propensities as well as their prophylactic and therapeutic capabilities in mouse models this article forms part of a symposium on flavivirus drug discovery in the journal antiviral research pancreatic cancer is one of the most malignant human tumors perineural invasion whereby a cancer cell invades the perineural spaces surrounding nerves is acknowledged as a gradual contributor to cancer aggressiveness furthermore perineural invasion is considered one of the root causes of the recurrence and metastasis observed after pancreatic resection and it is also an independent predictor of prognosis advanced research has demonstrated that the neural microenvironment is closely associated with perineural invasion in pancreatic cancer therapy targeting the molecular mechanism of perineural invasion may enable the durable clinical treatment of this formidable disease this review provides an overview of the present status of perineural invasion the relevant molecular mechanisms of perineural invasion pain and hyperglycemia associated with perineural invasion in pancreatic cancer and the targeted therapeutics based on these studies to examine the effect of metformin use on survival outcomes in patients with renal cell carcinoma rcc retrospective analysis of 1528 rcc patients from 2 centers between 1992 and 2012 was conducted a total of 390 diabetics with confirmed metformin use were included in the final analysis with a median follow up of 43 1 months primary outcomes were disease free survival dfs and cancer specific survival css cox regression models were performed to evaluate the effects of potential predictors on dfs and css following stratification of patients into local and metastatic disease we identified 290 diabetics with localized and 100 with metastatic rcc there were no clinicopathologic differences in the profiles of metformin users and non metformin users for patients with localized rcc metformin users had significantly better dfs hazard ratio 0 47 p 01 and css hazard ratio 0 21 p 01 than non users there was no difference in css between metformin users and non metformin users in diabetics with metastatic rcc hazard ratio 0 78 p 286 limitations include retrospective design and lack of data on metformin dosage and duration of use metformin use is correlated with improved survival in patients with localized rcc but not in metastatic rcc future studies should focus on its potential mechanisms and clinical utility our purpose was to 1 assess the level of consistency between the quality of life qol scores of men with prostate cancer for urinary bowel sexual bother collected via telephone versus self administered survey 2 determine factors associated with variation in level of agreement and 3 assess the efficacy of telephone interview as a mode of administration against the gold standard tool epic 26 cohen s kappa coefficients were calculated to investigate test retest reliability across modes of administration logistic regression models explored patients characteristics associated with the magnitude of urinary bowel sexual problem sensitivities and specificities of the telephone mode in reference to gold standard were further measured from 221 men who agreed to participate in the study 168 76 0 returned completed surveys kappa linear model resulted in a moderate agreement across the urinary bowel sexual bother scores for both modes of administration with greatest concordance recorded for bowel bother 90 patient s age 75 years disease risk and active treatment type determined a moderate to good level of agreement between administration modalities with a kappa varying between 0 44 and 0 73 \u03c7 2 8 18 p 042 sensitivity tests revealed that 68 of men with a moderate big problem during the phone interviews would respond to suffering from a moderate big sexual problem results of this pilot study revealed that qol outcomes from this registry will likely underestimate the true bother experienced by men more research is required to determine the differences between self administered and telephone interviews in men with prostate cancer because of the low incidence of penile carcinoma pc the value of p16 ink4a p53 and human papilloma virus hpv infection status in clinical practice remains unclear herein we report our experience with potential clinical utility of these markers in men with pc treated at our institution tissue microarrays of 57 cases of invasive penile squamous cell carcinomas were immunohistochemically stained for p16 and p53 hpv in situ hybridization ish for high risk subtypes was also performed association between marker status nodal disease overall os and cancer specific survival css were assessed p16 and hpv ish were positive in 23 40 and 24 42 of the cohort respectively the proportion of warty basaloid or mixed warty basaloid tumor subtypes were significantly greater in the p16 positive patients 48 vs 3 p 01 p53 expression was negative in 31 54 cases only in p16 negative patients positive p53 status was associated with pn disease odds ratio 4 4 95 confidence interval ci 1 04 18 6 in kaplan meier analysis the unadjusted estimated os was insignificantly longer in p16 positive patients median os 75 vs 27 months p 27 and median css was not reached p 16 in a multivariable cox proportional hazard model when controlling for pathological nodal status and adjuvant chemotherapy p16 status was a significant predictor for improved css hazard ratio 0 36 95 ci 0 13 0 99 the worst css was seen in pn patients with double negative p16 and p53 expression 8 vs 34 months p 01 in this current cohort p53 and p16 status showed clinical utility in predicting nodal disease as well as survival systemic arterial hypertension is the prevalentest disease worldwide that significantly increases cardiovascular risk an early diagnosis together to achieve goals decreases the risk of complications significatly recently have been updated the diagnostic criteria for hypertension and the introduction of ambulatory blood pressure monitoring the introduction into clinical practice of ambulatory blood pressure monitoring was to assist the diagnosis of \xabwhite coat hypertension and \xabmasked hypertension \xbb. today has also shown that ambulatory blood pressure monitoring is better than the traditional method of recording blood pressure in the office to the diagnosis and to adequate control and adjustment of drug treatment also there have been introduced important new concepts such as isloted nocturnal hypertension morning blood pressure elevation altered and altered patterns of nocturnal dip in blood pressure which have been associated with increased cardiovascular risk several studies have shown significant prognostic value in some stocks there are still other concepts on which further study is needed to properly establish their introduction to clinical practice as hypertensive load variability pulse pressure and arterial stiffness in addition to setting values according to further clinical studies in populations such as elderly and children enteric co innervation is a peculiar innervation pattern of striated esophageal musculature both anatomical and functional data on enteric co innervation related to various transmitters have been collected in different species although its function remains enigmatic however it is unclear whether catecholaminergic components are involved in such a co innervation thus we examined to identify catecholaminergic neuronal elements and clarify their relationship to other innervation components in the esophagus using immunohistochemistry with antibodies against tyrosine hydroxylase th vesicular acetylcholine transporter vacht choline acetyltransferase chat and protein gene product 9 5 pgp 9 5 \u03b1 bungarotoxin \u03b1 bt and pcr with primers for amplification of cdna encoding th and dopamine \u03b2 hydroxylase dbh th positive nerve fibers were abundant throughout the myenteric plexus and localized on about 14 of \u03b1 bt labelled motor endplates differing from vacht positive vagal nerve terminals th positive perikarya represented a subpopulation of only about 2 8 of all pgp 9 5 positive myenteric neurons analysis of mrna showed both th and dbh transcripts in the mouse esophagus as chat positive neurons in the compact formation of the nucleus ambiguus were negative for th the th positive nerve varicosities on motor endplates are presumably of enteric origin although a sympathetic origin cannot be excluded in the medulla oblongata the cholinergic ambiguus neurons were densely supplied with th positive varicosities thus catecholamines may modulate vagal motor innervation of esophageal striated muscles not only at the peripheral level via enteric co innervation but also at the central level via projections to the nucleus ambiguus as parkinson s disease with a loss of central dopaminergic neurons also affects the enteric nervous system and dysphagia is prevalent in patients with this disease investigation of intrinsic catecholamines in the esophagus may be worthwhile to understand such a symptom the wnts can be considered as candidates for the congenital anomaly of kidney and urinary tract cakut diseases since they take part in the control of kidney organogenesis of them wnt5a is expressed in ureteric bud ub and its deficiency leads to duplex collecting system 13 90 uni or bilateral kidney agenesis 10 90 hypoplasia with altered pattern of ureteric tree organization 42 90 and lobularization defects with partly fused ureter trunks 25 90 unlike in controls the ub had also notably less tips due to wnt5a deficiency being at e15 5 306 and at e16 5 765 corresponding to 428 and 1022 in control p 0 02 p 0 03 respectively these changes due to wnt5a knock out associated with anomalies in the ultrastructure of the ub daughter epithelial cells the basement membrane bm was malformed so that the bm thickness increased from 46 3 nm to 71 2 nm p 0 01 at e16 5 in the wnt5a knock out when compared to control expression of a panel of bm components such as laminin and of type iv collagen was also reduced due to the wnt5a knock out the p4ha1 gene that encodes a catalytic subunit of collagen prolyl 4 hydroxylase i c p4h i in collagen synthesis expression and the overall c p4h enzyme activity were elevated by around 26 due to impairment in wnt5a function from control the compound wnt5a p4ha1 embryos demonstrated wnt5a related defects for example local hyperplasia in the ub tree a r260h wnt5a variant was identified from renal human disease cohort functional studies of the consequence of the corresponding mouse variant in comparison to normal ligand reduced wnt5a signalling in vitro together wnt5a has a novel function in kidney organogenesis by contributing to patterning of ub derived collecting duct development contributing putatively to congenital disease the spread of an infectious disease may depend on the population size for simplicity classic epidemic models assume homogeneous mixing usually standard incidence or mass action for standard incidence the contact rate between any pair of individuals is inversely proportional to the population size and so the basic reproduction number and thus the initial exponential growth rate of the disease is independent of the population size for mass action this contact rate remains constant predicting that the basic reproduction number increases linearly with the population size meaning that disease invasion is easiest when the population is largest in this paper we show that neither of these may be true on a slowly evolving contact network the basic reproduction number of a short epidemic can reach its maximum while the population is still growing the basic reproduction number is proportional to the spectral radius of a contact matrix which is shown numerically to be well approximated by the average excess degree of the contact network we base our analysis on modeling the dynamics of the average excess degree of a random contact network with constant population input proportional deaths and preferential attachment for contacts brought in by incoming individuals i e individuals with more contacts attract more incoming contacts in addition we show that our result also holds for uniform attachment of incoming contacts i e every individual has the same chance of attracting incoming contacts and much more general population dynamics our results show that a disease spreading in a growing population may evade control if disease control planning is based on the basic reproduction number at maximum population size in patients with late onset pompe disease lopd progressive respiratory muscle involvement leads to reduced pulmonary function with respiratory failure the most common cause of mortality early disease manifestations include sleep disordered breathing which can be treated with non invasive ventilation however progressive diurnal deficits can require invasive ventilation to determine if pulmonary function tests pfts predict the thresholds for ventilation and wheelchair use a systematic literature review identified cross sectional clinical patient data n 174 that was classified into ventilation and wheelchair cohorts pfts included maximum inspiratory pressure mip maximum expiratory pressure mep forced vital capacity fvc and vital capacity vc with vital capacities measured in the upright u and supine s positions receiver operating characteristic roc curves were used to calculate cut points cp and area under the curve auc for all ventilation and mobility thresholds tested roc analyses demonstrated auc values from 86 89 for mip 72 96 for mep and 74 96 for all vital capacity metrics thus pfts are useful in predicting the thresholds for nighttime ventilation daytime ventilation and wheelchair use with mip and vc u having both high auc values and consistency the pft mobility cps were low mip cp 0 9 kpa mep cp 2 6 kpa vc u cp 19 predicted suggesting an endurance component associated with wheelchair use to determine if utilization of thoracoscopic resection of congenital cystic lung disease cld is increasing and if this approach is associated with improved outcomes using a large national sample children \u226420years old who underwent resection of a congenital cystic adenomatoid malformation bronchopulmonary sequestration or bronchogenic cyst were identified from the healthcare cost and utilization project kids inpatient database 2009 2012 and nationwide inpatient sample 2008 2010 2011 patient characteristics and outcomes were compared between thoracoscopic and open approaches using univariate and multivariable analyses stratified by magnitude of resection thoracoscopic resection was used in 39 4 of 1120 children who underwent resection of cld utilization of the thoracoscopic approach increased from 32 2 in 2008 to 48 2 in 2012 use of thoracoscopy was lower in lobectomy than segmental resection 32 5 vs 48 4 p 001 newborns those with comorbid congenital conditions and those with respiratory infections also had lower rates of thoracoscopy after stratifying by magnitude of resection and adjusting for patient complexity complication rates and postoperative length of stay were similar between thoracoscopic and open approaches utilization of thoracoscopic resection for cld in the united states is increasing with time after adjusting for patient complexity there is no difference in postoperative length of stay or complications between thoracoscopic and open lobectomy and sub lobar resection treatment with programmed death receptor 1 pd 1 antibodies is associated with high response rates in patients with advanced melanoma reliable markers for early response and outcome are still sparse we evaluated 66 consecutive patients with advanced metastatic melanoma treated with nivolumab or pembrolizumab between 2013 and 2014 the main objectives of this study were to investigate whether first serum lactate dehydrogenase ldh at baseline normal vs above the upper limit of normal correlates with overall survival os and second whether the change of ldh during treatment predicts response before the first scan and os in patients with an elevated baseline ldh after a median follow up of 9 months patients with an elevated baseline ldh n 34 had a significantly shorter os compared with patients with normal ldh n 32 6 month os 60 8 vs 81 6 and 12 month os 44 2 vs 71 5 log rank p 0 0292 in those 34 patients with elevated baseline ldh the relative change during treatment was significantly associated with an objective response on the first scan the 11 32 patients with partial remission had a mean reduction of 27 3 from elevated baseline ldh in contrast patients with progressive disease n 15 had a mean increase of 39 patients with a relative increase over 10 from elevated baseline ldh had a significantly shorter os compared with patients with 10 change 4 3 vs 15 7 months log rank p 0 00623 ldh could be a useful marker at baseline and during treatment to predict early response or progression in patients with advanced melanoma who receive anti pd 1 therapy accumulating evidence indicates that dysregulated microrna 146a mir 146a is involved in tumour genesis and cancer progression we aimed to evaluate its expression level and the potential for the diagnosis and prognosis in oesophageal squamous cell cancer escc we examined mir 146a expression in 62 pairs of escc cancerous and matched paracancerous tissue 115 formalin fixed paraffin embedded ffpe tissue samples and serum samples from 154 escc patients and 154 healthy volunteers using quantitative reverse transcription pcr qrt pcr kaplan meier method cox regression and receiver operating characteristic roc curve analysis were applied to analyse its prognostic and diagnostic value microrna 146a expression level was significantly decreased in escc tissue compared with paracancerous tissue p 0 001 its regulation level was negatively associated with t factor and tnm stage kaplan meier curve revealed that its downregulation level predicted worse overall survival os and progression free survival pfs both univariate and multivariate analyses identified mir 146a expression as independent prognostic factor for os and pfs serum mir 146a was significantly reduced in escc patients than in healthy controls p 0 001 area under the curve roc value sensitivity and specificity for this marker were 0 863 0 033 85 7 and 68 6 in the discovery group and 0 891 0 027 82 1 and 83 3 in the validation group microrna 146a is significantly reduced in cancerous tissue and serum samples of escc patients it is an ideal biomarker for the prognosis and diagnosis of escc one of the biggest challenges in the development of therapeutics for central nervous system cns disorders is achieving sufficient blood brain barrier bbb penetration research in the past few decades has revealed that the bbb is not only a substantial barrier for drug delivery to the cns but also a complex dynamic interface that adapts to the needs of the cns responds to physiological changes and is affected by and can even promote disease this complexity confounds simple strategies for drug delivery to the cns but provides a wealth of opportunities and approaches for drug development here i review some of the most important areas that have recently redefined the bbb and discuss how they can be applied to the development of cns therapeutics non alcoholic fatty liver disease the most common chronic liver disease encompasses a histological spectrum ranging from simple steatosis to non alcoholic steatohepatitis nash over the next decade nash is projected to be the most common indication for liver transplantation the absence of an effective pharmacological therapy for nash is a major incentive for research into novel therapeutic approaches for this condition the current focus areas for research include the modulation of nuclear transcription factors agents that target lipotoxicity and oxidative stress and the modulation of cellular energy homeostasis metabolism and the inflammatory response strategies to enhance resolution of inflammation and fibrosis also show promise to reverse the advanced stages of liver disease the eurorotanet surveillance network has conducted rotavirus genotype surveillance since 2007 in 16 european countries using epidemiological and microbiological data from 39 786 genotyped rotavirus positive specimens collected between september 2007 and august 2013 we assessed genotype distribution and age distribution of rotavirus gastroenteritis rvge cases in and out of peak season in 12 countries which were yet to implement routine rotavirus vaccination in multinomial multivariate logistic regression adjusting for year country and age the odds of infection caused by genotype constellation 2 ds 1 like stains adjusted multinomial odds ratio am or 1 25 95 confidence interval ci 1 13 1 37 p 0 001 mixed or untypable genotypes am or 1 55 95 ci 1 40 1 72 p 0 001 and less common genotypes am or 2 11 95 ci 1 78 2 51 p 0 001 increased out of season relative to g1p 8 age varied significantly between seasons the proportion of rvge cases younger than 12 months in the united kingdom increased from 34 in season to 39 out of season am or 1 66 95 ci 1 20 2 30 and the proportion five years and older increased from 9 in season to 17 out of season am or 2 53 95 ci 1 67 3 82 this study provides further understanding of the rotavirus ecology before vaccine introduction which will help interpret epidemiological changes in countries introducing or expanding rotavirus vaccination programmes although studies have shown that cerebral ischemic preconditioning ipc can ameliorate ischemia reperfusion i r induced brain damage but its precise mechanisms remain unknown therefore the aim of this study was to investigate the neuroprotective mechanisms of ipc against ischemic brain damage induced by cerebral i r and to explore whether the calcium calmodulin dependent protein kinase ii camkii mediated up regulation of nnos ser847 phosphorylation signaling pathway contributed to the protection provided by ipc transient global brain ischemia was induced by 4 vessel occlusion in adult male sprague dawley rats the rats were pretreated with 3 min of ipc alone or kn62 selective antagonist of camkii treatment before ipc after reperfusion for 3 days 6 min ischemia was induced cresyl violet staining was used to examine the survival of hippocampal ca1 pyramidal neurons immunoblotting was performed to measure the phosphorylation of camkii nnos c jun and the expression of fasl immunoprecipitation was used to examine the binding between psd95 and nnos the results showed that ipc could significantly protect neurons against cerebral i r injury furthermore the combination of psd95 and nnos was increased coinstantaneously the phosphorylation of camkii and nnos ser847 were up regulated however the activation of c jun and fasl were reduced conversely kn62 treatment before ipc reversed all these effects of ipc taken together the results suggest that ipc could diminish ischemic brain injury through camkii mediated up regulation of nnos ser847 phosphorylation signaling pathway the 99th percentile upper reference limit of high sensitivity cardiac troponin hs ctn from a healthy reference population is used for diagnosing acute myocardial infarction ami accepted current thresholds of hs ctnt roche and hs ctni abbott are 14 and 26 ng l respectively since thresholds for hs ctnt and hs ctni were derived from different reference cohorts it is unclear whether they are biologically equivalent we directly assessed sex specific and age specific 99th percentile upper reference limits of hs ctnt and hs ctni in a single reference cohort to investigate whether current divergent thresholds of hs ctnt and hs ctni stem from intrinsic assay differences or reflect cohort variation a healthy reference population was derived from a population based cohort the maastricht study n 3451 age 40 75 years individuals with diabetes mellitus a history of cardiovascular disease cardiac ischaemia on ecg n terminal pro brain natriuretic peptide 125 ng l or estimated glomerular filtration rate 60 ml min 1 73 m 2 were excluded non parametric analyses were performed to assess 99th percentile upper reference limits 1540 individuals were included in the healthy reference population age 57 \xb18 years 52 4 women overall 99th percentile upper reference limits of hs ctnt and hs ctni were 15 and 13 ng l respectively upper reference limits were higher in men than women hs ctnt 16 vs 12 ng l hs ctni 20 vs 11 ng l and increased with age direct comparison reveals numerically similar thresholds for hs ctnt and hs ctni assays this finding is in line with recently reported underdiagnosis of ami with the current decision limit of 26 ng l for hs ctni especially among women downwards adjustment of the hs ctni threshold differentiated for sex would equalise clinical decision limits for both assays and may prevent further underdiagnosis of ami the southern cattle tick rhipicephalus boophilus microplus canestrini is the most economically important cattle ectoparasite in the world rhipicephalus microplus and rhipicephalus annulatus say continue to threaten u s cattle producers despite eradication and an importation barrier based on inspection dipping of imported cattle in organophosphate op acaricide and quarantine of infested premises op acaricides inhibit acetylcholinesterase ache essential to tick central nervous system function unlike vertebrates ticks possess at least three genes encoding aches differing in amino acid sequence and biochemical properties genomic analyses of r microplus and the related tick ixodes scapularis suggest that ticks contain many genes encoding different aches this work is the first report of a salivary cholinesterase che activity in r microplus and discusses complexity of the cholinergic system in ticks and significance of tick salivary che at the tick host interface it further provides three hypotheses that the salivary che plausibly functions 1 to reduce presence of potentially toxic acetylcholine present in the large bloodmeal imbibed during rapid engorgement 2 to modulate the immune response innate and or acquired of the host to tick antigens and 3 to influence transmission and establishment of pathogens within the host animal ticks are vectors for a greater number and variety of pathogens than any other parasite and are second only to mosquitoes owing to malaria as vectors of serious human disease saliva assisted transmission sat of pathogens is well known however the salivary components participating in the sat process remain to be elucidated adult onset xanthogranuloma aox of the corneoscleral limbus is a rare inflammatory condition of unknown aetiology similar to limbal juvenile xanthogranuloma jxg it presents as a growing mass at the corneoscleral junction limbal aox and jxg can lead to sight threatening complications if not managed in a timely manner this systematic review summarises the main clinical and histopathological features of limbal aox jxg and discusses the management of this uncommon disease we performed a literature search in the medline database for all historical entries using the search terms limbus limbal and xanthogranuloma and retrieved all articles reporting on limbal xanthogranuloma after refining the search to articles relevant to limbal aox we were able to identify ten adult cases of limbal aox and compare those with all reported cases of limbal jxg clinically aox usually presents as an isolated smooth yellowish dome shaped nodule at the corneoscleral junction similar to an ocular presentation of jxg with which it also shares similar histopathological features limbal jxg and aox may represent the same disease entity diagnosis relies on the clinical presentation pathology and immunohistochemical profile spontaneous regression is unlikely and thus prompt surgical intervention should be considered to prevent sight threatening complications xanthogranuloma should be included in the differential diagnosis of corneoscleral limbal masses in patients of all age groups inflammatory bowel diseases ibds have a considerable impact on the health related quality of life hrqol of patients we aimed to investigate the effect of biological therapy on hrqol in ibd patients followed in an out patient clinical setting and to compare the hrqol scores to that of ibd patients without disease activity observational and retrospective study in patients treated with biologics a short health scale shs questionnaire on hrqol consisting of four items bowel symptoms interference in daily life worry and general well being was completed and registered in each patient s medical journal data on hrqol was collected at the beginning of treatment and every 3 months thereafter the biologically treated group was compared with a control group of ibd patients without disease activity we identified 114 patients who began a new round of biological treatment these were either na\xefve to biologics or had a break in treatment for more 3 months after 3 months of therapy significant improvements in hrqol compared to baseline were observed for every item on the shs p value 0 01 subgroup analysis showed a poorer hrqol performance in women patients with crohn s disease and smokers the median hrqol score regarding bowel symptoms and interference in daily life was similar to the control group after 6 months of treatment treatment with biological therapy leads to a statistically and clinically significant improvement in hrqol in all parameters after 6 months of treatment bowel symptoms and interference in daily life were similar to patients without disease activity context oxidative stress plays a key role in neurodegenerative disorders including parkinson s disease pd rice fermented with monascus purpureus went monascaceae ntu 568 red mould rice was found to contain antioxidants including dimerumic acid dma and deferricoprogen dfc objective the effects of dma and dfc on 6 hydroxydopamine 6 ohda induced cytotoxicity and potential protective mechanisms in differentiated pc 12 pheochromocytoma cells were investigated materials and methods dma 0 60 \u03bcm or dfc 0 10 \u03bcm was co treated with 6 ohda 200 \u03bcm 24 h exposure in differentiated pc 12 cells cell viability and intercellular reactive oxygen species ros were measured by 3 4 5 dimethylthiazol 2 yl 2 5 diphenyl tetrazolium bromide mtt and 2 7 dichlorofluorescein diacetate dcfh da assays respectively cell apoptosis was determined by dna fragmentation analysis and propidium iodide staining by flow cytometry western blot analysis was used to measure the levels of cell protein expression results dma and dfc significantly increased cell viability to 72 and 81 in 6 ohda induced differentiated pc 12 cell cultures respectively furthermore dma and dfc reduced 6 ohda induced formation of extracellular and intercellular ros by 25 and 20 respectively and decreased nadph oxidase 2 expression in differentiated pc 12 cells dma and dfc inhibited 6 ohda induced apoptosis and decreased activation of caspase 3 via regulation of bcl 2 associated x protein bax and bcl 2 protein expression in differentiated pc 12 cells conclusion dma and dfc may protect against 6 ohda toxicity by inhibiting ros formation and apoptosis these results showed that the metabolites from m purpureus ntu 568 fermentation were potential therapeutic agents for pd induced by oxidative damage and should be encouraged for further research to investigate the impact of an increase in supplemental nutrition assistance program snap benefits on medicaid costs and use in massachusetts using single and multigroup interrupted time series models i examined the effect of an april 2009 increase in snap benefits on inpatient medicaid cost and use patterns i analyzed monthly medicaid discharge data from 2006 to 2012 collected by the massachusetts center for health information and analysis inpatient costs for the overall massachusetts medicaid population grew by 0 55 percentage points per month p 001 before the snap increase after the increase cost growth fell by 73 to 0 15 percentage points per month 0 40 p 003 compared with the overall medicaid population cost growth for people with the selected chronic illnesses was significantly greater before the snap increase as was the decline in growth afterward reduced hospital admissions after the snap increase drove the cost declines medicaid cost growth fell in massachusetts after snap benefits increased especially for people with chronic illnesses with high sensitivity to food insecurity we identified hospital visits with reported exposure to harmful algal blooms an emerging public health concern because of toxicity and increased incidence we used the world health organization s international classification of disease icd medical code specifying environmental exposure to harmful algal blooms to extract hospital visit records in new york state from 2008 to 2014 using the icd code we identified 228 hospital visits with reported exposure to harmful algal blooms they occurred all year long and had multiple principal diagnoses of all hospital visits 94 7 were managed in the emergency department and 5 3 were hospitalizations as harmful algal bloom surveillance increases the icd code will be a beneficial tool to public health only if used properly to compare methods for estimating low hiv incidence among persons who inject drugs we examined 4 methods in new york city 2005 to 2014 1 hiv seroconversions among repeat participants 2 increase of hiv prevalence by additional years of injection among new injectors 3 the new york state and centers for disease control and prevention stratified extrapolation algorithm and 4 newly diagnosed hiv cases reported to the new york city department of health and mental hygiene the 4 estimates were consistent 1 repeat participants 0 37 per 100 person years py 95 confidence interval ci 0 05 100 py 1 33 100 py 2 regression of prevalence by years injecting 0 61 per 100 py 95 ci 0 36 100 py 0 87 100 py 3 stratified extrapolation algorithm 0 32 per 100 py 95 ci 0 18 100 py 0 46 100 py and 4 newly diagnosed cases of hiv 0 14 per 100 py 95 ci 0 11 100 py 0 16 100 py all methods appear to capture the same phenomenon of very low and decreasing hiv transmission among persons who inject drugs public health implications if resources are available the use of multiple methods would provide better information for public health purposes to quantify the characteristics of community health workers chws involved in community intervention research and in particular to characterize their job titles roles and responsibilities recruitment and compensation and training and supervision we developed and administered a structured questionnaire consisting of 25 closed and open ended questions to staff on national institutes of health funded centers for population health and health disparities projects between march and april 2014 we report frequency distributions for chw roles sought after skills education requirements benefits and incentives offered and supervision and training activities a total of 54 individuals worked as chws across the 18 research projects and held a diverse range of job titles the chws commonly collaborated on research project implementation provided education and support to study participants and collected data training was offered across projects to bolster chw capacity to assist in intervention and research activities our experience suggests national benefit in supporting greater efforts to recruit retain and support the work of chws in community engagement research hiv is having a significant impact on young people among whom the rate of new diagnoses is high and health disparities are more pronounced incidence is increasing among young gay and bisexual men and among black males the largest percentage of new infections occur among those aged between 13 and 24 years youths are least likely to experience the health and prevention benefits of treatment nearly half of young people with hiv are not diagnosed among those diagnosed nearly a quarter are not linked to care and three quarters are not virally suppressed addressing this burden will require renewed efforts to implement effective prevention strategies across multiple sectors including educational social policy and health care systems that influence prevention knowledge service use and treatment options for youths although much is known about ventriculoperitoneal shunts there are still large gaps in the literature and no evidence based guidelines on management to date there is no general consensus on workup and treatment and there are many differing diagnostic and therapeutic strategies for management of complications ventriculoperitoneal shunt complications can be separated into 3 categories mechanical failure infection and functional failure knowing the basic anatomy of ventriculoperitoneal shunts the time of shunt placement and the clinical manifestations suggestive of potential complications can help with the management of patients with ventriculoperitoneal shunts this review summarizes the literature on complications of ventriculoperitoneal shunts examines the literature regarding the workup and management of patients with ventriculoperitoneal shunts and makes recommendations for the management of these patients in the emergency department recent data support the renewed interest in hypertriglyceridemia as a possible important therapeutic target for cardiovascular risk reduction this study was designed to address the question of all cause mortality during extended follow up of the bip trial in patients stratified by baseline triglyceride levels in the bip trial 3090 patients with proven coronary artery disease were randomized to bezafibrate 400 mg day or placebo all cause mortality data after 20 years of follow up were obtained from the national israeli population registry patients with hypertriglyceridemia triglycerides \u2265200 mg dl n 458 were equally distributed among the study groups 15 in both placebo and bezafibrate groups during follow up 1869 patients died 952 in placebo vs 917 in bezafibrate group following multivariate adjustment allocation to bezafibrate was associated with small but significant 10 mortality risk reduction hr 0 90 95 ci 0 82 0 98 p 0 026 variables associated with significantly increased mortality risk were history of a past mi nyha class diabetes age higher bmi and glucose level in patients with hypertriglyceridemia multivariate analysis demonstrated a 25 all cause mortality risk reduction associated with allocation to bezafibrate hr 0 75 ci 95 0 60 0 94 p 0 012 in patients without hypertriglyceridemia bezafibrate had no significant effect on long term mortality during long term follow up bezafibrate allocated patients experienced a modest but significant 10 reduction in the adjusted risk of mortality this effect of bezafibrate was more prominent among patients with baseline hypertriglyceridemia 25 mortality risk reduction long lasting insecticidal nets continue to provide effective protection against disease vectors including mosquitoes that transmit malaria in many countries promotion of llin usage and ownership has focused on the attainment of universal coverage however modalities for achieving these objectives remain a challenge in many countries this paper shares ghana s experience and strategies adopted to attain universal llins coverage endotoxin induced uveitis eiu in rodents is a model of acute toll like receptor 4 tlr4 mediated organ inflammation and has been used to model human anterior uveitis examine leukocyte trafficking and test novel anti inflammatory therapeutics wider adoption has been limited by the requirement for manual non specific cell count scoring of histological sections from each eye as a measure of disease severity here we describe a comprehensive and efficient technique that uses ocular dissection and multimodal tissue analysis this allows matched disease scoring by multicolour flow cytometric analysis of the inflammatory infiltrate protein analysis on ocular supernatants and qpcr on remnant tissues of the same eye dynamic changes in cell populations could be identified and mapped to chemokine and cytokine changes over the course of the model to validate the technique dose responsive suppression of leukocyte infiltration by recombinant interleukin 10 was demonstrated as well as selective suppression of the monocyte cd11b ly6c infiltrate in mice deficient for eitherccl2orccr2 optical coherence tomography oct was used for the first time in this model to allowin vivoimaging of infiltrating vitreous cells and correlated with cd11b ly6g counts to provide another unique measure of cell populations in the ocular tissue multimodal tissue analysis of eiu is proposed as a new standard to improve and broaden the application of this model the epithelial to mesenchymal transition emt is a highly conserved morphogenetic program essential for embryogenesis regeneration and cancer metastasis in cancer cells emt also triggers cellular reprogramming and chemoresistance which underlie disease relapse and decreased survival hence identifying compounds that block emt is essential to prevent or eradicate disseminated tumor cells here we establish a whole animal based emt reporter in zebrafish for rapid drug screening calledtg snai1b gfp which labels epithelial cells undergoing emt to producesox10 positive neural crest nc cells time lapse and lineage analysis oftg snai1b gfp embryos reveal that cranial nc cells delaminate from two regions an early population delaminates adjacent to the neural plate whereas a later population delaminates from within the dorsal neural tube treatingtg snai1b gfp embryos with candidate small molecule emt inhibiting compounds identified tp 0903 a multi kinase inhibitor that blocked cranial nc cell delamination in both the lateral and medial populations rna sequencing rna seq analysis and chemical rescue experiments show that tp 0903 acts through stimulating retinoic acid ra biosynthesis and ra dependent transcription these studies identify tp 0903 as a new therapeutic for activating rain vivoand raise the possibility that ra dependent inhibition of emt contributes to its prior success in eliminating disseminated cancer cells infective endocarditis is a devastating disease with high morbidity and mortality the link to oral bacteria has been known for many decades and has caused ongoing concern for dentists patients and cardiologists since 2008 the uk has been out of step with the rest of the world where antibiotic prophylaxis is recommended for high risk patients undergoing invasive dental procedures recent evidence that identified an increase in endocarditis incidence prompted a guideline review by nice and the european society for cardiology which produces guidance for the whole of europe despite reviewing the same evidence they reached completely opposing conclusions the resulting conflict of opinions and guidance is confusing and poses difficulties for dentists cardiologists and their patients recent changes in the law on consent however may provide a patient centred and pragmatic solution to these problems this opinion piece examines the evidence and opposing guidance on antibiotic prophylaxis in the context of the recent changes in the law on consent and provides a framework for how patients at risk of endocarditis might be managed in practice several modulatory factors in the tlr signaling pathway including irf3 irf7 irf8 trim20 myd88 and nf \u03bab1 have been associated with autoimmune disease in this study we investigated the association of 13 snps for these genes with beh\xe7et s disease bd and vogt koyanagi harada vkh syndrome using a polymerase chain reaction restriction fragment length polymorphism pcr rflp assay haplotype and linkage disequilibrium ld analysis were performed by haploview4 2 irf8 mrna expression and cytokine production was tested by real time pcr and elisa two snps near irf8 were associated with bd for rs17445836 gg genotype pc 9 56 10 8 or 2 044 for rs11642873 aa genotype pc 9 24 10 7 or 1 776 no significant association was found for the 13 snps tested with vkh syndrome haplotype analysis of the two positive snps revealed that the ag haplotype was significantly increased in bd patients pc 2 60 10 8 or 1 646 functional studies revealed an increased mrna expression of irf8 and ifn \u03b3 production and a decreased production of il 10 in rs17445836 carriers with the gg genotype increased expression of irf8 as well as ifn \u03b3 production and a decreased production of il 10 were found in individuals carrying the rs11642873 aa genotype in conclusion this study indicates that irf8 may contribute to the genetic susceptibility of bd by regulating irf8 expression and cytokine production most eukaryotic proteins are modified by covalent addition of glycan molecules that considerably influence their function aberrant glycosylation is profoundly involved in malignant transformation tumor progression and metastasis some glycan structures are tumor specific and reflect disturbed glycan biosynthesis pathways we analyzed dna methylation and expression of 86 glyco genes in melanoma hepatocellular breast and cervical cancers using data from publicly available databases we also analyzed methylation datasets without the available matching expression data for glyco genes in lung cancer and progression of melanoma into lymph node and brain metastases ten glyco genes galnt3 galnt6 galnt7 galnt14 mgat3 man1a1 man1c1 st3gal2 st6gal1 st8sia3 showing changes in both methylation and expression in the same type of cancer belong to galnac transferases glcnac transferases mannosidases and sialyltransferases which is in line with changes in glycan structures already reported in the same type of tumors some of those genes were additionally identified as potentially valuable for disease prognosis the mgat5b gene so far identified as specifically expressed in brain emerged as a novel candidate gene that is epigenetically dysregulated in different cancers other than brain cancer we also report for the first time aberrant expression of the galnt and man genes in cancer by aberrant promoter methylation aberrant expression of glyco genes due to aberrant promoter methylation could be a way leading to characteristic glycosylation profiles commonly described in cancer methylation status in promoters of candidate glyco genes might serve as prognostic markers for specific tumors and point to potential novel targets for epigenetic drugs this article is part of a special issue entitled glycans in personalised medicine guest editor professor gordan lauc efforts to achieve the new worldwide goals for maternal and child survival will also prevent stillbirth and improve health and developmental outcomes however the number of annual stillbirths remains unchanged since 2011 and is unacceptably high an estimated 2 6 million in 2015 failure to consistently include global targets or indicators for stillbirth in post 2015 initiatives shows that stillbirths are hidden in the worldwide agenda this series paper summarises findings from previous papers in this series presents new analyses and proposes specific criteria for successful integration of stillbirths into post 2015 initiatives for women s and children s health five priority areas to change the stillbirth trend include intentional leadership increased voice especially of women implementation of integrated interventions with commensurate investment indicators to measure effect of interventions and especially to monitor progress and investigation into crucial knowledge gaps the post 2015 agenda represents opportunities for all stakeholders to act together to end all preventable deaths including stillbirths this first paper of the lancet series on ending preventable stillbirths reviews progress in essential areas identified in the 2011 call to action for stillbirth prevention to inform the integrated post 2015 agenda for maternal and newborn health worldwide attention to babies who die in stillbirth is rapidly increasing from integration within the new global strategy for women s children s and adolescents health to country policies inspired by the every newborn action plan supportive new guidance and metrics including stillbirth as a core health indicator and measure of quality of care are emerging prenatal health is a crucial biological foundation to life long health a key priority is to integrate action for prenatal health within the continuum of care for maternal and newborn health still specific actions for stillbirths are needed for advocacy policy formulation monitoring and research including improvement in the dearth of data for effective coverage of proven interventions for prenatal survival strong leadership is needed worldwide and in countries institutions with a mandate to lead global efforts for mothers and their babies must assert their leadership to reduce stillbirths by promoting healthy and safe pregnancies despite the frequency of stillbirths the subsequent implications are overlooked and underappreciated we present findings from comprehensive systematic literature reviews and new analyses of published and unpublished data to establish the effect of stillbirth on parents families health care providers and societies worldwide data for direct costs of this event are sparse but suggest that a stillbirth needs more resources than a livebirth both in the perinatal period and in additional surveillance during subsequent pregnancies indirect and intangible costs of stillbirth are extensive and are usually met by families alone this issue is particularly onerous for those with few resources negative effects particularly on parental mental health might be moderated by empathic attitudes of care providers and tailored interventions the value of the baby as well as the associated costs for parents families care providers communities and society should be considered to prevent stillbirths and reduce associated morbidity previous research demonstrates that physical activity participation is associated with longer leukocyte telomere length with shorter leukocyte telomere length being a hallmark characteristic of cellular aging what remains under investigated however is whether there is a mode specific association of physical activity on leukocyte telomere length which was this study s purpose data from the 1999 2002 national health and nutrition examination survey were used n 6474 adults analyzed leukocyte telomere length was assessed using quantitative polymerase chain reaction physical activity was assessed via self report with participants classified as meeting physical activity guidelines \u22652000 metabolic equivalent of task min month for 9 separate physical activities including aerobics unweighted percent meeting guidelines 2 98 n 193 basketball 2 0 n 129 bicycling 3 71 n 240 dance 2 30 n 149 running 3 09 n 200 stair climbing 1 33 n 86 swimming 1 85 n 120 walking 13 53 n 876 and weight lifting 2 61 n 169 in a single multivariable linear regression model including the independent variables of age gender race ethnicity weight status total cholesterol c reactive protein total metabolic equivalent of task min month of physical activity and the 9 binary meeting physical activity guideline variables the only mode of physical activity that was significantly associated with leukocyte telomere length was meeting physical activity guidelines from running \u03b2 0 06 95 ci 0 01 0 11 p 0 03 running specific physical activity was the only evaluated physical activity associated with leukocyte telomere length which may provide one potential mechanism i e leukocyte telomere length through which running based physical activity may help to prevent cardiovascular disease and premature mortality 123 i ioflupane spect datscan is an examination that detects presynaptic dopamine neuronal dysfunction and has been used as a diagnostic tool to identify degenerative parkinsonism additionally myocardial 123 i metaiodobenzyl guanidine mibg scintigraphy measures the concentration of cardiac sympathetic nerve fibers and is used to diagnose parkinson s disease pd these exams are used as adjuncts in the diagnosis of parkinsonism however the relationship of these two examinations are not well known we investigated the relationship of these two scanning results specifically for determining the use of deep brain stimulation therapy dbs subjects were japanese patients with suspected striatonigral degeneration including pd datscans and myocardial mibg scintigraphy were performed the mean values of the left right specific binding ratios sbrs from the datscan and the early delayed heart to mediastinum ratios hmrs from the mibg scintigraphy were calculated using simple linear regression analysis we compared the sbr and early delayed hmr values twenty four patients were enrolled in this study twenty one patients were positive via the datscan and the mibg scintigraphy results showed 14 patients were positive sbr and both early and delayed hmr were positively correlated in cases of pd but negative in non pd cases a mean sbr value less than 3 0 and a delayed hmr value less than 1 7 indicated a hoehn yahr stage 3 or 4 for pd which is commonly regarded as a level appropriate for initiating dbs therapy our results indicate that performing both datscan and mibg scintigraphy is useful for the evaluation of surgical intervention in pd we review the cardiac safety of the drugs available at present for the maintenance treatment of chronic obstructive pulmonary disease copd in stable disease focusing on inhaled long acting muscarinic antagonists lama and long acting \u03b22 agonists laba used either as a monotherapy or as a fixed dose combination we report the difficulties of and pitfalls in the investigation of the safety of drug treatments in copd which is hampered by the so called copd trial paradox on the one hand copd is defined as a systemic disease and is frequently associated with comorbidities especially cardiovascular comorbidities which have an important effect on the prognosis of individual patients on the other hand patients with copd and cardiovascular or other coexisting illnesses are often excluded from participation in randomised controlled clinical trials in these trials inhaled long acting bronchodilators both lama or laba or both seem to be safe when used in the appropriate dose in adherent patients with copd without uncontrolled cardiovascular disease or other notable comorbidities however the cardiac safety of lama and laba is less evident when used inappropriately eg overdosing or in patients with copd and substantial cardiovascular disease prolonged qtc interval or polypharmacy potential warnings about rare cardiac events caused by copd treatment from meta analyses and observational studies need to be confirmed in high quality large randomised controlled trials finally we briefly cover the cardiac safety issues of chronic oral drug treatments for copd encompassing theophylline phosphodiesterase inhibitors and macrolides immunochromatographic tests need to be improved in order to enhance their reliability recently several new kits have appeared on the market the objective was to evaluate the diagnostic accuracy of three monoclonal rapid stool tests the new uni gold h pylori antigen trinity biotech ireland the rapid hp star oxoid ltd uk and the immunocard stat hpsa meridian diagnostics usa for detecting h pylori infection prior to eradication treatment diagnostic accuracy sensitivity and specificity and reliability concordance between observers were evaluated in 250 untreated consecutive dyspeptic patients the gold standard for diagnosing h pylori infection was defined as the concordance of two or more of rapid urease test rut histopathology and urease breath test ubt or positive culture in isolation readings of immunochromatographic tests were performed by two different observers sensitivity specificity positive and negative predictive values and 95 confidence intervals were calculated sensitivity and specificity were compared using the mcnemar test the three tests showed a good correlation with kappa values 0 9 rapid hp star had a sensitivity of 91 92 and a specificity ranging from 77 to 85 its sensitivity was higher than that of uni gold h pylori antigen and immunocard stat hpsa p 0 01 uni gold h pylori antigen kit showed a sensitivity of 83 similar to immunocard stat hpsa specificity of uni gold h pylori antigen approached 90 87 89 and was superior to that of rapid hp star p 0 01 uni gold h pylori antigen and immunocard stat hpsa present similar levels of diagnostic accuracy rapid hp star was the most sensitive but less reliable of the three immunochromatographic stool tests none are as accurate and reliable as ubt rut and histology human carbonic anhydrase 9th isoform ca ix is an important marker of numerous cancers and is increasingly interesting as a potential anticancer drug target various synthetic aromatic sulfonamide bearing compounds are being designed as potent inhibitors of ca ix however sulfonamide compound binding to ca ix is linked to several reactions the deprotonation of the sulfonamide amino group and the protonation of the ca active site zn ii bound hydroxide these linked reactions significantly affect the affinities and other thermodynamic parameters such as enthalpies and entropies of binding the observed and intrinsic affinities of compound binding to ca ix were determined by the fluorescent thermal shift assay the enthalpies and entropies of binding were determined by the isothermal titration calorimetry the pka of ca ix was determined to be 6 8 and the enthalpy of ca ix zn ii bound hydroxide protonation was 24 kj mol these values enabled the analysis of intrinsic thermodynamics of a library of compounds binding to ca ix the most strongly binding compounds exhibited the intrinsic affinity of 0 01 nm and the observed affinity of 2 nm the intrinsic thermodynamic parameters of compound binding to ca ix helped to draw the compound structure to thermodynamics relationship it is important to distinguish the intrinsic from observed parameters of any disease target protein interaction with its inhibitors as drug candidates when drawing detailed compound structure to thermodynamics correlations despite the search for new therapeutic strategies for gastric cancer gc there is much evidence of progression due to resistance to chemotherapy multidrug resistance mdr is the ability of cancer cells to survive after exposure to chemotherapeutic agents the involvement of mirnas in the development of mdr has been well described but mirnas able to modulate the sensitivity to chemotherapy by regulating hypoxia signaling pathways have not yet been fully addressed in gc our aim was to analyze mir 20b mir 27a and mir 181a expression with respect to epirubicin oxaliplatin capecitabine eox chemotherapy regimen in a set of gc patients in order to investigate whether mirnas deregulation may influence gc mdr also via hypoxia signaling modulation cancer biopsy were obtained from 21 untreated her2 negative advanced gc patients retrospectively analyzed all patients received a first line chemotherapy eox regimen mirwalk database was used to identify mir 27a mir 181a and mir 20b target genes the expression of mirnas and of hipk2 hif1a and mdr1 genes were detected by real time pcr hipk2 localization was assessed by immunohistochemistry our data showed the down regulation of mir 20b mir 27a mir 181a concomitantly to higher levels of mdr1 hif1a and hipk2 genes in gc patients with a progressive disease respect to those with a disease control rate moreover immunohistochemistry assay highlighted a higher cytoplasmic hipk2 staining suggesting a different role for it we showed that aberrant expression of mir 20b mir27a and mir 181a was associated with chemotherapeutic response in gc through hif1a mdr1 and hipk2 genes modulation suggesting a possible novel therapeutic strategy the intracellular protozoal parasite theileria orientalis has rapidly spread across south eastern australia substantially impacting local cattle industries since 2006 haemaphysalis longicornis appears to be a biological vector in the endemic regions mechanical transfer of blood by biting arthropods in colostrum or iatrogenic transmission though husbandry procedures is another possible mode of transmission this study assesses the risk of these mechanical modes of transmission blood was collected from a t orientalis ikeda positive angus steer and was inoculated into the jugular vein of 9 calves in 3 treatment groups each with 3 animals calves in group 1 received 10 ml of cryopreserved blood while those in groups 2 and 3 received 1 ml fresh blood and 0 1 ml cryopreserved respectively an additional three animals remained as negative controls and the donor calf was also followed as a positive control blood was collected over 3 months and analysed via qpcr for the presence of the parasite samples of the sucking louse linognathus vituli were collected opportunistically from calves 5 months after inoculation and tested for t orientalis for the colostral transmission study 30 samples of blood and colostrum were collected from cows at calving in an endemic herd these samples along with blood from their calves were tested by qpcr for t orientalis and for antibodies to the major piroplasm surface protein mpsp eight of the nine inoculated calves became positive for t orientalis the prepatent period of these infections was inversely correlated with inoculation dose all negative control calves remained negative and the positive control calf remained positive samples of l vituli tested positive for t orientalis ikeda while some samples of colostrum were also shown to be qpcr and anti mpsp positive all calves in the colostral study tested qpcr negative although one was antibody positive t orientalis is capable of being mechanically transferred by intravenous inoculation with small volumes of blood and is detectable up to 5 months post infection animals infected by this means may play a significant role in the transmission of the disease by acting as asymptomatic carriers other modes of blood transfer including biting arthropods and colostral transfer are also possible modes of disease transmission the safety tolerability pharmacokinetics pk and anti tumor activity of enzalutamide were investigated in patients with castration resistant prostate cancer crpc in japan through a multicenter phase i ii study in phase i patients with progressive metastatic crpc received single then multiple ascending doses of enzalutamide 80 160 or 240 mg day after assessment of tolerability at multiple doses of 160 mg day for 4 weeks post docetaxel patients with crpc and measurable disease were enrolled into phase ii receiving long term administration of enzalutamide 160 mg day nine and 38 patients were enrolled in phase i and ii respectively during phase i enzalutamide was well tolerated in each cohort pk parameters were similar to those of non japanese populations in other studies by week 12 overall response rate was 5 3 and clinical benefit rate was 47 4 prostate specific antigen response rate \u226550 reduction from baseline was 28 9 treatment emergent adverse events reported in 20 of patients in phase ii were decreased weight decreased appetite and constipation no seizures were observed enzalutamide at 160 mg day was well tolerated with pk and safety profiles similar to the non japanese population anti tumor activity was observed in post docetaxel japanese patients with metastatic crpc apparent differences in anti tumor activity compared with the affirm study a phase iii trial in a diverse population of patients with crpc post docetaxel may be attributed to differences in treatment history prior to starting enzalutamide particularly in japan the influence of sequence in hormone treatments including combined androgen blockade therapy should be considered clinicaltrials gov nct01284920 mansonella perstans is a widespread but relatively unknown human filarial parasite transmitted by culicoides biting midges although it is found in many parts of sub saharan africa only few studies have been carried out to deepen the understanding of its ecology epidemiology and health consequences hence knowledge about ecological drivers of the vector and parasite distribution integral to develop spatially explicit models for disease prevention control and elimination strategies is limited we analyzed data from a comprehensive nationwide survey of m perstans infection conducted in 76 schools across uganda in 2000 2003 to identify environmental drivers a suite of bayesian geostatistical regression models was fitted and the best fitting model based on the deviance information criterion was utilized to predict m perstans infection risk for all of uganda additionally we investigated co infection rates and co distribution with wuchereria bancrofti and plasmodium spp infections observed at the same survey by mapping geographically overlapping areas several bioclimatic factors were significantly associated with m perstans infection levels a spatial bayesian regression model showed the best fit with diurnal temperature range normalized difference vegetation index and cattle densities identified as significant covariates this model was employed to predict m perstans infection risk at non sampled locations the level of co infection with w bancrofti was low 0 3 due to limited geographic overlap however where the two infections did overlap geographically a positive association was found this study presents the first geostatistical risk map for m perstans in uganda we confirmed a widespread distribution of m perstans and identified important potential drivers of risk the results provide new insight about the ecologic preferences of this otherwise poorly known filarial parasite and its culicoides vector species in uganda which might be relevant for other settings in sub saharan africa the purpose of this study was to investigate the incidence predictive factors and effect of post operative delirium pod among patients treated by transcatheter aortic valve replacement tavr patients undergoing operations that involve valve replacement appear at higher risk of pod than patients subjected to coronary artery bypass surgery alone in patients with severe aortic stenosis undergoing tavr little is known regarding the potential impact of pod on the clinical outcomes a retrospective observational cohort study of 268 consecutive patients who underwent tavr at our institute was conducted delirium was diagnosed according to the diagnostic and statistical manual of mental disorder 4th edition criteria the primary outcome of this study was the presence of in hospital pod after tavr the incidence of pod after tavr was 13 4 n 36 of these cases 18 were associated with post procedural complications including major vascular complications bleeding n 4 stroke n 3 acute kidney injury n 3 atrial fibrillation n 4 and infectious disease n 4 pod was most frequently diagnosed on the second day after tavr interquartile range iqr 1 to 5 days and was associated with prolonged in hospital stay regardless of complications in uncomplicated tavr 6 days iqr 5 to 10 days vs 5 days iqr 4 to 5 days p 0 001 and in complicated tavr 9 days iqr 8 to 15 days vs 6 days iqr 5 to 9 days p 0 001 predictors of pod were nontransfemoral transapical transaortic access odds ratio or 7 74 95 confidence interval ci 3 26 to 18 1 current smoking or 3 99 95 ci 1 25 to 12 8 carotid artery disease or 3 88 95 ci 1 50 to 10 1 atrial fibrillation or 2 74 95 ci 1 17 to 6 37 and age or 1 08 95 ci 1 00 to 1 17 per year increase after a median follow up of 16 months iqr 6 to 27 months pod remained an independent predictor of mortality in patients undergoing transfemoral tavr compared with the nontransfemoral tavr hazard ratio 2 81 95 ci 1 16 to 6 83 vs hazard ratio 0 43 95 cl 0 10 to 1 76 adjusted for possible confounders in a time dependent cox regression model i e age sex logistic euroscore and the occurrence of complications pod after tavr has an incidence of around 13 and occurs early in the post operative course nontransfemoral access is strongly associated with the occurrence of pod patients who develop pod show prolonged in hospital stay and impaired long term survival parkinson disease pd is a neurodegenerative disease characterized by the accumulation of alpha synuclein snca and other proteins in aggregates termed lewy bodies within neurons pd has both genetic and environmental risk factors and while processes leading to aberrant protein aggregation are unknown past work points to abnormal levels of snca and other proteins although several genome wide studies have been performed for pd these have focused on dna sequence variants by genome wide association studies gwas and on rna levels microarray transcriptomics while genome wide proteomics analysis has been lacking this study employed two state of the art technologies three stage mass spectrometry tandem mass tag proteomics 12 pd 12 controls and rna sequencing transcriptomics 29 pd 44 controls evaluated in the context of pd gwas implicated loci and microarray transcriptomics 19 pd 24 controls the technologies applied for this study were performed in a set of overlapping prefrontal cortex brodmann area 9 samples obtained from pd patients and sex and age similar neurologically healthy controls after appropriate filters proteomics robustly identified 3558 unique proteins with 283 of these 7 9 significantly different between pd and controls q value 0 05 rna sequencing identified 17 580 protein coding genes with 1095 of these 6 2 significantly different fdr p value 0 05 only 166 of the fdr significant protein coding genes 0 94 were present among the 3558 proteins characterized of these 166 eight genes 4 8 were significant in both studies with the same direction of effect functional enrichment analysis of the proteomics results strongly supports mitochondrial related pathways while comparable analysis of the rna sequencing results implicates protein folding pathways and metallothioneins ten of the implicated genes or proteins co localized to gwas loci evidence implicating snca was stronger in proteomics than in rna sequencing analyses we report the largest analysis of proteomics in pd to date and the first to combine this technology with rna sequencing to investigate gwas implicated loci notably differentially expressed protein coding genes were more likely to not be characterized in the proteomics analysis which lessens the ability to compare across platforms combining multiple genome wide platforms offers novel insights into the pathological processes responsible for this disease by identifying pathways implicated across methodologies successful treatment of life threatening community acquired pneumonia requires appropriate empiric antibiotic coverage but using conventional diagnostic techniques a microbiological diagnosis is often not achieved the diagnostic usefulness of tracheal aspirate at the time of intubation in patients with severe pneumonia has not been well studied the purpose of this study was to evaluate the use of tracheal aspirate culture in identifying pneumonia pathogens we identified all patients older than 18 years of age with international classification of disease ninth revision codes and radiographic evidence of pneumonia seen in the emergency departments at 2 university affiliated utah hospitals from december 2009 to november 2010 and from december 2011 to november 2012 patients intubated within 24 hours of arrival were then identified electronically postintubation orders instructed respiratory therapists to obtain tracheal aspirate for culture all culture results were reviewed individually and defined as positive if a pneumonia pathogen was identified results of other microbiology studies were obtained from the electronic medical record of 2 011 patients with pneumonia 94 were intubated and 84 had a tracheal aspirate obtained of these 84 patients 47 56 had a pulmonary pathogen identified by tracheal aspirate culture 80 also had blood cultures and 71 underwent pneumococcal and legionella urinary antigen testing a microbiological diagnosis was made in 55 patients 65 5 by any diagnostic method in 39 of patients 32 of 82 the tracheal aspirate culture was the only positive test resulting in a unique microbiological diagnosis in patients who would have otherwise been classified as culture negative tracheal aspirate cultures obtained as part of routine care identified a plausible pneumonia pathogen in more than one half of emergency department adult patients with severe pneumonia requiring intubation tracheal aspirate culture offers important additive diagnostic value to other routine tests whole blood packed red blood cells prbc units transfused in the u s totaled 13 785 000 in 2011 a single institution in south dakota transfused 6 485 units of prbc in 2013 current thresholds for transfusion have changed and each transfusion has the risk of causing an adverse reaction thus it is important to ensure prbcs are administered appropriately due to these changes and the potential risks associated with transfusion we reviewed the literature regarding appropriate indications for transfusion of prbc our review specifically focused on four disease entities iron deficiency anemia acute upper gastrointestinal gi bleeding acute coronary syndromes and chronic ischemic heart disease based on our findings we recommend utilizing an overall conservative approach to the transfusion of prbc in patients with iron deficiency anemia first try alternative methods to improve hemoglobin levels in those with acute gi bleeding transfuse for hemoglobin less than 7 g dl in patients with acute coronary syndromes let symptoms signs be your guide and in patients with ischemic heart disease transfuse for hemoglobin levels less than 8 g dl or if they are symptomatic most importantly be cautious to not fixate on numbers alone always incorporate patients symptoms and co morbidities when considering whether to transfuse prbcs hodgkin lymphoma hl typically presents in the nodal regions at an early stage of the disease occasionally patients can present with disease in extranodal regions we report a case of hl in a 25 year old female who presented to the emergency department following a motor vehicle accident with incidental findings of pulmonary cavitary lesions fever tachycardia anemia leukocytosis and thrombocytosis this case illustrates the difficulty in diagnosis when the disease presents in extranodal regions with nonspecific systemic symptoms complete workup for infectious and autoimmune etiology was performed and found to be negative ct guided biopsy and bronchoscopy failed to yield the diagnosis a video assisted thoracoscopic surgery was necessary to obtain the diagnosis of advanced stage hl in this patient focal status epilepticus and catastrophic epilepsy are not rare in infants epilepsy surgery can be safely done in selected infants to cure epilepsy we report on an infant who began having drug resistant status epilepticus at 2 weeks of age and developed epileptic spasms we discuss in detail how the clinical and electroencephalographic data were used to reach a consensus for epilepsy surgery and why a particular surgical approach was preferred over other alternatives presurgical evaluation consisted of 32 channel scalp video eeg using the standard 10 20 system of electrodes 3 tesla brain magnetic resonance imaging and 18 f fluorodeoxyglucose positron emission tomography the surgery consisted of resection of the extensive epileptogenic lesion in addition to disconnection of the left frontal lobe anterior to the motor strip the infant underwent epilepsy surgery at three months of age at two year follow up she remained seizure free with no focal motor deficit and the epileptic encephalopathy resolved the disconnected left frontal lobe shows epileptiform discharges restricted to the disconnected tissue we highlight the importance of epilepsy surgery in selected infants to achieve seizure freedom and to reverse epileptic encephalopathy in the process we demonstrate how epileptic spasms although clinically and electrographically generalized resolved after disconnecting the epileptogenic zone cortical lesions in status epilepticus have been reported but the underlying mechanisms are poorly elucidated we report on afemale patient 75 years with a history of alcohol abuse who presented with complex partial status epilepticus and lateralized epileptiform discharges in the left frontal and temporal regions in eeg while cranial magnetic resonance imaging mri showed left hippocampal t2 hyperintensity and diffusion restriction cerebrospinal fluid was normal and revealed no limbic encephalitis related antibodies following treatment with levitiracetam seizures ceased and the patient was dismissed nine months later she was readmitted with generalized status epilepticus cranial mi now showed hippocampal diffusion restriction and t2 hyperintensity but in the right hemisphere as well as atrophy and partial gliotic transformation of the initially affected left hippocampus although hippocampal damage due to antibody negative limbic encephalitis cannot be ruled out our observation of subsequent bilateral hippocampal diffusion restriction with gliotic transformation may demonstrate permanent seizure induced structural brain damage and underlines the importance of further research to elucidate the effects of prolonged epileptic discharges on cerebral structural integrity the prevalence of metabolic syndrome ms is increasing in japan because of westernization of diet and lifestyle previous epidemiological studies have demonstrated ms to relate with the malignant potential of prostate cancer pca while its relationship to the risk of pca has been still controversial several pathologies involved in ms such as insulin resistance abnormality of secreted adipokines chronic inflammation alteration of sex hormones have been reported to affect the progression of pca based on these evidences clinical studies for pca patients have been tried for suppressing the progression of pca through the management of ms prostate cancer is now the most commonly diagnosed cancer in japanese men in 2015 it is estimated 98 400 new cases are diagnosed in addition bone is the most common site for metastasis in prostate cancer and many patients will develop bone metastases during the natural course of their disease however current advances in the diagnosis treatment of metastatic prostate cancer lead to change treatment strategy dramatically in fact bone metastasis has been changed palliative to targeted organ aimed to extend overall survival in patients with metastatic castration resistant prostate cancer mcrpc we review the multiple issues involved in current diagnosis and the multidisciplinary approach to the treatment of bone metastases in patients with prostate cancer and future directions the merits of introducing psa based screening would be cause specific mortality reduction and prevention of developing metastatic disease which was recently confirmed by prospective randomized controlled trials on the other hand some men participating in the screening program may be of drawbacks in terms of overdetection and overtreatment therefore providing a fact sheet on screening for prostate cancer and also progress in an optimal screening system including more accurate cancer detection minimally invasive treatment and active surveillance strategy which can reduce overdetection overtreatment and loss of qol due to treatment would be very important recently new generation androgen receptor ak targeted agents enzautamide or abiraterone etc has been clinically utilized in patients with castration resistant prostate cancer crpc however metastatic crpc has also ar independent survival pathway which leads to lethal phenotype by either adaptation or clonal selection resistant mechanism after ar targeted therapy there are many studies regarding the progression mechanisms without ar signal transduction such as growth factor anti apoptotic factor and pten mtor pathway and so on also cancer microenvironment and cancer stem cell is a hot research area for crpc it is very important to repress both ar dependent and independent signaling pathway to improve the clinical outcome in crpc patients application of the new technology such as next generation sequencing would be developing for the prostate cancer research providing pre clinical proof of principle as a promising approach in crpc androgen receptor ar has a critical role in prostate cancer pca progression and targeting ar axis signaling by androgen deprivation therapy is a standard treatment for advanced pca recently the role of ar even in castration resistant pca crpc is well recognized and emerging evidence suggests survival advantages of treatment by targeting ar in crpc this review outlines ar functions that contribute to pca progression ar structural alterations and ar activation via intracrine co factors and kinase pathways in crpc finally we describe about recently reported bipolar androgen therapy as a novel treatment for crpc targeting ar cancer tissues are comprised of cell population including a variety of cells such as stem cell like cancer cells upon which a hierarchical society is constructed this hypothesis has been applied not only to leukemia in which the hypothesis was first experimentally confirmed but also to solid cancers recent topics shed light on the modified heterogeneity by various treatments which evolve disease progression in prostate cancer the identification of cancer stem cells using surface markers and the relationship with prostate origin are of current interest this article reviews studies related to the development of prostate cancer and introduce recent progress of our project focusing on cancer stemness and drug resistance it is evident that genetic factors play critical roles in prostate cancer development gwas genome wide association studies in multiple ethnic groups have been identifying more than 100 loci or genes which was significantly associated with prostate cancer susceptibility they include several loci at 8q24 prostate specific gene inflammation gene and metabolism related genes risk prediction for prostate cancer by combining multiple snps is still primitive and not sufficiently accurate for clinical use but this model could have a potential to affect clinical decision when it is applied to patients with gray zone psa or very high risk of prostate cancer most valuable tool for diagnosis of prostate cancer is psa although psa is highly specific for organ it is not so specific for disease therefore about 70 of patients whose psa value is 4 10 ng ml are forced to undergo unnecessary prostate biopsy in order to discriminate the unnecessary biopsies several markers such as free total psa ratio psa density and psa velocity have been developed however none of these markers were widely approved in daily clinical settings prostate cancer antigen 3 pca3 is thought to be a useful marker for necessity of repeat biopsy functional mr imaging such as dynamic contrast enhancement dce diffusion weighted imaging dwi mr spectroscopy mrs have been developed recently mri trus fusion biopsy is gathering attention in terms of pathology atypical glands but not high grade pin require repeat biopsy after 3 to 6 months from initial biopsy in patients with arterial hypertension ah pharmacotherapy often remains ineffective because of comorbid pathology research of haemodynamic and metabolic processes in such patients allows prescribe effective antihypertensive medicines improve life quality and prognosis 60 patients with ah coronary artery disease and obesity were divided into three groups 1st group was treated with lisinopril atorvastatin aspirin regimen i 2nd group was treated with lisinopril atorvastatin bisoprolol aspirin regimen ii 3rd group was treated with lisinopril bisoprolol indapamide atorvastatin aspirin regimen iii laser correlation spectrometry lcs was used to evaluate the homeostatic alterations all regimens were equally effective in normalization of systolic blood pressure and did not influence the ejection fraction only in the 3rd group was determined significant increase of glomerular filtration rate 92 73 2 12 vs 79 62 13 62 ml min 1 73m2 the lcs test showed that these patients had high level of light scattering particles iv which may be caused by activation of anabolic processes in other groups spectral alterations were not so expressive prescription of antihypertensive therapy cause homeostatic and metabolic alterations which may influence the efficacy of treatment chronic periaortitis represents a unique pathogenic concept for three entities inflammatory abdominal aortic aneurysm idiopathic retroperitoneal fibrosis and perianeurysmal retroperitoneal fibrosis the fundamental meaning of an inflammatory reaction to advanced atherosclerosis has been developed on the bottom of clinical and histological features the triad of abdominal pain weight loss and elevated inflammatory markers erythrocyte sedimentation rate c reactive protein in patients with abdominal aortic aneurysms revealed on contrast enhanced computer tomography is highly suggestive for inflammatory aneurysm we report a case of a heavy smoker adult male presented with suddenly abdominal symptoms suggestive for mesenteric ischemia which have proved to be due to inflammatory abdominal aortic aneurysm the most favorable management of patients with inflammatory aneurysm is ambiguous surgical approach seems reasonable even supposing inflammatory aneurysm emerges less likely to rupture than the atherosclerotic variant corticosteroids are used in inoperable inflammatory aneurysm even if is well known that this treatment does not change the long term outcome of the disease surgical open or endovascular repair of the aneurysm is the elective treatment polymyositis is an idiopathic inflammatory myopathy of unknown aetiology that affect skeletal muscles causing symmetrical proximal muscle weakness and also other internal organs the investigations reveal elevated skeletal muscle enzyme levels and characteristic electromyography emg and muscle biopsy findings pulmonary involvement in polymyositis includes respiratory muscle weakness aspiration pneumonia interstitial lung disease infection and drug induced pneumonia we expose the case of a young woman 47 years old who presented to the pulmonology clinic with fever cough purulent sputum discrete myalgia being diagnosed at that moment with interstitial lung disease and treated with antibiotics low dose of corticosteroids and symptomatic drugs the evolution was slowly favorable for the respiratory impairment but the patient developed exacerbated myalgia muscle weakness reaching even the impossibility of maintaining orthostatism and also joint pain biological investigations revealed an important hepatocytolysis syndrome and also increased levels of muscle enzyme the hypothetical diagnosis was polymyositis and to sustain this theory it was performed a muscle biopsy the patient was transferred afterwards to the rheumatology clinic in order to perform other specific investigations in our clinic the patient maintained elevated levels of skeletal muscle enzymes and the muscle biopsy revealed polymyositis findings also immunological investigations objectified the presence of jo1 antibodies therefore we pleaded for the diagnosis of idiopathic polymyositis acute form a multidisciplinary approach is needed in order to establish an accurate diagnosis and to institute a proper treatment encephalitis is a brain inflammation which could involve also the meninges the etiology of encephalitis could be viral bacterial fungal or autoimmune anti nmdar encephalitis is an immune disorder easy to diagnose and is a treatable condition most patients with anti nmdar encephalitis develop a multistage illness that progresses from psychosis memory deficits seizures to catatonic state and breathing instability we present a case report of a 20 year old woman who presented amnesia visual hallucination illusions seizures after that occurred following autoimmune encephalitis the exact incidence of anti nmdar encephalitis is unknown but it seems to be more frequent than any other known paraneoplastic encephalitis the present case is important considering that autoimmune encephalitis is a rare frequency disorder in romania with patients presenting resounding psychiatric and neurological manifestations localized cutaneous amyloidosis is a rare disease among white people being more common in south asia china and south america the disease is characterized by deposition of amyloid material in the papillary dermis without visceral involvement nevertheless there is a growing list of immune mediated disorders that have been linked to cutaneous amyloidosis we present two cases of concomitant occurrence of lichen amyloidosis and autoimmune thyroiditis atopic dermatitis in two caucasian women selenium se is an important element that exerts its effects through selenoproteins the thyroid gland has the highest se concentration and specific selenoprotein enzymes families are crucial in the thyroid hormone metabolism there is little evidence on the link between se and thyroid autoimmune disease therefore future studies are required to elucidate the nature of this associ ation to evaluate the se status in euthyroid subjects with autoimmune thyroiditis from january 2014 to january 2015 we recruited 100 consecutive euthyroid subjects with autoimmune thyroiditis living in the same region and with normal iodine intake serum concentrations of se thyroid antibodies antithyroperoxidase tpoab and antithyroglobulin tgab thyroid stimulating hormone tsh and thyroid ultrasound were performed in all patients mean age of the study group was 48 87 12 83 years range 18 82 years since thyroid pathology is more frequent in the 5th 6th decades of life we selected the age of 50 for the comparative analysis of the results 51 of patients were under 50 no statistical age group differences in antibody levels were found mean tpoab 420 95 iu ml p 0 840 mean tgab 327 98 iu ml p 0 977 tsh mean was 2 14 \u03bciu ml with no significant age group differences p 0 176 se levels ranged between 8 05 998 50 \u03bcg with a mean value of 294 96 \u03bcg l and no significant differences between age groups p 0 158 thyroid ultrasound showed inhomogeneity in 89 nodules in 35 of patients and a mean thyroid volume of 11 72ml with no significant age group differences p 0 366 the low tsh levels were associated with low se levels in 11 6 of cases but the direct correlation was statistically insignificant r 0 116 r2 0 0161 p 0 371 depend ing on tsh percentiles mean selevels showed no significant differences however pointing out the highest mean value at the 25th percentile f 0 441 df 61 p 0 646 a negative correlation trend was found between se and tpoab r 0 2276 or tgab r 0 2190 but lacking statistical significance p 0 099 our results showed a weak negative correlation between se and antithyroid antibodies suggesting that selenium supplementation may improve the course of thyroid autoimmunity the similar routes of transmission for hiv and hbv place patients with either infection at greater risk for hiv hbv co infection to determine the particularities of hepatitis b virus hbv coinfection in pregnant women infected with human immunodeficiency virus hiv and its influence on pregnancy retrospective study of 74 hiv infected women monitored during pregnancy in the iasi regional hiv aids center romania from 2010 to 2013 the subjects were divided into 2 groups according to the presence or absence of hbv coinfection most subjects belonged to age group 20 24 years 90 in the hiv group versus 75 5 in the hiv hbv coinfected group hiv infection was most commonly transmitted by parenteral route 65 5 vs 48 9 the majority of patients were married 60 vs 65 and primiparous at the time of enrollment 71 1 vs 96 6 in the hiv hbv coinfected group cd4 level was lower and mean plasma viral load higher 1 92 log10 copies ml vs 2 31 log10 copies ml the proportion of cases with severe immunosuppression was similar in both groups 18 1 vs 17 9 hbv hiv coinfection induced a risk of prematurity of 1 51 times but did not increase the risk of newborns with low birth weight advanced stages of hiv disease age group 21 30 years low cd4 counts and low levels of education are significant risk factors for preterm birth and low birth weight this study was intended to investigate the microcirculation endothelial dysfunction through a laser doppler method porh post occlusive reactive hyperemia in patients with chronic kidney disease the study included 299 patients diagnosed with chronic kidney disease which were divided into three groups hemodialysis patients peritoneal dialysis patients and patients with chronic kidney disease stages 3 4 endotelial dysfunction was assesed with the laser doppler perfusion monitor type device periflux system monitor 5001 the values of the parameters we evaluated with postocclusive reactive hyperemia were altered in all patients with chronic kidney disease in the dialysis groups there was no statistically significant correlation between parameters we tested by measuring porh and the method of renal replacement therapy or dialysis duration the same was observed in patients with pre dialysis chronic kidney disease post occlusive reactive hyperemia a novel method for assessing endothelial dysfunction on the microcirculatory system and early marker of cardiovascular damage requires more studies to validate in patients advanced renal disfunction the outcome of chronic hbv infection is variable approximately one half of individuals transition to an inactive carrier state 30 progress to cirrhosis and the remainder to chronic hepatitis ten different hbv genotypes and many subtypes have been identified with distinct geographical distributions over the years a lot of studies presented the efficiency of different genotyping methods for this reason we aimed to present a cost efficient genotyping diagnosis algorithm of chb infected patients especially useful to identify those at risk of disease progression and determine optimal anti viral therapy as useful instrument for physicians systemic lupus erythematosus sle is a chronic multisystem inflammatory disorder that occurs primarily in women of childbearing age immunologic abnormalities being a prominent feature of the disease psychiatric disorders frequently coexist depression being the most common mood disorder in neuropsychiatric lupus this literature review was performed through searching medline database for full text english language articles original research systematic review and updates published in the last five years 2010 2015 using the keywords depression and systemic lupus erythematosus the main outcomes identified were prevalence and predictors of depression in various cultural and ethnic groups depression related clinical issues suicidal ideation cognitive impairment altered body image sleep and sexual disturbances influence of sle treatment and influence on quality of life a multidisciplinary approach that takes into account the polymorphism and individual variability of the sle clinical manifestations helps to improve early detection of depression which is responsible for the increased risk of comorbidities suicidal attempts decreased treatment adherence and impaired quality of life physicians across all specialties involved in the care for lupus patients should be aware of the major prevalence of this condition while helping patients to cope with their disabling disease laryngopharyngeal reflux has been recognized since 2006 montreal consensus as an extradigestive manifestation of gastroesophageal reflux disease however despite numerous research studies the relationship between these two pathologies is yet to be fully understood the aim of this paper is to review the literature of the last five years available via the pubmed database looking at the controversies about the prevalence pathophysiology and diagnosis of laryngopharyngeal reflux backgrounds and study aims endoscopic sphincterotomy es is widely accepted as first line therapy for bile duct stones bds the major long term pancreaticobiliary complication is bds recurrence whether cholecystectomy should be performed after es especially in elderly patients remains controversial the aim of this study is to investigate the short term and long term outcomes after therapeutic endoscopic retrograde cholangiopancreatography ercp for bds and to analyze risk factors for pancreaticobiliary complications we also compared long term outcomes in patients older and younger than age 80 a total of 1210 patients who underwent therapeutic ercp for bds were retrospectively reviewed to identify risk factors for pancreaticobiliary complications we divided these patients into two groups group y 80 years 960 patients and group o 80 years 250 patients there were 192 matched pairs in the propensity score analysis the incidence of pancreaticobiliary complications was 13 1 126 960 in group y and 20 4 51 250 in group o p 0 00001 multivariate analysis showed that a gallbladder left in situ with stones was a significant independent risk factor hazard ratio 2 81 95 confidence interval 1 62 4 89 p 0 0002 there were no significant differences in the incidence of pancreaticobiliary complications between the propensity score matched groups a gallbladder in situ with stones was the only significant risk factor for pancreaticobiliary complications after treatment for bds age per se should not be the major factor when deciding on treatment that minimizes the occurrence of pancreaticobiliary disease endoscopic submucosal dissection esd is a standard treatment for early gastric cancer egc without lymph node metastasis however some patients undergo noncurative esd the aim of the present study was to assess the long term clinical outcomes of noncurative esd with or without additional surgery we investigated the chart data from all patients who had undergone esd for egc at saga medical school hospital and saga prefectural medical centre koseikan between 2001 and 2012 a total of 957 cases 1047 lesions of egc underwent esd and 99 had noncurative esd in total 20 cases were excluded because their follow up period was 3 years we divided the patients into observation and additional surgery groups and we compared the survival rate and related factors between the groups after noncurative esd 28 79 patients 35 4 underwent additional surgery and 51 79 64 6 were followed up without surgery the average age of patients in the observation group was higher than that of the additional surgery group 75 9 vs 71 6 years p 0 03 the incidence of hypertension was significantly higher in the observation group compared with the additional surgery group 51 0 vs 25 9 p 0 03 the overall survival rate of the additional surgery group was longer than that of the observation group however only one patient died from gastric cancer in the observation group the disease specific survival rate did not differ significantly between the groups it might be acceptable to follow up without additional surgery for some patients with comorbidity and who were elderly after noncurative esd for egc endoscopic ultrasound guided needle based confocal laser endomicroscopy eus ncle has been shown to aid in the diagnosis of cystic pancreatic lesions this is a pilot project to study its findings in patients with solid pancreatic lesions spls with a prospective single blinded study design patients with spls undergoing trans gastric eus fine needle aspiration eus fna from july 2013 to march 2014 were prospectively enrolled the ncle diagnoses were compared with the final diagnoses researchers learned about the eus ncle findings from previously published studies and applied it to diagnose spls in the meantime the findings were recorded in total 22 patients were recruited mean age 62 7 years sd 13 8 years 14 men and eight women the mean maximal tumor diameter was 36 0 mm sd 10 9 mm eus ncle yielded satisfactory images in all patients during the first eus procedure and diagnosed benign and malignant spls in 3 and 19 patients respectively final diagnoses of malignant spls were made in 19 patients benign spls were eventually diagnosed in three patients with confirmed the cytology and disease stability during the 12 month follow up period at the end of the project based on the results of this current study eus ncle findings for malignant spls were dark clumping with or without dilated vessels 40 \u03bcm there were two criteria for diagnosing benign lesions which were white fibrous bands and normal acini cells the accuracy rate of eus ncle was 90 9 20 22 one falsely diagnosed malignant spl was an inflammatory mass from a recent acute pancreatitis another one with a pancreatic neuroendocrine tumor presenting with a symptomatic pseudocyst was incorrectly diagnosed as an inflammatory mass this was likely from sampling error of the eus ncle probe in an inflammatory area only one patient had post eus fna bleeding but did not require a blood transfusion the inter observer agreement among three blinded endoscopists was almost perfect kappa 0 82 eus ncle is a promising technique for the diagnosis of spls with good inter observer agreement study registration \u200e: tctr20140402001 \u2022bevacizumab was an effective agent in one case of advanced uterine pnet \u2022vegf was expressed by the tumor supporting a mechanism for effectiveness \u2022cisplatin etoposide bevacizumab should be further studied in clinical trials \u2022patient remains disease free forty eight months following intervention \u2022the case presented is that of a primary debulking surgery for presumed ovarian cancer \u2022final pathology revealed diffusely metastatic endocervical adenocarcinoma \u2022after primary chemotherapy the patient has remained disease free 30 months after surgery \u2022inflammatory bowel disease increases the risk of radiation enteritis \u2022tissue expanders displace bowel from the radiation field \u2022thromboembolism and fistulae may be risks associated with tissue expander placement a vicryl mesh hammock may prevent bowel from entering the radiation field a 71 year old woman with suspected endometrial cancer underwent robotic assisted hysterectomy bilateral salpingo oophorectomy pelvic and para aortic lymph node dissection and infracolic omentectomy revealing a stage ii uterine carcinosarcoma with components of serous adenocarcinoma and undifferentiated spindle cell sarcoma there was no evidence of distant metastasis at the time of surgery however pelvic washings were positive for malignant cells she received adjuvant chemotherapy and vaginal cuff brachytherapy forty months later she developed a subcutaneous mass at the location of previous port site which was confirmed to be recurrence of the uterine primary she subsequently developed additional distant metastases to the abdominal wall lungs and bone port site metastasis psm was the earliest indicator of disseminated metastatic disease in this patient we review challenges in the management of patients with psm and propose that psm be considered as a sign of systemic disease even when presenting as an apparently isolated recurrence glomerular filtration rate egfr by serum creatinine egfrcr or standardized cystatin c egfrcysc were estimated in japanese patients with graves disease gd of different sex clinical samples were collected from patients with gd with normal renal function to accurately validate egfrcr and egfrcysc levels and evaluate how hyperthyroidism affects renal function levels of egfrcr and egfrcysc showed clinical usefulness in successfully treated euthyroid patients with gd regardless of sex the article includes detailed experimental methods and data used in our analysis the data relates to the paradoxical effect of thyroid function on the estimated glomerular filtration rate by serum creatinine or standardized cystatin c in japanese graves disease patients suzuki et al 2015 1 prostate cancer has been reported as the second leading cause of cancer death among men in 2013 prevention and early detection of cancer are considered as critical factors in controlling the disease and increasing the survival of patients therefore we aimed to investigate the effect of health belief model hbm based education on knowledge and prostate cancer screening behaviors in a randomized controlled trial this study was a non blinded randomized controlled trial we enrolled 210 men aged 50 70 balanced block randomization method was used to randomize the final participants who had inclusion criteria into intervention n 93 and control n 87 groups the participants of the intervention group attended training workshops based on hbm data were collected using three questionnaires i e demographic questionnaire prostate cancer screening health belief model scale pcs hbms and the knowledge about prostate cancer screening questionnaire all given before and immediately one month after the intervention the mean scores of the perceived susceptibility severity barriers and benefits increased significantly after the intervention p 0 05 in the intervention group in the control group such a difference was reported only for perceived susceptibility p 0 05 the rate of participation in prostate cancer screening in the intervention group increased from 7 5 to 24 and 43 3 one month and three months after the intervention respectively our findings showed that the health education programs designed based on hbm could positively affect prostate cancer preventive behaviors of individuals by improving their knowledge level and leaving positive effects on perceived susceptibility and severity as well as considering the perceived barriers benefits and health motivations irct2013090911691n3 patient s dignity is an important issue which is highlighted in nursing it is an issue that is highly dependent on context and culture heart disease is the most common disease in iran and the world identification of facilitator and threatening patient dignity in heart patients is vital this study aimed to explore facilitator and threatening patient dignity in hospitalized patients with heart disease this qualitative content analysis study was performed in 2014 in kerman iran 20 patients admitted to coronary care units and 5 personnel were selected using purposeful sampling in semi structured and in depth interviews researchers also used documentation and field notes until data saturation qualitative data analysis was done constantly and simultaneously with data collection three central themes emerged a care context which includes human environment and physical environment b holistic safe care including meeting the needs of patients both in the hospital and after discharge c creating a sense of security and an effective relationship between patient and nurse including a respectful relationship and account the family in health team the results of this study showed that care context is important for patient dignity as well as physical environment and safe holistic care establishment of effective communication between the clinician and patient is essential in order to increase the effectiveness of treatment these skills have been less investigated among dental students this study aimed to evaluate communication skills of dental students in shiraz with patients through direct observation patients perspectives and students self assessments this cross sectional study enrolled the fifth and sixth year dental students and one of each student s patients who was chosen using simple random sampling method we used a checklist for data collection students communication skills were assessed at three steps of the student patient interview at the beginning of the interview during the interview and at the end of the interview the checklist was completed by three groups 1 an observer 2 the patient and 3 the student as self assessment the validity of the checklist was confirmed by clinical professors and the reliability was determined by cronbach s alpha test data were analyzed using descriptive statistics and student s t test a repeated measure manova was used to compare the mean communication skills in the researcher patients and students at each step of the patient interviews there were 110 students mean age 22 3 \xb18 4 years and 110 patients mean age 32 \xb18 8 years who completed the checklists overall the communication skills of dental students were rated as good according to the patients however the observer and student participants rated the skills at the moderate level we observed significant differences between communication skills in all three groups and in the three steps of the patient interviews p 0 001 according to patients beliefs and students self assessments there were no differences between male and female students in communication skills in the three steps of the patient interviews all p 0 05 however from the observer s viewpoint female students showed better communication skills during the interviews p 0 001 there was a degree of failure in communication skills of dental students with patients in the interview process it will be necessary that communication skills be taught particularly for students involved in clinical practice stress is an important factor in the educational process teaching and learning are stressful processes this stress can affect one s ability and change his her performance the purpose of this study was to investigate stressors of clinical education from the perspective of medical students in yazd university of medical sciences this descriptive analytic study was conducted in yazd university of medical science during year 2014 2015 the sample size was 170 medical students who were selected randomly the data were collected by a questionnaire including four components interpersonal relationship educational environment clinical experience and the unpleasant emotions a significance level of 0 05 was considered for analysis the statistical analyses included descriptive statistics anova and t tests using spss software version 14 the results showed that the highest domain score belonged to interpersonal relationship 3 33 \xb10 3 followed by unpleasant emotions domain 3 3 \xb10 3 the lowest domain score of clinical education stressors was educational environment 3 12 \xb10 1 the results showed that the mean score of interpersonal relationship domain was more in women than in men p 0 05 the relationship between teachers and students is an effective factor in all dimensions of clinical education stressors so proper measures such as the promotion of scientific awareness of teachers and educational staff about factors that lead to stress and the best way to communicate with students should be taken to reduce the students stress endovascular aneurysm repair has been associated with changes in arterial stiffness as estimated by pulse wave velocity pwv this marker is influenced by the medical status of the patient the elastic characteristics of the aneurysm wall and the presence of intraluminal thrombus therefore in order to delineate the influence of the endograft implantation in the early post operative period we conducted non invasively pulse wave analysis in a male patient with an abdominal aortic aneurysm containing no intraluminal thrombus unremarkable past medical history and absence of peripheral arterial disease the estimated parameters were the systolic and diastolic pressure calculated at the aortic level central pressures pwv augmentation pressure ap and augmentation index ai pressure wave reflection magnitude rm and peripheral resistance central systolic and diastolic pressure decreased post operatively pwv showed subtle changes from 11 6 to 10 6 and 10 9 m s at 1 week and 1 month respectively accordingly the ai decreased from 28 to 14 and continued to drop to 25 the ap decreased gradually from 15 to 6 and 4 mmhg the wave rm dropped from 68 to 52 at 1 month finally the peripheral resistance dropped from 1 41 to 0 99 and 0 85 dyn s cm 5 our example shows that the implantation of an aortic endograft can modify the pressure wave reflection over the aortic bifurcation without causing significant alterations in pwv interleukin il 22 is a member of the il 10 family of cytokines that has been extensively studied since its discovery in 2000 this review article aims to describe the cellular sources and signaling pathways of this cytokine as well as the functions of il 22 in the intestine in addition this article describes the roles of il 22 in the pathogenesis of several gastrointestinal diseases including inhibition of inflammation and barrier defense against pathogens within the intestine since many of the functions of il 22 in the intestine are incompletely understood this review is meant to assess our current understanding of the roles of il 22 and provide new opportunities for inquiry to improve human intestinal health and disease generalized edema is a major presenting clinical feature of children with nephrotic syndrome ns exemplified by such primary conditions as minimal change disease mcd in these children with classical ns and marked proteinuria and hypoalbuminemia the ensuing tendency to hypovolemia triggers compensatory physiological mechanisms which enhance renal sodium na and water retention this is known as the underfill hypothesis edema can also occur in secondary forms of ns and several other glomerulonephritides in which the degree of proteinuria and hypoalbuminemia are variable in contrast to mcd in these latter conditions the predominant mechanism of edema formation is primary or pathophysiological na and water retention this is known as the overfill hypothesis a major clinical challenge in children with these disorders is to distinguish the predominant mechanism of edema formation identify other potential contributing factors and prevent the deleterious effects of diuretic regimens in those with unsuspected reduced effective circulatory volume i e underfill this article reviews the starling forces that become altered in ns so as to tip the balance of fluid movement in favor of edema formation an understanding of these pathomechanisms then serves to formulate a more rational approach to prevention evaluation and management of such edema a pseudo tail is defined as a tail like lesion in the lumbosacrococcygeal region that is not a true tail but one caused by disease perineal lipoma is one of the conditions that may present as a pseudo tail congenital perineal lipoma is a rare disease and in particular isolated congenital perineal lipoma without other anomalies is extremely rare here we report a case of congenital isolated perineal lipoma presenting as a pseudo tail and also include a literature review of the condition hcv related liver disease is the most common indication for liver transplantation lt in western countries whereas hcv lt is rare in korea we conducted a survey of hcv rna positive patients who underwent lt and investigated the prognostic factors for patient survival and the effects of immunosuppression we retrospectively reviewed the multicenter records of 192 hcv rna positive patients who underwent lt the 1 3 and 5 year overall survival rates were 78 8 75 3 and 73 1 respectively excluding the cases of hospital mortality n 23 169 patients were evaluated for patient survival most patients were genotype 1 n 111 65 7 or genotype 2 n 42 24 9 the proportion of living donors for lt n 135 79 9 was higher than that of deceased donors deceased donor liver transplantation ddlt n 34 20 1 the median donor and recipient ages were 32 years and 56 years respectively twenty eight patients 16 6 died during the observation period seventy five patients underwent universal prophylaxis and 15 received preemptive therapy hcv recurrence was detected in 97 patients recipients who were older than 60 received ddlt used cyclosporine or suffered acute rejection had lower rates of survival patent survival rates of hcv patients after lt in korea were comparable with other countries treatment of patients with para aortic lymph node metastasis from colorectal cancer is controversial the goal of this study was to investigate the technical feasibility of laparoscopic intrarenal para aortic lymph node dissection in patients with colorectal cancer and clinically suspected para aortic lymph node dissection the inclusion criteria for the laparoscopic approach were patients with infrarenal para aortic lymph node metastasis from colorectal cancer patients who had any other distant metastatic lesion or metachronous para aortic lymph node metastasis were excluded from this study perioperative outcomes and survival outcomes were analyzed between november 2004 and october 2013 40 patients underwent laparoscopic para aortic lymph node dissection the mean operating time was 192 3 68 8 minutes range 100 400 minutes and the mean estimated blood loss was 65 6 52 6 ml range 20 210 ml no patient required open conversion the postoperative complication rate was 15 0 sixteen patients 40 0 had pathologically positive lymph nodes in patients with metastatic para aortic lymph nodes the 3 year overall survival rate and disease free survival rate were 65 7 and 40 2 respectively the results of our study suggest that a laparoscopic approach for patients with colorectal cancer with metastatic para aortic lymph nodes can be a reasonable option for selected patients nodal infiltration has been one of the most important prognostic factors in breast cancer in recent decades risk stratification has greatly changed and is applied in accordance with hormone receptor and human epidermal growth factor receptor 2 her2 status we compared the prognostic power of tumor subtype to nodal involvement in early breast cancer we reviewed the medical records of 505 patients who had curative surgery for stage i or ii breast cancer we analyzed clinicopathologic factors according to tumor subtype and nodal involvement tumors were classified into 4 subtypes according to immunohistochemical status of estrogen receptor progesterone receptor her2 and ki67 labeling index disease free survival dfs and overall survival were analyzed there were 363 node negative patients 71 9 and 142 node positive patients 28 1 luminal a luminal b her2 and triple negative breast cancer subtypes were composed of 207 41 0 147 29 1 42 8 3 and 109 patients 21 6 respectively the median follow up period was 89 5 months node negative luminal a subtype showed the best prognosis with regard to 5 year dfs and the pn1 triple negative subtype was associated with the shortest dfs 95 1 vs 67 8 hazard ratio 9 554 p 0 001 however the node negative triple negative subtype was associated with a worse 5 year dfs than the pn1 luminal a subtype 86 4 hazard ratio 2 647 p 0 048 vs 93 2 hazard ratio 2 061 p 0 194 node negative triple negative breast cancer was associated with a poorer prognosis than pn1 luminal a subtype tumor subtype has greater prognostic power compared to nodal status in early breast cancer human health problems due to long life are becoming major issues in society and in particular greater interest collected on women s health after menopause many substances can be introduced to women s health however materials from the substances have not shown all of the safety and efficacy properties that are not easily found currently it is known about the effects of the disease on the female insect derived material that is capable of overcoming this problem significantly when using the insect derived material through the results of several studies suggest that it is possible to solve a hormonal imbalance and nutritional imbalance in the elderly here we d like to try to dissertate about the new trends for women s health improvement using novel materials derived from insects women s health has been threatened by various diseases mainly including heart disease breast cancer osteoporosis depression and autoimmune disease but development of medication for these diseases has been restricted by high development costs and low success rates herein the attempt to develop valid bioactive materials from a traditional natural material has been made resveratrol has been reported to be effective in treatment of breast cancer and heart disease goji berry has received attention as a natural based therapeutic material to treat a diabetes cardiovascular disease and osteoporosis leonurus family has been reported to be effective particularly in pregnant women due to high contents of vitamin as well as stimulation of uterine contraction annona family has effects such as anti anxiety anticonvulsant and recently it is proposed to be as a therapeutic material to cure depression based on its strong antidepressant effect shiraia bambusicola has been utilized to cure angiogenesis related disease from ancient china and furthermore recently it was proved to be effective in rheumatoid arthritis getting an understanding of utilization of these traditional natural materials not only enhances the interest in development of therapeutic materials for preventing and treating various women s diseases but also makes it possible to develop novel therapeutic materials constrictive pericarditis is characterized by constriction of the heart secondary to pericardial inflammation cardiovascular magnetic resonance cmr imaging is useful imaging modality for addressing the challenges of confirming this diagnosis it can be used to exclude other causes of right heart failure such as pulmonary hypertension or myocardial infarction determine whether the pericardium is causing constriction and differentiate it from restrictive cardiomyopathy which also causes impaired cardiac filling a 77 year old man from a country with high incidence of tuberculosis presented with severe dyspnea echocardiography revealed a small left ventricle with normal systolic and mildly impaired diastolic function left heart catheterization revealed non obstructive coronary disease not felt contributory to the dyspnea anatomy imaging with cardiovascular magnetic resonance imaging cmr showed global severely thickened pericardium short tau inversion recovery stir sequences for detection of oedema inflammation showed increased signal intensity and free breathing sequences confirmed septal flattening on inspiration late gadolinium imaging confirmed enhancement in the pericardium with all findings suggestive of pericardial inflammation and constriction cmr with stir sequences free breathing sequences and late gadolinium imaging can prove extremely useful for diagnosing constrictive pericarditis peripheral arterial disease is a source of morbidity and mortality surgical vascular reconstruction is a treatment option but probability of failure and complications are important concerns in this study we evaluated outcome of surgical infrainguinal reconstruction and factors affecting graft patency for a period of one year in this cohort study 85 consecutive patients with chronic ischemia who underwent lower extremity surgical vascular reconstruction including 52 femoropopliteal and 25 femorofemoral bypass from march 2007 to feb 2009 were recruited graft patency was evaluated before discharge from hospital and one year after the surgical operation using duplex ultrasonography association between possible risk factors and graft patency were evaluated in general 71 37 patients of femoropopliteal and 52 13 patients of femorofemoral reconstructions were patent during the follow up period diabetes mellitus hypertension smoking opium use and ischemic heart disease were significantly associated with decreased rate of patency p 0 05 assessing risk factors that predict perioperative mortality and graft patency is essential for selecting patients that would benefit from surgery omitting surgical reconstruction and endovascular intervention may be preferable especially when multiple risk factors are present or in the absence of critical limb ischemia infectious diseases are major public health problems among which blood borne ones are the most important infections patients who undergo orthopedic surgery are at higher risk of transmitting infectious diseases from and to others due to repeated blood examinations and injection drains secretion and receiving blood products accordingly in this study we determined prevalence of hepatitis b virus hbv hepatitis c virus hcv and human immunodeficiency virus hiv infections in patients who underwent surgery in a general training hospital in this cross sectional study the prevalence of hbv hcv and hiv infections was determined among 320 patients under orthopedic trauma surgeries in a general training hospital in tehran iran from 2009 to 2011 associations of these rates with age gender marital status residence location substance abuse history hospital admission history previous surgery blood transfusion dentistry procedures and previous medical history were also assessed a total of 320 patients 290 male 30 female were studied ten patients 3 2 had at least one of these three infections totally 10 patients 3 2 2 subjects 0 6 and 8 patients 2 5 had hcv hiv and hbv infections respectively none of the evaluated variables had significant relationship with hcv hbv and hiv infections p 0 05 according to the obtained results routine use of diagnostic tests for infectious disease such as hiv and viral hepatitis is recommended and should be considered before orthopedic operations alzheimer disease is the main cause of dementia in middle aged and elderly people considering the improving effects of creatine supplementation on cognitive performance this study aimed to determine the effects of creatine supplementation on learning memory and apoptosis in an experimental model of alzheimer s disease thirty two male wistar rats each weighing 250 \xb150 grams were divided into four groups the adcr a\u03b2 injection creatine supplementation and adcr groups a\u03b2 injection no creatine supplementation were injected bilaterally with amyloid beta a\u03b2 0 2\u03bcg in each ca1 area and the sham group was injected with normal saline in the same area after the injection the adcr group received a diet of 2 creatine for six weeks the control group underwent no surgical or dietary intervention after six weeks the morris water maze mwm test was administered to measure learning and memory retrieval after sacrificing the animals tunel staining for an anti apoptosis assay was performed for the sham adcr and adcr groups all groups were compared by independent ttest using spss software results of mwm show that rats in sham and control groups performed better than those in the adcr and adcr groups compared to sham group adcr and adcr groups had more tunel positive neurons count results indicated no differences between the adcr and adcrgroups in learning memory retrieval and percentage of tunel positive neurons after a\u03b2 injection creatine supplementation had no effect on learning memory retrieval or neuron apoptosis in male wistar rats manometry is the gold standard diagnostic test for motility disorders in the esophagus the development of high resolution manometry catheters and software displays of manometry recordings in color coded pressure plots have changed the diagnostic assessment of esophageal disease the diagnostic value of particular esophageal clinical symptoms among patients suspected of esophageal motor disorders emds is still unknown the aim of this study was to explore the sensitivity specificity and predictive accuracy of presenting esophageal symptoms between abnormal and normal esophageal manometry findings we conducted a cross sectional study of 623 patients aged 11 80 years data were collected from clinical examinations as well as patient questionnaires the sensitivity specificity and accuracy were calculated after high resolution manometry plots were reviewed according to the most recent chicago criteria the clinical symptoms were not sensitive enough to discriminate between emds nevertheless dysphagia noncardiac chest pain hoarseness vomiting and weight loss had high specificity and high accuracy to distinguish emds from normal findings regurgitation and heartburn did not have good accuracy for the diagnosis of emds clinical symptoms are not reliable enough to discriminate between emds clinical symptoms can however discriminate between normal findings and emds especially achalasia there are widespread misconceptions about the positive effects of opium on coronary artery disease cad thus we performed a study to explore the opium addiction process contributing factors among cad patients using a grounded theory approach the sample comprised 30 addicted cad patients and their family members physicians nurses and friends purposive and theoretical sampling was employed semi structured interviews were conducted coding and constant comparative analysis techniques were as proposed by strauss and corbin 1998 the core category was fighting for survival comprising three main themes namely the gateway blowing into the fire and getting stuck in the mud increasing knowledge about the adverse effects of opium on the cardiovascular system would reinforce prevention and rehabilitation measures involving patients family members in addiction prevention and rehabilitation programs and referring patients to specialized rehabilitation centres could help patients quit opium healthcare providers hcps should notice to the effects of opium consumption among cad patients nursing care must be holistic in nature although opium is stigmatised in iran hcps must treat addicted cad patients similar to other patients nursing students must be aware of the negative effects of illegal drugs on cad patients and the misconceptions regarding the positive effects thereof any misconceptions must be probed and clarified rehabilitation centres must be supervised by cardiologists and hcps this study compares the clinical characteristics of patients with mesial temporal lobe epilepsy with hippocampal sclerosis mtle hs with those who have temporal lobe epilepsy tle due to other etiologies in this retrospective study all patients with a clinical diagnosis of tle were recruited in a referral outpatient epilepsy clinic at shiraz university of medical sciences from september 2008 to may 2013 we classified the patients with tle as having mesial temporal sclerosis if they had clear signs of mesial temporal sclerosis and or atrophy in their mri and others who had any other mri abnormality a total of 174 patients were studied including 105 patients with mtle hs and 69 patients with tle due to other etiologies frequency of seizure types was not significantly different between these two groups earlier age at epilepsy onset p 0 005 a past history of febrile seizures p 0 010 and presence of affective auras p 0 008 were commonly seen in patients with mtlehs while auditory auras p 0 020 were more frequent in those with tle due to other etiologies the mainstay for making a correct diagnosis when evaluating a patient with seizure is having a standardized approach particularly with regard to taking a detailed clinical history one may find important clues in the clinical history e g age at disease onset detailed seizure description and past history to make a correct diagnosis multiple sclerosis ms is the most common disabling neurological disease hand dysfunction is one of the main complaints of patients with ms the present study aimed to compare hand dexterity of ms patients with low expanded disability status scale edss scores and healthy adults it also sought to identify the predictors of disability status of patients with ms based on their manual dexterity and demographic characteristics in this cross sectional study 60 16 male 44 female patients with ms and 60 19 male 41 female healthy people who matched in terms of age and sex were recruited their hand dexterity was evaluated by the purdue pegboard test the disability status of the ms group was determined by the expanded disability status scale the data were analyzed using spss15 the hand dexterity in ms group even with low edss score 1 5 1 07 was weaker than control group moreover the dexterity of dominant hand and alternating two hands coordination subtests of the ppt was a good discriminator between two groups p 0 001 the results of linear regression analysis suggested dominant hand dexterity and disease duration as predictors of disability status that predict 60 5 per cent of the variation in edss scores in patients with ms p 0 001 reduced dominant hand dexterity in patients with ms is a disabling factor further research is recommended to determine if early hand rehabilitation can reduce the severity of disability in patients with ms the incidence of ulcerative colitis uc is rising in populations with western style diet rich in fat and protein and low in fruits and vegetables in the present study we aimed to evaluate the association between dietary protein intakes and the risk of developing incident uc sixty two cases of uc and 124 controls were studied using country specific food frequency questionnaire ffq group comparisons by each factor were done using \u03c72 test and significance level was set at \u03b1 0 05 logistic regression adjusted for potential confounding variables was carried out univariate analysis suggested positive associations between processed meat red meat and organ meat with risk of ulcerative colitis comparing highest versus lowest categories of consumption multivariate conditional logistic regression analysis accounting for potential confounding variables indicated that patients who consumed a higher amount of processed meat were at a higher risk for developing uc p value for trend 0 02 similarly patients who consumed higher amounts of red meat were at a higher risk for uc p value for trend 0 01 the highest tertile of intake of organ meat was associated with an increased risk of ulcerative colitis with a statistically significant trend across tertiles p value for trend 0 01 when adjusted in this case control study we observed that higher consumptions of processed meat red meat and organ meat were associated with increased risk for uc cardiovascular disease cvd is the cause of one third of deaths worldwide and this will progress because of increasing cvd s risk factors the most basic task of dealing with the epidemic of cvd is primary prevention of risk factors as atherogenic index of plasma aip is a strong marker to predict the risk of atherosclerosis and coronary heart disease we assessed the correlation between aip and other important factors this cross sectional study was a part of national non communicable risk factors surveillance system data that has been established since 2004 in iran this was done on 1000 people between 2008 and 2010 the study was approved by ethics committee of mashhad university of medical science chi square mann whitney u correlation tests were used in this study statistical analysis was performed using spss version 11 in all calculations p 0 05 was considered as statistically significant level the study population consisted of 500 men and 500 women with mean \xb1sd age 41 9 \xb114 2 years according to the aip category 9 8 98 were in low risk group 12 7 127 were in intermediate risk and 77 5 775 were in increased risk of cvd aip was significantly correlated with waist circumference r 0 35 p 0 001 bmi r 0 33 p 0 001 and physical activity r 0 09 p 0 01 aip can be used as a regular monitoring index of cvd in every day practice especially in persons with other cardiovascular risk factors osteoporosis or porous bone is a disease characterized by low bone mass density bmd and structural deterioration of bone tissue leading to bone fragility and increased risk of hip spine and wrist fractures there are numerous risk factors for osteoporosis while many of these factors are non genetic in nature there is a definite genetic component responsible for this condition the main aim of this study was to evaluate the association between vdr vitamin d receptor gene polymorphisms fok1 a g rs2228570 and bone mineral density in an iranian defined population the study participants comprised of 1032 iranians recruited from the city of sanandaj during imos iranian multi center osteoporosis study bone mineral density measurement was performed in all the participants with and without osteoporosis all samples were genotyped for vdr genes fok1 polymorphism with polymerase chain reaction using a predesigned taqman allele discrimination assay there was a significant association between fok1 polymorphism and osteoporosis in postmenopausal women 0 138 0 025 0 768 it seems that cohort studies which are more powerful than case control studies can be useful in evaluating the roles of genetic variants as risk or protective factors for osteoporosis embolus is one of the causes of ischemic stroke that can be due to cardiac sources such as valvular heart diseases and atrial fibrillation and atheroma of the aorta transesophageal echocardiography tee is superior in identifying potential cardiac sources of emboli due to insufficient data on tee findings in ischemic stroke in iran the present study was done to evaluate tee in detecting cardiac sources of emboli the main aim of this study was to describe the cardiogenic sources of emboli using tee in the ischemic stroke patients this is a cross sectional study conducted during a 13 month period from january 2012 to february 2013 in shiraz nemazee teaching hospital patients admitted with stroke diagnosis were included but hemorrhagic stroke cases were excluded 229 patients with ischemic stroke diagnosis were included and underwent tee causes of cardiac emboli were detected in 65 cases 40 7 and categorized to high risk 29 7 and potential risk 11 high risk cardiac sources included atrial fibrillation 8 7 mitral valve disease ms or mi 11 cases 4 75 aortic valve disease as or ai 8 3 5 prosthetic valve 3 1 35 dilated cardiomyopathy 45 19 65 and congestive heart failure with ejection fraction 30 in 8 cases 3 5 potential cardiac sources of emboli comprised 7 cases 3 05 of septal aneurysm 4 1 75 left ventricular hypokinesia 13 5 7 mitral annular calcification and 9 cases 3 95 complex atheroma in the ascending aorta or proximal arch our study showed that high risk cardiac sources of emboli can be detected using tee in a considerable percentage of ischemic stroke patients the most common high risk cardiac etiologies were dilated cardiomyopathy and valvular heart diseases the present study aimed to investigate the nailfold capillaroscopy nc features of the patients with dermatomyositis dm and its correlation with their disease activity indices physical findings and laboratory results the present cross sectional study was conducted on 27 dm patients above 16 years old who had referred to an there are 3 clinics not one outpatient rheumatology clinics from 2012 to 2013 nailfold capillaroscopy and calculation of disease activity indices were performed separately for all the patients by two rheumatologists who were blinded to each other s results statistical analyses were performed using chi square and mann whitney u tests the mean age of the patients was 39 2 \xb114 1 years with the mean disease duration of 13 1 \xb115 2 months range 1 72 months myopathic electromyography emg findings showed a strong association with scleroderma pattern p 0 015 however disease activity in each organ system and global disease activity showed no significant association between scleroderma pattern and other nc findings disease activity in each organ system and also global disease activity were both assessed to see if they are associated with scleroderma pattern and other nc findings so if we use between it means we are looking for an association between scleroderma pattern and other nc findings and this is not what we have done and is wrong this study revealed no significant relationship between disease activity indices and nc features thus it may be more precise to interpret the results of nc in conjunction with other physical and laboratory findings periodontitis a formidable global health burden is a common chronic disease that destroys tooth supporting tissues biomarkers of the early phase of this progressive disease are of utmost importance for global health in this context saliva represents a non invasive biosample by using systems biology tools we aimed to 1 identify an integrated interactome between matrix metalloproteinase mmp redox nitric oxide no and apoptosis upstream pathways of periodontal inflammation and 2 characterize the attendant topological network properties to uncover putative biomarkers to be tested in saliva from patients with periodontitis hence we first generated a protein protein network model of interactions biomark interactome by using the string 10 database a search tool for the retrieval of interacting genes proteins with experiments and databases as input options and a confidence score of 0 400 second we determined the centrality values closeness stress degree or connectivity and betweenness for the biomark members by using the cytoscape software we found ubiquitin c ubc jun proto oncogene jun and matrix metalloproteinase 14 mmp14 as the most central hub and non hub bottlenecks among the 211 genes proteins of the whole interactome we conclude that ubc jun and mmp14 are likely an optimal candidate group of host derived biomarkers in combination with oral pathogenic bacteria derived proteins for detecting periodontitis at its early phase by using salivary samples from patients these findings therefore have broader relevance for systems medicine in global health as well insulin like growth factor 1 receptor igf 1r regulates cell growth proliferation and apoptosis adenocarcinoma and never smokers have a higher expression of igf 1r which is associated with worse overall survival dalotuzumab mk0646 d is a humanized monoclonal antibody that targets igf 1r pemetrexed p has higher activity in non squamous lung cancer nsql we initiated a randomized phase ii trial to test the combination of p and cisplatin c d in nsql eligibility criteria were untreated nsql stage iv ecog 0 or 1 measurable disease adequate renal hepatic and hematologic function and no other intercurrent illness p at 500 mg m 2 and c at 75 mg m 2 iv were given every 3 weeks d was given at 10 mg kg iv weekly on days 1 8 and 15 of every 3 week cycle in the experimental group the patients had a radiographic assessment after every two cycles and were treated for a maximum of six cycles if there was a response or stable disease the primary objective of the study was to compare the clinical response rates of pc vs pc d from 1 2009 to 2 2011 the study accrued 26 subjects 16 male and 10 female with a median age of 59 14 were treated with pc and 12 were treated with pc d we observed two partial responses pr seven stable disease sd three progressive disease pd and two not evaluable ne in the pc arm in comparison for the pc d arm there were three pr four sd four pd and one ne the hematologic toxicity was similar in both groups there was higher incidence of hyperglycemia in the experimental group four cases with grade 3 and one case with grade 4 pc d had a similar response rate compared to pc with a higher rate of hyperglycemia identification of responders using predictive markers would be key to continuing the study of d in nsql nct00799240 clinicaltrials gov to assess the immunohistochemical profile of the atypical nuclei in leiomyoma with bizarre nuclei and compare with benign and malignant counterparts 26 cases of uterine smooth muscle tumors including 12 leiomyosarcoma lms 10 leiomyoma with bizarre nuclei lbn and 4 smooth muscle tumor with uncertain malignant potential stump were selected using whole tissue sections for this study and analysis six cases of ordinary leiomyoma were included as benign control group all representative section were stained for p53 ki67 estrogen receptor and progestrone receptor analysis was carried out using spss 16 0 for windows software six out of 12 cases of lms showed strong and diffuse nuclear staining with p53 antibody 50 in contrast none of stumps and only one case of lbn cases showed focal positive reaction with p53 percentage of positive cells for ki67 in lms was 14 92 while only 0 85 of cells in lbns was labeled with ki67 proliferative marker p 0 001 regarding steroid hormone receptors a significant loosing trend was found in these receptors from benign toward malignant tumors through lbn and stump cases loss of inhibitory function of wild type p53 gene in leiomyosarcoma is an essential event that discriminate frankly malignant tumors from stump and atypical leiomyoma toll like receptors tlr are well known components of the innate immune system among them tlr4 is related to the inflammatory processes involved in atherosclerotic plaque formation our purpose was to compare the monocytic expression of tlr4 following implantation of drug eluting des and bare stents bms in this study patients with chronic stable angina undergoing elective percutaneous coronary intervention pci in shahidmadani heart hospital tabriz iran were included ninety five patients receiving des and 95 patients receiving bms were selected between 2012 and 2014 everolimus eluting stents were implanted for des group both groups received similar medications and procedure blood samples were taken before pci 2 hours and 4 hours after termination of pci expression of tlr4 on monocytes was measured using flowcytometry patients were matched for age sex and coronary artery disease risk factors but not for tlr4 expression rate before pci a significant difference was seen between des and bms in tlr4 expression before 21 3 \xb12 8 vs 15 5 \xb12 7 p 0 05 and four hours after pci 30 1 3 3 vs 39 2 3 2 p 0 05 due to the unmatched rate of tlr4 expression before pci we measured the percentage of increase in tlr4 expression between groups des compared to bms significantlycaused less increase in the tlr4 expression 50 23 \xb110 03 vs 446 35 \xb170 58 p 0 001 our findings suggest thateverolimuseluted from the stents can decrease pci induced increase in the tlr4 expression on the surface of monocytes human toll like receptors tlrs are a family of transmembrane receptors which play a key role in both innate and adaptive immune responses beside of recognizing specific molecular patterns that associated with different types of pathogens tlrs may also detect a number of self proteins and endogenous nucleic acids activating tlrs lead to the heightened expression of various inflammatory genes which have a protective role against infection data rising predominantly from human patients and animal models of autoimmune disease indicate that inappropriate triggering of tlr pathways by exogenous or endogenous ligands may cause the initiation and or perpetuation of autoimmune reactions and tissue damage given their important role in infectious and non infectious disease process tlrs and its signaling pathways emerge as appealing targets for therapeutics in this review we demonstrate how tlrs pathways could be involved in autoimmune disorders and their therapeutic application type 1 diabetes t1d is a pancreatic beta cell specific autoimmune disease one of the most significant current discussions in t1d studies is therapy since the conventional therapy islet transplantation and external insulin e g cannot prevent the destructive autoimmune process against original beta cells and persistent hyperglycemia remains so recent developments in the field of t1d therapy paved the way to a renewed interest in immunotherapy based on the disease process especially monoclonal antibody therapy due to encouraging laboratory results cytokine antibody based drugs could be effective in the clinical direction of the t1d disease process hence implementation of this approach can be useful to improve clinical and laboratory manifestations of t1d metastatic renal cell carcinoma is potentially a lethal disease with in some cases aggressive behavior the given fact that the patterns of metastases from rcc are not clearly identified which may involve some rare metastatic locations we present a case of 58 years old male presented with painless left scrotal mass which was discovered to be an intrascrotal metastases appeared 3 years after nephrectomy for ipsilateral renal cell carcinoma we believe that the rarity of the metastatic site and the intriguing possible mechanism of spread make an interesting case for clinicians and could add more follow up measures for patients treated from renal cell carcinoma metastatic spread of differentiated thyroid cancer to genitourinary organs is rare synchronous presentation of renal and adrenal thyroid metastasis is even less common this case being only the 3rd reported we describe a case of a 60 year old male with oligometastatic thyroid cancer where adrenal and renal metastases were the only extracervical sites of disease and triggered the patient s presentation enterovesical fistulas are a well known complication of inflammatory and malignant bowel disease bladder carcinoma however is an extremely rare etiology we describe a case of squamous cell carcinoma of the bladder with an enterovesical fistula this rare phenomenon has never been previously reported in western literature we review the diagnosis work up and treatment of enterovesical fistulas unfortunately the prognosis for these highly invasive tumors is very poor and the treatment is often palliative the high morbidity and mortality makes management of these patients exceptionally challenging delayed puberty secondary to hypogonadism is commonly seen in sickle cell disease scd affecting normal growth and development the condition is rarely treated in scd for fear of inducing priapism episodes we present a case report of an afro jamaican adolescent male at 16 years of age who presented with symptoms of delayed puberty as well as frequent stuttering priapism episodes endocrinological assessment revealed low serum total testosterone levels treatment was commenced monthly with testosterone enanthate which resulted in improved symptoms of delayed puberty improvement in anthropometric parameters while apparently ameliorating priapism episodes we present a rare finding of concurrent right testis non seminomatous mixed germ cell tumor and muscle invasive urothelial carcinoma of the bladder in a 57 year old homeless man the socioeconomic factors and the disease presentation caused a treatment dilemma in terms of the appropriate type of neoadjuvant chemotherapy the patient ultimately underwent upfront surgery with retroperitoneal lymph node dissection and radical cystoprostatectomy followed by adjuvant cisplatin based chemotherapy upper tract urothelial carcinomas in the proximal ureter are an uncommon disease we present a case in which it was firstly detected by fluorescence in situ hybridization and not by endoscopy and radiologic imaging consequently a radical nephroureterectomy with excision of the bladder cuff was performed as the gold standard treatment xanthogranulomatous cystitis xc is a rare benign chronic inflammatory disease of unknown etiology curative treatment of xc requires surgical resection and most of reported cases were treated by partial cystectomy here we describe a case with xc that was treated using transurethral resection hydatid disease is a parasitic infestation by larval form of echinococcus granulosus isolated renal involvement is extremely rare there are no specific signs and symptoms of renal hydatidosis however it may present as palpable mass flank pain hematuria malaise fever and hydatiduria or as a complication of it such as infection abscess hemorrhage necrosis and pelviureteric junction obstruction renal failure etc except hydatiduria none are pathognomonic for renal hydatidosis there is no literature on renal hydatidosis presenting as renal mass we report 2 cases of isolated renal hydatidosis which mimicked a renal mass on imaging study bladder cancer rarely presents clinically with a myelophthisic picture from diffuse bone marrow infiltration especially in the absence of detectable skeletal metastases a 75 year old man presented with newly diagnosed urothelial cell carcinoma of the bladder pathology from transurethral resection of bladder tumor demonstrated muscle invasive disease pre therapy imaging including ct abdomen pelvis cxr and bone scan demonstrated liver lesions concerning for metastatic disease but no skeletal metastases labs were notable for isolated thrombocytopenia hypercalcemia and acute kidney injury prompting hospitalization hematologic work up including bone marrow aspiration and biopsy revealed diffuse infiltration of the bone marrow by urothelial cancer the case illustrates the importance of fully investigating otherwise unexplained clinical findings in patients with clinically localized urothelial cancer prior to curative intent surgery eosinophilic cystitis is a rare inflammatory disease of the bladder which origin and pathogenesis are unknown since the first description in 1960 hundreds of cases have been reported 20 pseudotumor forms we report a case of cystitis eosinophils in tumor form a patient of 72 years without urological or allergic history the patient was treated with endoscopic resection alone the outcome was favorable with disappearance symptoms and no recurrence at 1 3 and 6 months controls we carry a literature review of cystitis eosinophils on the different clinical manifestations the means diagnostic and therapeutic modalities seeding of prostate cancer along a needle biopsy track is a rare complication the diagnosis of this presents a significant upstaging of the disease and profound potential changes to the treatment strategy in this report we present a 71 year old male with otherwise low risk prostate cancer on final pathology except for extraprostatic extension epe along a probable needle track we further review the relevant literature regarding this rare but important complication with prostate needle biopsy penile mondor s disease is a thrombophlebitis of the superficial dorsal vein of the penis it is a rare clinical diagnosis and generally resolves spontaneously a simple physical examination is sufficient for diagnosis but color doppler ultrasonography is often carried out as a further investigation we describe two patients who developed priapism due to penile doppler ultrasonography which was used for diagnosis of these patients now in our opinion this examination was unnecessary we present an application of head mounted display hmd to patient s self monitoring of transurethral resection of bladder tumor turb six patients wore the hmd as an imaging monitor to view the operation in real time during their turb following the operation the patients completed a questionnaire that evaluates understanding of the state of their disease and satisfaction with the hmd as a result monitoring the operation in real time through the hmd helped to increase patients understanding of the state of their disease and satisfaction for selected patients the use of hmd could help to increase the patient s understanding of their disease castleman s disease is a rare benign lymphoproliferative disorder characterized by benign growths of the lymph node tissue it is associated with a number of malignancies including kaposi sarcoma non hodgkin s and hodgkins lymphoma and poems syndrome this report describes the case of a 38 year old gentleman presenting with painless hematuria initial investigations including flexible cystoscopy were unremarkable however subsequent imaging including ct urogram and mr pelvis revealed multiple prevesical lesions histology obtained from excision biopsy revealed histological features consistent with castleman s disease in this report we discuss the nature presentation and treatment modalities of this rare condition in immunocompromised patients fusarium species cause infections that lead to high mortality our case report describes a case of disseminated fusariosis in a neutropenic patient with aml after myelosuppressive chemotherapy and a neutropenic multiple myeloma patient with fusarium fungemia awaiting stem cell collection both cases highlight the fact that fusarium can grow as yeast like structures in the blood causing a delay in diagnosis and that fusarium has a tendency to be a resistant organism fusarium was only susceptible to amphotericin b in both cases but we chose to continue treatment with voriconazole in the first case with disseminated infection despite culture results in view of his good clinical response despite high mortality rates in disseminated infection our two patients had good outcomes hiv aids patients often present with orogenital ulcers in the immunocompromised patient diagnosis of these ulcers pose a challenge as there is a myriad of etiologies we present a case of an hiv aids patient with recurrent orogenital aphthosis that was confirmed to have concomitant diagnosis of behcet s disease proper awareness of the causes of these ulcers is essential for prompt and effective treatment while rare causes may be at the bottom of a differential list in an immunocompetent host when hiv aids is involved these rare causes often percolate to the top incidence of infective endocarditis during pregnancy is around 0 006 with high maternal and fetal mortality bacillus cereus is an extremely rare cause for endocarditis in intravenous drug abusers ivda or those with valvular disease or devices such as pacemakers we report a case of b cereus endocarditis which to the best of our knowledge has never been reported in pregnancy a 30 year old 25 week pregnant female presented with right shoulder pain swelling and erythema on the lateral aspect of deltoid muscle from large abscess over her deltoid muscle she was found to have a vegetation on the native tricuspid valve cultures from abscess fluid and blood cultures grew b cereus she was appropriately treated with antimicrobials and had favorable outcomes there are 20 cases of b cereus endocarditis reported but none during pregnancy when cultures grow unusual organisms the case must be thoroughly investigated this case illustrates a rare situation endocarditis in pregnancy with an unusual outcome b cereus on an uncommon valve tricuspid valve we report on an unusual case of oro rhinocerebral disease caused by mucormycosis and aspergillus co infection in a 54 year old insulin dependent diabetic patient although she was successfully treated with parenteral amphotericin b followed by oral posaconazole she was left with irreversible blindness of the right eye and multiple cranial nerve palsies trichosporon fungemia is a life threatening opportunistic infection that is increasing in frequency invasive disease occurs almost exclusively in immunocompromised hosts particularly in neutropenic adults with hematological malignancies and uncommonly in children we report the case of a pediatric patient where disseminated trichosporonosis progressed while on micafungin between treatments with voriconazole and amphotericin b demonstrating the difficulty with and importance of prolonged and continuous treatment visceral leishmaniasis is an infection with an insidious and disabling course caused by parasites of the genus leishmania in europe it is mostly associated with hiv infection systemic lupus erythematosus and its treatment are associated with increased risk of infection neoplastic and concomitant autoimmune disorders the association of these diseases may go unnoticed a 60 year old caucasian woman with lupus presented with a one year history of fever malaise weakness and weight loss the highlights on physical examination were pallor palpable hepatosplenomegaly and low grade fever blood tests showed pancytopenia hyperproteinemia with hypoalbuminemia and hypergammaglobulinemia electrophoresis showed a polyclonal gamma curve full body ct scan revealed massive hepatosplenomegaly microbiology investigation was negative for the most common pathogens including tuberculosis there were no signs of hematologic malignancy in the bone marrow smear pcr for leishmania infantum was positive both in blood and bone marrow the patient was treated with liposomal amphotericin b and immunosuppression was adjusted she showed rapid clinical improvement and 6 months later had no signs of disease the differential diagnosis in a patient with lupus presenting with fever and multisystemic manifestations includes infectious or neoplastic disorders the patient lived in an endemic area of leishmania and typical clinical and analytical changes were all present making this case highly educational the case highlights the importance of a patient s epidemiological background and how it can lead to the diagnosis and timely treatment of a rare disease chikungunya is an infection caused by the chikungunya virus and transmitted by the bite of infected mosquito the most common symptoms of chikungunya virus infection are fever joint pain or rash chikungunya virus outbreaks had been identified in countries in africa asia europe and the indian and pacific oceans in late 2013 the first local transmission of chikungunya virus in the americas was identified in caribbean countries and territories chikungunya virus disease became a nationally notifiable condition in 2015 there is a threat that chikungunya will continue to spread to new areas in the americas we describe 5 patients who presented to our hospital with chikungunya infection shortly after returning from endemic areas fever and travel history to endemic areas were documented in all of our cases skin rash arthralgia and contact history were also reported by these patients persons with suspected chikungunya infection should be counseled to avoid mosquito bites during illness to decrease the risk of local transmission the transmitting mosquitos are present in the us and limiting the viral spread is essential in this report we describe the clinical presentation risk factors and laboratory tests of each patient and attempt to ensure awareness on the risk of potential spread of the disease severe malaria is a life threatening condition caused by plasmodium falciparum rupture of red blood cells when merozoites release to the bloodstream is responsible for the clinical manifestations febrile fever reaching 39 \xb0c and other unspecific symptoms p falciparum is considered as the worst form of malaria moreover this species has cytoadherence to red blood cells this can lead to an organic dysfunction people coming from hyper endemic areas have developed a partial immunity but immunodepressed people are a group with a greater risk due to the high mortality rate associated to this disease early diagnosis and a prompt treatment implementation are essential however the missed or delayed diagnosis is one of the major reasons of reaching a severe malaria disease this case reflects the complexity of the diagnosis in an immigrant and immunodepressed patient with a haematological neoplasm with a severe infection by p falciparum due to the unspecified symptoms and the overlapping of the same bacteremia is currently one of the infections with the highest mortality in hospitals 1 acinetobacter lwoffii and acinetobacter baumannii are gram negative bacteria and both represent opportunistic pathogens in certain cases the management can be challenging since these organisms can be highly resistant to antimicrobial agents clinical illnesses associated with acinetobacter include pneumonia meningitis peritonitis endocarditis and infections of the urinary tract and skin 1 acinetobacter bacteremia represents a serious and ever increasing problem because of the high associated morbidity and mortality a patient presented with tetanus ten days after blunt trauma with a lawn mower our case describes the diagnosis and treatment of this patient with an infectious disease commonly seen in the developing world but rarely seen in the developed world malaria is a serious and sometimes fatal disease caused by an intraerythrocytic parasite and is commonly seen in developing countries approximately 1500 cases of malaria are diagnosed in the united states each year mostly in travelers and immigrants returning from endemic areas 1 there are many different regimens used to treat malaria some of which are not approved in the usa the side effects of these medications may not be familiar to physicians in the usa we report a case of a returning traveler from nigeria presenting with fever and hemolytic anemia caused by a delayed response to artesunate given 3 weeks earlier while in nigeria to our knowledge there are few cases reported in the united states of hemolytic anemia secondary to artesunate therapy 2 mycobacterium avium complex olecranon bursitis resolves without antimicrobials or surgical intervention a case report and review of the literature tetanus after a minor injury leading to death in a previously non immunized elderly norwegian woman pseudomonas aeruginosa causing inflammatory mass of the nasopharynx in an immunocompromised hiv infected patient a mimic of malignancy pulmonary cavitary mycobacterium kyorinense m kyorinense infection in an australian woman osteomyelitis caused by achromobacter xylosoxidans ebola virus disease the use of fluorescents as markers of contamination for personal protective equipment chikungunya fever atypical and lethal cases in the western hemisphere a venezuelan experience the importance of tetanus risk assessment during wound management acute hypothalamic suppression significantly affects trabecular bone but not cortical bone following recovery and ovariectomy surgery in a rat model the identification of immune genes in the milk transcriptome of the tasmanian devil sarcophilus harrisii activity and biophysical inhibition resistance of a novel synthetic lung surfactant containing super mini b datk peptide deciphering the microrna transcriptome of skeletal muscle during porcine development the kiss of death a rare case of anaphylaxis to the bite of the red margined kissing bug mouth in foot disease igg4 related disease imitating a great imitator dopaminergic modulation of medial prefrontal cortex deactivation in parkinson depression clinical phenotype of digeorge syndrome with negative genetic tests a case of digeorge like syndrome management of membranous glomerulonephritis in pregnancy a multidisciplinary challenge accuracy of intraocular lens power formulas involving 148 eyes with long axial lengths a retrospective chart review study histopathological findings in a critically ill patient with avian influenza a h7n9 primary tracheobronchial non hodgkin lymphoma causing life threatening airway obstruction a case report marker or mediator is the link between anemia and outcomes in patients with coronary artery disease growing any clearer early stage lung cancer with nodal involvement occult to pet ct treat the image or treat the disease atrial fibrillation and sleep disordered breathing radical resection of right upper lung cancer using uniportal video assisted thoracic surgery with non intubated anesthesia pulmonary lymphoepithelioma like carcinoma a surveillance epidemiology and end results database analysis prevalence of carotid artery stenosis in chinese patients with angina pectoris prognostic analysis of the bronchoplastic and broncho arterioplastic lobectomy of non small cell lung cancers 10 year experiences of 161 patients a cross sectional and follow up study of leukopenia in tuberculosis patients prevalence risk factors and impact of anti tuberculosis treatment diagnosis of pneumocystis pneumonia using serum 1 3 \u03b2 d glucan a bivariate meta analysis and systematic review history of pneumonia is a strong risk factor for chronic obstructive pulmonary disease copd exacerbation in south korea the epidemiologic review and prospective observation of copd and health in korea epoch study the total artificial heart anticoagulation management in mechanical circulatory support high fat diet induced obesity triggers alveolar bone loss and spontaneous periodontal disease in growing mice self reported symptoms of chronic cough and breathlessness in working age men in the city of izhevsk russia associations with cardiovascular disease risk factors and comorbidities an isolated vaginal metastasis from rectal cancer value of rare low bone mass diseases for osteoporosis genetics fgf23 in chronic kidney disease are we lost in translation current strategies for the treatment of aneurysmal bone cysts non hematopoietic essential functions of bone marrow cells a review of scientific and clinical literature and rationale for treating bone defects a matter of perspective comparison of the characteristics of persons with hiv infection in the united states from the hiv outpatient study medical monitoring project and national hiv surveillance system utility of the neurobehavioral cognitive status examination cognistat in differentiating between depressive states in late life depression and late onset alzheimer s disease a preliminary study the adult prevalence of hiv in zambia results from a population based mobile testing survey conducted in 2013 2014 hiv 1 genetic diversity and its distribution characteristics among newly diagnosed hiv 1 individuals in hebei province china effect of hope therapy on depression anxiety and stress among the patients undergoing hemodialysis type 1 diabetes through two lenses comparing adolescent and parental perspectives with photovoice clinical assessment and management of spondyloarthritides in the middle east a multinational investigation editorial biology of cognitive aging model systems technologies and beyond transient expression of secretory iga in planta is optimal using a multi gene vector and may be further enhanced by improving joining chain incorporation gene association with leprosy a review of published data meningeal tertiary lymphoid tissues and multiple sclerosis a gathering place for diverse types of immune cells during cns autoimmunity antigen specific regulatory t cells and low dose of il 2 in treatment of type 1 diabetes individual based modeling of tuberculosis in a user friendly interface understanding the epidemiological role of population heterogeneity in a city antibiotics and the human gut microbiome dysbioses and accumulation of resistances an intracellular arrangement of histoplasma capsulatum yeast aggregates generates nuclear damage to the cultured murine alveolar macrophages the unspecific side of acquired immunity against infectious disease causes and consequences interaction between tat and drugs of abuse during hiv 1 infection and central nervous system disease the pi3k akt pathway in tumors of endocrine tissues circadian mechanisms underlying reward related neurophysiology and synaptic plasticity mitochondrial quality control and muscle mass maintenance critical role of intracellular ryr1 calcium release channels in skeletal muscle function and disease c jun n terminal kinase jnk signaling as a therapeutic target for alzheimer s disease structural insights into high density lipoprotein old models and new facts though active on rinm5f insulinoma cells and cultured pancreatic islets recombinant il 22 fails to modulate cytotoxicity and disease in a protocol of streptozotocin induced experimental diabetes altered cortical synaptic plasticity in response to 5 hz repetitive transcranial magnetic stimulation as a new electrophysiological finding in amnestic mild cognitive impairment converting to alzheimer s disease results from a 4 year prospective cohort study non human primate an essential building brick in the discovery of the subthalamic deep brain stimulation therapy bilingualism and cognitive reserve a critical overview and a plea for methodological innovations parkin regulation and neurodegenerative disorders hippocampal injections of oligomeric amyloid \u03b2 peptide 1 42 induce selective working memory deficits and long lasting alterations of erk signaling pathway the gaain entity mapper an active learning system for medical data mapping cognitive training at a young age attenuates deficits in the zq175 mouse model of hd spinal muscular atrophy patient ipsc derived motor neurons have reduced expression of proteins important in neuronal development novel missense mutation a789v in iqsec2 underlies x linked intellectual disability in the mrx78 family huntington s disease as neurodevelopmental disorder altered chromatin regulation coding and non coding rna transcription turning on lights to stop neurodegeneration the potential of near infrared light therapy in alzheimer s and parkinson s disease mild white matter changes in un medicated obsessive compulsive disorder patients and their unaffected siblings use of the mini mac scale in the evaluation of mental adjustment to cancer clinical experience in appendiceal neuroendocrine neoplasms dietary habits of lung cancer patients from the lower silesia region of poland uracil tegafur as a possible salvage therapy in chemo refractory colorectal cancer patients a single institutional retrospective study evaluation of prognostic factors in the surgical treatment of pulmonary metastases current concepts in diagnosis and treatment of chronic lymphocytic leukemia cancer treatment in pregnant women delaying chemotherapy in the treatment of hormone receptor positive human epidermal growth factor receptor 2 negative advanced breast cancer predicting frequent asthma exacerbations using blood eosinophil count and other patient data routinely available in clinical practice the clinical pathological characteristics and prognosis of fgfr1 gene amplification in non small cell lung cancer a meta analysis bioengineering models for breast cancer research long term outcomes of antipsychotic treatment in patients with first episode schizophrenia a systematic review effect of ultrafine poly \u03b5 caprolactone fibers on calcium phosphate cement in vitro degradation and in vivo regeneration roflumilast a review of its use in the treatment of copd specific role of combination aclidinium formoterol in the treatment of chronic obstructive pulmonary disease impact of individualized care on readmissions after a hospitalization for acute exacerbation of copd baicalein attenuates the quorum sensing controlled virulence factors of pseudomonas aeruginosa and relieves the inflammatory response in p aeruginosa infected macrophages by downregulating the mapk and nf\u03bab signal transduction pathways urinary vitamin d binding protein as a biomarker of steroid resistant nephrotic syndrome genome wide analysis of nbs lrr genes in sorghum genome revealed several events contributing to nbs lrr gene evolution in grass species association between periodontal diseases and systemic illnesses a survey among internal medicine residents in nigeria for dentists and doctors the neglected concepts about the factors influencing the effects of drugs type i hypersensitivity reaction as a complication of lepa targeting th17 cells with small molecules and small interference rna the potential for fungal biopesticides to reduce malaria transmission under diverse environmental conditions management of endocrine disease reversible hypogonadotropic hypogonadism six months of daily treatment with vardenafil improves parameters of endothelial inflammation and of hypogonadism in male patients with type 2 diabetes and erectile dysfunction a randomized double blind prospective trial blood flow analysis of the aortic arch using computational fluid dynamics hypertrophic obstructive cardiomyopathy the mitral valve could be the key the fate of mild to moderate proximal aortic dilatation after isolated aortic valve replacement for bicuspid aortic valve stenosis a magnetic resonance imaging follow up study \u2020. long term results of mitral valve surgery for degenerative anterior leaflet or bileaflet prolapse analysis of negative factors for repair early and late failures and survival is a third arterial conduit necessary comparison of the radial artery and saphenous vein in patients receiving bilateral internal thoracic arteries for triple vessel coronary disease building noncommunicable disease research capacity in the south asian region the ascend program health promotion through existing community structures a case of churches roles in promoting rotavirus vaccination in rural zambia activating patients for sustained chronic disease self management thinking beyond clinical outcomes question 1 are household contacts of patients with invasive group a streptococcal disease at higher risk of secondary infection cerebellar role in parkinson s disease ablation of the inferior olive prevents h reflex down conditioning in rats living history of medicine vascular scaffolding from dream to reality proposal for a revised definition of dilated cardiomyopathy hypokinetic non dilated cardiomyopathy and its implications for clinical practice a position statement of the esc working group on myocardial and pericardial diseases the long term public health benefits of breastfeeding growth related metabolism of the carbon storage poly 3 hydroxybutyrate in legionella pneumophila transcriptional regulation of x box binding protein one xbp1 by hepatocyte nuclear factor 4\u03b1 hnf4\u03b1 is vital to beta cell function spirituality and religiosity in adolescents living with sickle cell disease association between non alcoholic hepatic steatosis and hyper reactive blood pressure response on the exercise treadmill test pulmonary pseudo tumour aortitis and igg4 disease residual enzymatic activity as a prognostic factor in patients with gaucher disease type 1 correlation with zimran and gauss i index and the severity of bone disease a proteomic analysis of sarcoptes scabiei acari sarcoptidae polioencephalomalacia and heart failure secondary to presumptive thiamine deficiency hepatic lipidosis and starvation in 2 abandoned siamese cats histologic lesions induced by murine norovirus infection in laboratory mice the spinal ependymal layer in health and disease characterization of a cardiorenal like syndrome in aged chimpanzees pan troglodytes a robust platform for chemical genomics in bacterial systems hippocampal neurochemical markers in bipolar disorder patients following the first manic episode a prospective 12 month proton magnetic resonance spectroscopy study type 1 diabetes genetic susceptibility and dendritic cell function potential targets for treatment cigarette smoke inhibits efferocytosis via deregulation of sphingosine kinase signaling reversal with exogenous s1p and the s1p analogue fty720 comparative effects of biologics on cardiovascular risk among older patients with rheumatoid arthritis apremilast an oral phosphodiesterase 4 inhibitor in patients with psoriatic arthritis and current skin involvement a phase iii randomised controlled trial palace 3 abca7 deletion does not affect adult neurogenesis in the mouse galectin 1 couples glycobiology to inflammation in osteoarthritis through the activation of an nf \u03bab regulated gene network a recombinant g protein plus cyclosporine a based respiratory syncytial virus vaccine elicits humoral and regulatory t cell responses against infection without vaccine enhanced disease ctl promoting effects of il 21 counteract murine lupus in the parent \u2192f1 graft versus host disease model a multidimensional investigation into the predictors of physical activity in canadian adolescents importance of survival strategies after a zombie pandemic progression to stage 3 and 4 chronic kidney disease and risk factor stratification following endovascular aortic aneurysm repair thyrotropin secreting pituitary adenomas epidemiology diagnosis and management a systematic review of cost effectiveness models in type 1 diabetes mellitus dietary behaviors of adults born prematurely may explain future risk for cardiovascular disease prime mover or fellow traveller 25 hydroxyvitamin d s seasonal variation cardiovascular disease and death in the scottish heart health extended cohort shhec re prime mover or fellow traveller 25 hydroxyvitamin d s seasonal variation cardiovascular disease and death in the scottish heart health extended study the collective nature of personalized medicine oral medicine stomatology across the globe birth growth and future codon deletions in the influenza a virus pa gene generate temperature sensitive viruses ddx3 interacts with influenza a virus ns1 and np proteins and exerts antiviral function through regulation of stress granule formation c terminal dxd containing sequences within paramyxovirus nucleocapsid proteins determine matrix protein compatibility and can direct foreign proteins into budding particles human cytomegalovirus encoded human interleukin 10 il 10 homolog amplifies its immunomodulatory potential by upregulating human il 10 in monocytes glycoprotein specific antibodies produced by dna vaccination protect guinea pigs from lethal argentine and venezuelan hemorrhagic fever during infection theiler s virions are cleaved by caspases and disassembled into pentamers niclosamide suppresses rankl induced osteoclastogenesis and prevents lps induced bone loss prkci negatively regulates autophagy via pik3ca akt mtor signaling rab11 fip2 promotes colorectal cancer migration and invasion by regulating pi3k akt mmp7 signaling pathway the vp1 s154d mutation of type asia1 foot and mouth disease virus enhances viral replication and pathogenicity temporal geographic and host distribution of avian paramyxovirus 1 newcastle disease virus risk factors for short term complications of anterior cruciate ligament reconstruction in the united states effect of toll like receptor 2 on the inhibition role of sevoflurane on airway inflammation in asthmatic mice prevalence of asymptomatic carotid artery stenosis in patients with arteriosclerosis obliterans of lower extremities and risk factor analysis safety and prognosis of allogenetic stem cell transplantation in younger patients with multiple myeloma clinicopathological diagnosis of diffuse alveolar hemorrhage relationship between interleukin 8 levels in expressed prostatic secretion and expressions of bfgf and bcl 2 in benign prostatic hyperplasia risk and protective factors for cats with naturally occurring chronic kidney disease microbiota manipulation for weight change evaluation of alternative school feeding models on nutrition education agriculture and other social outcomes in ghana rationale randomised design and baseline data possible role of kr\xfcppel like factor 5 in the remodeling of small airways and pulmonary vessels in chronic obstructive pulmonary disease what is the reasonable option for elderly patients with incidental pancreatic cystic neoplasms follow up observation versus surgical resection conditional deletion of murine fgf23 interruption of the normal skeletal responses to phosphate challenge and rescue of genetic hypophosphatemia incidence and prevalence of acromegaly in a large us health plan database identification and validation of lymphovascular invasion as a prognostic and staging factor in node negative esophageal squamous cell carcinoma effect of thermo sensitive matrigel on minimization of thermal injury to the nearby structures in radiofrequency ablation of subcapsular hepatic tumors in a rat model efficacy and mechanism of local delivery of rapamycin and rapamycin loaded poly lactic co glycolic acid nanoparticles on coronary restenosis of injury stenosis model of minipigs application of swallow tail appearance in patients with parkinson s disease effect of brain atrophy on the cognition in patients with subcortical ischemic vascular disease the clinical study of iga nephropathy with severe chronic periodontitis and aggressive periodontitis prevalence of hypothyroidism in rheumatoid arthritis and its correlation with disease activity genetic susceptibility loci of idiopathic interstitial pneumonia do not represent risk for systemic sclerosis a case control study in caucasian patients determinants of renal shape in chronic kidney disease patients microrna 132 and early growth response 1 in nucleus basalis of meynert during the course of alzheimer s disease the natural history of splanchnic artery aneurysms and outcomes after operative intervention fenestrated and branched endovascular aneurysm repair outcomes for type ii and iii thoracoabdominal aortic aneurysms crystal structure and stability of gyrase fluoroquinolone cleaved complexes from mycobacterium tuberculosis tauopathy in transgenic shr72 rats impairs function of central noradrenergic system and promotes neuroinflammation practice and experience establishment of digital cdc and intelligent public health informationization platform in jinan effectiveness of vaccination following varicella outbreaks among schools in hongkou district shanghai study of relationship between atmospheric fine particulate matter concentration and one grade a tertiary hospital emergency room visits during 2012 and 2013 in beijing status of exclusive breastfeeding and influencing factors for 1 882 pairs of mother and neonate during 0 7 days postpartum in china evaluation on the validity and reliability of the diabetes self management knowledge attitude and behavior assessment scale dskab study on developing a brief version of diabetes self management knowledge attitude and behavior assessment scale dskab sf development on the diabetes self management knowledge attitude and behavior assessment scale dskab association of childhood and adolescents obesity with adult diabetes guidelines on outbreak investigation prevention and control of norovirus infection 2015 research and application of diabetes self management scale developmental origins of cardiovascular disease and early intervention windows machine learning derived risk prediction of anorexia nervosa limitations of pet ct in the detection of occult n1 metastasis in clinical stage i t1 2an0 non small cell lung cancer for staging prior to stereotactic body radiotherapy increased risk of pulmonary tuberculosis in patients with gastroesophageal reflux disease incidence of toxic optic neuropathy with low dose ethambutol anaemia in patients with hiv associated tb relative contributions of anaemia of chronic disease and iron deficiency undertreated hiv and drug resistant tuberculosis at a referral hospital in irkutsk siberia identification of patients who could benefit from bedaquiline or delamanid a multisite mdr tb cohort study mycobacterial diversity causing multi and extensively drug resistant tuberculosis in djibouti horn of africa impact of sleeve gastrectomy on gastroesophageal reflux disease in a morbidly obese population undergoing bariatric surgery enhanced long term potentiation in mature rats in a model of epileptic spasms with betamethasone priming and postnatal n methyl d aspartate administration what s new in clinical dermatology viral etiology of medically attended influenza like illnesses in children less than five years old in suzhou china 2011 2014 climbing fibers in spinocerebellar ataxia a mechanism for the loss of motor control the new \u03b2 amyloid derived peptide a\u03b21 6a2v tat d prevents a\u03b2 oligomer formation and protects transgenic c elegans from a\u03b2 toxicity protocatechuic acid attenuates osteoclastogenesis by downregulating jnk c fos nfatc1 signaling and prevents inflammatory bone loss in mice association of abcg2 rs2231142 a allele and serum uric acid levels in male and obese individuals in a han taiwanese population functional and anatomic esophagogastic junction outflow obstruction manometry timed barium esophagram findings and treatment outcomes comparative pharmacokinetics of three major bioactive components in rats after oral administration of typhae pollen trogopterus feces drug pair before and after compatibility essential psychiatric medicines wrong selection high consumption and social problems early ficolin 1 is a sensitive prognostic marker for functional outcome in ischemic stroke medtronic freestyle aortic bioprosthesis a potential option for haemodialysis patients \u2020. clinical evaluation of laparoscopic hepatectomy for liver tumors in couinaud \u2170, \u2173a \u2176, and \u2177] higher expression of tnf\u03b1 induced genes in the synovium of patients with early rheumatoid arthritis correlates with disease activity and predicts absence of response to first line therapy longitudinal diffusion tensor imaging in dementia with lewy bodies and alzheimer s disease the role of gp130 receptor cytokines in the regulation of metabolic homeostasis mitochondria to motion optimizing oxidative phosphorylation to improve exercise performance effects of hypertrophic and dilated cardiomyopathy mutations on power output by human \u03b2 cardiac myosin acute heart failure can modern therapy delay or prevent death diagnosis of iron deficiency anaemia in hospital patients use of the reticulocyte haemoglobin content to differentiate iron deficiency anaemia from anaemia of chronic disease the nitrate nitrite no pathway and its implications for heart failure and preserved ejection fraction endothelial directed collective migration depends on substrate stiffness via localized myosin contractility and cell matrix interactions mucin microbiota interaction during postnatal maturation of the intestinal ecosystem clinical implications perioperative outcomes of elective inflow revascularization for lower extremity claudication in the american college of surgeons national surgical quality improvement program database bone disease in myeloma the claws of crab thyroid disease and the heart an analysis of permanent work disability among construction sheet metal workers tomato yellow leaf curl virus infection mitigates the heat stress response of plants grown at high temperatures travellers profile travel patterns and vaccine practices a 10 year prospective study in a swiss travel clinic quantifying the risk of heart disease following acute ischaemic stroke a meta analysis of over 50 000 participants activated prostaglandin d2 receptors on macrophages enhance neutrophil recruitment into the lung \u03c9 3 fatty acids contribute to the asthma protective effect of unprocessed cow s milk transient receptor potential cation channel subfamily v member 4 and airway sensory afferent activation role of adenosine triphosphate occupational exposure to magnetic fields and breast cancer among canadian men outcomes of hypofractionated stereotactic body radiotherapy boost for intermediate and high risk prostate cancer predictors of outcomes and hospital charges following atlantoaxial fusion functional involvement of \u03b3 secretase in signaling of the triggering receptor expressed on myeloid cells 2 trem2 research hotspot in igg4 related sialadenitis germline sftpa1 mutation in familial idiopathic interstitial pneumonia and lung cancer dyspepsia prevalence and impact on quality of life among rwandan healthcare workers a cross sectional survey the diagnostic accuracy of integrated positron emission tomography computed tomography in the evaluation of pulmonary mass lesions in a tuberculosis endemic area molecular characterisation and epidemiological investigation of an outbreak of blaoxa 181 carbapenemase producing isolates of klebsiella pneumoniae in south africa ebola personal view from the field sierra leone ebola experiences from the field liberia the impact of neoadjuvant therapy for gastroesophageal adenocarcinoma on postoperative morbidity and mortality in hospital outcomes in patients with peripheral arterial disease comparison of 2 treatments prevention of treacher collins syndrome craniofacial anomalies in mouse models via maternal antioxidant supplementation screening of celiac disease in children with henoch schoenlein purpura a new decision tree to solve the puzzle of alzheimer s disease pathogenesis through standard diagnosis scoring system molecular characterization and antimicrobial activity of an endolichenic fungus aspergillus sp isolated from parmelia caperata of similipal biosphere reserve india demethylation profile of the tnf \u03b1 promoter gene is associated with high expression of this cytokine in dengue virus patients acupuncture promotes mtor independent autophagic clearance of aggregation prone proteins in mouse brain mood differences among parkinson s disease patients with mild cognitive impairment psychogenic ophthalmologic movement disorders porphyromonas gingivalis induces autophagy in thp 1 derived macrophages genomics of worms with an emphasis on opisthorchis viverrini opportunities for fundamental discovery and biomedical outcomes second line treatment of recurrent hnscc tumor debulking in combination with high dose rate brachytherapy and a simultaneous cetuximab paclitaxel protocol persistent low levels of serum hcg due to heterophilic mouse antibodies an unrecognized pitfall in the diagnosis of trophoblastic disease new perspective of clc kb 2 cl channel physiology in the distal renal tubule human podocyte depletion in association with older age and hypertension combining patient proteomics and in vitro cardiomyocyte phenotype testing to identify potential mediators of heart failure with preserved ejection fraction the diagnostic utility of the macao predictive values of impulse oscillometry for chronic obstructive pulmonary disease in patients over 45 years old the diagnostic utility of virtual bronchoscopic navigation combined with endobronchial ultrasound guided transbronchial lung biopsy for peripheral pulmonary lesions effects of oxcarbazepine and levetiracetam on calcium ionized calcium and 25 oh vitamin d3 levels in patients with epilepsy practice of acute and maintenance electroconvulsive therapy in the psychiatric clinic of a university hospital from turkey between 2007 and 2013 paraspinal abdominal mass and pain in a toddler receiving therapy for pneumonia white matter hyperintensity microstructure in amyloid dysmetabolism ethnic minorities and coronary heart disease an update and future directions the role of ezetimibe in the treatment of cardiovascular disease polymicrobial pulmonary infection in patients with hematological malignancies prevalence co pathogens course and outcome rethinking on the concept of biomarkers in preclinical alzheimer s disease increased susceptibility to infections before the diagnosis of immune thrombocytopenia prostate cancer part 1 review of cell kinetics over the years 1966 2015 and future perspectives of the new grading of the international society of urological pathology isup almanac 2015 atrial fibrillation research in heart introducing contactless blood pressure assessment using a high speed video camera production purification and characterization of \xb9\u2075n labeled dna repair proteins as internal standards for mass spectrometric measurements using a cardiac event recorder in children with potentially arrhythmia related symptoms the dynamic genome transposons and environmental adaptation in the nervous system clinical relevance of cyclooxygenase 2 and peroxisome proliferator activated receptor \u03b3 in eyelid sebaceous gland carcinoma who uses nhs health checks investigating the impact of ethnicity and gender and method of invitation on uptake of nhs health checks quantifying prion disease penetrance using large population control cohorts big data gets personal clinical outcome of stereotactic body radiotherapy for primary and oligometastatic lung tumors a single institutional study with almost uniform dose with different five treatment schedules mitochondrial dna variants correlate with symptoms in myalgic encephalomyelitis chronic fatigue syndrome the genetic diversity and geographical separation study of oncomelania hupensis populations in mainland china using microsatellite loci assessing cancer risk on novel 29 mhz micro ultrasound images of the prostate creation of the micro ultrasound protocol for prostate risk identification thoracolumbar spinal cord tolerance to high dose conformal proton photon radiation therapy clinical and genetic features of x linked alport syndrome in men positive for the collagen \u03b15 chain in epidermal basement membrane clinical and molecular analysis of two chinese siblings with cockayne syndrome application of magnetic resonance enterography for diagnosis of small intestinal diseases in children report of 14 cases with pancreatoblastoma clinical effectiveness of different doses of caffeine for primary apnea in preterm infants assessment of energy metabolism and nutritional supply in children with mechanical ventilation immune dysregulation mediated by the oral microbiome potential link to chronic inflammation and atherosclerosis classifying the population by socioeconomic factors associated with support for policies to reduce social inequalities in health leg to trunk ratio and the risk of hypertension in children and adolescents a population based study socioeconomic development of cities and risk factors for non communicable diseases a comparative study across brazilian state capitals polyarthritis in primary sj\xf6gren s syndrome represents a distinct subset with less pronounced b cell proliferation a dutch cohort with long term follow up congenital heart block related to maternal autoantibodies descriptive analysis of a series of 18 cases from a single center screening for potential serum biomarkers in rat mesangial proliferative nephritis validity of new methods to evaluate renal function in cancer patients treated with cisplatin calculating measures of treatment effect for use in clinical practice mendelian randomization for the identification of causal pathways in atherosclerotic vascular disease map4k family kinases in immunity and inflammation the pathogenesis and immunobiology of mousepox gene map of the hla region graves disease and hashimoto thyroiditis and hematopoietic stem cell transplantation rheumatoid rescue of misfolded cellular proteins by mhc class ii molecules a new hypothesis for autoimmune diseases detection and replication of qtl underlying resistance to gastrointestinal nematodes in adult sheep using the ovine 50k snp array clinical management of uveal and conjunctival melanoma neoadjuvant treatment for surgically resectable metastatic colorectal cancer comparative mapping of powdery mildew resistance gene pm21 and functional characterization of resistance related genes in wheat systematic review with meta analysis diagnostic accuracy of transient elastography for staging of fibrosis in people with alcoholic liver disease interactions between the bud rot disease of oil palm and rhynchophorus palmarum coleoptera curculionidae response to dr cerasa s commentary on the article unsupervised learning based feature extraction for differential diagnosis of neurodegenerative diseases a case study on early stage diagnosis of parkinson disease non small cell lung cancer patients with brain metastases treated with first line platinum doublet chemotherapy analysis from the european frame study non coding rna repertoires in malignant pleural mesothelioma cyclooxygenase 2 cox2 and p53 protein expression are interdependent in breast cancer but not associated with clinico pathological surrogate subtypes tumor aggressiveness and patient survival effect of adipose derived mesenchymal stem cells adsc on the t cell immune status of allergic rhinitis mouse model the orai1 antibody treatment for a mouse model of allergic rhinitis midline2 is overexpressed and a prognostic indicator in human breast cancer and promotes breast cancer cell proliferation in vitro and in vivo breast cancer associated fibroblasts their roles in tumor initiation progression and clinical applications risk factors related to toxoplasma gondii seroprevalence in indoor housed dutch dairy goats safety and tolerability of anthracycline containing adjuvant chemotherapy in elderly high risk breast cancer patients adrenomedullin a potential therapeutic target for retinochoroidal disease pneumocystis pneumonia biological diagnosis at fann teaching hospital in dakar senegal multigland primary hyperparathyroidism frequently considered seldom encountered effects of postmortem delays on protein composition and oxidation antibacterial drug discovery in the resistance era protein misfolding in the endoplasmic reticulum as a conduit to human disease tranexamic acid in life threatening military injury and the associated risk of infective complications comparison of left ventricular contractile abnormalities in stress induced cardiomyopathy versus obstructive coronary artery disease using two dimensional strain imaging dietary exposure to an environmental toxin triggers neurofibrillary tangles and amyloid deposits in the brain seminal fluid of honeybees contains multiple mechanisms to combat infections of the sexually transmitted pathogen nosema apis ligand independent adenosine a2b receptor constitutive activity as a promoter of prostate cancer cell proliferation the selective monoacylglycerol lipase inhibitor mjn110 produces opioid sparing effects in a mouse neuropathic pain model clinical application of vestibular evoked myogenic potential vemp nasopharyngeal granulomatous mass after radiotherapy for nasopharyngeal carcinoma papillary thyroid cancer located in malignant struma ovarii with omentum metastasis a case report and review of the literature improving the outcome of kidney transplantation by ameliorating renal ischemia reperfusion injury lost in translation oxadiazole 2 oxides may have other functional targets in addition to sjtgr through which they cause mortality in schistosoma japonicum plasmablastic lymphoma a clinicopathologic analysis of 11 cases with review of literature pathologic markers for evaluation of reversibility in pulmonary hypertension related to congenital heart disease liposclerosing myxofibrous tumor of bone a clinicopathologic analysis epithelioid myxofibrosarcoma a clinicopathologic analysis of 10 cases haemorrhagic fever with renal syndrome literature review and distribution analysis in china sildenafil prevents renal dysfunction in contrast media induced nephropathy in wistar rats tissue of origin specific gene repositioning in breast and prostate cancer independent at heart persistent association of altitude with ischaemic heart disease mortality after consideration of climate topography and built environment mental and emotional impairment in patients with hepatitis c is related to lower work productivity practical considerations in choosing a factor viii prophylaxis regimen role of clinical phenotype and trough levels mesenchymal stem cells of dental origin their potential for anti inflammatory and regenerative actions in brain and gut damage the effects of genes implicated in cardiovascular disease on blood pressure response to treatment among treatment naive hypertensive african americans in the genhat study evaluation of aortic elasticity parameters in arsenic exposed workers salivary pathogen and serum antibody to assess the progression of chronic periodontitis a 24 mo prospective multicenter cohort study effects of stem cell therapy on protein profile of parkinsonian rats using an 18 o labeling quantitative proteomic approach is low serum klotho level associated with alterations in coronary flow reserve hypoxia induces no dependent release of heparan sulfate in fibroblasts from the alzheimer mouse tg2576 by activation of nitrite reduction temporal aspects of air pollutant measures in epidemiologic analysis a simulation study x linked retinoschisis associated to a novel intragenic microdeletion case report recurrence of pancreatic cancer presented as cervical lymphadenopathy the association of liver fat content and serum alanine aminotransferase with bone mineral density in middle aged and elderly chinese men and postmenopausal women charcot marie tooth 2b associated rab7 mutations cause axon growth and guidance defects during vertebrate sensory neuron development altered emotional experiences attributed to antipsychotic medications a potential link with estimated dopamine d2 receptor occupancy eradication of missing liver metastases after fiducial placement influence of tumour size on the efficacy of targeted alpha therapy with 213 bi dota 0 tyr 3 octreotate soluble interleukin 2 receptor index predicts the development of acute graft versus host disease after allogeneic hematopoietic stem cell transplantation from unrelated donors prognostic value of pretransplant serum c reactive protein in patients receiving reduced intensity conditioning allogeneic hematopoietic stem cell transplantation cigarette smoking among working women of reproductive age united states 2009 2013 development and evaluation of a loop mediated isothermal amplification method for rapid detection of aspergillus fumigatus comparison of nonculture blood based tests for diagnosing invasive aspergillosis in an animal model pneumococcal colonization rates in patients admitted to a united kingdom hospital with lower respiratory tract infection a prospective case control study adoptive transfer of autoimmune diabetes using immunodeficient nonobese diabetic nod mice methylation analysis in distinct immune cell subsets in type 1 diabetes frequency of usher syndrome type 1 in deaf children by massively parallel dna sequencing a functional snp in flt1 increases risk of coronary artery disease in a japanese population prevalence and determinants of chronic kidney disease among hypertensive cameroonians according to three common estimators of the glomerular filtration rate a novel eremophilane lactone inhibits fc\u03b5ri dependent release of pro inflammatory mediators structure dependent bioactivity presynaptic release regulating mglu2 preferring and mglu3 preferring autoreceptors in cns pharmacological profiles and functional roles in demyelinating disease does improve it prove it early results of clinical application of autologous whole bone marrow stem cell transplantation for critical limb ischemia with buerger s disease elevated hoxa1 expression correlates with accelerated tumor cell proliferation and poor prognosis in gastric cancer partly via cyclin d1 excess mortality due to depression and anxiety in the united states results from a nationally representative survey erratum to telmisartan in the management of abdominal aortic aneurysm tedy the study protocol for a randomized controlled trial diminished amygdala activation and behavioral threat response following traumatic brain injury cell based therapy for degenerative retinal disease spongy white matter a novel neuroimaging finding in canavan disease il 10 controls early microglial phenotypes and disease onset in als caused by misfolded superoxide dismutase 1 pathological tau promotes neuronal damage by impairing ribosomal function and decreasing protein synthesis rapid mechanically controlled rewiring of neuronal circuits evidence for the integration of stress related signals by the rostral posterior hypothalamic nucleus in the regulation of acute and repeated stress evoked hypothalamo pituitary adrenal response in rat short fibrils constitute the major species of seed competent tau in the brains of mice transgenic for human p301s tau direct transcriptional effects of apolipoprotein e serum aminotransferases in nonalcoholic fatty liver disease are a signature of liver metabolic perturbations at the amino acid and krebs cycle level lipid emulsions in the treatment and prevention of parenteral nutrition associated liver disease in infants and children the association between dietary saturated fatty acids and ischemic heart disease depends on the type and source of fatty acid in the european prospective investigation into cancer and nutrition netherlands cohort executive summary evaluation of the evidence to support practice guidelines for nutritional care of preterm infants the pre b project group based exercise combined with dual task training improves gait but not vascular health in active older adults without dementia a novel elisa based diagnosis of acquired von willebrand disease with increased vwf proteolysis medical therapies for pulmonary arterial hypertension association of arterial stiffness with progression of subclinical brain and cognitive disease asymmetric pathology in primary progressive aphasia with progranulin mutations and tdp inclusions differences in the role of black race and stroke risk factors for first vs recurrent stroke national characteristics and predictors of neurologic 30 day readmissions salbutamol responsive fetal acetylcholine receptor inactivation syndrome structural cure for reflex syncope st elevation myocardial infarction in a young adult secondary to giant coronary aneurysm thrombosis an important sequela of kawasaki disease and a management challenge idiopathic 20 nail dystrophy a man with dark urine and shortness of breath a case based review of paravalvular leaks sweet s syndrome complicating ulcerative colitis a rare association autoimmune hepatitis unmasked by nimesulide synchronous colonic lymphoma and adenocarcinoma in a patient with crohn s disease treated with thiopurine therapy and a tnf\u03b1 inhibitor a challenge to occam s razor leukocytoclastic vasculitis associated with perforated diverticular disease effect of tricyclic antidepressants on l dopa induced dyskinesia and motor improvement in hemi parkinsonian rats azacitidine induced cryptogenic organizing pneumonia a case report and review of the literature a clinical role of staging laparoscopy in patients with radiographically defined locally advanced pancreatic ductal adenocarcinoma differential visual system organization and susceptibility to experimental models of optic neuropathies in three commonly used mouse strains different human vaccine adjuvants promote distinct antigen independent immunological signatures tailored to different pathogens reply outcomes after transcatheter aortic valve replacement with balloon expandable versus self expandable valves choice trial results outcomes after transcatheter aortic valve replacement with balloon expandable versus self expandable valves choice trial results dual lipid lowering strategy with ezetimibe and atorvastatin on coronary plaque regression after pci precise ivus reply dual lipid lowering strategy with ezetimibe and atorvastatin on coronary plaque regression after pci precise ivus depressive symptoms and subclinical vascular disease the role of regular physical activity lipoprotein associated phospholipase a2 loss of function variant and risk of vascular diseases in 90 000 chinese adults discordance between apolipoprotein b and ldl cholesterol in young adults predicts coronary artery calcification the cardia study trends in the management and outcomes of acute pulmonary embolism analysis from the riete registry predictive models of atherosclerotic cardiovascular disease in search of the philosopher s stone of cardiology utility of nontraditional risk markers in atherosclerotic cardiovascular disease risk assessment sex versus gender related characteristics which predicts outcome after acute coronary syndrome in the young primary immunodeficiencies and inflammatory disease a growing genetic intersection more isn t always better but is less commentary on an article by juuso heikkinen md et al augmented compared with nonaugmented surgical repair after total achilles rupture results of a prospective randomized trial with thirteen or more years of follow up prelude to a biological phenotype for osteoarthritis commentary on an article by nobuaki chinzei md phd et al inflammation and degeneration in cartilage samples from patients with femoroacetabular impingement inflammation and degeneration in cartilage samples from patients with femoroacetabular impingement augmented compared with nonaugmented surgical repair after total achilles rupture results of a prospective randomized trial with thirteen or more years of follow up genomic variation in the porcine immunoglobulin lambda variable region design synthesis and biological evaluation of 1 3 6 trisubstituted \u03b2 carboline derivatives for cytotoxic and anti leishmanial potential acr appropriateness criteria \xae) aggressive nonmelanomatous skin cancer of the head and neck self enforcing regional vaccination agreements analysis of the psychological impact of cancer related symptoms on patients with non small cell lung cancer carotid endarterectomy for critical stenosis prior to cardiac surgery should it be done a retrospective cohort study clinical characteristics and continued epidermal growth factor receptor tyrosine kinase inhibitor administration in egfr mutated non small cell lung cancer with skeletal metastasis splenomegaly and its associations with genetic polymorphisms and treatment outcome in colorectal cancer patients treated with adjuvant folfox submucosal lipoma of the sigmoid colon as a rare cause of mucoid diarrhea a case report clinical assessment of patients with chest pain a systematic review of predictive tools axotomy induced hif serotonin signalling axis promotes axon regeneration in c elegans influence of integrated molecular pathology test results on real world management decisions for patients with pancreatic cysts analysis of data from a national registry cohort control of swine pseudorabies in china opportunities and limitations different counteracting host immune responses to clade 2 2 1 1 and 2 2 1 2 egyptian h5n1 highly pathogenic avian influenza viruses in na\xefve and vaccinated chickens novel chimeric foot and mouth disease virus like particles harboring serotype o vp1 protect guinea pigs against challenge investigation on host susceptibility of tibetan pig to infection of porcine reproductive and respiratory syndrome virus through viral challenge study reconstruction of the schmallenberg virus epidemic in belgium complementary use of disease surveillance approaches phocine distemper virus pdv seroprevalence as predictor for future outbreaks in harbour seals epidemiological evolution of canine parvovirus in the portuguese domestic dog population effects of rispens cvi988 vaccination followed by challenge with marek s disease viruses of differing virulence on the replication kinetics and shedding of the vaccine and challenge viruses an outbreak of monophasic and biphasic salmonella typhimurium and salmonella derby associated with the consumption of dried pork sausage in castellon spain psa and beyond alternative prostate cancer biomarkers bioanalytical approaches for the detection of protein acetylation related enzymes in vivo effects of methamphetamine on hiv 1 replication a population based study multiple fixed drug eruption caused by ropinirole in a patient with parkinson s disease unexpected wear of an unicompartimental knee arthroplasty in oxidized zirconium prepatellar friction syndrome a common cause of knee pain in the elite cyclist the impact of fdg pet ct in the management of patients with vulvar and vaginal cancer the influence of polypharmacy on grade iii iv toxicity prior discontinuation of chemotherapy and overall survival in ovarian cancer a case of kartagener s syndrome in infertile male patients a case of muscle invasive bladder cancer in a patient with systemic lupus erythematosus clinical characteristics of prostate ductal adenocarcinoma in kyoto university hospital comprehensive evaluation of plasma 7 ketocholesterol and cholestan 3\u03b2 5\u03b1 6\u03b2 triol in an italian cohort of patients affected by niemann pick disease due to npc1 and smpd1 mutations did dumbo suffer a heart attack independent association between earlobe crease and cardiovascular disease prevalence of giardia in dairy cattle in lusaka and chilanga districts zambia evaluation of larviposition site selection of glossina brevipalpis identification of differentially expressed proteins between free living and activated third stage larvae of haemonchus contortus evaluation of two recombinant leishmania proteins identified by an immunoproteomic approach as tools for the serodiagnosis of canine visceral and human tegumentary leishmaniasis distribution of cryptosporidium species in tibetan sheep and yaks in qinghai china temperature dependent embryonic development of trichuris suis eggs in a medicinal raw material bumped kinase inhibitor prohibits egression in babesia bovis dingoes canis dingo meyer 1793 continue to be an important reservoir host of dirofilaria immitis in low density housing areas in australia apolipoprotein e polymorphism modulation of asymmetric dimethylarginine in hypertensive patients is determined by renal function chronic graft versus host disease following allogeneic hematopoietic stem cell transplantation in chronic myelomonocytic leukemia a way to improve the outcome inhibition of glucose transporter 1 induces apoptosis and sensitizes multiple myeloma cells to conventional chemotherapeutic agents management of the cardiovascular disease risk during nilotinib treatment in chronic myeloid leukemia 2015 recommendations from the france intergroupe des leuc\xe9mies my\xe9lo\xefdes chroniques what future for circulating tumor dna current data and prospects in colorectal non small cell lung and pancreatic cancers inborn errors of metabolism detectable by tandem mass spectrometry in egypt the first newborn screening pilot study stem cell mobilisation by granulocyte colony stimulating factor in patients with acute myocardial infarction long term results of the revival 2 trial impact of nonoptimal intakes of saturated polyunsaturated and trans fat on global burdens of coronary heart disease risk factors of early onset of ms in women in reproductive age period survival analysis approach clinical outcomes and prognostic factors for salivary duct carcinoma a multi institutional analysis of 141 patients a comprehensive program for the enhancement of accrual to clinical trials circulating maternal total cell free dna cell free fetal dna and soluble endoglin levels in preeclampsia predictors of adverse fetal outcome a cohort study measuring the impact of skin disease in adolescents which score and when ifn\u03b1 enhances the production of il 6 by human neutrophils activated via tlr8 genomic variations in non coding rnas structure function and regulation prevalence of depression in type 2 diabetes patients in german primary care practices the urinary inflammatory profile in gluten free diet adherent adolescents with type 1 diabetes and celiac disease the relationship between serum uric acid levels and the major risk factors for the development of nonalcoholic fatty liver disease orbital wall infarction in child with sickle cell disease a case report antiviral triple therapy with telaprevir in a haemodialysed hcv patient in turkey nontuberculous mycobacteria are an uncommon cause of septic olecranon bursitis though cases have increasingly been described in both immunocompromised and immunocompetent hosts guidelines recommend a combination of surgical resection and antimicrobials for treatment this case is the first reported case of nontuberculous mycobacterial olecranon bursitis that resolved without medical or surgical intervention a 67 year old female developed a painless fluctuant swelling of the olecranon bursa following blunt trauma to the elbow due to persistent bursal swelling she underwent three separate therapeutic bursal aspirations two involving intrabursal steroid injection after the third aspiration the bursa became erythematous and severely swollen and bursal fluid grew mycobacterium avium complex triple drug antimycobacterial therapy was initiated but discontinued abruptly due to a rash surgery was not performed the patient was observed off antimicrobials and gradually clinically improved with a compressive dressing by 14 months after initial presentation clinical exam revealed complete resolution of the previously erythematous bursal mass this is the first reported case of nontuberculous mycobacterial olecranon bursitis managed successfully without surgery or antimicrobials musculoskeletal nontuberculous mycobacterial infections are challenging given the lack of clinical data about optimal duration and choice of antimicrobials or the role of surgery additionally the potential toxicity and drug interactions of antimycobacterials are not insignificant and warrant close monitoring if treatment is pursued this case raises an important clinical question of whether close observation off antimicrobials is appropriate in select cases of immunocompetent patients with localized atypical mycobacterial disease of soft tissue and skeletal structures tetanus vaccination is part of the norwegian childhood vaccination program an elderly woman injured her arm and leg after a minor fall on her outdoor stairs two weeks later she presented with trismus this developed into tetanic spasms obstructed airways and the need for a tracheostomy she died 14 days later due to pneumonia and multi organ failure elisa for tetanus toxoid igg was negative probably because the patient was born before the introduction of tetanus vaccination in the norwegian childhood vaccination program lack of adherence to the vaccination programs should be considered in patients presenting with symptoms resembling diseases they normally would be protected from although the patient presented with typical symptoms the diagnosis was not suspected initially probably due to the rareness of this disease in norway head and neck manifestations of acquired immunodeficiency syndrome are among the most common complications of this disease the sinonasal and oral manifestations are more common that the otologic and range from malignancies to infectious processes caused by both opportunistic and nonopportunistic organisms we report the case of a nasopharyngeal mass of infectious etiology in a severely immunocompromised hiv infected patient the patient was admitted with a presumptive diagnosis of infectious gastroenteritis and was found to have a nasopharyngeal mass the mass was extending into the oropharynx and paravertebral soft tissues and was associated with extensive secretions causing near complete occlusion of the oropharynx ct scan findings favored malignant verses infectious etiology the surgical biopsy performed twice ruled out malignancy and the bacterial culture proved to be a pure growth of pseudomonas aeruginosa pseudomonas can inhabit the nasopharynx and lower digestive tract and is only occasionally associated with causing disease in non susceptible patients but is a common infection in immunocompromised patients to the best of our knowledge and after considering the current literature we believe this case is unique we discuss this rare entity and its management clinicians should be aware of this potential life threatening condition in the hiv population and add p aeruginosa infection to the differential diagnosis of an acute inflammatory nasopharyngeal mass we describe a patient with pulmonary cavitary pneumonia from whom we serially isolated mycobacterium kyorinense an organism not previously reported in australia or associated with cavitary disease we discuss the clinical presentation the isolation of the organism on several specimens and initial management m kyorinense is a recently characterized species which has previously only been described in japan and brazil 1 achromobacter xylosoxidans is an aerobic nonfermenting gram negative rod and described as a waterborne bacterium since it habits aquatic environments ubiquitously it has frequently been isolated from aquatic surroundings in the hospital and from various human body sites although occasionally considered a non pathogen a xylosoxidans has been associated with outbreaks of nosocomial infection due to contaminated fluids moreover a wide variety of infectious etiologies due to a xylosoxidans has been reported primarily in immunocompromised individuals heightened awareness of this bacterium and associated clinical importance is warranted for clinicians since its broad disease spectrum in humans and frequent multi drug resistance may result in an increased mortality rate in this report we describe a case of osteomyelitis caused by a xylosoxidans in a patient with a history of diabetes mellitus the recent ebola virus disease evd outbreak has created interest in personal protective equipment ppe content and usage ppe testing has historically been done by individual component rather than as a bundle for contact isolation fluorescent agents are commonly used in training for infection control techniques the purpose of our study was to compare 2 ppe bundles and to evaluate the feasibility of fluorescent markers as an assessment tool for ppe effectiveness eight healthcare providers volunteered for this preliminary study participants were randomized to 1 of 2 ppe bundles that meet current october 20 2014 cdc recommendations one ppe bundle utilized commercial evd recommended components the other ppe bundle used components already available at local hospitals or retail stores participants were also randomized to standard or high volume exposures hve to simulate fluid splash each participant was assisted in ppe donning and doffing by an experienced trainer a training mannequin was contaminated with fluorescent agents to simulate bodily fluids participants were then given clinical tasks to care for the evd patient de gowned participants were examined under black light for fluorescence indicative of contamination one participant in each ppe arm had evidence of contamination one of the contamination events was suspected during the patient care exercise the other contamination event was not suspected until black light examination in spite of a large difference in cost of ppe the two bundle arms performed similarly bundle testing using fluorescent markers could help identify optimal ppe systems a large epidemic of chikungunya fever currently affects the caribbean central and south america despite a high number of reported cases little is known on the occurrence of severe clinical complications we describe four venezuelan patients with a severe and or lethal course who exhibit unusual manifestations of the disease case 1 describes a 75 year old man with rapid onset of septic shock and multi organ failure cases 2 and 3 describe two patients with rapid aggressive clinical course who developed shock severe purpuric lesions and a distinct area large of necrosis in the nasal region case 4 depicts a splenectomized woman with shock generalized purpuric lesions bullous dermatosis and acronecrosis of an upper limb chikungunya fever in the western hemisphere may also associate with atypical and severe manifestations some patients experience a life threatening aggressive clinical course with rapid deterioration and death due to multisystem failure public health england undertakes surveillance of vaccine preventable diseases including enhanced surveillance of clinically suspected tetanus in the united kingdom tetanus has become increasingly rare due to the success of the national routine immunization program consequently few practitioners have experience of diagnosing and managing patients with clinical tetanus we report two cases of tetanus where comparatively minor wounds proved fatal these cases highlight the importance of the accurate identification and management of tetanus prone wounds and the fatal consequences from untreated injuries in susceptible individuals we conclude that appropriate risk assessment for tetanus prophylaxis forms an essential part of wound management background osteoporosis is a pediatric disease with geriatric consequences bone morphology and tissue quality co adapt during ontogeny for sufficient bone stiffness altered bone morphology from hypothalamic amenorrhea a risk factor for low bone mass in women may affect bone strength later in life our purpose was to determine if altered morphology following hypothalamic suppression during development affects cortical bone strength and trabecular bone volume bv tv at maturity methods female rats 25 days old were assigned to a control c group n 45 that received saline injections 2 cc or an experimental group gnrh a n 45 that received gonadotropin releasing hormone antagonist injections 24 mg per dose for 25 days fifteen animals from each group were sacrificed immediately after the injection protocol at day 50 c gnrh a the remaining animals recovered for 135 days and a subset of each group was sacrificed at day 185 c r n 15 and g r n 15 the remaining animals had an ovariectomy surgery ovx at 185 days of age and were sacrificed 40 days later c ovx n 15 and g ovx n 15 after sacrifice femurs were mechanically tested and scanned using micro ct serum c terminal telopeptides ctx and insulin like growth factor 1 igf 1 were measured two way anova 2 groups gnrh a and control x 3 time points injection protocol recovery post ovx was computed results gnrh a injections suppressed uterine weights 72 and increased ctx levels by 59 bone stiffness was greater in the gnrh a groups compared to c ash content and cortical bone area were similar between groups at all time points polar moment of inertia a measure of bone architecture was 15 larger in the gnrh a group and remained larger than c 19 following recovery both the polar moment of inertia and cortical area increased linearly with the increases in body weight following the injection protocol trabecular bv tv was 31 lower in the gnrh a group compared to c a similar deficit in bv tv was also measured following recovery and post ovx the trabecular number and thickness were lower in the gnrh a group compared to control conclusion these data suggest that following a transient delay in pubertal onset trabecular bone volume was significantly lower and no restoration of bone volume occurred following recovery or post ovx surgery however cortical bone strength was maintained through architectural adaptations in the cortical bone envelope an increase in the polar moment of inertia offset increased bone resorption the current data are the first to suppress trabecular bone during growth and then add an ovx protocol at maturity trabecular bone and cortical bone differed in their response to hypothalamic suppression during development trabecular bone was more sensitive to the negative effects of hypothalamic suppression tasmanian devil sarcophilus harrisii pouch young like other marsupials are born underdeveloped and immunologically na\xefve and are unable to mount an adaptive immune response the mother s milk provides nutrients for growth and development as well as providing passive immunity to better understand immune response in this endangered species we set out to characterise the genes involved in passive immunity by sequencing and annotating the transcriptome of a devil milk sample collected during mid lactation at mid lactation we expect the young to have heightened immune responses as they have emerged from the pouch encountering new pathogens a total of 233 660 transcripts were identified including approximately 17 827 unique protein coding genes and 846 immune genes the most highly expressed transcripts were dominated by milk protein genes such as those encoding early lactation protein late lactation proteins \u03b1 lactalbumin \u03b1 casein and \u03b2 casein there were numerous highly expressed immune genes including lysozyme whey acidic protein ferritin and major histocompatibility complex i and ii genes encoding immunoglobulins antimicrobial peptides chemokines and immune cell receptors were also identified the array of immune genes identified in this study reflects the importance of the milk in providing immune protection to tasmanian devil young and provides the first insight into tasmanian devil milk background objectives this study examines the surface activity resistance to biophysical inhibition and pulmonary efficacy of a synthetic lung surfactant containing glycerophospholipids combined with super mini b s mb datk a novel and stable molecular mimic of lung surfactant protein sp b the objective of the work is to test whether s mb datk synthetic surfactant has favorable biophysical and physiological activity for future use in treating surfactant deficiency or dysfunction in lung disease or injury methods the structure of s mb datk peptide was analyzed by homology modeling and by ftir spectroscopy the in vitro surface activity and inhibition resistance of synthetic s mb datk surfactant was assessed in the presence and absence of albumin lysophosphatidylcholine lyso pc and free fatty acids palmitoleic and oleic acid adsorption and dynamic surface tension lowering were measured with a stirred subphase dish apparatus and a pulsating bubble surfactometer 20 cycles min 50 area compression 37 \xb0c in vivo pulmonary activity of s mb datk surfactant was measured in ventilated rabbits with surfactant deficiency dysfunction induced by repeated lung lavages that resulted in arterial po2 values 100 mmhg results s mb datk surfactant had very high surface activity in all assessments the preparation adsorbed rapidly to surface pressures of 46 48 mn m at 37 \xb0c low equilibrium surface tensions of 22 24 mn m and reduced surface tension to 1 mn m under dynamic compression on the pulsating bubble surfactometer s mb datk surfactant showed a significant ability to resist inhibition by serum albumin c16 0 lyso pc and free fatty acids but surfactant inhibition was mitigated by increasing surfactant concentration s mb datk synthetic surfactant quickly improved arterial oxygenation and lung compliance after intratracheal instillation to ventilated rabbits with severe surfactant deficiency conclusions s mb datk is an active mimic of native sp b synthetic surfactants containing s mb datk or related peptides combined with lipids appear to have significant future potential for treating clinical states of surfactant deficiency or dysfunction such as neonatal and acute respiratory distress syndromes micrornas mirnas play critical roles in many important biological processes such as growth and development in mammals various studies of porcine muscle development have mainly focused on identifying mirnas that are important for fetal and adult muscle development however little is known about the role of mirnas in middle aged muscle development here we present a comprehensive investigation of mirna transcriptomes across five porcine muscle development stages including one prenatal and four postnatal stages we identified 404 known porcine mirnas 118 novel mirnas and 101 mirnas that are conserved in other mammals a set of universally abundant mirnas was found across the distinct muscle development stages this set of mirnas may play important housekeeping roles that are involved in myogenesis a short time series expression miner analysis indicated significant variations in mirna expression across distinct muscle development stages we also found enhanced differentiation and morphogenesis related mirna levels in the embryonic stage conversely apoptosis related mirna levels increased relatively later in muscle development these results provide integral insight into mirna function throughout pig muscle development stages our findings will promote further development of the pig as a model organism for human age related muscle disease research triatoma kissing bugs a predatory genus of blood sucking insects which belongs to the family reduviidae subfamily triatominae is a well known vector in the transmission of trypanosoma cruzi the causative agent in chagas disease however it is less well appreciated that bites from these insects can cause a range of symptoms varying from localized cutaneous symptoms to a generalized anaphylactic reaction while anaphylactic reactions following bites have been reported with five of the eleven species endemic to the united states the majority are associated with triatoma protracta and triatoma rubida there have been very few reported cases of anaphylactic reaction to the bite triatoma rubrofasciata which is endemic to florida and hawai i we report a case of a 50 year old previously healthy female from a rural area in honolulu county who suffered three separate bites from triatoma rubrofasciata and experienced a generalized anaphylactic reaction on each occasion there is currently no commercially available skin test to determine allergy to triatoma bites and there is likewise no immunotherapy avoidance is the best strategy and allergic patients should always have an epinephrine auto injector readily available toothpicks are commonly used household items that rarely cause serious injury or infection toothpick related injuries often occur due to ingestion with subsequent trauma infection at distal sites within the gastrointestinal tract however cardiovascular pleural and soft tissue infections have been reported eikenella corrodens is a gram negative facultative anaerobic bacillus found in oral flora associated with bite wound infections a few case reports describe e corrodens osteomyelitis from toothpick puncture wounds we report a case of foot cellulitis and abscess in an elderly diabetic after toothpick puncture injury that was unresponsive to empiric antibiotics wound cultures grew e corrodens and rare peptostreptococcus species e corrodens is resistant to first generation cephalosporins macrolides aminoglycosides clindamycin and metronidazole this case highlights the insidious nature of e corrodens infections and the need to tailor empiric antibiotics for skin and soft tissue infections based on the mechanism of injury in addition this case stresses the importance of protective footwear in diabetics and serves as a cautionary tale regarding the use of seemingly innocuous toothpicks immunoglobulin g4 related disease igg4 rd is a rare but increasingly recognized multi organ fibro inflammatory condition characterized by distinct pathologic and histologic features the clinical variability and relative novelty of igg4 rd make accurate diagnosis of the condition quite challenging we report a case of a 71 year old man presenting with hypertrophy of the facial glands and generalized lymphadenopathy who was previously diagnosed with sarcoidosis we recognized that he had atypical epidemiologic characteristic for sarcoidosis and his prior work up documented elevated serum igg4 to 300 mg dl immunostaining of an axillary lymph node biopsy showed an igg4 igg plasma cell ratio of 40 and a plasma cell concentration of 100 igg4 plasma cells per high powered field findings consistent with the diagnosis of igg4 rd this case report is an example of how analysis of collective clinicopathologic data led to a diagnosis of igg4 rd the pathologic complexities which contribute to the elusive nature of igg4 rd are also illustrated parkinson s disease pd is associated with emotional abnormalities dopaminergic medications ameliorate parkinsonian motor symptoms but less is known regarding the impact of dopaminergic agents on affective processing particularly in depressed pd dpd patients the aim of this study was to examine the effects of dopaminergic pharmacotherapy on brain activation to emotional stimuli in depressed versus nondepressed parkinson disease ndpd patients participants included 18 ndpd patients 11 men 7 women and 10 dpd patients 7 men 3 women patients viewed photographs of emotional faces during functional mri scans were performed while the patient was taking anti parkinson medication and the day after medication had been temporarily discontinued results indicate that dopaminergic medications have opposite effects in the prefrontal cortex depending upon depression status dpd patients show greater deactivation in the ventromedial prefrontal cortex vmpfc on dopaminergic medications than off while ndpd patients show greater deactivation in this region off drugs the vmpfc is in the default mode network dmn dmn activity is negatively correlated with activity in brain systems used for external visual attention thus dopaminergic medications may promote increased attention to external visual stimuli among dpd patients but impede normal suppression of dmn activity during external stimulation among ndpd patients we report a case of digeorge like syndrome in which immunodeficiency coexisting with juvenile idiopathic arthritis congenital heart disease delay in emergence of language and in motor milestones feeding and growing problems enamel hypoplasia mild skeletal anomalies and facial dysmorphisms are associated with no abnormalities found on genetic tests we present a case of 28 year old female who had a past obstetrical history complicated by uncontrolled blood pressure early onset preeclampsia and a fetal demise at 29 weeks her blood pressure normalized after each pregnancy and no diagnosis of renal disease was ever established in her most recent pregnancy she remained normotensive and initially presented with normal blood urea nitrogen and creatinine levels however after the early first trimester she developed nephrotic range proteinuria hypoalbuminemia and peripheral edema after delivery of the baby all clinical symptoms rapidly resolved and laboratory values normalized we review the clinical course diagnosis and management of new onset nephrotic syndrome in pregnancy purpose this study aims to compare the accuracy of intraocular lens power calculation formulas in eyes with long axial lengths from chinese patients subjected to cataract surgery methods a total of 148 eyes with an axial length of 26 mm from 148 patients who underwent phacoemulsification with intraocular lens implantation were included the haigis hoffer q holladay 1 and srk t formulas were used to calculate the refractive power of the intraocular lenses and the postoperative estimated power results overall the haigis formula achieved the lowest level of median absolute error 1 025 d p 0 01 for haigis versus each of the other formulas followed by srk t formula 1 040 d all formulas were least accurate when eyes were with axial length of 33 mm and median absolute errors were significantly higher for those eyes than eyes with axial length 26 01 30 00 mm absolute error was correlated with axial length for the srk t r 0 212 p 0 010 and hoffer q r 0 223 p 0 007 formulas for axial lengths 33 mm eyes exhibited a postoperative hyperopic refractive error conclusions the haigis and srk t formulas may be more suitable for calculating intraocular lens power for eyes with axial lengths ranging from 26 to 33 mm and for axial length over 33 mm the haigis formula could be more accurate to date data regarding the pulmonary histopathology of human h7n9 disease are scarce we herein describe a patient with a severe case of avian influenza a h7n9 a chest computerized tomography ct scan showed diffuse ground glass opacities and consolidation throughout the lungs a resection of pulmonary bullae in the right middle lobe was performed by video assisted thoracic surgery vats based on the extracorporeal membrane oxygenation ecmo supportive technique on the 23 rd day after the onset of symptoms because of a right pneumothorax persistent air leak the histopathological findings of the resected lung tissue revealed pneumocyte hyperplasia and fibroproliferative changes along with diffuse alveolar damage bronchoalveolar lavage fluid balf specimens for influenza a h7n9 virus were continuously positive for more than three weeks despite oseltamivir treatment and continuous viral replication significantly prolonged the course of the disease the patient s clinical status continuously deteriorated with the development of refractory hypoxemia due to progressive and rapid lung fibrosis which was confirmed by the final histological changes observed from a limited post mortem biopsy of lung tissue pre terminally he developed multi organ failure and died on the 39 th day after symptom onset despite corticosteroid treatment primary tracheobronchial non hodgkin lymphoma nhl is a rare tracheobronchial tumor that typically presents as an endobronchial mass and or mucosal infiltration together with lymphadenopathy here we report a case of primary tracheobronchial nhl which was confirmed by histopathological analysis of the endobronchial biopsy specimens we initially could not treat with chemotherapy because the life threatening obstruction of the bilateral main bronchi caused by nhl after interventional bronchoscopy involving cryotherapy electrocautery and argon plasma coagulation to successfully alleviate airway obstruction we were able to administer chemotherapy which elicited a good response this case illustrates that nhl should be considered in the differential diagnosis of central airway obstruction interventional bronchoscopy is an effective method to alleviate airway obstruction in primary tracheobronchial nhl and prepare the patient to receive tumor specific chemotherapy and other treatments atrial fibrillation af is a common supraventricular arrhythmia that increases in prevalence with increasing age and in the presence of comorbidities such as heart failure hf af increases the risk of a number of serious complications including stroke and hf as a result the rate of hospitalization is high making af a costly disease treatment strategies for af are broadly based around rate and rhythm control either pharmacological or mechanical there appear to be a number of links between sleep disordered breathing sdb and af although further studies are needed to fully understand the physiological mechanisms that link these conditions patients with af and sdb share a number of risk factors and comorbidities including age male sex hypertension congestive hf and coronary artery disease cad and the prevalence of sdb in af is higher than in the general population prevalence rates of obstructive sleep apnea osa in patients with af have been reported to range from 21 to just over 80 the prevalence of central sleep apnea csa in patients with af is less well defined but appears to be particularly high in patients who also have hf and a reduced left ventricular ejection fraction lvef the frequency of apneas can be reduced by effective treatment of af while co existing osa reduces the effectiveness of treatments for af and there is an increased risk of arrhythmia recurrence in the presence of sdb treating osa with continuous positive airway pressure cpap therapy has shown the potential to decrease the incidence of af improve the effectiveness of af interventions and decrease the risk of arrhythmia recurrence although data from large randomized controlled clinical trials are lacking based on available data inclusion of sdb recognition and management strategies as part of af management appears to have the potential to reduce the impact of this arrhythmia at both the individual and societal levels and has been recognized as important in recent guidelines presently the clinical effect of radical video assisted thoracic surgery vats is equal to that of traditional open chest surgery and has received worldwide recognition of its advantages less trauma and faster recovery in the attempt to further the advancement of minimally invasive surgery the operative techniques of uniportal vats and non intubated anesthesia have been developed these techniques have been widely applied in hospitals around the world however there are few reports on the combined use of these techniques non intubated uniportal vats we report a case of peripheral lung cancer in the right upper lobe for which a non intubated uniportal vats resection was performed this method was chosen as a result of the small size of the lesion and the placement in the right upper lobe the postoperative course of this patient was good pathological results indicated infiltrating adenocarcinoma of the right upper lobe there was no metastasis in hilar or mediastinal lymph nodes pathology results of the stump of the bronchus and vessels were also negative uniportal vats with non intubated anesthesia was a feasible and safe option for this patient and may be an alternative minimally invasive option for patients with peripheral lung cancer pulmonary lymphoepithelioma like carcinoma lelc is one of the rare histological non small cell lung cancers only a few case reports have been published the knowledge of its characteristics and prognosis in western population is limited based on the data of the surveillance epidemiology and end results database seer an analysis was performed to fill the gap of our knowledge characteristics treatment and outcomes of all pulmonary lelc patients was extracted both from the seer database from 1973 to 2011 using seer stat 8 2 1 statistical analysis was performed using spss 16 0 and graphpad prism 5 a total of 62 patients with pulmonary lelc are identified and analyzed the median age at diagnosis is 65 among them the majority was male 64 4 early stage patients account for the largest proportion 67 8 the median survival of all lelc patients is 107 months 95 confidence interval ci 67 147 the 1 3 and 5 years survival rates of lelc are 85 6 74 5 and 55 2 in the comparisons incorporating with other types of large cell lung cancer lcc adenocarcinoma ad and squamous cell lung cancer sq the overall survival os of lelc is superior to others most of the early stage localized and regional lelc patients 37 45 82 2 received surgical resection as the primary treatment patients older than 65 years predicted a worse prognosis pulmonary lelc is a rare pathological type of lung cancer in this cohort most lelc cases were male and in early stage majority of early stage lelc patients have received surgical resection patients older than 65 years had worse survival unfortunately no other prognostic factor has been identified in our study in addition we observed that lelc had an ideal prognosis comparing to other types of lcc ad and sq in order to understand pulmonary lelc more thoroughly more cases are required the prevalence of carotid artery stenosis cas in chinese patients with angina pectoris is unknown the study population consisted of 989 consecutive patients who were scheduled to undergo nonemergent coronary angiography for suspicion of coronary artery disease cad because of angina pectoris between january 2013 and december 2014 all patients underwent carotid ultrasonography to screen for cas within one month before or after coronary angiography we defined cases with 0 50 50 70 and 70 stenosis as mild moderate and severe stenosis respectively cad was presented in 853 patients 86 2 of whom 191 patients 19 3 had 1 vessel disease 246 patients 24 9 had 2 vessel disease and 416 patients 42 1 had 3 vessel disease left main trunk stenosis present in 137 patients 13 9 in carotid ultrasonography the prevalence of mild moderate and severe stenosis as well as that of total occlusion of the carotid artery was 54 5 13 4 7 and 0 8 respectively significant cas 50 stenosis and total occlusion was present in 10 3 13 9 19 9 and 22 8 of patients with 0 vessel 1 vessel 2 vessel and 3 vessel cad the severity of cas was directly correlated r 0 194 p 0 001 with the extent of cad the independent predictors of severe cas and total carotid artery occlusion were increased age male sex hypertension diabetes mellitus hyperhomocysteinemia a previous history of stroke and 3 vessel cad the prevalence of cas was not rare in china when compared with that in western countries and the presence of cas was weakly correlated with the extent of cad screening for cas should be recommended in chinese patients with cad especially in those with one or more cas associated risk factors bronchoplastic and broncho arterioplastic lobectomy is technically demanding present study performed a prognostic analysis of lobectomy patient based on 10 year data in a high volume center overall 161 non small cell lung cancer nsclc cases underwent bronchoplastic and broncho arterioplastic lobectomy between january 2004 and november 2013 follow up information was obtained for 88 8 patients prognostic analysis was performed with the cox proportional hazards model there were 133 bronchoplastic and 28 broncho arterioplastic procedures in detail 97 sleeve and 64 wedge broncho resection and reconstructions were conducted pulmonary artery sleeve reconstructions were performed in 26 cases and tangential resection in 135 cases 90 day post operative mortality was 3 1 5 161 and 24 8 40 161 patients had post operative complications 5 year overall survival was 53 4 and 5 year disease free survival dfs was 48 2 for the entire case series these survival rates were 67 7 and 55 7 for stage i n 31 64 4 and 58 9 for stage ii n 62 and 36 9 and 31 9 for stage iii disease respectively univariate analysis revealed that age 65 and higher grade of pn were associated with worse overall survival while right side tumor non squamous histology type and higher grade of pt and pn were associated with worse dfs multivariate analysis revealed that pn is the only independent factor of worse outcome bronchoplastic and broncho arterioplastic lobectomy are safe procedures for indicated nsclc patients associated with a low rate of post operative complications but favorable long term survival recognition of prognostic factors helps improve outcomes for these patients to investigate the prevalence of and risk factors for leukopenia in tuberculosis patients and the impact of anti tuberculosis regimens on the occurrence of leukopenia in newly treated tuberculosis patients a total of 1 904 tuberculosis patients were included in the study a cross sectional survey of the prevalence of leukopenia was initially conducted and then factors influencing leukopenia were identified using logistic regression analysis non treatment factors influencing peripheral blood leukocyte counts were analyzed using univariate cox proportional hazards models covariate analysis was used to assess the independent effect of different anti tuberculosis regimens on peripheral blood leukocyte counts being female advanced age and longer duration of previous anti tuberculosis treatment 6 month were risk factors for leukopenia in tuberculosis patients while secondary pulmonary tuberculosis higher body mass index bmi 24 27 9 kg m 2 and higher degree of education senior high school or above were protective factors gender vegetable consumption drinking pulmonary infection other chronic diseases and use of antibiotics were significantly associated with the development of leukopenia in patients on anti tuberculosis treatment in tuberculosis patients treated with anti tuberculosis regimens not containing antibiotics peripheral blood leukocyte levels gradually declined with the prolongation of treatment duration in tuberculosis patients treated with anti tuberculosis regimens containing antibiotics peripheral blood leukocyte levels showed a declining trend female patients patients at advanced age and recurrent tuberculosis patients having longer previous anti tuberculosis treatment are high risk populations for leukopenia attention should be paid to the influence of vegetable consumption and drinking co morbidities and use of antibiotics during anti tuberculosis treatment the 1 3 \u03b2 d glucan bg assay has been approved for making a diagnosis of invasive fungal disease however the role of serum bg assay for the diagnosis of pneumocystis pneumonia pcp is controversial especially between patients with human immunodeficiency virus hiv and non hiv we conducted a meta analysis to determine the difference of the overall accuracy of serum bg assay for the diagnosis of pcp in immunocompromised patients with and without hiv after a systematic review of english language studies and manual researching sensitivity se specificity sp and other measures of accuracy of serum bg for the diagnosis of pcp were pooled using random effects models for bivariate meta analysis summary receiver operating characteristic sroc curve was used to summarize overall test performance subgroup analyses were performed to explore the heterogeneity in se and sp thirteen studies met our inclusion criteria the summary estimates for serum bg assay for definite pcp were as follows se 0 91 95 confidence interval ci 0 88 0 93 sp 0 75 95 ci 0 68 0 81 as for the patients with and without hiv the se and sp were 0 92 and 0 78 0 85 and 0 73 respectively significant heterogeneity between se was presented p 0 04 contrary to the results of the previous meta analysis a negative result of serum bg determination is sufficient for ruling out pcp only in hiv cases for non hiv patients the results should be interpreted in parallel with clinical and radiological findings besides further prospective studies with larger sample size are needed to confirm the diagnosis strategy of bg detection in south korea chronic obstructive pulmonary disease copd is one of the ten leading causes of death copd exacerbations are significantly associated with mortality in copd patients this study was conducted to investigate the epidemiology of copd in south korea specifically the clinical characteristics of south korean copd patients the copd exacerbation rate and the risk factors associated with copd exacerbations this study covers a 2 year interval one year was data collected retrospectively and the second year was prospectively obtained data a total of 1 114 subjects were enrolled in the study these subjects were observed for a period of 1 year from the enrollment and a total of 920 subjects completed the study a total of 1 357 copd exacerbations occurred in 711 subjects 63 8 out of the total of 1 114 subjects during the study period of 2 years multivariate logistic regression results showed that if patients had had a pneumonia before the retrospective year of analysis they had a 18 times greater chance of having an exacerbation during the prospective year when other variables were controlled also the subjects who had a history of two or more exacerbations during the retrospective year were approximately 6 times more likely to experience the copd exacerbation compared to those who did not this study examined the demographic and clinical characteristics of south korean copd patients and found that a history of pneumonia and two or more occurrences of exacerbation within 1 year was significantly associated with a higher rate of copd exacerbation the total artificial heart tah is a form of mechanical circulatory support in which the patient s native ventricles and valves are explanted and replaced by a pneumatically powered artificial heart currently the tah is approved for use in end stage biventricular heart failure as a bridge to heart transplantation however with an increasing global burden of cardiovascular disease and congestive heart failure the number of patients with end stage heart failure awaiting heart transplantation now far exceeds the number of available hearts as a result the use of mechanical circulatory support including the tah and left ventricular assist device lvad is growing exponentially the lvad is already widely used as destination therapy and destination therapy for the tah is under investigation while most patients requiring mechanical circulatory support are effectively treated with lvads there is a subset of patients with concurrent right ventricular failure or major structural barriers to lvad placement in whom tah may be more appropriate the history indications surgical implantation post device management outcomes complications and future direction of the tah are discussed in this review heart failure continues to be a worldwide epidemic effecting over 23 million persons despite advances in medical therapy the disease is progressive and a significant proportion of patients will need advanced heart replacement therapy continuous flow assist devices have become a standard approach for many patients both as a bridge to cardiac transplantation and as destination therapy dt however device related complications such as bleeding and thrombosis continue to hinder further advancements of this technology the field is rapidly advancing and efforts to reduce pump complications are directed towards improving hemocompatibility and maximizing blood flow without clinically significant hemolysis areas of stasis or turbulent flow the relationship between high fat food consumption and obesity is well established however it is as yet unclear whether high fat diet hfd induced obesity in childhood and adolescence determines age related changes in jaw bone health the aim of this study is to examine the age related influence of hfd induced obesity on mandibular bone architecture and the structure of the periodontium in growing mice male c57bl 6 j mice 6 weeks old were divided into two groups n 6 each the control group received a control diet and the experimental group a hfd after treatment for 4 8 or 12 weeks trabecular and cortical bone architecture was assessed using micro computed tomography the periodontium and alveolar bone structure were evaluated by histopathology in hfd mice body weight serum total cholesterol and serum leptin levels were significantly higher than those in age matched control mice p 0 05 all comparisons reductions in trabecular bone volume and in cortical bone growth measured as the thickness and cross sectional area in hfd mice were significant compared with the control mice after 4 weeks of treatment p 0 05 both comparisons significant decreases in cortical bone density in hfd fed vs age matched control mice were determined after 12 weeks p 0 05 in the hfd mice the periodontal ligament fibres were disrupted having lost their orientation with respect to the bone surface and constriction of the periodontal ligament space was inhibited these results suggest that hfd induced obesity during growth not only triggers mandibular osteoporosis but also increases the risk of spontaneous periodontal disease very little is known about the prevalence of respiratory symptoms or their associations with other health conditions in russia between 2008 and 2010 a sample of 983 men resident in izhevsk russia took part in a cross sectional survey presence of respiratory symptoms was determined from self report of chronic productive cough and breathlessness assessed using the british medical research council mrc breathlessness scale self reported physical and mental health were measured using the 12 item short form health survey sf 12 hypertension was assessed from mean blood pressure measured at the health check and or self reported use of antihypertensive medication other comorbidities were assessed from self report logistic regression models were fitted assessing the association between respiratory symptoms and comorbidities linear regression models were fitted to investigate the association between respiratory symptoms and self reported health scores all models were adjusted for age education and smoking status the age standardised prevalence of cough and breathlessness was 20 9 prevalence with breathlessness mrc grade 3 or above 3 7 the majority of men with respiratory symptoms 87 3 were current smokers cough and breathlessness were associated with substantially worse self reported physical and mental health test for trend with severity of breathlessness p 0 001 those with chronic cough and grade 3 or above breathlessness had higher odds of having hypertension or 3 03 95 ci 1 36 to 6 74 diabetes or 10 55 95 ci 2 69 to 41 37 angina pectoris or 7 54 95 ci 3 61 to 15 73 previous myocardial infarction or 7 61 95 ci 2 10 to 27 4 and previous stroke or 6 61 95 ci 1 75 to 23 34 compared with those without respiratory symptoms the prevalence of respiratory symptoms was high strong associations were found between respiratory symptoms and cardiovascular comorbidities these are of particular importance given the extremely high level of cardiovascular disease mortality in russia isolated vaginal metastases from colorectal cancer are extremely rare there are only a few reported cases in the english literature and the characteristics of such cases of metastasis remain relatively unknown we present a case of isolated vaginal metastasis from rectal cancer in a 78 year old female patient the patient had no symptoms related to vaginal tumor magnetic resonance imaging mri showed thickening of the middle rectum and a vaginal tumor biopsy from the vaginal tumor showed adenocarcinoma similar to the rectal lesion low anterior resection with ileostomy hystero oophorectomy and transvaginal tumor resection was performed after nineteen months computed tomography scan revealed multiple lung metastases and recurrent tumor in the pelvis the patient refused chemotherapy and is alive three months after developing recurrent disease most cases of primary vaginal carcinoma are squamous cell carcinoma other histologic types such as adenocarcinoma are usually metastatic lesions primary lesions associated with metastatic vaginal adenocarcinoma are most often the uterus and are very rarely from the colon or rectum we review previous case reports of isolated vaginal metastases from colorectal cancer and discuss their symptoms treatments and outcomes we should keep the vagina within the field of view of pelvic mri which is one of the preoperative diagnostic tools for colorectal cancer if female patients show gynecological symptoms gynecological examination should be recommended isolated vaginal metastases are an indication for surgical resection and adjuvant chemotherapy is also recommended osteoporosis presents as increased susceptibility to fractures due to bone loss and compromised bone microstructure osteoporosis mainly affects the elderly population but it is increasingly recognized that compromised bone health with low bone mass and increased fractures may have its onset already in childhood in such cases genetic component is likely to contribute more than lifestyle factors to disease onset during the last decade our understanding of the genetic determinants of osteoporosis has significantly increased through family studies candidate gene studies and genome wide association studies gwass gwass have led to identification of several genetic loci associated with osteoporosis a valuable contribution to the research field has been made through studies involving families with childhood onset rare bone diseases such as osteogenesis imperfecta osteoporosis pseudoglioma syndrome and various other skeletal dysplasias with reduced bone mass some genes involved in rare low bone mass diseases such as lrp5 and wnt1 participate in the wnt \u03b2 catenin pathway and their discovery has underscored the importance of this pathway for normal skeletal health the still continuing discovery of gene defects underlying various low bone mass phenotypes contributes to our understanding of normal bone metabolism and enables development of new therapies for osteoporosis aneurysmal bone cysts are benign bone tumors that usually present in childhood and early adulthood they usually manifest as expansile osteolytic lesions with a varying potential to be locally aggressive since their first description in 1942 a variety of treatment methods has been proposed traditionally these tumors were treated with open surgery either intralesional surgical procedures or en bloc excisions have been described furthermore a variety of chemical or physical adjuvants has been utilized in order to reduce the risk for local recurrence after excision currently there is a shift to more minimally invasive procedures in order to avoid the complications of open surgical excision good results have been reported during percutaneous surgery or the use of embolization recently sclerotherapy has emerged as a promising treatment showing effective consolidation of the lesions and functional results that appear to be superior to the ones of open surgery lastly non invasive treatment such as pharmaceutical intervention with denosumab or bisphosphonates has been reported to be effective in the management of the disease radiotherapy has also been shown to confer good local control either alone or in conjunction to other treatment modalities but is associated with serious adverse effects here we review the current literature on the methods of treatment of aneurysmal bone cysts the indication for each type of treatment along reported outcome of the intervention as well as potential complications are systematically presented our review aims to increase awareness of the different treatment modalities and facilitate decision making regarding each individual patient hematopoiesis as the only essential function of bone marrow cells has been challenged for several decades through basic science in vitro and in vivo and clinical data such work has shed light on two other essential functions of bone marrow cells osteopoiesis and angio genesis vasculogenesis clinical utility of autologous concentrated bone marrow aspirate cbma has demonstrated both safety and efficacy in treating bone defects moreover cbma has been shown to be comparable to the gold standard of iliac crest bone graft icbg or autograft with regard to being osteogenic and osteoinductive icbg is not considered an advanced therapy medicinal product atmp but cbma may become regulated as an atmp the european medicines agency committee for advanced therapies ema cat has issued a reflection paper 20 june 2014 in which reversal of the 2013 ruling that cbma is a non atmp has been proposed we review bone marrow cell involvement in osteopoiesis and angiogenesis vasculogenesis to examine ema cat 2013 decision to use cbma for treatment of osteonecrosis e g of the femoral head should be considered a non atmp this paper is intended to provide discussion on the 20 june 2014 reflection paper by reviewing two non hematopoietic essential functions of bone marrow cells additionally we provide clinical and scientific rationale for treating osteonecrosis with cbma comparative analyses of the characteristics of persons living with hiv infection plwh in the united states us captured in surveillance and other observational databases are few to explore potential joint data use to guide hiv treatment and prevention in the us we examined three cdc funded data sources in 2012 the hiv outpatient study hops a multisite longitudinal cohort the medical monitoring project mmp a probability sample of plwh receiving medical care and the national hiv surveillance system nhss a surveillance system of all plwh overall data from 1 697 hops 4 901 mmp and 865 102 nhss plwh were analyzed compared with the mmp population hops participants were more likely to be older non hispanic latino white not using injection drugs insured diagnosed with hiv before 2009 prescribed antiretroviral therapy and to have most recent cd4 t lymphocyte cell count \u2265500 cells mm3 and most recent viral load test 2 00 copies ml the mmp population was demographically similar to all plwh in nhss except it tended to be slightly older hiv diagnosed more recently and to have aids our comparative results provide an essential first step for combined epidemiologic data analyses to inform hiv care and prevention for plwh in the us it is often difficult to differentiate between the depressive states seen in late life depression and late onset alzheimer disease ad in the clinical setting thirty four outpatients were recruited all fulfilling the criteria of aged 65 years or above scores of 14 or more on the hamilton depression rating scale ham d and 26 or less on the mini mental state examination mmse at the initial visit they were administered the neurobehavioral cognitive status examination cognistat at 1 month a diagnosis of either senile depression n 24 or alzheimer disease n 10 was made the cognistat revealed that the late life depression group showed significantly higher scores in orientation and comprehension subtests compared with the ad group at the study endpoint 6 months after treatment mmse detected significant improvements in the late life depression group n 15 but no changes in the late onset ad group n 7 scores for memory similarities and judgment on the second cognistat were significantly improved in the depressed group whereas calculation scores deteriorated significantly in the ad group the cognistat could prove useful in differentiating late life depression from late onset ad despite similar scores on mmse to estimate the adult prevalence of hiv among the adult population in zambia and determine whether demographic characteristics were associated with being hiv positive a cross sectional population based survey to asses hiv status among participants aged 15 years and above in a national tuberculosis prevalence survey counselling was offered to participants who tested for hiv the prevalence was estimated using a logistic regression model univariate and multivariate associations of social demographic characteristics with hiv were determined of the 46 099 individuals who were eligible to participate in the survey 44 761 97 1 underwent pre test counselling for hiv out of which 30 605 68 4 consented to be tested and 30 584 99 9 were tested hiv prevalence was estimated to be 6 6 95 ci 5 8 7 4 with females having a higher prevalence than males 7 7 95 ci 6 8 8 7 versus 5 2 95 ci 4 4 5 9 hiv prevalence was higher among urban 9 8 95 ci 8 8 10 7 than rural residents 5 0 95 ci 4 3 5 8 the risk of hiv was double among urban dwellers than among their rural counterparts being divorced or widowed was associated with a threefold higher risk of being hiv positive than being never married the risk of being hiv positive was four times higher among those with tuberculosis than those without tuberculosis hiv prevalence was lower than previously estimated in the country the burden of hiv showed sociodemographic disparities signifying a need to target key populations or epidemic drivers mobile testing for hiv on a national scale in the context of tb prevalence surveys could be explored further in other settings since the first hiv 1 case in 1989 hebei province has presented a clearly rising trend of hiv 1 prevalence and hiv 1 genetic diversity has become the vital barrier to hiv prevention and control in this area to obtain detailed information of hiv 1 spread in different populations and in different areas of hebei a cross sectional hiv 1 molecular epidemiological investigation was performed across the province blood samples of 154 newly diagnosed hiv 1 individuals were collected from ten prefectures in hebei using stratified sampling partial gag and env genes were amplified and sequenced hiv 1 genotypes were identified by phylogenetic tree analyses among the 139 subjects genotyped six hiv 1 subtypes were identified successfully including subtype b 41 0 crf01 ae 40 3 crf07 bc 11 5 crf08 bc 4 3 unique recombinant forms urfs 1 4 and subtype c 1 4 subtype b was identified as the most frequent subtype two urf recombination patterns were the same as crf01 ae b hiv 1 genotype distribution showed a significant statistical difference in different demographic characteristics such as source p 0 05 occupation p 0 05 and ethnicity p 0 05 the distributions of subtype b p 0 05 crf01 ae p 0 05 crf07 bc p 0 05 and subtype c p 0 05 showed significant differences in all ten prefectures and the distributions of all six subtypes were significantly different in shijiazhuang p 0 05 and xingtai p 0 05 but not in other prefectures p 0 05 the differences in hiv 1 genotype distribution were closely associated with transmission routes particularly all six subtype strains were found in heterosexuals showing that hiv 1 has spread from the high risk populations to the general populations in hebei china in addition crf01 ae instead of subtype b has become the major strain of hiv 1 infection among homosexuals our study revealed hiv 1 evolution and genotype distribution by investigating newly diagnosed hiv 1 individuals in hebei china this study provides important information to enhance the strategic plan for hiv prevention and control in china renal failure is a major public health problem in the world these patients experience high levels of psychological tension anxiety and depression which leads to their lowered quality of life increased health care costs and early mortality due to medication side effects in these patients non medicational methods are more in demand now this study aimed to investigate the effect of hope therapy on depression anxiety and stress among the patients undergoing hemodialysis this is a clinical trial fifty patients undergoing hemodialysis were selected patients were assigned to two groups of hope therapy and placebo intervention of hope therapy was administered for 60 90 min during dialysis sessions once a week for eight sessions in the placebo group non specific intervention was administered with the same number of sessions depression anxiety and stress scale dass 21 questionnaire was completed at the end of the last session and 4 weeks later data were analyzed by paired t test repeated measures analysis of variance anova and least significant difference lsd post hoc test through spss 18 there was a significant difference in mean scores of depression anxiety and stress in hope therapy group before immediately after and 1 month after intervention p 0 05 while there was no significant difference in mean scores of depression anxiety and stress before and immediately after intervention in the placebo group changes in mean scores of depression anxiety and stress were significantly higher in hope therapy group compared to placebo p 0 05 the obtained results showed that hope therapy is effective on reduction of depression anxiety and stress parental support and care coordination are vital for youth with type 1 diabetes t1d in achieving positive health outcomes yet studies are rarely designed to identify factors that influence parent youth collaboration or how their perspectives about diabetes may vary photovoice was used to explore how adolescent and parental perspectives on t1d compare to identify factors that may influence care collaboration a follow up study was conducted where parents caregivers of adolescents with t1d were prompted to take and explain five photos capturing what diabetes meant to them selection criteria included having a child 12 19 years with a diagnosis of t1d \u22652 years since onset thirty three parents caregivers participated 24 mothers six fathers two grandmothers and one grandfather of 19 sons 14 daughters mean age 15 years \xb12 1 mean disease duration 6 years \xb13 3 content analysis was used to compare parent caregiver photos with those captured by adolescents in a previous study with 40 youth participants 20 males 20 females mean age 15 years \xb11 9 mean disease duration 6 years \xb13 9 through a method of constant comparison socioeconomic status was measured by household income and parental education glycemic control was captured by hba1c mann whitney u testing was used to compare representations across demographic variables 202 youth photos 153 parental photos over half of adolescents and parents took at least one photo of 1 diabetes supplies 2 food 3 coping mechanisms resilience and 4 disease encroachment parents and adolescents similarly framed food related issues as a major source of frustration in diabetes care however narratives about diabetes supplies differed adolescents framed supplies as a negative aspect of diabetes whereas parents tended to celebrate supplies as improving life also images of disease encroachment differed adolescents took photos of their bodies to depict how diabetes trespasses on their lives whereas parents took pictures of clocks to denote sleep disruption or exhaustion from constant care demands food related issues and varying views on supplies may trigger diabetes specific conflicts contrasting viewpoints about the most cumbersome aspects of diabetes may provide insight into differential paths for interventions aimed at offsetting the burdens of t1d for adolescents and parents data on spondyloarthritis spa from the middle east are sparse and the management of these diseases in this area of the world faces a number of challenges including the relevant resources to enable early diagnosis and referral and sufficient funds to aid the most appropriate treatment strategy the objective was to report on the characteristics disease burden and treatment of spa in the middle east region and to highlight where management strategies could be improved with the overall aim of achieving better patient outcomes this multicenter observational cross sectional study collected demographic clinical laboratory and treatment data on 169 consecutive spa patients at four centers egypt kuwait qatar and saudi arabia the data collected presents the average time from symptom onset to diagnosis along with the presence of comorbidities in the region and comparisons between treatment with nsaids and biologics in the absence of regional registries of spa patients the data presented here provide a rare snapshot of the characteristics disease burden and treatment of these patients highlighting the management challenges in the region secretory iga siga is a crucial antibody in host defense at mucosal surfaces it is a promising antibody isotype in a variety of therapeutic settings such as passive vaccination and treatment of inflammatory disorders however heterologous production of this heteromultimeric protein complex is still suboptimal the challenge is the coordinate expression of the four required polypeptides the alpha heavy chain the light chain the joining chain and part of the polymeric ig receptor called the secretory component in a 4 4 1 1 ratio we evaluated the transient expression of three siga\u03ba variants harboring the heavy chain isotype \u03b11 \u03b12m1 or \u03b12m2 of the clinical antibody ustekinumab in planta ustekinumab is directed against the p40 subunit that is shared by the pro inflammatory cytokines interleukin il 12 and il 23 a siga variant of this antibody may enable localized treatment of inflammatory bowel disease of the three different siga variants we obtained the highest yield with siga1\u03ba reaching up to 373 \u03bcg siga mg total soluble protein the use of a multi cassette vector containing all four expression cassettes was most efficient however not the expression strategy but the incorporation of the joining chain turned out to be the limiting step for siga production our data demonstrate that transient expression in planta is suitable for the economic production of heteromultimeric protein complexes such as siga leprosy is a chronic infectious disease caused by an obligate intracellular bacterium known as mycobacterium leprae exposure to the bacillus is necessary but this alone does not mean an individual will develop clinical symptoms of the disease in recent years several genes have been associated with leprosy and the innate immune response pathways converge on the main hypothesis that genes are involved in the susceptibility for the disease in two distinct steps for leprosy per se and in the development of the different clinical forms these genes participate in the sensing main metabolic pathway of immune response activation and subsequently on the evolution of the disease into its clinical forms the aim of this review is to highlight the role of innate immune response in the context of leprosy stressing their participation in the signaling and targeting processes in response to bacillus infection and on the evolution to the clinical forms of the disease collections of leukocytes in the meningeal space have been documented in multiple sclerosis ms these meningeal aggregates which in the context of other autoimmune diseases have often been termed tertiary lymphoid tissues tlt have been associated with sub pial cortical damage and disease progression however the key molecular and cellular signals required for their formation and maintenance remain unclear herein we review tlt structures in other disease states in order to provide a framework for understanding these structures in the ms meninges we then assess the evidence that the meningeal compartment serves as an important nexus for immune cells as well as a location for drainage of antigen into cervical lymph nodes extrapolating what is known about the molecular and cellular cues that initiate the formation of leukocyte aggregates in non lymphoid tissues we speculate on what signals lead to the formation and maintenance of meningeal tlt structures referring to the animal model of ms experimental autoimmune encephalomyelitis eae we also explore what is known about these structures in supporting b cell and t cell responses during neuroinflammation last we examine the evidence that connects these structures to ongoing neuropathology collectively our review points to the meningeal compartment as an important player in neuroinflammatory processes moreover we hypothesize that in order to gain insights into pro and anti inflammatory properties of lymphocytes in ms one must understand the cellular scaffolds that support lymphocyte retention within the meninges thus highlighting the importance of non immune cells stromal cells in the neuroinflammatory process regulatory t cells tregs play an important role in preventing effector t cell teff targeting of self antigens that can lead to tissue destruction in autoimmune settings including type 1 diabetes t1d autoimmunity is caused in part by an imbalance between teff and tregs early attempts to treat with immunosuppressive agents have led to serious side effects thus requiring a more targeted approach low dose il 2 ld il 2 can provide immunoregulation with few side effects by preferentially acting on tregs to drive tolerance the concept of ld il 2 as a therapeutic approach is supported by data in mouse models where autoimmunity is cured and further strengthened by success in human clinical studies in hepatitis c virus induced vasculitis chronic graft versus host disease and alopecia areata treatment will require identification of a safe therapeutic window which is a difficult task given that patients are reported to have deficient or defective il 2 production or signaling and have experienced mild activation of nk cells and eosinophils with ld il 2 therapy in t1d an ld il 2 clinical trial concluded that tregs can be safely expanded in humans however the study was not designed to address efficacy antigen specific therapies have also aimed at regulation of the autoimmune response but have been filled with disappointment despite an extensive list of diverse islet antigens tested in humans this approach could be enhanced through the addition of ld il 2 to the antigenic treatment regimen to improve the frequency and function of antigen specific tregs without global immunosuppression here we will discuss the use of ld il 2 and islet antigen to enhance antigen specific tregs in t1d and focus on what is known about their immunological impact their safety and potential efficacy and need for better methods to identify therapeutic effectiveness for millennia tuberculosis tb has shown a successful strategy to survive making it one of the world s deadliest infectious diseases this resilient behavior is based not only on remaining hidden in most of the infected population but also by showing slow evolution in most sick people the course of the disease within a population is highly related to its heterogeneity thus classic epidemiological approaches with a top down perspective have not succeeded in understanding its dynamics in the past decade a few individual based models were built but most of them preserved a top down view that makes it difficult to study a heterogeneous population we propose an individual based model developed with a bottom up approach to studying the dynamics of pulmonary tb in a certain population considered constant individuals may belong to the following classes healthy infected sick under treatment and treated with a probability of relapse several variables and parameters account for their age origin native or immigrant immunodeficiency diabetes and other risk factors smoking and alcoholism the time within each infection state is controlled and sick individuals may show a cavitated disease or not that conditions infectiousness it was implemented in netlogo because it allows non modelers to perform virtual experiments with a user friendly interface the simulation was conducted with data from ciutat vella a district of barcelona with an incidence of 67 tb cases per 100 000 inhabitants in 2013 several virtual experiments were performed to relate the disease dynamics with the structure of the infected subpopulation e g the distribution of infected times moreover the short term effect of health control policies on modifying that structure was studied results show that the characteristics of the population are crucial for the local epidemiology of tb the developed user friendly tool is ready to test control strategies of disease in any city in the short term the human microbiome is overly exposed to antibiotics due not only to their medical use but also to their utilization in farm animals and crops microbiome composition can be rapidly altered by exposure to antibiotics with potential immediate effects on health for instance through the selection of resistant opportunistic pathogens that can cause acute disease microbiome alterations induced by antibiotics can also indirectly affect health in the long term the mutualistic microbes in the human body interact with many physiological processes and participate in the regulation of immune and metabolic homeostasis therefore antibiotic exposure can alter many basic physiological equilibria promoting long term disease in addition excessive antibiotic use fosters bacterial resistance and the overly exposed human microbiome has become a significant reservoir of resistance genes contributing to the increasing difficulty in controlling bacterial infections here the complex relationships between antibiotics and the human microbiome are reviewed with focus on the intestinal microbiota addressing 1 the effects of antibiotic use on the composition and function of the gut microbiota 2 the impact of antibiotic induced microbiota alterations on immunity metabolism and health and 3 the role of the gut microbiota as a reservoir of antibiotic resistances histoplasma capsulatum is responsible for a human systemic mycosis that primarily affects lung tissue macrophages are the major effector cells in humans that respond to the fungus and the development of respiratory disease depends on the ability of histoplasma yeast cells to survive and replicate within alveolar macrophages therefore the interaction between macrophages and h capsulatum is a decisive step in the yeast dissemination into host tissues although the role played by components of cell mediated immunity in the host s defense system and the mechanisms used by the pathogen to evade the host immune response are well understood knowledge regarding the effects induced by h capsulatum in host cells at the nuclear level is limited according to the present findings h capsulatum yeast cells display a unique architectural arrangement during the intracellular infection of cultured murine alveolar macrophages characterized as a formation of aggregates that seem to surround the host cell nucleus resembling a crown this extranuclear organization of yeast aggregates generates damage on the nucleus of the host cell producing dna fragmentation and inducing apoptosis even though the yeast cells are not located inside the nucleus and do not trigger changes in nuclear proteins the current study highlights a singular intracellular arrangement of h capsulatum yeast near to the nucleus of infected murine alveolar macrophages that may contribute to the yeast s persistence under intracellular conditions since this fungal pathogen may display different strategies to prevent elimination by the host s phagocytic mechanisms acquired immunity against infectious disease aiid has long been considered as strictly dependent on the b and t lymphocytes of the adaptive immune system consequently aiid has been viewed as highly specific to the antigens expressed by pathogens however a growing body of data motivates revision of this central paradigm of immunology unrelated past infection vaccination and chronic infection have been found to induce cross protection against numerous pathogens these observations can be partially explained by the poly specificity of antigenic t and b receptors the mackaness effect and trained immunity in addition numerous studies highlight the importance of microbiota composition on resistance to infectious disease via direct competition or modulation of the immune response all of these data support the idea that a non negligible part of aiid in nature can be nonspecific to the pathogens encountered and even of the antigens expressed by pathogens as this protection may be dependent on the private t and b repertoires produced by the random rearrangement of genes past immune history chronic infection and microbiota composition it is largely unpredictable at the individual level however we can reasonably expect that a better understanding of the underlying mechanisms will allow us to statistically predict cross protection at the population level from an evolutionary perspective selection of immune mechanisms allowing for partially nonspecific aiid would appear to be advantageous against highly polymorphic and rapidly evolving pathogens this new emerging paradigm may have several important consequences on our understanding of individual infectious disease susceptibility and our conception of tolerance vaccination and therapeutic strategies against infection and cancer it also underscores the importance of viewing the microbiota and persisting infectious agents as integral parts of the immune system in many individuals drug abuse is intimately linked with hiv 1 infection in addition to being associated with one third of all hiv 1 infections in the united states drug abuse also plays a role in disease progression and severity in hiv 1 infected patients including adverse effects on the central nervous system cns specific systems within the brain are known to be damaged in hiv 1 infected individuals and this damage is similar to that observed in drug abuse even in the era of anti retroviral therapy art cns pathogenesis occurs with hiv 1 infection with a broad range of cognitive impairment observed collectively referred to as hiv 1 associated neurocognitive disorders hand a number of hiv 1 proteins tat gp120 nef vpr have been implicated in the etiology of pathogenesis and disease as a result of the biologic activity of the extracellular form of each of the proteins in a number of tissues including the cns even in art suppressed patients in this review we have made tat the center of attention for a number of reasons first it has been shown to be synthesized and secreted by hiv 1 infected cells in the cns despite the most effective suppression therapies available to date second tat has been shown to alter the functions of several host factors disrupting the molecular and biochemical balance of numerous pathways contributing to cellular toxicity dysfunction and death in addition the advantages and disadvantages of art suppression with regard to controlling the genesis and progression of neurocognitive impairment are currently under debate in the field and are yet to be fully determined in this review we discuss the individual and concerted contributions of hiv 1 tat drug abuse and art with respect to damage in the cns and how these factors contribute to the development of hand in hiv 1 infected patients the phosphatidylinositol 3 kinase pi3k akt pathway is a key driver in carcinogenesis defects in this pathway in human cancer syndromes such as cowden s disease and multiple endocrine neoplasia result in tumors of endocrine tissues highlighting its importance in these cancer types this review explores the growing evidence from multiple animal and in vitro models and from analysis of human tumors for the involvement of this pathway in the following thyroid carcinoma subtypes parathyroid carcinoma pituitary tumors adrenocortical carcinoma phaeochromocytoma neuroblastoma and gastroenteropancreatic neuroendocrine tumors while data are not always consistent immunohistochemistry performed on human tumor tissue has been used alongside other techniques to demonstrate akt overactivation we review active akt as a potential prognostic marker and the pi3k pathway as a therapeutic target in endocrine neoplasia evidence from clinical and preclinical research provides an undeniable link between disruptions in the circadian clock and the development of psychiatric diseases including mood and substance abuse disorders the molecular clock which controls daily patterns of physiological and behavioral activity in living organisms when desynchronized may exacerbate or precipitate symptoms of psychiatric illness one of the outstanding questions remaining in this field is that of cause and effect in the relationship between circadian rhythm disruption and psychiatric disease focus has recently turned to uncovering the role of circadian proteins beyond the maintenance of homeostatic systems and outside of the suprachiasmatic nucleus scn the master pacemaker region of the brain in this regard several groups including our own have sought to understand how circadian proteins regulate mechanisms of synaptic plasticity and neurotransmitter signaling in mesocorticolimbic brain regions which are known to be critically involved in reward processing and mood this regulation can come in the form of direct transcriptional control of genes central to mood and reward including those associated with dopaminergic activity in the midbrain it can also be seen at the circuit level through indirect connections of mesocorticolimbic regions with the scn circadian misalignment paradigms as well as genetic models of circadian disruption have helped to elucidate some of the complex interactions between these systems and neural activity influencing behavior in this review we explore findings that link circadian protein function with synaptic adaptations underlying plasticity as it may contribute to the development of mood disorders and addiction in light of recent advances in technology and sophisticated methods for molecular and circuit level interrogation we propose future directions aimed at teasing apart mechanisms through which the circadian system modulates mood and reward related behavior loss of muscle mass and force occurs in many diseases such as disuse inactivity diabetes cancer renal and cardiac failure and in aging sarcopenia in these catabolic conditions the mitochondrial content morphology and function are greatly affected the changes of mitochondrial network influence the production of reactive oxygen species ros that play an important role in muscle function moreover dysfunctional mitochondria trigger catabolic signaling pathways which feed forward to the nucleus to promote the activation of muscle atrophy exercise on the other hand improves mitochondrial function by activating mitochondrial biogenesis and mitophagy possibly playing an important part in the beneficial effects of physical activity in several diseases optimized mitochondrial function is strictly maintained by the coordinated activation of different mitochondrial quality control pathways in this review we outline the current knowledge linking mitochondria dependent signaling pathways to muscle homeostasis in aging and disease and the resulting implications for the development of novel therapeutic approaches to prevent muscle loss the skeletal muscle ca 2 release channel also known as ryanodine receptor type 1 ryr1 is the largest ion channel protein known and is crucial for effective skeletal muscle contractile activation ryr1 function is controlled by cav1 1 a voltage gated ca 2 channel that works mainly as a voltage sensor for ryr1 activity during skeletal muscle contraction and is also fine tuned by ca 2 several intracellular compounds e g atp and modulatory proteins e g calmodulin dominant and recessive mutations in ryr1 as well as acquired channel alterations are the underlying cause of various skeletal muscle diseases the aim of this mini review is to summarize several current aspects of ryr1 function structure regulation and to describe the most common diseases caused by hereditary or acquired ryr1 malfunction c jun n terminal kinases jnks are a family of protein kinases that play a central role in stress signaling pathways implicated in gene expression neuronal plasticity regeneration cell death and regulation of cellular senescence it has been shown that there is a jnk pathway activation after exposure to different stressing factors including cytokines growth factors oxidative stress unfolded protein response signals or a\u03b2 peptides altogether jnks have become a focus of screening strategies searching for new therapeutic approaches to diabetes cancer or liver diseases in addition activation of jnk has been identified as a key element responsible for the regulation of apoptosis signals and therefore it is critical for pathological cell death associated with neurodegenerative diseases and among them with alzheimer s disease ad in addition in vitro and in vivo studies have reported alterations of jnk pathways potentially associated with pathogenesis and neuronal death in ad jnk s particularly jnk3 not only enhance a\u03b2 production moreover it plays a key role in the maturation and development of neurofibrillary tangles this review aims to explain the rationale behind testing therapies based on inhibition of jnk signaling for ad in terms of current knowledge about the pathophysiology of the disease keeping in mind that jnk3 is specifically expressed in the brain and activated by stress stimuli it is possible to hypothesize that inhibition of jnk3 might be considered as a potential target for treating neurodegenerative mechanisms associated with ad the physiological link between circulating high density lipoprotein hdl levels and cardiovascular disease is well documented albeit its intricacies are not well understood an improved appreciation of hdl function and overall role in vascular health and disease requires at its foundation a better understanding of the lipoprotein s molecular structure its formation and its process of maturation through interactions with various plasma enzymes and cell receptors that intervene along the pathway of reverse cholesterol transport this review focuses on summarizing recent developments in the field of lipid free apoa i and hdl structure with emphasis on new insights revealed by newly published nascent and spherical hdl models constructed by combining low resolution structures obtained from small angle neutron scattering sans with contrast variation and geometrical constraints derived from hydrogen deuterium exchange hdx crosslinking mass spectrometry electron microscopy f\xf6rster resonance energy transfer and electron spin resonance recently published low resolution structures of nascent and spherical hdl obtained from sans with contrast variation and isotopic labeling of apolipoprotein a i apoa i will be critically reviewed and discussed in terms of how they accommodate existing biophysical structural data from alternative approaches the new low resolution structures revealed and also provided some answers to long standing questions concerning lipid organization and particle maturation of lipoproteins the review will discuss the merits of newly proposed sans based all atom models for nascent and spherical hdl and compare them with accepted models finally naturally occurring and bioengineered mutations in apoa i and their impact on hdl phenotype are reviewed and discuss together with new therapeutics employed for restoring hdl function interleukin il 22 is a cytokine displaying tissue protective and pro regenerative functions in various preclinical disease models anti bacterial pro proliferative and anti apoptotic properties mediated by activation of the transcription factor signal transducer and activator of transcription stat 3 are key to biological functions of this il 10 family member herein we introduce rinm5f insulinoma cells as rat \u03b2 cell line that under the influence of il 22 displays activation of stat3 with induction of its downstream gene targets socs3 bcl3 and reg3b in addition il 22 also activates stat1 in this cell type to refine those observations il 22 biological activity was evaluated using ex vivo cultivated murine pancreatic islets in accord with data on rinm5f cells islet exposure to il 22 activated stat3 and upregulation of stat3 inducible socs3 bcl3 and steap4 was evident under those conditions as these observations supported the hypothesis that il 22 may exert protective functions in toxic \u03b2 cell injury application of il 22 was investigated in murine multiple low dose streptozotocin stz induced diabetes for that purpose recombinant il 22 was administered thrice either immediately before and at disease onset at d4 d6 d8 or closely thereafter at d8 d10 d12 these two il 22 treatment periods coincide with two early peaks of \u03b2 cell injury detectable in this model notably none of the two il 22 treatment strategies affected diabetes incidence or blood glucose levels in stz treated mice moreover pathological changes in islet morphology analyzed 28 days after disease induction were not ameliorated by il 22 administration taken together despite being active on rat rinm5f insulinoma cells and murine pancreatic islets recombinant il 22 fails to protect pancreatic \u03b2 cells in the tested protocols from toxic effects of stz and thus is unable to ameliorate disease in the widely used model of stz induced diabetes to investigate cortical excitability and synaptic plasticity in amnestic mild cognitive impairment amci using 5 hz repetitive transcranial magnetic stimulation 5 hz rtms and to assess whether specific tms parameters predict conversion time to alzheimer s disease ad forty amci patients single and multi domain and 20 healthy controls underwent at baseline a neuropsychological examination and 5 hz rtms delivered in trains of 10 stimuli and 120 of resting motor threshold rmt intensity over the dominant motor area the rmt and the ratio between amplitude of the 1st and the 10th motor evoked potential elicited by the train x i mep ratio were calculated as measures of cortical excitability and synaptic plasticity respectively patients were followed up annually over a period of 48 months analysis of variance for repeated measures was used to compare tms parameters in patients with those in controls spearman s correlation was performed by considering demographic variables amci subtype neuropsychological test scores tms parameters and conversion time thirty five amci subjects completed the study 60 of these converted to ad the baseline rmt and x i mep ratio were significantly lower in patients than in controls p 0 04 and p 0 01 spearman s analysis showed that conversion time correlated with the rmt 0 40 and x i mep ratio 0 51 amci patients displayed cortical hyperexcitability and altered synaptic plasticity to 5 hz rtms when compared with healthy subjects the extent of these changes correlated with conversion time these alterations which have previously been observed in ad are thus present in the early stages of disease and may be considered as potential neurophysiological markers of conversion from amci to ad the decline of cognitive skills throughout healthy or pathological aging can be slowed down by experiences which foster cognitive reserve cr recently some studies on alzheimer s disease have suggested that cr may be enhanced by life long bilingualism however the evidence is inconsistent and largely based on retrospective approaches featuring several methodological weaknesses some studies demonstrated at least 4 years of delay in dementia symptoms while others did not find such an effect moreover various methodological aspects vary from study to study the present paper addresses contradictory findings identifies possible lurking variables and outlines methodological alternatives thereof first we characterize possible confounding factors that may have influenced extant results our focus is on the criteria to establish bilingualism differences in sample design the instruments used to examine cognitive skills and the role of variables known to modulate life long cognition second we propose that these limitations could be largely circumvented through experimental approaches proficiency in the non native language can be successfully assessed by combining subjective and objective measures confounding variables which have been distinctively associated with certain bilingual groups e g alcoholism sleep disorders can be targeted through relevant instruments and cognitive status might be better tapped via robust cognitive screenings and executive batteries moreover future research should incorporate tasks yielding predictable patterns of contrastive performance between bilinguals and monolinguals crucially these include instruments which reveal bilingual disadvantages in vocabulary null effects in working memory and advantages in inhibitory control and other executive functions finally paradigms tapping proactive interference which assess the disruptive effect of long term memory on newly learned information could also offer useful data since this phenomenon seems to be better managed by bilinguals and it becomes conspicuous in early stages of dementia such considerations may shed light not just on the relationship between bilingualism and cr but also on more general mechanisms of cognitive compensation parkin is a unique multifunctional ubiquitin ligase whose various roles in the cell particularly in neurons are widely thought to be protective the pivotal role that parkin plays in maintaining neuronal survival is underscored by our current recognition that parkin dysfunction represents not only a predominant cause of familial parkinsonism but also a formal risk factor for the more common sporadic form of parkinson s disease pd accordingly keen research on parkin over the past decade has led to an explosion of knowledge regarding its physiological roles and its relevance to pd however our understanding of parkin is far from being complete indeed surprises emerge from time to time that compel us to constantly update the paradigm of parkin function for example we now know that parkin s function is not confined to mere housekeeping protein quality control qc roles but also includes mitochondrial homeostasis and stress related signaling furthermore emerging evidence also suggest a role for parkin in several other major neurodegenerative diseases including alzheimer s disease ad and amyotrophic lateral sclerosis als yet it remains truly amazing to note that a single enzyme could serve such multitude of functions and cellular roles clearly its activity has to be tightly regulated in this review we shall discuss this and how dysregulated parkin function may precipitate neuronal demise in various neurodegenerative disorders increasing evidence suggests that abnormal brain accumulation of soluble rather than aggregated amyloid \u03b21 42 oligomers a\u03b2o 1 42 plays a causal role in alzheimer s disease ad however as yet animal s models of ad based on oligomeric amyloid \u03b21 42 injections in the brain have not investigated their long lasting impacts on molecular and cognitive functions in addition the injections have been most often performed in ventricles but not in the hippocampus in spite of the fact that the hippocampus is importantly involved in memory processes and is strongly and precociously affected during the early stages of ad thus in the present study we investigated the long lasting impacts of intra hippocampal injections of oligomeric forms of a\u03b2o 1 42 on working and spatial memory and on the related activation of erk1 2 indeed the extracellular signal regulated kinase erk which is involved in memory function had been found to be activated by amyloid peptides we found that repeated bilateral injections 1injection day over 4 successive days of oligomeric forms of a\u03b2o 1 42 into the dorsal hippocampus lead to long lasting impairments in two working memory tasks these deficits being observed 7 days after the last injection while spatial memory remained unaffected moreover the working memory deficits were correlated with sustained impairments of erk1 2 activation in the medial prefrontal cortex mpfc and the septum two brain areas tightly connected with the hippocampus and involved in working memory thus our study is first to evidence that sub chronic injections of oligomeric forms of a\u03b2o 1 42 into the dorsal hippocampus produces the main sign of cognitive impairments corresponding to the early stages of ad via long lasting alterations of an erk mapk pathway in an interconnected brain networks this work is focused on mapping biomedical datasets to a common representation as an integral part of data harmonization for integrated biomedical data access and sharing we present gem an intelligent software assistant for automated data mapping across different datasets or from a dataset to a common data model the gem system automates data mapping by providing precise suggestions for data element mappings it leverages the detailed metadata about elements in associated dataset documentation such as data dictionaries that are typically available with biomedical datasets it employs unsupervised text mining techniques to determine similarity between data elements and also employs machine learning classifiers to identify element matches it further provides an active learning capability where the process of training the gem system is optimized our experimental evaluations show that the gem system provides highly accurate data mappings over 90 accuracy for real datasets of thousands of data elements each in the alzheimer s disease research domain further the effort in training the system for new datasets is also optimized we are currently employing the gem system to map alzheimer s disease datasets from around the globe into a common representation as part of a global alzheimer s disease integrated data sharing and analysis network called gaain gem achieves significantly higher data mapping accuracy for biomedical datasets compared to other state of the art tools for database schema matching that have similar functionality with the use of active learning capabilities the user effort in training the system is minimal huntington s disease hd is a progressive neurodegenerative disorder that causes motor cognitive and psychiatric symptoms in these experiments we tested if operant training at an early age affected adult cognitive deficits in the zq175 ki het zq175 mouse model of hd in experiment 1 we trained zq175 mice in a fixed ratio progressive ratio fr pr task to assay learning and motivational deficits we found pronounced deficits in response rates and task engagement in na\xefve adult zq175 mice 32 33 weeks age while deficits in zq175 mice trained from 6 7 weeks age were either absent or less severe when those mice were re tested as adults fr pr performance deficits were absent or otherwise less severe than deficits observed in na\xefve adult zq175 relative to wild type wt mice in experiment 2 we used a go no go operant task to assess the effects of early cognitive testing on response inhibition deficits in zq175 mice we found that zq175 mice that began testing at 7 8 weeks did not exhibit deficits in go no go testing but when re tested at 28 29 weeks age exhibited an initial impairment that diminished with training these transient deficits were nonetheless mild relative to deficits observed among adult zq175 mice without prior testing experience in experiment 3 we trained mice in a two choice visual discrimination test to evaluate cognitive flexibility as in prior experiments we found performance deficits were mild or absent in mice that started training at 6 9 weeks of age while deficits in naive mice exposed to training at 28 29 weeks were severe re testing mice at 28 29 weeks age were previously trained starting at 6 9 weeks revealed that deficits in learning and cognitive flexibility were absent or reduced relative to effects observed in naive adults in experiment 4 we tested working memory deficits with a delayed non match to position dnmtp test mice with prior experience exhibited mild working memory deficits with males zq175 exhibiting no deficits and females performing significantly worse than wt mice at a single delay interval whereas naive zq175 exhibited severe delay dependent deficits at all intervals exceeding 1 s in sum these experiments indicate that cag dependent impairments in motivation motor control cognitive flexibility and working memory are sensitive to the environmental enrichment and experience these findings are of clinical relevance as hd carrier status can potentially be detected at an early age spinal muscular atrophy sma is an inherited neuromuscular disease primarily characterized by degeneration of spinal motor neurons and caused by reduced levels of the smn protein previous studies to understand the proteomic consequences of reduced smn have mostly utilized patient fibroblasts and animal models we have derived human motor neurons from type i sma and healthy controls by creating their induced pluripotent stem cells ipscs quantitative mass spectrometry of these cells revealed increased expression of 63 proteins in control motor neurons compared to respective fibroblasts whereas 30 proteins were increased in sma motor neurons vs their fibroblasts notably uba1 was significantly decreased in sma motor neurons supporting evidence for ubiquitin pathway defects subcellular distribution of uba1 was predominantly cytoplasmic in sma motor neurons in contrast to nuclear in control motor neurons suggestive of neurodevelopmental abnormalities many of the proteins that were decreased in sma motor neurons including beta iii tubulin and uchl1 were associated with neurodevelopment and differentiation these neuron specific consequences of smn depletion were not evident in fibroblasts highlighting the importance of ipsc technology the proteomic profiles identified here provide a useful resource to explore the molecular consequences of reduced smn in motor neurons and for the identification of novel biomarker and therapeutic targets for sma disease gene discovery in neurodevelopmental disorders including x linked intellectual disability xlid has recently been accelerated by next generation dna sequencing approaches to date more than 100 human x chromosome genes involved in neuronal signaling pathways and networks implicated in cognitive function have been identified despite these advances the mutations underlying disease in a large number of xlid families remained unresolved we report the resolution of mrx78 a large family with six affected males and seven affected females showing x linked inheritance although a previous linkage study had mapped the locus to the short arm of chromosome x xp11 4 p11 23 this region contained too many candidate genes to be analyzed using conventional approaches however our x chromosome exome resequencing bioinformatics analysis and inheritance testing revealed a missense mutation c c2366t p a789v in iqsec2 encoding a neuronal gdp gtp exchange factor for arf family gtpases arfgef previously implicated in xlid molecular modeling of iqsec2 revealed that the a789v substitution results in the insertion of a larger side chain into a hydrophobic pocket in the catalytic sec7 domain of iqsec2 the a789v change is predicted to result in numerous clashes with adjacent amino acids and disruption of local folding of the sec7 domain consistent with this finding functional assays revealed that recombinant iqsec2 a789v was not able to catalyze gdp gtp exchange on arf6 as efficiently as wild type iqsec2 taken together these results strongly suggest that the a789v mutation in iqsec2 is the underlying cause of xlid in the mrx78 family alzheimer s and parkinson s disease are the two most common neurodegenerative disorders they develop after a progressive death of many neurons in the brain although therapies are available to treat the signs and symptoms of both diseases the progression of neuronal death remains relentless and it has proved difficult to slow or stop hence there is a need to develop neuroprotective or disease modifying treatments that stabilize this degeneration red to infrared light therapy \u03bb 600 1070 nm and in particular light in the near infrared nir range is emerging as a safe and effective therapy that is capable of arresting neuronal death previous studies have used nir to treat tissue stressed by hypoxia toxic insult genetic mutation and mitochondrial dysfunction with much success here we propose nir therapy as a neuroprotective or disease modifying treatment for alzheimer s and parkinson s patients obsessive compulsive disorder ocd is a common neuropsychiatric disorder with moderate genetic influences and white matter abnormalities in frontal striatal and limbic regions inconsistencies in reported white matter results from diffusion tensor imaging dti studies can be explained at least partly by medication use and between group differences in disease profile and stage we used a family design aiming to establish whether white matter abnormalities if present in un medicated ocd patients also exist in their unaffected siblings forty four ocd patients un medicated for at least the past 4 weeks 15 of their unaffected siblings and 37 healthy controls hc underwent dti using a 3 tesla mri scanner data analysis was done using tract based spatial statistics tbss fractional anisotropy fa axial diffusivity ad radial diffusivity rd and mean diffusivity md values were compared within seven skeletonised regions of interest rois i e corpus callosum bilateral cingulum bundle bilateral inferior longitudinal fasciculus frontal occipital fasciculus ilf fof and bilateral superior longitudinal fasciculus slf un medicated ocd patients compared with hc had significantly lower fa in the left cingulum bundle fa was trend significantly lower in all other rois except for the corpus callosum significant three group differences in fa and in rd at trend significant level were observed in the left cingulum bundle with the unaffected siblings representing an intermediate group between ocd patients and hc ocd patients showed lower fa in the left cingulum bundle partly driven by trend significantly higher values in rd since the unaffected siblings were found to be an intermediate group between ocd patients and hc this white matter alteration may be considered an endophenotype for ocd the objective of the study was to evaluate mental adjustment to cancer in patients diagnosed with an oncologic disease through identification of the coping strategies they had adopted seventy four patients of the clinic of oncology and haematology at the central clinical hospital csk of the ministry of interior msw in warsaw were included in the study the degree of adaptation to cancer was evaluated with the use of the mini mental adjustment to cancer mini mac scale the individual subscales i e fighting spirit positive redefinition helplessness hopelessness and anxious preoccupation were collated with socio demographic characteristics study findings indicate that 1 tumour patients typically manifest behaviour that allows one to identify their adjustment to cancer 2 in malignant tumour patients constructive behaviour prevails over destructive behaviour 3 the helplessness hopelessness response is more pronounced in men than women 4 metastatic patients manifest stronger helplessness hopelessness response than patients with locally limited tumours 5 pensioners more often than people of working age adopt the helplessness hopelessness strategy and 6 patients with the shortest disease period manifest the strongest fighting spirit cancer patients employ various strategies of coping with disease depending on socio demographic factors to analyse the incidence of appendiceal neuroendocrine neoplasms in appendectomy specimens and establish the epidemiological and histopathological features treatment and clinical course between 2004 and 2013 975 patients who underwent appendectomy in ankara oncology education and research hospital were retrospectively analysed neuroendocrine neoplasm was detected in the nine of 975 0 9 patients neuroendocrine neoplasms were diagnosed in eight patients by appendectomy which was performed because of the prediagnosis of acute appendicitis and in one patient by the suspicious mass detection during surgical procedures that were done in the appendix for a different reason eight of the patients tumours were in the tip of the appendix and one of the patients tumours was at the base of appendix tumour size in 77 8 of patients was equal or less than 1 cm in 22 2 patients it was 1 2 cm there was tumour invasion in the muscularis propria layer in four patients in the serosa layer in three patients and in the deep mesoappendix in two patients patients were followed for a median of 78 months in the follow up of patients who were operated because of colon cancer metachronous colon tumour evolved this patient died due to progressive disease other patients are still disease free the diagnosis of neuroendocrine neoplasm is often incidentally done after appendectomy tumour size is important in determining the extent of disease and in the selection of the surgical method during operation assessment of lung cancer patients dietary habits before treatment enable medical staff to provide more individual precise and complex care to patients taking into consideration their nutritional status the aim of this study was therefore to evaluate dietary habits related to lung cancer risk of lung cancer patients in comparison with controls from the lower silesia region of poland assessments of dietary habits based on a validated questionnaire related to lung cancer risk were performed on 92 lung cancer patients and compared with the results obtained in 157 controls dietary patterns were evaluated concerning on eating frequency of high and low glycemic index products vegetables and fruits vegetable and fruit juices green tea liquid dairy products meat and fried products over the previous year alcohol consumption was assessed on a dichotomous scale yes or no majority of patients had inappropriate dietary habits such as low consumption of low gi cereal products vegetables fruit and green tea and a high consumption frequency of fried products reported dietary mistakes indicate the need for dietary education among people at lung cancer risk and with newly diagnosed disease to enhance their nutritional status our aim was to determine the activity and toxicity of uracil tegafur and leucovorin combination in metastatic colorectal cancer mcrc patients who have progressed with all currently active agents this study was a retrospective analysis of 50 mcrc patients who had previously failed to respond to all available chemotherapeutics and who received subsequent treatment with uracil tegafur 250 mg m 2 d1 5 in combination with leucovorin 90 mg day d1 5 followed by two days rest the median age of the patients was 60 years most of them 60 were male bevacizumab was used in 65 and cetuximab in 55 of the patients thirty nine patients 78 were treated with uracil tegafur in the fourth line setting the median treatment duration was 4 2 months range 2 24 months the objective response rate and the disease control rate were 4 and 34 respectively median progression free survival was 4 1 months 95 ci 3 6 4 6 months and overall survival was 6 6 months 95 ci 4 5 8 6 months grade 3 or 4 toxicity was seen in 20 n 10 of the patients while 60 n 6 of them required dose reductions this retrospective data show that uracil tegafur may be considered in heavily pretreated mcrc patients because of its activity lower toxicity and feasibility the resection of pulmonary metastases is a routine practice of thoracic surgery wards however clear protocols or prognostic factors defining the surgical treatment criteria are still not available the aim of the study is to evaluate the prognostic factors associated with long term survival in a group of patients who underwent resection of pulmonary metastases a retrospective analysis was conducted on a group of 250 patients admitted to the wroc\u0142aw thoracic surgery centre for radical resection of pulmonary lesions in the years 1996 2010 the patients included in the study n 250 underwent 339 thoracotomies in total the overall five year survival was 52 8 the univariate data analysis showed that the survival rate was significantly better in patients subjected to more than one thoracotomy p 0 01674 among the other data such as sex tumour histology disease free interval dfi 12 and 12 months dfi 36 and 36 months age number of tumours identified in ct and number of tumours subject to resection operated side resection type radicality of resection extent of lymphadenectomy and adjuvant therapy no statistical significance was observed in univariate and multivariate analysis p 0 05 outcomes of re metastasectomy are satisfactory if patients meet the baseline criteria for surgical treatment none of the evaluated factors potentially influencing the patient survival was demonstrated to have any prognostic value further research including the biology of tumours with pulmonary metastases is necessary to select the group of patients that will benefit most from surgical treatment chronic lymphocytic leukemia cll is the most commonly diagnosed type of leukemia in western europe and north america and represents about 30 of all leukemias in adults chronic lymphocytic leukemia is a disease of the elderly who are often in poorer general health and burdened with multiple comorbidities these factors affect the decision making when choosing an appropriate method of treatment in recent years there has been significant progress in the treatment of chronic lymphocytic leukemia first due to the introduction of immunochemotherapy with monoclonal antibodies and latterly small molecules like tyrosine kinase inhibitors targeting b cell receptor signaling this article discusses the current diagnostic principles the most important prognostic factors and therapeutic options available in first line treatment and in refractory resistant disease including high risk cll both for patients with good and those with poor performance status it also presents important novel molecules which have been evaluated in clinical trials in general strategies for the treatment of cancer in pregnancy should not differ significantly from the treatment regimens in non pregnant women however this is difficult due to either the effects of anticancer drugs on the developing foetus or the possibility of long term complications after the exposure to drugs and radiation the decision about the introduction and continuation of treatment in the event of pregnancy should be preceded by a detailed analysis of the potential benefits and risks there are no data to suggest that pregnancy termination alters the biological behaviour of the tumour or patient prognosis in the presence of appropriate antineoplastic therapy all patients should be given appropriate advice and informed that there are insufficient scientific data to determine any generally accepted consensus it is very important to always respect the will of the patient and the moral judgment of the physician should have no impact on the decisions taken by the woman if the woman decides to undergo active treatment and maintain her pregnancy it is necessary to carry out consultations with experts in the field appropriate to the type of cancer this paper presents a basic review of the literature on the targeted therapies currently used in selected cancers diagnosed during pregnancy breast cancer cervical cancer hodgkin s disease melanoma thyroid cancer ovarian cancer and colorectal cancer global guidelines for the management of locally advanced or metastatic hormone receptor positive hr positive human epidermal growth factor 2 negative her2 negative breast cancer recommend endocrine therapy as first line treatment for all patients regardless of age or postmenopausal status however current practice patterns in the united states and europe suggest that these modes of therapy are not being used as recommended and many patients with advanced hr positive her2 negative disease are being treated first line with chemotherapy or switched to chemotherapy after a single endocrine therapy given that chemotherapy is associated with increased toxicity and reduced quality of life qol compared with endocrine therapy prolonging the duration of response obtained with endocrine therapy may help delay chemotherapy and its attendant toxicities several strategies to delay or overcome endocrine resistance and thereby postpone chemotherapy have been explored including the use of second line endocrine agents with different mechanisms of action adding targeted agents that inhibit specific resistance pathways and adding agents that act in complementary or synergistic ways to inhibit tumor cell proliferation this review analyzes the different therapy options available to hr positive her2 negative patients with advanced breast cancer that can be used to delay chemotherapy and enhance qol acute severe asthma exacerbations can be difficult to predict and thus prevent patients who have frequent exacerbations are of particular concern practical exacerbation predictors are needed for these patients in the primary care setting medical records of 130 547 asthma patients aged 12 80 years from the uk optimum patient care research database and clinical practice research datalink 1990 2013 were examined for 1 year before baseline and 1 year after outcome their most recent blood eosinophil count baseline variables predictive p 0 05 of exacerbation in the outcome year were compared between patients who had two or more exacerbations and those who had no exacerbation or only one exacerbation using uni and multivariable logistic regression models exacerbation was defined as asthma related hospital attendance admission emergency or inpatient or acute oral corticosteroid ocs course blood eosinophil count 400 \xb5l versus \u2264400 \xb5l increased the likelihood of two or more exacerbations 1 4 fold odds ratio or 1 48 95 confidence interval ci 1 39 1 58 p 0 001 variables that significantly increased the odds by up to 1 4 fold included increasing age per year female gender versus male being overweight or obese versus normal body mass index being a smoker versus nonsmoker having anxiety depression diabetes eczema gastroesophageal reflux disease or rhinitis and prescription for acetaminophen or nonsteroidal anti inflammatory drugs compared with treatment at british thoracic society step 2 daily controller reliever treatment at step 0 none or 1 as needed reliever increased the odds by 1 2 and 1 6 fold respectively and treatment at step 3 4 or 5 increased the odds by 1 3 1 9 or 3 1 fold respectively all p 0 05 acute ocs use was the single best predictor of two or more exacerbations even one course increased the odds by more than threefold or 3 75 95 ci 3 50 4 01 p 0 001 and three or more courses increased the odds by 25 fold or 25 7 95 ci 23 9 27 6 p 0 001 blood eosinophil count and several other variables routinely available in patient records may be used to predict frequent asthma exacerbations fgfr1 amplification is recognized as a novel therapy target for non small cell lung cancer nsclc especially in squamous cell carcinoma scc however the association between fgfr1 amplification and the clinicopathological characteristics of nsclc remains controversial we performed a meta analysis of 17 eligible studies to examine the correlation between fgfr1 gene amplification and clinicopathological characteristics fgfr1 amplification was closely related to these clinicopathological features including sex odds ratio or 2 05 95 confidence interval ci 1 50 2 80 smoking or 3 31 95 ci 2 02 5 44 and histology or 3 60 95 ci 2 82 4 59 fgfr1 amplification was associated with shorter overall survival and no significant heterogeneity existed between studies i 2 3 8 we should note that publication bias may partly account for these results but our findings remained significant after the trim and fill method hazard ratio 1 22 95 ci 1 06 1 40 however no significant correlation was found with poor disease free survival hazard ratio 1 43 95 ci 0 96 2 12 in conclusion this study showed that fgfr1 amplification was significantly associated with sex smoking and histology fgfr1 amplification could be a marker of poor prognosis in nsclc patients especially in scc patients despite substantial advances in early diagnosis breast cancer bc still remains a clinical challenge most bc models use complex in vivo models and two dimensional monolayer cultures that do not fully mimic the tumor microenvironment the integration of cancer biology and engineering can lead to the development of novel in vitro approaches to study bc behavior and quantitatively assess different features of the tumor microenvironment that may influence cell behavior in this review we present tissue engineering approaches to model bc in vitro recent advances in the use of three dimensional cell culture models to study various aspects of bc disease in vitro are described the emerging area of studying bc dormancy using these models is also reviewed treatment during first episode psychosis fep or early schizophrenia may affect the rates of relapse and remission as well as cognitive functioning over time prolonged duration of psychosis is associated with a poor prognosis but the effects of treatment in patients with fep or early schizophrenia on the long term outcomes are not well defined to understand the long term effects of treatment with antipsychotic agents on remission relapse and cognition in patients with fep or early schizophrenia using pubmed and scopus databases a systematic review was undertaken of articles published between january 1 2000 and may 20 2015 that reported randomized and nonrandomized prospective clinical trials on the long term effects of oral or long acting injectable antipsychotics on measures of relapse remission or cognition in patients with fep or early schizophrenia for comparative purposes trials reporting the effects of later intervention with antipsychotics in patients with longer disease history were also evaluated titles abstracts and full text articles were independently screened for eligibility by all the authors based on the predefined criteria nineteen studies met inclusion criteria 13 reported long term outcomes of relapse remission or cognition following antipsychotic treatment in patients with fep and six reported on patients with a longer disease history antipsychotic treatment in patients with fep produced high rates of remission in the year following treatment initiation and untreated fep reduced the odds of later achieving remission maintenance therapy was more effective than treatment discontinuation or intermittent guided discontinuation in preventing relapse initiating antipsychotic treatment in patients with fep also produced sustained cognitive improvement for up to 2 years antipsychotic therapy also reduced the risk or rate of relapse in patients with a longer disease history with outcomes in one study favoring a long acting injectable formulation over an oral antipsychotic treatment of patients with fep is associated with benefits in the long term outcomes of remission relapse and cognition more long term studies of treatment in patients with fep are needed to confirm these findings we incorporated ultrafine polymer fibers into calcium phosphate cement cpc to improve the resorption rate of cpc with fiber degradation different weight percentages of electrospun poly \u03b5 caprolactone fibers 0 3 and 7 named as ultrafine fiber incorporated cpc0 uficpc0 uficpc3 and uficpc7 were included into preset cpc specimens for in vitro immersion in lipase phosphate buffered solution and long term in vivo implantation in the femoral condyle of rabbits the effect of the ultrafine poly \u03b5 caprolactone fibers with a diameter ranging from nanometer to micrometer on cpc degradation was evaluated by measuring the ph of the medium mass loss porosity and physiochemical properties for the in vivo evaluation histomorphometrical analysis as well as three dimensional 3d reconstruction was applied to assess the osteogenic properties of the cpc composite after in vitro immersion and in vivo implantation the total porosity and macroporosity as well as the bone formation and ingrowth increased significantly during time in the fiber incorporated cpc specimens after 24 weeks of implantation the degraded space was occupied by newly formed bone and the uficpc3 and uficpc7 composites showed 3 5 times higher fraction of bone volume than that of the pristine cpc uficpc0 in vitro and in vivo results proved that the introduction of ultrafine degradable fibers within a cpc matrix can be used to improve macroporosity efficiently and enhance cpc degradation and bone ingrowth largely copd is a progressive condition involving chronic inflammation and parenchymal destruction with resulting airflow limitation copd is associated with worsening airflow limitation over time and increased frequency of copd exacerbations leading to increased mortality and morbidity the effects of copd extend beyond the lungs as multiple comorbidities may occur with copd including cardiovascular disease diabetes mellitus osteoporosis depression and pneumonia copd exacerbations are associated with a rapid worsening of baseline symptoms that requires prompt management and may necessitate hospitalization in the case of a severe episode patients with copd exacerbations require urgent management of symptoms to prevent further worsening and preventative steps may be taken to help reduce the number and frequency of future exacerbations roflumilast is a potent and selective inhibitor of the enzyme phosphodiesterase 4 that targets the systemic inflammation associated with copd roflumilast has a variety of anti inflammatory effects including decreasing inflammatory mediators and the expression of cell surface markers and inhibition of apoptosis several clinical trials evaluating roflumilast in the treatment of copd have demonstrated significant improvements from baseline versus placebo in lung function including increases in mean pre and postbronchodilator forced expiratory volume in 1 second and forced vital capacity data suggest that roflumilast reduces moderate to severe exacerbations with the benefit most well established in patients with severe disease given this evidence roflumilast as part of a combination regimen with long acting bronchodilators appears to be a reasonable treatment option for patients with severe to very severe copd associated with chronic bronchitis and a history of exacerbations co administration of a long acting \u03b22 agonist and a long acting muscarinic antagonist produces superior bronchodilation compared with their individual effects our preclinical data indicated that combining aclidinium bromide acli and formoterol fumarate form provides synergistic benefit on smooth muscle relaxation of both large and small human airways data from more than 2 000 patients in eleven clinical trials documented that acli form a twice daily fixed dose combination produces a greater degree of bronchodilation than acli or form monotherapy alone and is safe and well tolerated two large key trials have shown that there is a benefit in using acli form when the clinical target is the variability of symptoms and mainly nighttime and or early morning symptoms acli form is the only long acting muscarinic antagonist long acting \u03b22 agonist fixed dose combination that has been studied for this therapeutic indication acute exacerbations of chronic obstructive pulmonary disease aecopd increase copd morbidity and mortality and impose a great burden on health care systems early readmission following a hospitalization for aecopd remains an important clinical problem we examined how individualized comprehensive care influences readmissions following an index hospital admission for aecopd we retrospectively reviewed data of patients admitted for aecopd to two inner city teaching hospitals to determine the impact of a comprehensive and individualized care management strategy on readmissions for aecopd the control group consisted of 271 patients whose index aecopd occurred the year before the comprehensive program and the experimental group consisted of 191 patients who received the comprehensive care the primary outcome measure was the total number of readmissions in 30 and 90 day postindex hospitalizations secondary outcome measures included the length of time between the index admission and first readmission and all cause mortality the two groups were similar in terms of age sex forced expiratory volume in 1 second body mass index bmi pack years and the number and types of comorbidities comprehensive care significantly reduced 90 day readmission rates in females p 0 0205 corrected for age bmi number of comorbidities substance abuse and mental illness but not in males or in the whole group p 0 05 the average times between index admission and first readmission were not different between the two groups post hoc multivariate analysis showed that substance abuse p 0 01 increased 30 and 90 day readmissions corrected for age sex bmi number of comorbidities and mental illness the 90 day all cause in hospital mortality rates were significantly less in the care package group 2 67 versus 7 97 p 0 0268 comprehensive individualized care for subjects admitted to hospital for aecopd did not reduce 30 and 90 day readmission rates but did reduce 90 day total mortality interestingly it reduced 90 day readmission rate in females we speculate that an individualized care package could impact copd morbidity and mortality after an acute exacerbation burgeoning antibiotic resistance and unfavorable outcomes of inflammatory injury after pseudomonas aeruginosa infection have necessitated the development of novel agents that not only target quorum sensing qs but also combat inflammatory injury with the least risk of resistance this study aimed to assess the anti qs and anti inflammatory activities of baicalein a traditional herbal medicine that is widely used in the people s republic of china against p aeruginosa infection we found that subminimum inhibitory concentrations of baicalein efficiently interfered with the qs signaling pathway of p aeruginosa via downregulation of the transcription of qs regulated genes and the translation of qs signaling molecules this interference resulted in the global attenuation of qs controlled virulence factors such as motility and biofilm formation and the secretion into the culture supernatant of extracellular virulence factors including pyocyanin lasa protease lasb elastase and rhamnolipids moreover we examined the anti inflammatory activity of baicalein and its mode of action via a p aeruginosa infected macrophage model to address its therapeutic effect baicalein reduced the p aeruginosa induced secretion of the inflammatory cytokines il 1\u03b2 il 6 il 8 and tnf\u03b1 in addition baicalein suppressed p aeruginosa induced activation of the mapk and nf\u03bab signal transduction pathways in cocultured macrophages this may be the mechanism by which baicalein inhibits the production of proinflammatory cytokines therefore our study demonstrates that baicalein represents a potential treatment for p aeruginosa infection because it clearly exhibits both antibacterial and anti inflammatory activities idiopathic nephrotic syndrome ns is one of the most common glomerular disorders of childhood and is associated with increased urinary vitamin d binding protein uvdbp excretion we tested the hypothesis that uvdbp represents a biomarker to differentiate steroid resistant nephrotic syndrome srns from the more benign forms of steroid sensitive nephrotic syndrome ssns this cross sectional study included children with srns n 24 ssns n 28 and normal controls n 5 urine and clinical data were collected from patients measurements of uvdbp were performed with a commercially available elisa kit and normalized to urine creatinine concentrations of uvdbp were significantly higher p 0 001 in patients with srns 13 659 ng ml interquartile range iqr 477 22 979 than in patients with ssns 94 ng ml iqr 53 202 and normal controls 23 ng ml iqr 22 99 p 0 002 significance did not change when the results were corrected for urine creatinine uvdbp was significantly negatively correlated with estimated glomerular filtration rate egfr r 0 76 p 0 03 however uvdbp was still markedly elevated in patients with srns with egfr 100 ml minute 1 73 m 2 there was a positive correlation between microalbuminuria malb cr and uvdbp r 0 67 p 0 001 however uvdbp displayed a much higher discriminatory ability for distinguishing srns than malb cr area under the curve 0 92 vs 0 67 respectively an uvdbp cutoff of 362 ng ml yielded the optimal sensitivity 80 and specificity 83 to distinguish srns from ssns in this preliminary study uvdbp represents a noninvasive biomarker that could distinguish srns from the more benign ssns with high discriminatory power the nucleotide binding site nbs leucine rich repeat lrr gene family is crucially important for offering resistance to pathogens to explore evolutionary conservation and variability of nbs lrr genes across grass species we identified 88 107 24 and 44 full length nbs lrr genes in sorghum rice maize and brachypodium respectively a comprehensive analysis was performed on classification genome organization evolution expression and regulation of these nbs lrr genes using sorghum as a representative of grass species in general the full length nbs lrr genes are highly clustered and duplicated in sorghum genome mainly due to local duplications nbs lrr genes have basal expression levels and are highly potentially targeted by mirna the number of nbs lrr genes in the four grass species is positively correlated with the gene clustering rate the results provided a valuable genomic resource and insights for functional and evolutionary studies of nbs lrr genes in grass species to assess internal medicine residents knowledge of associations between periodontal disease and systemic illnesses and attitudes toward patients periodontal health a cross sectional survey using a self administered questionnaire was conducted among internal medicine residents attending the faculty of internal medicine 2014 update course organized by the national postgraduate medical college of nigeria participants came from all over the country data on respondents demographic characteristics periodontal disease knowledge knowledge of associations between periodontal disease and systemic illnesses and attitudes toward patients periodontal health were collected data were analyzed using epi info software the pearson chi square test was used to measure significant association between categorical variables such as the knowledge of periodontal disease and gender age group and designation of the participants p 0 05 of 150 questionnaires distributed 123 were returned 82 response rate 109 questionnaires were completed properly and included in the analysis the most common source of residents information on oral health was television 59 4 only 11 2 of respondents were aware that gingival bleeding was the earliest sign of periodontal disease respondents correctly identified periodontal disease as a risk factor for coronary heart disease 45 9 stroke 43 5 hospital acquired pneumonia 53 2 diabetes mellitus 13 8 and preterm birth 11 increased age p 0 032 and male gender p 0 022 were associated significantly with knowledge of periodontal disease as a risk factor for stroke higher designation p 0 002 and longer duration in residency training p 0 004 were associated significantly with knowledge of periodontal disease as risk factor for peripheral arterial disease the majority 90 9 of respondents had positive attitudes toward the referral of their patients for regular periodontal care knowledge of periodontal disease as a risk factor for systemic illnesses among medical residents in nigeria is inadequate these relationships should be emphasized in continuing medical education courses adverse drug reaction is defined as response to a drug which is noxious and unintended and which occurs at doses normally used in man for the prophylaxis diagnosis or therapy of disease or for the modification of physiological functions type i hypersensitivity reaction is known as anaphylactic reaction which is due to immediate immunoglobulin e mediated reaction it is characterized by symptoms such as fever nausea back pain angiodema rash flushing etc lepa generally refers to the application of pastes formed by mixing powder of herbs with water milk etc and liquids complementary and alternative medicines are frequently used by the general population many people consider them to be without side effects ayurvedic treatment involves shodhana biopurification shaman pacification bahya external therapy and abhyantara karma s internal therapy for treating different diseases one such bahya karma or external therapy is lepa even though lepa is said as aadhya upakrama undue hypersensitivity is observed in many patients a 60 year old woman had an adverse reaction to lepa after being administered as an external medication the observations were erythema eruptions and itching such case of hypersensitivity is discussed in the present study t helper 17 th17 cells play a central role in inflammatory and autoimmune diseases via the production of proinflammatory cytokines interleukin il 17 il 17f and il 22 anti il 17 monoclonal antibodies show potent efficacy in psoriasis but poor effect in rheumatoid arthritis ra and crohn s disease alternative agents targeting th17 cells may be a better way to inhibit the development and function of th17 cells than antibodies of blocking a single effector cytokine retinoic acid related orphan receptor gamma t ror\u03b3t which acts as the master transcription factor of th17 differentiation has been an attractive pharmacologic target for the treatment of th17 mediated autoimmune disease recent progress in technology of chemical screen and engineering nucleic acid enable two new classes of therapeutics targeting ror\u03b3t chemical screen technology identified several small molecule specific inhibitors of ror\u03b3t from a small molecule library systematic evolution of ligands by exponential enrichment selex technology enabled target specific aptamers to be isolated from a random sequence oligonucleotide library in this review we highlight the development and therapeutic potential of small molecules inhibiting th17 cells by targeting ror\u03b3t and aptamer mediated cd4 t cell specific delivery of small interference rna against ror\u03b3t gene expression to inhibit pathogenic effector functions of th17 lineage the effectiveness of conventional malaria vector control is being threatened by the spread of insecticide resistance one promising alternative to chemicals is the use of naturally occurring insect killing fungi numerous laboratory studies have shown that isolates of fungal pathogens such as beauveria bassiana can infect and kill adult mosquitoes including those resistant to chemical insecticides unlike chemical insecticides fungi may take up to a week or more to kill mosquitoes following exposure this slow kill speed can still reduce malaria transmission because the malaria parasite itself takes at least eight days to complete its development within the mosquito however both fungal virulence and parasite development rate are strongly temperature dependent so it is possible that biopesticide efficacy could vary across different transmission environments we examined the virulence of a candidate fungal isolate against two key malaria vectors at temperatures from 10 34 \xb0c regardless of temperature the fungus killed more than 90 of exposed mosquitoes within the predicted duration of the malarial extrinsic incubation period a result that was robust to realistic diurnal temperature variation we then incorporated temperature sensitivities of a suite of mosquito parasite and fungus life history traits that are important determinants of malaria transmission into a stage structured malaria transmission model the model predicted that at achievable daily fungal infection rates fungal biopesticides have the potential to deliver substantial reductions in the density of malaria infectious mosquitoes across all temperatures representative of malaria transmission environments synthesis and applications our study combines empirical data and theoretical modelling to prospectively evaluate the potential of fungal biopesticides to control adult malaria vectors our results suggest that beauveria bassiana could be a potent tool for malaria control and support further development of fungal biopesticides to manage infectious disease vectors congenital hypogonadotropic hypogonadism chh is characterized by lack of puberty and infertility traditionally it has been considered a life long condition yet cases of reversibility have been described wherein patients spontaneously recover function of the reproductive axis following treatment reversibility occurs in both male and female chh cases and appears to be more common 10 15 than previously thought these reversal patients span a range of gnrh deficiency from mild to severe and many reversal patients harbor mutations in genes underlying chh however to date there are no clear factors for predicting reversible chh importantly recovery of reproductive axis function may not be permanent thus chh is not always life long and the incidence of reversal warrants periodic treatment withdrawal with close monitoring and follow up reversible chh highlights the importance of environmental epigenetic factors such as sex steroid treatment on the reproductive axis in modifying the phenotype this review provides an overview and an update on what is known about this phenomenon type 2 diabetes mellitus t2dm is associated with endothelial dysfunction characterized by a reduction of nitric oxide no mediated relaxation phosphodiesterase type 5 inhibitors pde5i improve no levels the aim of the study was to investigate whether long term chronic treatment with the pde5i vardenafil improves systemic endothelial function in diabetic men a prospective investigator initiated randomized placebo controlled double blind clinical trial was conducted in total 54 male patients affected by t2dm diagnosed within the last 5 years and erectile dysfunction were enrolled regardless of testosterone levels in all 26 and 28 patients were assigned to verum and placebo groups respectively the study consisted of an enrollment phase a treatment phase 24 weeks vardenafil placebo 10 mg twice in a day and a follow up phase 24 weeks parameters evaluated were as follows international index of erectile function 15 iief 15 flow mediated dilation fmd serum interleukin 6 il6 endothelin 1 et 1 gonadotropins and testosterone measured by liquid chromatography tandem mass spectrometry iief 15 erectile function improved during the treatment p 0 001 at the end of the treatment both fmd p 0 040 and il6 p 0 019 significantly improved fmd correlated with serum testosterone levels r 2 0 299 p 0 001 testosterone increased significantly under vardenafil treatment and returned in the eugonadal range only in hypogonadal men n 13 without changes in gonadotropins chronic vardenafil treatment did not result in relevant side effects this is the first double blind placebo controlled clinical trial designed to evaluate the effects of chronic treatment of vardenafil on endothelial health related parameters and sexual hormones in patients affected by a chronic disease chronically administered vardenafil is effective and improves endothelial parameters in t2dm patient moreover chronic vardenafil therapy improves hypogonadism in diabetic hypogonadal men to obtain predictive information regarding aortic disease we evaluated how blood flow inside the aortic arch was influenced by thoracic aortic aneurysms in addition to reveal the optimal intraoperative management in these cases we examined blood flow during right subclavian arterial rsca perfusion using computational fluid dynamics cfd patient specific models of the aortic arch were made with six different patterns based on the computed tomographic images cfd models with finite volume methods were created to simulate the physiological pulsatile flow including the peripheral reflection wave characteristic impedance and autonomous regulation system flow stream patterns wall shear stress wss and the oscillatory shear index osi were calculated during one cardiac cycle furthermore flow streamlines during rsca perfusion were simulated under different perfusion flows aortic dilatation caused vortical disturbed flow in a dilated space resulting in turbulent flow not only inside the aneurysm but also in the proximal and or distal normal aortic portion in patients with a dilated thoracic aorta there was a helical spiral flow with a circumferential vortex in systole in patients with an arch aneurysm turbulent flow inside the aneurysm caused a high osi at the tip of the aneurysm a high osi was detected at the orifice of the supra aortic branches sinotubular junction posterior lateral side of the ascending aorta and lesser curvature of the proximal descending aorta rsca perfusion revealed that the right common carotid artery was perfused by blood flow from rsca throughout the cardiac cycle with 75 of the flow from the rsca blood flow from the heart reached the left common carotid and subclavian artery only during a short period during the peak of systole a dilated aorta causes a turbulent flow pattern in the aortic arch the high osi site was similar to the favourite entry site for acute aortic dissection indicating the causal relationship between mechanical stress and acute aortic dissection rsca cannulation might be cerebroprotective from ascending aortic plaque as we strongly believe that treating the mitral valve abnormalities is a key feature of hypertrophic obstructive cardiomyopathy hocm we have systematically corrected both the anterior and posterior leaflet pl size and geometry we have analysed our immediate results and at mid term follow up from march 2010 until june 2015 16 patients with hocm underwent surgical correction of obstruction the mean age was 51 years old range 32 72 years all were symptomatic being new york heart association nyha class 3 n 4 or 4 n 12 all had systolic anterior motion at echocardiogram with severe mitral regurgitation mr intraventricular gradient preoperatively was 73 5 mmhg range 50 120 mmhg all patients underwent a double stage procedure first septal resection through i the aortic valve and ii the detached anterior leaflet al of the mitral valve and at second mitral valve repair by i reducing pl height leaflet resection or artificial neochordae ii increasing al height with pericardial patch there was no in hospital or late death all patients were class 1 nyha at latest follow up control echocardiography showed no mr mean rest intraventricular gradient was 15 mmhg range 9 18 mmhg our good mid term results support the concept that hocm is not only a septal disease and that the mitral valve pathology is a key component that should be addressed for most patients the ideal surgical treatment should consist in a two step procedure it is even necessary to be studied whether treating the mitral valve alone could not suffice the treatment of mild to moderate aortic dilatation at the time of aortic valve replacement avr in patients with bicuspid aortic valve bav disease is still controversial we aimed to estimate late progression of aortopathy in patients who underwent isolated avr for bav stenosis with concomitant proximal aortic dilatation of \u226540 mm the review of our institutional bav database n 510 revealed a subgroup of 96 consecutive bav patients 57 10 years 78 male with bav stenosis and concomitant ascending aortic dilatation of \u226540 mm i e as defined by magnetic resonance imaging mri computed tomography ct who underwent isolated avr from 1995 to 2006 aortic diameters were quantified by preoperative mri ct in all patients i e all cases without mri ct were excluded moreover we excluded all cases of simultaneous aortic surgery mri ct follow up 855 patient years was obtained in 83 87 patients study end points were progression of proximal aortic diameters mm patient year and prevalence of aortic events sudden death aortic dissection and aortic surgery mri ct follow up mean 10 3 3 8 years post avr revealed no significant progress of maximal cross sectional aortic diameters i e 46 4 4 4 mm pre avr vs 46 9 4 6 mm post avr p 0 1 aortic diameters were identical in 54 65 patients the mean progression rate of maximal cross sectional aortic diameter was 0 09 mm patient year for the whole study cohort whereas diameter increase of \u22655 mm was revealed in 1 1 patient no aortic dissection occurred five 5 patients underwent redo aortic surgery for aneurysm whereas 3 of them had aortic diameters identical to pre avr mild to moderate ascending aortic dilatation remains stable in most bav patients who underwent isolated avr surgery for aortic valve stenosis at least 10 year post avr to evaluate the feasibility of mitral valve repair in patients with anterior leaflet alp or bileaflet prolapse blp and identify factors predisposing patients to replacement to compare long term survival of patients submitted to repair group repair against those submitted to replacement group replacement and investigate causes of early and late failures of repair from january 1992 through december 2012 768 patients with alp or blp were submitted to mitral valve surgery of whom 501 had degenerative involvement myxomatous myx 336 67 1 or fibroelastic deficiency fed 165 32 9 and constituted the study population isolated alp was present in 274 patients 54 7 and blp in 227 45 3 associated procedures were admitted patients with fed were significantly older 64 4 12 1 vs 54 8 15 5 years p 0 001 more symptomatic 63 vs 44 3 p 0 001 and with higher incidence of atrial fibrillation 43 6 vs 26 2 p 0 001 repair was achieved in 94 8 of patients with an overall 30 day mortality rate of 1 2 0 3 in the last decade and no differences regarding aetiology age moderate to severe left ventricular lv dysfunction previous cardiac surgery multiple segment prolapse mitral calcification leaflet retraction and the performing surgeon were independently associated with replacement group repair patients had a greater adjusted 20 year survival by comparison with group replacement 43 4 5 5 vs 13 6 11 3 p 0 001 and similar to that of the age and sex adjusted general population p 0 10 valve replacement new york heart association nyha class iii iv pulmonary hypertension and lv dysfunction emerged as independent predictors of late mortality patients in nyha class i ii experienced a higher repair rate 98 4 and better survival than those in class iii iv two repair patients were reoperated during the first year after surgery early failure and both were rerepaired late failure was observed in 21 patients mostly for progression of the disease the 20 year rate of freedom from reoperation was 88 2 7 significantly worse in alp patients p 0 040 and not different between fed and myx patients with alp or blp can be submitted to surgery with low mortality and great probability of repair in expert hands patients should be operated on at an early phase asymptomatic or mildly symptomatic because there is a higher probability of repair and greater benefit on long term survival the use of bilateral internal thoracic arteries bitas is associated with improved long term survival after coronary artery bypass grafting cabg however it is unclear whether the addition of a radial artery ra in patients already receiving bita confers any additional survival benefit over that of a saphenous vein sv as such we reviewed our multicentre experience and compared both strategies from 1995 to 2010 1497 patients underwent primary isolated cabg for three vessel coronary disease using bitas an sv was used as a third conduit in 460 31 patients and an ra in 1037 69 a total of 1258 distal anastomoses were performed using ras and these were to the diagonal territory in 169 the circumflex in 454 and the right coronary in 635 survival data were obtained using the national death index and propensity score matching was used for risk adjustment the overall cohort was young mean age 61 9 years patients receiving ras were more likely to be younger and were less likely to have experienced a prior myocardial infarction at 30 days mortality was similar bita sv 5 1 1 vs bita ra 9 0 9 p 0 77 at 15 years bita ra patients experienced improved unadjusted survival bita sv 67 4 6 vs bita ra 82 3 2 p 0 0001 multivariable cox regression in the entire cohort also showed the bita ra group to be associated with better survival hr 0 58 95 ci 0 44 0 75 p 0 001 after propensity score matching of 262 patient pairs bita ra experienced similar 30 day mortality bita sv 3 1 1 vs bita ra 3 1 1 p 0 99 however at 15 years bita ra patients experienced improved risk adjusted survival bita sv 72 6 0 vs bita ra 82 5 2 p 0 021 the ra was associated with better risk adjusted survival for grafting of the right coronary and its branches 148 matched pairs sv rca 74 7 8 vs ra rca 86 6 5 p 0 0046 at 15 years the addition of an ra graft even in patients already receiving bitas is associated with a survival benefit in younger patients with a reasonable long term life expectancy surgeons should strive to achieve total arterial revascularization with bitas and radial arteries rural populations particularly in africa suffer worse health outcomes from poor health services access community health workers chws effectively improve health outcomes but the best means for chws reaching rural populations is unknown since zambia is predominantly christian this study explored the use of chws through churches as an existing community structure for promoting preventive health behaviors specifically rotavirus vaccine uptake a noncontrolled cross sectional study of 32 churches receiving a packaged intervention of diarrhea prevention and treatment messaging was conducted with repeated time points of data collection over 13 months 2013 2014 in the kafue district of zambia two churches were selected for each of the 17 catchment areas and chws were identified and trained in the intervention of promoting 4 key messages related to diarrhea prevention and treatment hand washing with soap exclusive breast feeding rotavirus vaccination and treating diarrhea with oral rehydration solution and zinc the intervention was conducted within existing church s women s groups and data was collected on attendance and the distribution of rota cards for tracking rotavirus immunizations nineteen 59 churches completed the study and chws delivered health messages at a total of 890 women s group meetings the overall reach of the intervention was to 37 0 of church attending women and the efficacy was 67 7 317 of 468 rota cards collected at health centers implementing community health programs is often expensive and unsustainable but the reach and efficacy levels achieved through existing structures like churches are encouraging in resource constrained countries churches can be effective channels for delivering health prevention strategies to often difficult to reach rural populations further research is needed to investigate the impact of the intervention on health outcomes this article describes the impact of an 8 week community program implemented by trained volunteers on the hypertension self management of 185 patients who were batch randomized to intervention or wait list control groups compared with control group participants a higher proportion of treatment group participants moved from the cognitive to behavioral stages of motivational readiness for being physically active p 001 practicing healthy eating habits p 001 handling stress well p 001 and living an overall healthy lifestyle p 003 they also demonstrated a greater average increase in perceived competence for self management f 1 134 4 957 p 028 \u03b72 036 and a greater increase in mean hypertension related knowledge f 1 160 16 571 p 0005 \u03b7 2 094 enduring lifestyle changes necessary for chronic disease self management require that psychosocial determinants of health behavior are instilled which is typically beyond standard medical practice we recommend peer led community based programs as a complement to clinical care and support the increasing health system interest in promoting population health beyond clinical walls parkinson s disease pd is a common neurodegenerative disorder associated with motor and cognitive impairments the mechanisms underlying the pathophysiology and treatments have traditionally focused on basal ganglia thalamo cortical pathways due to striatal dopamine loss but more recent evidence has highlighted the role of the cerebellum here we review evidence from neuroimaging and non invasive brain stimulation that demonstrate altered cerebellar activity in pd may be both a pathophysiological and compensatory mechanism depending on dopaminergic medication and symptoms we evaluated the role of the inferior olive io in acquisition of the spinal cord plasticity that underlies h reflex down conditioning a simple motor skill the io was chemically ablated before a 50 day exposure to an operant conditioning protocol that rewarded a smaller soleus h reflex in normal rats down conditioning succeeds i e h reflex size decreases at least 20 in 80 of animals down conditioning failed in every io ablated rat p 0 001 vs normal rats io ablation itself had no long term effect on h reflex size these results indicate that the io is essential for acquisition of a down conditioned h reflex with previous data they support the hypothesis that io and cortical inputs to cerebellum enable the cerebellum to guide sensorimotor cortex plasticity that produces and maintains the spinal cord plasticity that underlies the down conditioned h reflex they help to further define h reflex conditioning as a model for understanding motor learning and as a new approach to enhancing functional recovery after trauma or disease following the launch of balloon angioplasty in 1977 its deficiencies abrupt occlusion requiring emergency bypass surgery in one in twenty attempts and recurrence in one in three cases became soon apparent the attempts to eliminate the element of chance from this otherwise highly attractive technique resulted in the concept of intra vascular scaffolding following the inception of self expanding mesh stents made from stainless steel and extensive bench testing and animal experiments the first clinical data were obtained in switzerland almost 30 years ago in 1986 with promising albeit not undisputed results technical improvements including potent platelet inhibitors have made the technique a cornerstone of catheter treatment of vascular disease this paper gives an account of the sometimes difficult beginnings of coronary and non coronary stenting at the university of lausanne in switzerland in this paper the working group on myocardial and pericardial disease proposes a revised definition of dilated cardiomyopathy dcm in an attempt to bridge the gap between our recent understanding of the disease spectrum and its clinical presentation in relatives which is key for early diagnosis and the institution of potential preventative measures we also provide practical hints to identify subsets of the dcm syndrome where aetiology directed management has great clinical relevance breastfeeding has many health benefits both in the short term and the longer term to infants and their mothers there is an increasing number of studies that report on associations between breastfeeding and long term protection against chronic disease recent research evidence is reviewed in this study building on previous authoritative reviews the recent world health organization reviews of the short and long term benefits of breastfeeding concluded that there was strong evidence for many public health benefits of breastfeeding cognitive development is improved by breastfeeding and infants who are breastfed and mothers who breastfeed have lower rates of obesity other chronic diseases that are reduced by breastfeeding include diabetes both type 1 and type 2 obesity hypertension cardiovascular disease hyperlipidemia and some types of cancer legionella pneumophila the causative agent of legionnaires disease has a biphasic life cycle with a switch from a replicative to a transmissive phenotype during the replicative phase the bacteria grow within host cells in legionella containing vacuoles during the transmissive phenotype and the postexponential pe growth phase the pathogens express virulence factors become flagellated and leave the legionella containing vacuoles using 13 c labeling experiments we now show that under in vitro conditions serine is mainly metabolized during the replicative phase for the biosynthesis of some amino acids and for energy generation during the pe phase these carbon fluxes are reduced and glucose also serves as an additional carbon substrate to feed the biosynthesis of poly 3 hydroxybuyrate phb an essential carbon source for transmissive l pneumophila whole cell ftir analysis and comparative isotopologue profiling further reveal that a putative 3 ketothiolase lpp1788 and a phb polymerase lpp0650 but not enzymes of the crotonyl coa pathway lpp0931 0933 are involved in phb metabolism during the pe phase however the data also reflect that additional bypassing reactions for phb synthesis exist in agreement with in vivo competition assays using acanthamoeba castellannii or human macrophage like u937 cells as host cells the data suggest that substrate usage and phb metabolism are coordinated during the life cycle of the pathogen the transcription factor x box binding protein 1 xbp1 controls the development and maintenance of the endoplasmic reticulum er in multiple secretory cell lineages we show here that hepatocyte nuclear factor 4\u03b1 hnf4\u03b1 directly induces xbp1 expression mutations in hnf4\u03b1 cause mature onset diabetes of the young i modyi a subset of diabetes characterized by diminished gsis in mouse models cell lines and ex vivo islets using dominant negative and human disease allele point mutants or knock out and knockdown models we show that disruption of hnf4\u03b1 caused decreased expression of xbp1 and reduced cellular er networks gsis depends on er ca 2 signaling we show that diminished xbp1 and or hnf4\u03b1 in \u03b2 cells led to impaired er ca 2 homeostasis restoring xbp1 expression was sufficient to completely rescue gsis in hnf4\u03b1 deficient \u03b2 cells our findings uncover a transcriptional relationship between hnf4\u03b1 and xbp1 with potentially broader implications about modyi and the importance of transcription factor signaling in the regulation of secretion this study purports to address paucity in the literature regarding how adolescents with sickle cell disease scd describe and experience spirituality and religiosity s r this was a qualitative descriptive study two semi structured interviews were conducted with nine adolescents mage 16 2 years data were analyzed using a template analysis style and a concurrent analysis process of data reduction three major themes encompassed the participants descriptions of the relationships between s r health and illness in their lives including s r as sources for coping influence of s r beliefs on health and illness and sharing s r with health care providers hcps s r as coping mechanisms included six threads interconnecting with god interconnecting with others interconnecting with creative arts scriptural metanarratives transcendent experiences and acceptance and finding meaning expectations of health providers included two threads religiosity is private personal and sharing spiritual and religious beliefs is risky s r are particularly salient for adolescents with scd non alcoholic hepatic steatosis hs is associated with hypertension and increased cardiovascular risk while blood pressure hyper reactive response hrr during peak exercise indicates an increased risk of incident hypertension and increased cardiovascular risk no data on the association of non alcoholic hs and hrr exists in this study we have evaluated the association of hs with hrr we included 13 410 consecutive individuals with a mean age 42 4 8 9 years 3561 26 6 female with normal resting blood pressure and without a previous diagnosis of hypertension who underwent symptom limited exercise treadmill test abdominal ultrasonography and clinical and laboratory evaluation hs was detected by abdominal ultrasonography hrr was defined by a peak exercise systolic blood pressure 220 mmhg and or elevation of 15 mmhg or more in diastolic blood pressure from rest to peak exercise the prevalence of hs was 29 5 n 3956 overall 4 6 n 619 of the study population presented a hrr subjects with hs had a higher prevalence of hrr 8 1 vs 3 1 odds ratio 2 8 95 ci 2 4 3 3 p 0 001 after adjustment for body mass index waist circumference fasting plasma glucose and low density lipoprotein cholesterol hs odds ratio 1 4 95 ci 1 1 1 6 p 0 002 remained independently associated with hrr hs was additive to obesity markers in predicting exercise hrr non alcoholic hs is independently associated with hyper reactive exercise blood pressure response gaucher disease gd is an autosomal recessive disorder produced by mutations in the glucocerebrosidase gene gba causing storage of glucosylceramide in reticuloendothelial cells in multiple organs traditionally the prediction of the phenotype based on the genotype has been reported to be limited we investigated the correlation between the enzymatic residual activity era and the phenotype at diagnosis of the disease in 45 gd spanish patients 44 with type i and 1 with type iii gd the genotype involved two of the following previously expressed proteins c 517a c t134p 1 c 721g a g202r 17 c 1090g t g325w 13 9 c 1208g a s364n 4 1 c 1226a g n370s 17 8 c 1246g a g377s 17 6 c 1289c t p391l 8 5 c 1448t c l444p 3 and c 1504c t r463c 24 5 recombinant alleles deletion of 55 bp in exon 9 and 84gg mutation were considered as mutations with no residual enzymatic activity the era showed a statistically significant correlation with chitotriosidase p 0 001 age p 0 001 spleen size p 0 001 zimran s severity score index p 0 01 and the gaucher disease severity score index type i p 0 0001 at diagnosis of the disorder previous to any medical intervention a comparison between the era and bone involvement demonstrated a statistically significant relationship p 0 01 between the two variables this study data allowed us to define a new criterion for prognostic assessment of the disease at diagnosis called protein severity index which expresses the theoretical severity of the genotype presented by patients according to the corresponding era the pruritic skin disease scabies is caused by the burrowing of the itch mite sarcoptes scabiei de geer it is difficult to diagnose this disease because its symptoms often resemble those of other skin diseases no reliable blood or molecular diagnostic test is available the aim of this project was to begin to characterize the scabies proteome to identify scabies mite proteins including those that may be useful in the development of a diagnostic test or vaccine various scabies mite extracts were separated by two dimensional electrophoresis and 844 coomassie blue stained protein spots were excised subjected to trypsin digestion and analyzed by matrix assisted laser desorption ionization time of flight time of flight maldi tof tof mass spectrometry ms tryptic fragment sequences determined by ms were searched against the recently completed s scabiei annotated genome leading to the identification of 150 proteins only 10 proteins hit to previously identified scabies proteins including actin tropomyosin and several abc transporters thirteen proteins had homology to dust mite allergens members of groups 8 10 13 17 20 25 and 28 most other sequences showed some homology to proteins in other mites and ticks including homologs of calmodulin calreticulin lipocalin and glutathione s transferase these data will now allow the identification of the proteins to which scabies patients produce antibodies including those that may be good candidates for inclusion in a diagnostic test and vaccine two 4 year old spayed female siamese cats were seized by the british columbia society for the prevention of cruelty to animals after confinement to an abandoned housing unit without food for 9 weeks one cat was found dead and the second was euthanized within 24 hours due to neurologic deterioration despite therapy polioencephalomalacia of the caudal colliculus hepatic lipidosis cachexia and congestive heart failure with cardiomyocyte atrophy were identified in both cats through postmortem examination and attributed to a prolonged period of starvation brain lesions were likely the result of thiamine deficiency chastek paralysis which can be associated with both malnutrition and liver disease this case highlights the importance of thiamine supplementation during realimentation of cats with hepatic lipidosis heart failure resulting from cachexia may have contributed to the death of the first cat and the morbidity of the second cat murine noroviruses mnvs are highly prevalent in laboratory mice can cause persistent infections and have been shown to infect macrophages dendritic cells and b cells to address the potential impact of mnv infection on research outcomes numerous studies have been conducted with various mouse models of human disease and have generated mixed results ranging from no impact to significant disease many of these studies included histologic evaluations after mnv infection and these results have similarly been variable in terms of whether mnv induces lesions despite the fact that localization of mnv by viral culture and molecular techniques have demonstrated systemic distribution regardless of mouse immune status the aim of this review is to summarize the histologic findings that have been reported with mnv infection in several mouse models the studies demonstrate that experimental infection of mnv in wild type mice results in minimal to no histologic changes in contrast immunodeficient mice consistently have detectable mnv induced lesions that are typically inflammatory and in the most severe cases accompanied by necrosis in these the liver is commonly affected with more variable lesions reported in the lung gastrointestinal tract mesenteric lymph nodes brain and spleen in specific disease models including atherosclerosis mnv infection had a variable impact that was dependent on the mouse model viral strain timing of infection or other experimental variables it is important to recognize the reported mnv lesions to help discern the possible influence of mnv infection on data generated in mouse models ependymal cells are epithelial support cells that line the central canal and ventricular cavities of the central nervous system providing the interface between the cerebrospinal fluid and the parenchyma of the brain and spinal cord the spinal ependymal layer sel is composed of 3 main cell types tanycytes ependymocytes and cerebrospinal fluid contacting neurons a fourth cell type termed the supraependymal cell is also occasionally described cells of the sel show restricted proliferative capacity in health but display neural stem cell properties both in vitro and in vivo in various disease states a growing body of literature is devoted to the regenerative roles of the sel particularly in the context of spinal cord injury where mechanical damage to the spinal cord leads to a significant increase in sel proliferation sel derived cell progeny migrate to sites of injury within the injured spinal cord parenchyma and contribute primarily to glial scar formation in additional to their role as endogenous neural stem cells cells of the sel may be an important source of cytokines and other cell signaling molecules such as tumor necrosis factor heat shock proteins and various growth factors the sel has become of recent interest to neuroscience researchers because of its potential to participate in and respond to diseases affecting the spinal cord eg traumatic spinal cord injury and neurodegenerative disease the intimate association of the sel with the cerebrospinal fluid makes intrathecal therapies a viable option and recent studies highlight the potential promise of treatments that augment sel responses to disease cardiorenal syndrome involves disease and dysfunction of the heart that leads to progressive renal dysfunction this study investigated the relationship between cardiac and renal disease in 91 aged chimpanzees at the alamogordo primate facility by evaluation of the medical histories metabolic parameters functional measurements of the cardiovascular system clinical pathology and histopathology focused on the heart and kidney cardiac fibrosis was the most frequent microscopic finding in 82 of 91 animals 90 followed by glomerulosclerosis with tubulointerstitial fibrosis in 63 of 91 69 cardiac fibrosis with attendant glomerulosclerosis and tubulointerstitial fibrosis was observed in 58 of 91 animals 63 there was a statistically significant association between the 2 conditions as the severity of cardiac fibrosis increased there was corresponding increase in severity of glomerulosclerosis with tubulointerstitial fibrosis altered metabolic cardiovascular and clinical pathology parameters indicative of heart and kidney failure were commonly associated with the moderate to severe microscopic changes and concurrent heart and kidney failure were considered the cause of death the constellation of findings in the chimpanzees were similar to cardiorenal syndrome in humans while genetic perturbation has been the conventional route to probing bacterial systems small molecules are showing great promise as probes for cellular complexity indeed systematic investigations of chemical genetic interactions can provide new insights into cell networks and are often starting points for understanding the mechanism of action of novel chemical probes we have developed a robust and sensitive platform for chemical genomic investigations in bacteria the approach monitors colony volume kinetically using transmissive scanning measurements enabling acquisition of growth rates and conventional endpoint measurements we found that chemical genomic profiles were highly sensitive to concentration necessitating careful selection of compound concentrations roughly 20 000 000 data points were collected for 15 different antibiotics while 1052 chemical genetic interactions were identified using the conventional endpoint biomass approach adding interactions in growth rate resulted in 1564 interactions a 50 200 increase depending on the drug with many genes uncharacterized or poorly annotated the chemical genetic interaction maps generated from these data reveal common genes likely involved in multidrug resistance additionally the maps identified deletion backgrounds exhibiting class specific potentiation revealing conceivable targets for combination approaches to drug discovery this open platform is highly amenable to kinetic screening of any arrayable strain collection be it prokaryotic or eukaryotic previous studies reported decreased n acetyl aspartate and increased glx the sum of glutamate plus glutamine in bipolar disorder since these studies included patients at different stages of illness it is unknown whether these changes have a causal role or a consequence of multiple episodes and treatments the studies in early stage bipolar disorder patients have the potential to provide answers to these issues therefore we evaluated n acetyl aspartate and glx levels in hippocampi of first episode bipolar disorder patients and health subjects at baseline and at 12 months and examined the impact of episode recurrence on these measures we used single voxel proton magnetic resonance spectroscopy to compare the hippocampal neurometabolites n acetyl aspartate and glx levels between 41 patients with bipolar disorder following recovery from their first manic episode and 27 matched healthy subjects at recruitment and 12 months later we also compared n acetyl aspartate and glx levels between patients who had a recurrence of a mood episode and those who did not there was no main effect of either group diagnosis or time for hippocampal n acetyl aspartate and glx levels in bipolar disorder patients and healthy subjects we also did not find any group by time interaction for the levels of these metabolites there were also no differences in n acetyl aspartate and glx between patients who experienced a recurrence of a mood episode and those who did not over 12 month follow up our data suggest that n acetyl aspartate and glx levels are not altered in early stage bipolar disorder further these data suggest that episode recurrence in early stages does not have a significant impact on the levels of these metabolites these may suggest that there may be an early window for intervention to potentially arrest neuroprogression of the disease type 1 diabetes is an autoimmune disease that results from the defective induction or maintenance of t cell tolerance against islet \u03b2 cell self antigens under steady state conditions dendritic cells with tolerogenic properties are critical for peripheral immune tolerance tolerogenic dendritic cells can induce t cell anergy and deletion and in some contexts induce or expand regulatory t cells dendritic cells contribute to both immunomodulatory effects and triggering of pathogenesis in type 1 diabetes this immune equilibrium is affected by both genetic and environmental factors that contribute to the development of type 1 diabetes genome wide association studies and disease association studies have identified 50 polymorphic loci that lend susceptibility or resistance to insulin dependent diabetes mellitus in parallel diabetes susceptibility regions known as insulin dependent diabetes loci have been identified in the nonobese diabetic mouse a model for human type 1 diabetes providing a better understanding of potential immunomodulatory factors in type 1 diabetes risk most genetic candidates have annotated immune cell functions but the focus has been on changes to t and b cells however it is likely that some of the genomic susceptibility in type 1 diabetes directly interrupts the tolerogenic potential of dendritic cells in the pathogenic context of ongoing autoimmunity here we will review how gene polymorphisms associated with autoimmune diabetes may influence dendritic cell development and maturation processes that could lead to alterations in the tolerogenic function of dendritic cells these insights into potential tolerogenic and pathogenic roles for dendritic cells have practical implications for the clinical manipulation of dendritic cells toward tolerance to prevent and treat type 1 diabetes alveolar macrophages from chronic obstructive pulmonary disease patients and cigarette smokers are deficient in their ability to phagocytose apoptotic bronchial epithelial cells efferocytosis we hypothesized that the defect is mediated via inhibition of sphingosine kinases and or their subcellular mislocalization in response to cigarette smoke and can be normalized with exogenous sphingosine 1 phosphate or fty720 fingolimod a modulator of sphingosine 1 phosphate signaling which has been shown to be clinically useful in multiple sclerosis measurement of sphingosine kinase 1 2 activities by 32 p labeled sphingosine 1 phosphate revealed a 30 reduction of sphingosine kinase 1 p 0 05 and a nonsignificant decrease of sphingosine kinase 2 in thp 1 macrophages after 1 h cigarette smoke extract exposure by confocal analysis macrophage sphingosine kinase 1 protein was normally localized to the plasma membrane and cytoplasm and sphingosine kinase 2 to the nucleus and cytoplasm but absent at the cell surface cigarette smoke extract exposure 24 h led to a retraction of sphingosine kinase 1 from the plasma membrane and sphingosine kinase 1 2 clumping in the golgi domain selective inhibition of sphingosine kinase 2 with 25 \xb5m abc294640 led to 36 inhibition of efferocytosis p 0 05 10 \xb5m sphingosine kinase inhibitor 5c sphingosine kinase 1 selective inhibitor induced a nonsignificant inhibition of efferocytosis but its combination with abc294640 led to 56 inhibition p 0 01 vs control and 0 05 vs single inhibitors cigarette smoke inhibited efferocytosis was significantly p 0 05 reversed to near control levels in the presence of 10 100 nm exogenous sphingosine 1 phosphate or fty720 and fty720 reduced cigarette smoke induced clumping of sphingosine kinase 1 2 in the golgi domain these data strongly support a role of sphingosine kinase 1 2 in efferocytosis and as novel therapeutic targets in chronic obstructive pulmonary disease to compare the coronary heart disease risk among patients with rheumatoid arthritis ra initiating common biologic disease modifying antirheumatic drugs of different mechanisms we conducted a retrospective cohort study of patients with ra enrolled in medicare a public health plan covering 90 of us residents 65 years or older from 2006 to 2012 who 1 initiated a biologic 2 had complete medical and pharmacy coverage for at least 12 months before biologic initiation and 3 were free of coronary heart disease at the time of initiation we compared the incidence rates irs of 1 acute myocardial infarction ami and 2 a composite outcome of ami or coronary revascularisation and used multivariable adjusted cox regression models to examine the associations between the type of biologic and the two outcomes we identified 47 193 eligible patients with ra with mean age 64 sd 13 years 85 were women crude irs for ami ranged from 5 7 to 8 8 cases per 1000 person years pys ami risk was significantly elevated among antitumour necrosis factor anti tnf initiators overall adjusted hr ahr 1 3 95 ci 1 0 to 1 6 and individually among etanercept ahr 1 3 95 ci 1 0 to 1 8 and infliximab ahr 1 3 95 ci 1 0 to 1 6 compared with abatacept initiators crude irs for the composite outcome ranged from 7 6 to 14 5 per 1000 pys tocilizumab initiators were at reduced risk of the composite outcome compared with abatacept initiators ahr 0 64 95 ci 0 41 to 0 99 findings from this observational study of patients with ra suggested that anti tnf biologics may be associated with higher ami risk compared with abatacept to evaluate apremilast treatment in patients with active psoriatic arthritis including current skin involvement despite prior therapy with conventional disease modifying antirheumatic drugs and or biologic agents patients n 505 were randomised 1 1 1 to placebo apremilast 20 mg twice daily or apremilast 30 mg twice daily rescue therapy with apremilast was designated at week 16 for placebo patients not achieving 20 improvement in swollen and tender joint counts at week 24 the remaining placebo patients were then randomised to apremilast 20 mg twice daily or 30 mg twice daily the efficacy and safety of apremilast were assessed over 52 weeks at week 16 significantly more patients receiving apremilast 20 mg twice daily 28 and 30 mg twice daily 41 achieved 20 improvement in american college of rheumatology response criteria versus placebo 18 p 0 0295 and p 0 0001 respectively and mean decrease in the health assessment questionnaire disability index score was significantly greater with apremilast 30 mg twice daily 0 20 versus placebo 0 07 p 0 0073 in patients with baseline psoriasis body surface area involvement \u22653 significantly more apremilast 30 mg twice daily patients achieved 50 reduction from baseline psoriasis area and severity index score 41 versus placebo 24 p 0 0098 at week 16 at week 52 observed improvements in these measures demonstrated sustained response with continued apremilast treatment most adverse events were mild to moderate in severity the most common were diarrhoea nausea headache and upper respiratory tract infection apremilast demonstrated clinically meaningful improvements in psoriatic arthritis and psoriasis at week 16 sustained improvements were seen with continued treatment through 52 weeks apremilast was generally well tolerated and demonstrated an acceptable safety profile nct01212770 atp binding cassette transporter a7 abca7 is highly expressed in the brain recent genome wide association studies gwas have identified abca7 single nucleotide polymorphisms snps that increase alzheimer s disease ad risk however the mechanisms by which abca7 may control ad risk remain to be fully elucidated based on previous research suggesting that certain abc transporters may play a role in the regulation of neurogenesis we conducted a study of cell proliferation and neurogenic potential using cellular bromodeoxyuridine brdu incorporation and doublecortin dcx immunostaining in adult abca7 deficient mice and wild type like wt littermates in the present study counting of brdu positive and dcx positive cells in an established adult neurogenesis site in the dentate gyrus dg indicated there were no significant differences when wt and abca7 deficient mice were compared we also measured the area occupied by immunohistochemical staining for brdu and dcx in the dg and the subventricular zone svz of the same mice and this confirmed that abca7 does not play a significant role in the regulation of cell proliferation or neurogenesis in the adult mouse osteoarthritis is a degenerative joint disease that ranks among the leading causes of adult disability mechanisms underlying osteoarthritis pathogenesis are not yet fully elucidated putting limits to current disease management and treatment based on the phenomenological evidence for dysregulation within the glycome of chondrocytes and the network of a family of adhesion growth regulatory lectins that is galectins we tested the hypothesis that galectin 1 is relevant for causing degeneration immunohistochemical analysis substantiated that galectin 1 upregulation is associated with osteoarthritic cartilage and subchondral bone histopathology and severity of degeneration p 0 0001 n 29 patients in vitro the lectin was secreted and it bound to osteoarthritic chondrocytes inhibitable by cognate sugar glycan dependent galectin 1 binding induced a set of disease markers including matrix metalloproteinases and activated nf \u03bab hereby switching on an inflammatory gene signature p 10 16 inhibition of distinct components of the nf \u03bab pathway using dedicated inhibitors led to dose dependent impairment of galectin 1 mediated transcriptional activation enhanced secretion of effectors of degeneration such as three matrix metalloproteinases underscores the data s pathophysiological relevance this study thus identifies galectin 1 as a master regulator of clinically relevant inflammatory response genes working via nf \u03bab because inflammation is critical to cartilage degeneration in osteoarthritis this report reveals an intimate relation of glycobiology to osteoarthritic cartilage degeneration respiratory syncytial virus rsv infection can cause severe disease in the lower respiratory tract of infants and older people vaccination with a formalin inactivated rsv vaccine fi rsv and subsequent rsv infection has led to mild to severe pneumonia with two deaths among vaccinees the vaccine enhanced disease ved was recently demonstrated to be due to an elevated level of th2 cell responses following loss of regulatory t treg cells from the lungs to induce high levels of neutralizing abs and minimize pathogenic t cell responses we developed a novel strategy of immunizing animals with a recombinant rsv g protein together with cyclosporine a this novel vaccine induced not only a higher level of neutralizing abs against rsv infection but most importantly also significantly higher levels of treg cells that suppressed ved in the lung after rsv infection the induced responses provided protection against rsv challenge with no sign of pneumonia or bronchitis treg cell production of il 10 was one of the key factors to suppress ved these finding indicate that g protein plus cyclosporine a could be a promising vaccine against rsv infection in children and older people il 21 promotes b cell and ctl responses in vivo conferring il 21 with a role in both humoral and cellular responses because ctl can target and eliminate autoreactive b cells we investigated whether il 21r signaling in cd8 t cells would alter the expansion of autoreactive b cells in an autoimmune setting we addressed this question using the parent \u2192f1 murine model of acute and chronic lupus like graft versus host disease gvhd as models of a ctl mediated or t dependent b cell mediated response respectively induction of acute gvhd using il 21r deficient donor t cells resulted in decreased peak donor cd8 t cell numbers and decreased ctl effector function due to impaired granzyme b perforin and fas fas ligand pathways and a phenotype of low intensity chronic gvhd with persistent host b cells autoantibody production and mild lupus like renal disease ctl effector maturation was critically dependent on il 21r signaling in ag specific donor cd8 but not cd4 t cells conversely treatment of dba 2j \u2192f1 chronic gvhd mice with il 21 strongly promoted donor cd8 t cell expansion and rescued defective donor anti host ctls resulting in host b cell elimination decreased autoantibody levels and attenuated renal disease despite evidence of concurrently enhanced cd4 help for b cells and heightened b cell activation these results demonstrate that in the setting of lupus like cd4 t cell driven b cell hyperactivity il 21 signaling on ag specific donor cd8 t cells is critical for ctl effector maturation whereas a lack of il 21r downregulates ctl responses that would otherwise limit b cell hyperactivity and autoantibody production the percentage of overweight and obese canadian children and youth is dramatically increasing approaches to reducing obesity in adolescents should include the promotion of physical activity pa because a continued physically active lifestyle into adulthood may lower rates of chronic diseases associated with unhealthy body weight the current study expands on existing assessments of pa to include predictors based in a multidimensional adolescent wellness and ecological model canadian adolescents n 603 were surveyed and the resulting data analyzed using multiple regression analysis overall 57 5 and 52 9 of the unique variance in pa for females and males respectively were explained by the predictors significant predictors for females included age recreational time family leadership and social comparison cognitive development skills for males equipment at home was also associated with increased pa the finding that social comparison and leadership skills are significant predictors of pa in adolescents is new nurses should consider a holistic approach to promoting pa whereby these developmental dimensions are included in assessment and prioritized in providing nursing care additionally individualized pa intervention strategies can then be tailored to this unique population risk of progression to various stages of chronic kidney disease ckd after endovascular aortic aneurysm repair evar is unknown this study estimates progression rates to stage 3 and 4 ckd after evar and identifies potential predictors for progression evar cases 2006 2012 were retrospectively reviewed freedom of progression to ckd was estimated using kaplan meier analysis and predictors for progression were identified using cox proportional hazards model two hundred and twelve consecutive patients at a single academic institution underwent evar for infrarenal aneurysms estimated freedom from progression to stage 3 ckd was 80 76 and 63 at 6 12 and 18 months respectively and for stage 4 97 96 and 93 at 6 12 and 18 months respectively stage 3 ckd predictors of progression included age odds ratio or 1 106 p 0 001 diabetes or 3 052 p 0 04 perioperative use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers or 3 249 p 0 02 and operative blood loss or 1 002 p 0 01 stage 4 predictors included preoperative hemoglobin or 0 473 p 0 04 and baseline renal function or 0 928 p 0 001 intraoperative contrast administration did not impact ckd development progression to stage 3 ckd after evar occurs more frequently and at a higher rate compared with progression to stage 4 different risk factors are associated with progression to each of those stages of ckd inappropriate secretion of tsh was first described in 1960 in a patient with evidence of hyperthyroidism and expanded sella on imaging it was later found that a type of pituitary adenoma that secretes tsh thyrotropinoma was the underlying cause the objective of the present review article is to summarize data on the epidemiology pathogenesis diagnosis and management of thyrotropinomas the prevalence of thyrotropinomas is lower than that of other pituitary adenomas early diagnosis is now possible thanks to the availability of magnetic resonance imaging and sensitive laboratory assays as a corollary many patients now present earlier in the course of their disease and have smaller tumors at the time of diagnosis treatment also has evolved over time transsphenoidal surgery is still considered definitive therapy meanwhile radiation therapy including radiosurgery is effective in achieving tumor control in the majority of patients in the past radiation therapy was used as second line treatment in patients with residual or recurrent tumor after surgery however the availability of somatostatin analogs which can lead to normalization of thyroid function as well as shrink these tumors has led to an increase in the role of medical therapy in patients who are not in remission after pituitary surgery in addition dopamine agonists have shown some efficacy in the management of these tumors better understanding of the molecular pathogenesis of thyrotropinomas may lead to rationally designed therapies for patients with thyrotropinomas critiques of cost effectiveness modelling in type 1 diabetes mellitus t1dm are scarce and are often undertaken in combination with type 2 diabetes mellitus t2dm models however t1dm is a separate disease and it is therefore important to appraise modelling methods in t1dm this review identified published economic models in t1dm and provided an overview of the characteristics and capabilities of available models thus enabling a discussion of best practice modelling approaches in t1dm a systematic review of embase \xae) medline \xae) medline \xae) in process and nhs eed was conducted to identify available models in t1dm key conferences and health technology assessment hta websites were also reviewed the characteristics of each model e g model structure simulation method handling of uncertainty incorporation of treatment effect data for risk equations and validation procedures based on information in the primary publication were extracted with a focus on model capabilities we identified 13 unique models overall the included studies varied greatly in scope as well as in the quality and quantity of information reported but six of the models archimedes cdm core diabetes model crc des cardiff research consortium discrete event simulation dcct diabetes control and complications trial sheffield and eagle economic assessment of glycaemic control and long term effects of diabetes were the most rigorous and thoroughly reported most models were markov based and cohort and microsimulation methods were equally common all of the more comprehensive models employed microsimulation methods model structure varied widely with the more holistic models providing a comprehensive approach to microvascular and macrovascular events as well as including adverse events the majority of studies reported a lifetime horizon used a payer perspective and had the capability for sensitivity analysis several models have been developed that provide useful insight into t1dm modelling based on a review of the models identified in this study we identified a set of best in class methods for the different technical aspects of t1dm modelling being born prematurely associates with greater cardiovascular disease cvd risk in adulthood less understood are the unique and joint associations of dietary patterns and behaviors to this elevated risk among adults who are born prematurely we aimed to model the associations between term status dietary and lifestyle behaviors with cvd risk factors while accounting for the longitudinal effects of family protection and medical or environmental risks in wave viii of a longitudinal study 23 year olds born prematurely pt adults n 129 and full term ft adults n 38 survey reported liking for foods beverages and activities constructed into indexes of dietary quality and sensation seeking dietary restraint and physical activity measured cvd risk factors included fasting serum lipids and glucose blood pressure and adiposity in bivariate relationships pt adults reported lower dietary quality including less affinity for protein rich foods and higher affinity for sweets less liking for sensation seeking foods activities and less restrained eating than did ft adults in comparison to nationally representative values and the ft adults pt adults showed greater level of cvd risk factors for blood pressure and serum lipids in structural equation modeling dietary quality completely mediated the association between term status and hdl cholesterol higher quality lower hdl cholesterol yet joined term status to explain variability in systolic blood pressure pt adults with lowest dietary quality had highest blood pressures through lower dietary quality being born prematurely was indirectly linked to higher cholesterol hdl higher ldl hdl and elevated waist hip ratios the relationship between dietary quality and cvd risk was strongest for pt adults who had developed greater cumulative medical risk protective environments failed to attenuate relationships between dietary quality and elevated cvd risk among pt adults in summary less healthy dietary behaviors contribute to elevated cvd risk among young adults who are born prematurely precision medicine incorporating personalized medicine is an emerging medical model that holds great promise for improving the prevention diagnosis and treatment of many diseases the future success of precision medicine however depends on the establishment of large databases that collate diverse data including family genealogies disease histories drug sensitivities and genomic data herein i raise some of the social and ethical challenges that such a system faces specifically the enrolment of volunteers into large genetic databases the need for a change in mindset of clinicians patients and the wider public and the need for interdisciplinary ethics considering the emerging issues finally i argue that the future potential of personalized medicine crucially depends on collective participation of informed citizens oral medicine stomatology is a recognized and increasingly important dental specialty in many parts of the world that recognizes and fosters the interplay between medical health and oral health its dental activities rely greatly on the underlying biology of disease and evidence based outcomes however full recognition of the importance of oral medicine to patient care research and education is not yet totally universally acknowledged to address these shortcomings we outline the birth growth and future of oral medicine globally and record identifiable past contributions to the development of the specialty providing an accurate unique and valuable resource on oral medicine although it was challenging to gather the data we present this information as a review that endeavors to summarize the salient points about oral medicine based on medline other internet searches communication with oral medicine and stomatological societies across the world the web page http en wikipedia org wiki list of dental organizations and discussions with a wide range of key senior persons in the specialty the influenza virus rna dependent rna polymerase which is composed of three subunits pb1 pb2 and pa catalyzes genome replication and transcription within the cell nucleus the pa linker residues 197 to 256 can be altered by nucleotide substitutions to engineer temperature sensitive ts attenuated mutants that display a defect in the transport of the pa pb1 complex to the nucleus at a restrictive temperature in this study we investigated the ability of the pa linker to tolerate deletion mutations for further in vitro and in vivo characterization four viable mutants with single codon deletions were generated all of them exhibited a ts phenotype that was associated with the reduced efficiency of replication transcription of a pseudoviral reporter rna in a minireplicon assay using fluorescently tagged pb1 we observed that the deletion mutants did not efficiently recruit pb1 to reach the nucleus at a restrictive temperature 39 5 \xb0c mouse infections showed that the four mutants were attenuated and induced antibodies that were able to protect mice from challenge with a lethal homologous wild type virus serial in vitro passages of two deletion mutants at 39 5 \xb0c and 37 \xb0c did not allow the restoration of a wild type phenotype among virus progeny thus our results identify codons that can be deleted in the pa gene to engineer genetically stable ts mutants that could be used to design novel attenuated vaccines in order to generate genetically stable live influenza a virus vaccines we constructed viruses with single codon deletions in a discrete domain of the rna polymerase pa gene the four rescued viruses exhibited a temperature sensitive phenotype that we found was associated with a defect in the transport of the pa pb1 dimer to the nucleus where viral replication occurs these ts deletion mutants were shown to be attenuated and to be able to produce antibodies in mice and to protect them from a lethal challenge assays to select revertants that were able to grow efficiently at a restrictive temperature failed showing that these deletion mutants are genetically more stable than conventional substitution mutants these results are of interest for the design of genetically stable live influenza virus vaccines ddx3 belongs to the dead box rna helicase family and is a multifunctional protein affecting the life cycle of a variety of viruses however its role in influenza virus infection is unknown in this study we explored the potential role of ddx3 in influenza virus life cycle and discovered that ddx3 is an antiviral protein since many host proteins affect virus life cycle by interacting with certain components of the viral machinery we first verified whether ddx3 has any viral interaction partners immunoprecipitation studies revealed ns1 and np as direct interaction partners of ddx3 stress granules sgs are known to be antiviral and do form in influenza virus infected cells expressing defective ns1 protein additionally a recent study showed that ddx3 is an important sg nucleating factor we thus explored whether ddx3 plays a role in influenza virus infection through regulation of sgs our results showed that sgs were formed in infected cells upon infection with a mutant influenza virus lacking functional ns1 del ns1 protein and ddx3 colocalized with np in sgs we further determined that the ddx3 helicase domain did not interact with ns1 and np however it was essential for ddx3 localization in virus induced sgs knockdown of ddx3 resulted in impaired sg formation and led to increased virus titers taken together our results identified ddx3 as an antiviral protein with a role in virus induced sg formation ddx3 is a multifunctional rna helicase and has been reported to be involved in regulating various virus life cycles however its function during influenza a virus infection remains unknown in this study we demonstrated that ddx3 is capable of interacting with influenza virus ns1 and np proteins ddx3 and np colocalize in the del ns1 virus induced sgs furthermore knockdown of ddx3 impaired sg formation and led to a decreased virus titer thus we provided evidence that ddx3 is an antiviral protein during influenza virus infection and its antiviral activity is through regulation of sg formation our findings provide knowledge about the function of ddx3 in the influenza virus life cycle and information for future work on manipulating the sg pathway and its components to fight influenza virus infection paramyxovirus particles are formed by a budding process coordinated by viral matrix m proteins m proteins coalesce at sites underlying infected cell membranes and induce other viral components including viral glycoproteins and viral ribonucleoprotein complexes vrnps to assemble at these locations from which particles bud m proteins interact with the nucleocapsid np or n components of vrnps and these interactions enable production of infectious genome containing virions for the paramyxoviruses parainfluenza virus 5 piv5 and mumps virus m np interaction also contributes to efficient production of virus like particles vlps in transfected cells a dld sequence near the c terminal end of piv5 np protein was previously found to be necessary for m np interaction and efficient vlp production here we demonstrate that 15 residue long dld containing sequences derived from either the piv5 or nipah virus nucleocapsid protein c terminal ends are sufficient to direct packaging of a foreign protein renilla luciferase into budding vlps mumps virus np protein harbors dwd in place of the dld sequence found in piv5 np protein and consequently piv5 np protein is incompatible with mumps virus m protein a single amino acid change converting dld to dwd within piv5 np protein induced compatibility between these proteins and allowed efficient production of mumps vlps our data suggest a model in which paramyxoviruses share an overall common strategy for directing m np interactions but with important variations contained within dld like sequences that play key roles in defining m np protein compatibilities paramyxoviruses are responsible for a wide range of diseases that affect both humans and animals paramyxovirus pathogens include measles virus mumps virus human respiratory syncytial virus and the zoonotic paramyxoviruses nipah virus and hendra virus infectivity of paramyxovirus particles depends on matrix nucleocapsid protein interactions which enable efficient packaging of encapsidated viral rna genomes into budding virions in this study we have defined regions near the c terminal ends of paramyxovirus nucleocapsid proteins that are important for matrix protein interaction and that are sufficient to direct a foreign protein into budding particles these results advance our basic understanding of paramyxovirus genome packaging interactions and also have implications for the potential use of virus like particles as protein delivery tools the human cytomegalovirus hcmv gene ul111a encodes cytomegalovirus encoded human interleukin 10 cmvil 10 a homolog of the potent immunomodulatory cytokine human interleukin 10 hil 10 this viral homolog exhibits a range of immunomodulatory functions including suppression of proinflammatory cytokine production and dendritic cell dc maturation as well as inhibition of major histocompatibility complex mhc class i and class ii here we present data showing that cmvil 10 upregulates hil 10 and we identify cd14 monocytes and monocyte derived macrophages and dcs as major sources of hil 10 secretion in response to cmvil 10 monocyte activation was not a prerequisite for cmvil 10 mediated upregulation of hil 10 which was dose dependent and controlled at the transcriptional level furthermore cmvil 10 upregulated expression of tumor progression locus 2 tpl2 which is a regulator of the positive hil 10 feedback loop whereas expression of a negative regulator of the hil 10 feedback loop dual specificity phosphatase 1 dusp1 remained unchanged engagement of the hil 10 receptor hil 10r by cmvil 10 led to upregulation of heme oxygenase 1 ho 1 an enzyme linked with suppression of inflammatory responses and this upregulation was required for cmvil 10 mediated upregulation of hil 10 we also demonstrate an important role for both phosphatidylinositol 3 kinase pi3k and stat3 in the upregulation of ho 1 and hil 10 by cmvil 10 in addition to upregulating hil 10 cmvil 10 could exert a direct immunomodulatory function as demonstrated by its capacity to upregulate expression of cell surface cd163 when hil 10 was neutralized this study identifies a mechanistic basis for cmvil 10 function including the capacity of this viral cytokine to potentially amplify its immunosuppressive impact by upregulating hil 10 expression human cytomegalovirus hcmv is a large double stranded dna virus that causes significant human disease particularly in the congenital setting and in solid organ and hematopoietic stem cell transplant patients a prominent feature of hcmv is the wide range of viral gene products that it encodes which function to modulate host defenses one of these is cmvil 10 which is a homolog of the potent immunomodulatory cytokine human interleukin 10 hil 10 in this study we report that in addition to exerting a direct biological impact cmvil 10 upregulates the expression of hil 10 by primary blood derived monocytes and that it does so by modulating existing cellular pathways this capacity of cmvil 10 to upregulate hil 10 represents a mechanism by which hcmv may amplify its immunomodulatory impact during infection several members of the arenaviridae can cause acute febrile diseases in humans often resulting in lethality the use of convalescent phase human plasma is an effective treatment in humans infected with arenaviruses particularly species found in south america despite this little work has focused on developing potent and defined immunotherapeutics against arenaviruses in the present study we produced arenavirus neutralizing antibodies by dna vaccination of rabbits with plasmids encoding the full length glycoprotein precursors of jun\xedn virus junv machupo virus macv and guanarito virus gtov geometric mean neutralizing antibody titers as measured by the 50 plaque reduction neutralization test prnt 50 exceeded 5 000 against homologous viruses antisera against each targeted virus exhibited limited cross species binding and to a lesser extent cross neutralization anti junv glycoprotein rabbit antiserum protected hartley guinea pigs from lethal intraperitoneal infection with junv strain romero when the antiserum was administered 2 days after challenge and provided some protection \u223c30 when administered 4 days after challenge treatment starting on day 6 did not protect animals we further formulated an igg antibody cocktail by combining anti junv macv and gtov antibodies produced in dna vaccinated rabbits this cocktail protected 100 of guinea pigs against junv and gtov lethal disease we then expanded on this cocktail approach by simultaneously vaccinating rabbits with a combination of plasmids encoding glycoproteins from junv macv gtov and sabia virus sabv sera collected from rabbits vaccinated with the combination vaccine neutralized all four targets these findings support the concept of using a dna vaccine approach to generate a potent pan arenavirus immunotherapeutic arenaviruses are an important family of emerging viruses in infected humans convalescent phase plasma containing neutralizing antibodies can mitigate the severity of disease caused by arenaviruses particularly species found in south america because of variations in potency of the human derived product limited availability and safety concerns this treatment option has essentially been abandoned accordingly despite this approach being an effective postinfection treatment option research on novel approaches to produce potent polyclonal antibody based therapies have been deficient here we show that dna based vaccine technology can be used to make potently neutralizing antibodies in rabbits that exclusively target the glycoproteins of several human pathogenic arenaviruses found in south america including junv macv gtov and sabv these antibodies protected guinea pigs from lethal disease when given post virus challenge we also generated a purified antibody cocktail with antibodies targeting three arenaviruses and demonstrated protective efficacy against all three targets our findings demonstrate that use of the dna vaccine technology could be used to produce candidate antiarenavirus neutralizing antibody based products infected macrophages in spinal cords of mice persistently infected with theiler s murine encephalomyelitis virus tmev undergo apoptosis resulting in restricted virus yields as do infected macrophages in culture apoptosis of murine macrophages in culture occurs via the intrinsic pathway later in infection 10 h postinfection p i after maximal virus titers 150 to 200 pfu cell have been reached with loss of most infectious virus 5 pfu cell by 20 to 24 h p i here we show that bean virus rna replication translation polyprotein processing into final protein products and assembly of protomers and pentamers in infected m1 d macrophages did not differ from those processes in tmev infected bhk 21 cells which undergo necroptosis however the initial difference from bhk 21 cell infection was seen at 10 to 12 h p i where virions from the 160s peak in sucrose gradients had incompletely processed vp0 compared to that in infected bhk 21 cells thereafter there was a gradual loss of the 160s virion peak in sucrose gradients with replacement by a 216s peak that was observed to contain pentamers among lipid debris in negatively stained grids by electron microscopy after infection or incubation of purified virions with activated caspase 3 in vitro 13 and 17 kda capsid peptide fragments were observed and were predicted by algorithms to contain cleavage sites within proteins by cysteine dependent aspartate directed proteases these findings suggest that caspase cleavage of sites in exposed capsid loops of assembled virions occurs contemporaneously with the onset and progression of apoptosis later in the infection theiler s murine encephalomyelitis virus tmev infection in mice results in establishment of virus persistence in the central nervous system and chronic inflammatory demyelinating disease providing an experimental animal model for multiple sclerosis virus persistence takes place primarily in macrophages recruited into the spinal cord that undergo apoptosis and in turn may facilitate viral spread via infected apoptotic blebs infection of murine macrophages in culture results in restricted virus yields late in infection here it is shown that the early steps of the virus life cycle in infected macrophages in vitro do not differ from these processes in tmev infected bhk 21 cells which undergo necroptosis however the findings late in infection suggest that caspases cleave sites in exposed capsid loops and possibly internal sites of assembled virions occurring contemporaneously with onset and progression of apoptosis mechanistically this would explain the dramatic loss in virus yields during tmev induced apoptosis and attenuate the virus enabling persistence niclosamide 5 chloro salicyl 2 chloro 4 nitro anilide is an oral anthelmintic drug used for treating intestinal infection of most tapeworms recently niclosamide was shown to have considerable efficacy against some tumor cell lines including colorectal prostate and breast cancers and acute myelogenous leukemia specifically the drug was identified as a potent inhibitor of signal transducer and activator of transcription 3 stat3 which is associated with osteoclast differentiation and function in this study we assessed the effect of niclosamide on osteoclastogenesis in vitro and in vivo our in vitro study showed that receptor activator of nuclear factor kappab ligand rankl induced osteoclast differentiation was inhibited by niclosamide due to inhibition of serine threonine protein kinase akt phosphorylation inhibitor of nuclear factor kappab i\u03bab and stat3 serine 727 niclosamide decreased the expression of the major transcription factors c fos and nfatc1 and thereafter abrogated the mrna expression of osteoclast specific genes including trap oscar \u03b1v \u03b23 integrin integrin \u03b1v integrin \u03b23 and cathepsin k ctsk in an in vivo model niclosamide prevented lipopolysaccharide induced bone loss by diminishing osteoclast activity taken together our results show that niclosamide is effective in suppressing osteoclastogenesis and may be considered as a new and safe therapeutic candidate for the clinical treatment of osteoclast related diseases such as osteoporosis the atypical protein kinase c isoform prkc iota prkci plays a key role in cell proliferation differentiation and carcinogenesis and it has been shown to be a human oncogene here we show that prkci overexpression in u2os cells impaired functional autophagy in normal or cell stress conditions as characterized by decreased levels of light chain 3b ii protein lc3b ii and weakened degradation of endogenous and exogenous autophagic substrates conversely prkci knockdown by small interference rna resulted in opposite effects additionally we identified two novel prkci mutants prkci l485m and prkci p560r which induced autophagy and exhibited dominant negative effects further studies indicated that prkci knockdown mediated autophagy was associated with the inactivation of phosphatidylinositol 3 kinase alpha akt mammalian target of rapamycin pik3ca akt mtor signaling these data underscore the importance of prkci in the regulation of autophagy moreover the finding may be useful in treating prkci overexpressing carcinomas that are characterized by increased levels of autophagy rab11 family interacting proteins rab11 fips belong to an evolutionarily conserved protein family and act as effector molecules for the rab11 family of small gtpases recent evidence suggests that rab11 fips have important roles in tumor progression and metastasis however the contribution of rab11 fips to colorectal carcinoma crc remains elusive our study focuses on elucidating the role of rab11 fip2 in the migration and invasion of colorectal cancer cells we firstly found upregulation of rab11 fip2 in crc tissues compared with peritumor tissues by oncomine data mining analysis western blot analysis and immunohistochemistry ihc analysis respectively then we demonstrated that knockdown of rab11 fip2 via sirnas transfection resulted in a decrease in migration and invasion of crc cells while overexpression of rab11 fip2 via lentiviral infection increased migration and invasion of crc cells in addition we verified that rab11 fip2 promoted migration and invasion of crc cells through upregulating mmp7 expression finally using several kinase inhibitors our results showed that rab11 fip2 regulated mmp7 expression through activating pi3k akt signaling our data suggested a potential role of rab11 fip2 in tumor progression and provided novel insights into the mechanism of how rab11 fip2 positively regulated cell migration and invasion in crc cells one of the proteins encoded by the foot and mouth disease virus fmdv the vp1 protein a capsid protein plays an important role in integrin receptor attachment and humoral immunity mediated host responses the integrin receptor recognition motif and an important antigenic epitope exist within the g h loop which is comprised of amino acids 134 160 of the vp1 protein fmdv strain asia1 hn cha 06 isolated from a pig was passaged four times in suckling mice and sequenced sequencing analyses showed that there was a mutation of the integrin receptor recognition motif arg gly asp arg asp asp rgd rdd vp1 143 145 and a vp1 154 serine asp vp1 s154d mutation in the g h loop of the vp1 protein the influence of the rgd rdd mutation on asia1 fmdv disease phenotype has been previously studied in this study to determine the influence of the vp1 s154d mutation on fmdv asia1 replication and pathogenicity two recombinant fmdvs with different residues only at the vp1 154 site were rescued by reverse genetics techniques and their infectious potential in host cells and pathogenicity in pigs were compared our data indicates that the vp1 s154d mutation increases the replication level of fmdv asia1 hn cha 06 in bhk 21 ib rs 2 and pk 15 cells and enhances pathogenicity in pigs through the transient transfection infection assay to compare integrin receptor usage of two recombinant viruses the result shows that the vp1 s154d mutation markedly increases the ability of type asia1 fmdv to use the integrin receptors \u03b1\u03c5\u03b26 and \u03b1\u03c5\u03b28 from pig this study identifies a key research target for illuminating the role of residues located at g h loop in fmdv pathogenicity newcastle disease is caused by virulent forms of avian paramyxovirus of serotype 1 apmv 1 and has global economic importance the disease reached panzootic proportions within two decades after first being identified in 1926 in the united kingdom and indonesia and still remains endemic in many countries across the world here we review information on the host temporal and geographic distribution of apmv 1 genetic diversity based on the evolutionary systematics of the complete coding region of the fusion gene strains of apmv 1 are phylogenetically separated into two classes class i and class ii and further classified into genotypes based on genetic differences class i viruses are genetically less diverse generally present in wild waterfowl and are of low virulence class ii viruses are genetically and phenotypically more diverse frequently isolated from poultry with occasional spillovers into wild birds and exhibit a wider range of virulence waterfowl cormorants and pigeons are natural reservoirs of all apmv 1 pathotypes except viscerotropic velogenic viruses for which natural reservoirs have not been identified genotypes i and ii within class ii include isolates of high and low virulence the latter often being used as vaccines viruses of genotypes iii and ix that emerged decades ago are now isolated rarely but may be found in domestic and wild birds in china containing only virulent viruses and responsible for the majority of recent outbreaks in poultry and wild birds viruses from genotypes v vi and vii are highly mobile and have been isolated on different continents conversely virulent viruses of genotypes xi madagascar xiii mainly southwest asia xvi north america and xiv xvii and xviii africa appear to have a more limited geographic distribution and have been isolated predominantly from poultry anterior cruciate ligament reconstruction aclr is a commonly performed procedure that is highly successful in restoring knee stability and function the incidence of early aclr complications and the risk factors for these complications are not well defined to determine the incidence of 30 day complications and patient and surgical risk factors for complications after aclr cohort study level of evidence 3 patients who underwent aclr between 2005 and 2013 were identified in the american college of surgeons national surgical quality improvement program nsqip database using current procedural terminology billing codes postoperative complications in the 30 day period after surgery were identified potential patient and surgical risk factors for 30 day complications after aclr were analyzed using univariate and multivariate analyses a total of 4933 patients were identified major complications occurred in 27 patients 0 55 and minor complications occurred in 43 patients 0 87 with overall complications occurring in 66 patients 1 34 the most common complications were symptomatic deep venous thrombosis requiring treatment n 27 0 55 return to the operating room n 18 0 36 superficial infections n 10 0 20 deep infections n 7 0 14 and pulmonary embolism n 6 0 12 a single mortality 0 02 occurred multivariate analyses demonstrated that smoking dyspnea a history of chronic obstructive pulmonary disease and recent weight loss were all risk factors for the development of overall complications although in combination these factors accounted for only 3 of the variance in the complication rate aclr has a low incidence of complications 1 34 in the early postoperative period with the most common being symptomatic venous thromboembolic disease requiring treatment return to the operating room and infections because aclr is an elective procedure surgeons should use this information to counsel patients on risks and to guide their decision making about patient selection to investigate the effect of toll like receptor 2 tlr2 on the inhibition role of sevoflurane on airway inflammation in asthmatic mice the lung tissue samples of c 57 bl 6 mice used in this study were from previous research including control group asthma group and sevoflurane group 8 samples in each group twenty four specific pathogen free female tlr2 gene deletion tlr2 mice were randomly assigned to control group asthma group and sevoflurane group with 8 mice in each group asthma group and sevoflurane group were then sensitized and challenged with ovalbumin ova to establish asthma model combined with repeated inhalation of 3 sevoflurane in sevoflurane group in c 57 mice expression levels of tlr2 were detected using western blotting analyses in tlr2 mice numbers of differential inflammatory cells were investigated levels of tumor necrosis factor alpha tnf \u03b1 and interleukin 10 il 10 in bronchoalveolar lavage fluid balf were measured by enzyme linked immunosorbent assay elisa lung tissue inflammation was detected with he staining in lung tissues from c 57 mice levels of protein expression of tlr2 in asthma group 0 547 \xb10 042 were higher than those in control group 0 312 \xb10 023 p 0 023 and sevoflurane group 0 287 \xb10 033 p 0 020 in tlr2 mice the number of total cells 83 13 \xb119 43 \xd710 3 ml numbers of differential inflammatory cells and tnf \u03b1 level 546 \xb116 pg ml in balf in sevoflurane group were lower than those in asthma group 206 43 \xb141 82 \xd710 3 ml 732 \xb141 pg ml but still higher than those in control group 44 64 \xb17 17 \xd710 3 ml 380 \xb124 pg ml all p 0 05 lung tissue inflammation was inhibited in sevoflurane group than in asthma group but still more obvious than that in control group toll like receptor 2 involved in the anti inflammatory effect of sevoflurane on asthmatic airway inflammation in mice to evaluate the prevalence of asymptomatic carotid artery stenosis in patients with arteriosclerosis obliterans of lower extremities and evaluate its effect on the treatment strategies for lower extremity artery lesions totally 348 patients with arteriosclerosis obliterans of lower extremities who had no cerebrovascular symptoms or events in the past were enrolled from september 2012 to september 2014 in the department of vascular surgery peking union medical college hospital preoperative color doppler ultrasonography results of carotid arteries and demographic characteristics were retrospectively collected the peak systolic velocity and the presence of plaque on gray scale in the internal carotid arteries were used for diagnosing and grading internal carotid artery stenosis a stenosis \u226550 was diagnosed as carotid artery stenosis binary logistic regression analysis was used to evaluate related risk factors treatment strategies for the artery lesions of lower extremities were compared between those with and without asymptomatic carotid artery stenosis seventy seven 22 1 patients were found to have carotid artery stenosis forty four 12 6 patients were found to have a stenosis \u226570 or occlusion smoking or 2 122 95 ci 1 143 3 940 coronary artery disease or 1 939 95 ci 1 058 3 552 and hypertension or 1 882 95 ci 1 025 3 457 were found to be related risk factors in patients combined with asymptomatic carotid stenosis open surgery with general anesthesia was less frequently used than those without asymptomatic carotid stenosis 6 5 vs 18 1 \u03c7 2 6 142 p 0 013 prevalence of asymptomatic carotid artery stenosis is high in patients with arteriosclerosis obliterans of lower extremities smoking coronary artery disease and hypertension are related risk factors to evaluate the safety and prognosis of allogenetic stem cells transplantation in younger patients with multiple myeloma we retrospectively investigated 32 young patients median age 45 years diagnosed with multiple myeloma and received allogenetic stem cells transplantation in changzheng hospital the non relapse mortality disease related mortality incidences of acute and chronic graft versus host disease gvhd and survivals of the patients were analyzed transplantation was successful in 31 of all the patients response could be evaluated in 28 patients the complete response cr rate before transplantation was 25 0 8 32 which rose to 82 1 23 28 after transplantation and 53 1 17 32 of the patients developed acute gvhd with 43 8 14 32 developing grade \u2170- \u2171; 40 6 13 32 of the patients developed chronic gvhd with no extensive one the median follow up time was 18 1 0 4 145 8 months sixteen patients died including 10 cases of non relapse deaths and 6 cases of disease related deaths the non relapse mortality within 100 days was 9 4 3 32 the 1 2 and 3 year non relapse mortality rates were 21 9 7 32 28 1 9 32 and 31 3 10 32 respectively the common causes of non relapse mortality were pulmonary infection 7 10 acute gvhd 1 10 acute renal failure 1 10 and acute myocardial infarction 1 10 the disease related mortality was 18 8 6 32 the 1 2 and 3 year progression free survival rates were 61 6 42 2 and 37 5 respectively the median duration of progression free survival was 20 3 months the 1 2 and 3 years overall survival were 68 4 52 4 and 42 8 respectively the median duration of overall survival was 28 3 months patients that survived for over 2 years were all alive at the end of the follow up allogenetic stem cell transplantation may be a promising curative therapeutic choice for young multiple myeloma patients transplantation related death is the primary factor of prognosis pulmonary infection with infectious shock is the most common cause of non relapse mortality prevention of infection after transplantation is the key to improve survivals to improve knowledge about the clinical and pathological features of diffuse alveolar hemorrhage dah six cases dah with intact clinical and pathological data were retrospectively analyzed during the period from may 1999 to may 2015 in beijing hospital there were altogether 2 males and 4 females with age ranging from 32 to 68 years mean 58 8 years specimens were obtained by autopsy 3 cases open lung biopsy 2 cases and renal biopsy 2 cases including 1 case of open lung biopsy in 2003 renal biopsy in 2012 clinically the patients presented with cough shortness of breath and dyspnea including 5 cases of hemoptysis 4 cases of fever 3 cases of skin and mucosa bleeding 2 cases of gross hematuria 2 cases of microscopic hematuria 3 cases of renal functional impairment a total of 5 cases had different levels of elevated erythrocyte sedimentation rate and c reactive protein 6 cases had moderate anemia hypoxemia diffuse infiltrates with alveolar filling in chest ct serum antineutrophil cytoplasmic antibody was positive in 3 cases anti glomerular basement membrane antibody was present in 1 case pathological diagnosis 2 cases of granulomatosis with polyangiitis gpa 2 cases of microscopic polyangiitis mpa 1 case of goodpasture syndrome 1 case of pulmonary veno occlusive disease pvod 3 cases died 2 cases were discharged 1 case received symptomatic treatment follow up after discharge the mainly clinical characteristics of dah are varied degree of dyspnea anemia hypoxemia and extensive ground glass opacification or consolidation in image with or without haemoptysis diffuse acute or chronic pulmonary hemorrhage in lung tissue is the main pathological feature to investigate the relationship between interleukin 8 levels in expressed prostatic secretion and expressions of basic fibroblast growth factor bfgf and bcl 2 in benign prostatic hyperplasia bph a series of 50 consecutive patients diagnosed with bph and scheduled for transurethral resection of the prostate turp were included patients were divided into two groups simple bph and bph with chronic prostatitis cp the grade of inflammatory changes in the prostate was then determined blindly by two experienced pathologists according to the classification system expressed prostatic secretion eps was collected right before turp for il 8 detection using elisa kits the resected prostatic tissue was harvested for immunohistochemistry to measure the expression of bcl 2 and bfgf a total of 30 60 patients were confirmed to have prostatic histologic inflammation the volume of the prostate in bph with cp was obviously larger than that in simple bph p 0 022 the nih chronic prostatitis symptom index nih cpsi and international prostate symptom score ipss of bph with cp were both higher than those of simple bph p 0 05 significantly increased levels of il 8 were observed in eps obtained from bph patients with cp mean level 43 29 ng l compared with patients with simple bph mean level 36 90 ng l p 0 003 the expression of bcl 2 in bph with cp mean level 6 17 increased significantly compared with those in simple bph mean level 2 45 p 0 013 the expression of bfgf in bph with cp mean level 7 57 also obviously elevated compared with those in simple bph mean level 5 05 p 0 008 correlation coefficients of il 8 levels in eps and expression of bcl 2 or bfgf indicated that il 8 had strong correlation with bcl 2 and bfgf respectively both in simple bph and bph with cp 0 r 1 p 0 05 il 8 bcl 2 and bfgf are significantly up regulated in bph with cp patients compared with simple bph patients inflammation might play an important role in the outcome and development of benign prostatic hyperplasia and makes it more severe chronic kidney disease ckd is a significant disease in cats identifying risk and protective factors may help to prevent this significant disease an age matched case control study was performed to determine the risk factors in cats with naturally occurring ckd twenty nine clinically normal cats aged \u2a7e5 years and 101 cats with naturally occurring ckd were studied risk factors were determined by interviewing cat owners from the small animal hospital faculty of veterinary science chulalongkorn university and veterinary hospitals in the bangkok metropolitan area through questionnaires completed between june 2004 and november 2014 univariable and multivariable analyses were performed using two independent proportional test methods and logistic regression analysis with backward elimination male sex odd ratios or 2 80 95 confidence interval ci 1 02 8 87 p 0 02 tap water or 3 43 95 ci 1 08 11 45 p 0 03 and an outdoor lifestyle or 3 77 95 ci 1 03 17 99 p 0 04 were associated with an increased risk for ckd commercial dry cat food or 0 06 95 ci 0 02 0 17 p 0 00 filtered water or 0 13 95 ci 0 03 0 52 p 0 01 and an indoor lifestyle or 0 28 95 ci 0 07 0 98 p 0 02 were associated with a decreased risk logistic regression analysis using backward elimination demonstrated that cats fed with commercial dry cat food or 0 042 95 ci 0 01 0 17 p 0 00 had a decreased risk for ckd compared with cats on other types of diet multivariable analysis found only feeding commercial dry cat food to be significant suggesting that commercial dry cat food may be the potential protective factor for ckd in cats manipulation of the intestinal microbiota has been linked to weight changes and obesity to explore the influence of specific agents that alter the intestinal flora on weight in different patient groups we conducted a meta analysis of randomized controlled trials rcts reporting on the effects of probiotics prebiotics synbiotics and antibiotics on weight we searched the pubmed and cochrane library databases for trials on adults children and infants evaluating the effects of these substances on weight our primary outcome was weight change from baseline standardized mean differences smds with 95 confidence intervals were calculated we identified and included 13 adult 17 children and 23 infant rcts effects were opposite among adults and children showing weight loss among adults smd 0 54 0 83 0 25 and minor weight gains among children smd 0 20 0 04 0 36 and infants smd 0 30 0 01 0 62 taking mainly lactobacillus probiotic supplements heterogeneity was substantial in the adult and infant analyses and could not be explained by intervention or patient characteristics azithromycin administration in children with pulmonary disease was associated with weight gain smd 0 39 0 24 0 54 without heterogeneity a high risk of selective reporting and attrition bias was detected across the studies making it difficult to draw firm conclusions overall our meta analysis suggests that there may be a role for probiotics in promoting weight loss in adults and weight gain in children however additional studies are needed though we cannot recommend antibiotic administration for weight manipulation its use provides advantageous weight gain in children with cystic fibrosis and bronchiectasis home grown school feeding programmes are complex interventions with the potential to link the increased demand for school feeding goods and services to community based stakeholders including smallholder farmers and women s groups there is limited rigorous evidence however that this is the case in practice this evaluation will examine explicitly and from a holistic perspective the simultaneous impact of a national school meals programme on micronutrient status alongside outcomes in nutrition education and agriculture domains the 3 year study involves a cluster randomised control trial designed around the scale up of the national school feeding programme including 116 primary schools in 58 districts in ghana the randomly assigned interventions are 1 a school feeding programme group including schools and communities where the standard government programme is implemented 2 home grown school feeding including schools and communities where the standard programme is implemented alongside an innovative pilot project aimed at enhancing nutrition and agriculture and 3 a control group including schools and households from communities where the intervention will be delayed by at least 3 years preferably without informing schools and households primary outcomes include child health and nutritional status school participation and learning and smallholder farmer income intermediate outcomes along the agriculture and nutrition pathways will also be measured the evaluation will follow a mixed method approach including child household school and community level surveys as well as focus group discussions with project stakeholders the baseline survey was completed in august 2013 and the endline survey is planned for november 2015 the tests of balance show significant differences in the means of a number of outcome and control variables across the intervention groups important differences across groups include marketed surplus livestock income per capita food consumption and intake school attendance and anthropometric status in the 2 5 and 5 15 years age groups in addition approximately 19 of children in the target age group received some form of free school meals at baseline designing and implementing the evaluation of complex interventions is in itself a complex undertaking involving a multi disciplinary research team working in close collaboration with programme and policy level stakeholders managing the complexity from an analytical and operational perspective is an important challenge the analysis of the baseline data indicates that the random allocation process did not achieve statistically comparable treatment groups differences in outcomes and control variables across groups will be controlled for when estimating treatment effects isrctn66918874 registered on 5 march 2015 small airway remodeling is an important cause of the airflow limitation in chronic obstructive pulmonary disease copd a large population of patients with copd also have pulmonary hypertension kr\xfcppel like factor 5 klf5 is a zinc finger transcription factor that contributes to tissue remodeling in cardiovascular diseases here we evaluate the possible involvement of klf5 in the remodeling of small airways and pulmonary vessels in copd lung tissues were obtained from 23 control never smokers 17 control ex smokers and 24 ex smokers with copd the expression of klf5 in the lung tissues was investigated by immunohistochemistry we investigated whether oxidative nitrosative stress which is a major cause of the pathogenesis in copd could augment the production of klf5 we examined the role of klf5 in the stress mediated tissue remodeling responses we also investigated the susceptibility of klf5 expression to nitrosative stress using bronchial fibroblasts isolated from the lung tissues the expression of klf5 was up regulated in the small airways and pulmonary vessels of the copd patients and it was mainly expressed in bronchial fibroblasts and cells of the pulmonary vessels the extent of the klf5 expression in the small airway of the copd group had a significant correlation with the severity of the airflow limitation oxidative nitrosative stress augmented the production of klf5 in lung fibroblasts as well as the translocation of klf5 into the nuclei silencing of klf5 suppressed the stress augmented differentiation into myofibroblasts the release of collagens and metalloproteinases bronchial fibroblasts from the patients with copd highly expressed klf5 compared to those from the control subjects under basal condition and were more susceptible to the induction of klf5 expression by nitrosative stress compared to those from the control subjects we provide the first evidence that the expression of klf5 is up regulated in small airways and pulmonary vessels of patients with copd and may be involved in the tissue remodeling of copd pancreatic cystic neoplasms pcn with malignant potential are thought to be less aggressive than ordinary ductal adenocarcinoma even in the setting of malignant transformation therefore deciding whether or not to carry out surgery is very difficult especially in elderly and asymptomatic patients because of the high risk of perioperative morbidities the aim of the present study was to examine clinical outcomes of pcn patients aged 65 years or older this retrospective analysis included patients with incidentally detected pcn with follow up durations 1 year patients diagnosed with obvious simple cysts pseudocysts or pancreatic cancer and patients with a history of pancreatic disease were excluded from the study the present study included 201 patients older group 104 patients \u226565 years younger group 97 patients 65 years surgical resections were carried out for 27 patients in the older group and 41 patients in the younger group there were 133 patients who were followed up without surgery mean follow up duration 41 months postoperative morbidity occurred in 22 2 of the patients in the older group and 21 9 of the patients in the younger group malignancy occurred in one patient in the older group and in two patients in the younger group the pcn diameter increased in 20 patients during follow up 16 9 of the older group and 12 5 of the younger group the malignancy rate was very low in incidental pcn patients irrespective of age follow up observation without surgery appears to be a safe option in older patients with morbidity geriatr gerontol int 2016 \u25cf\u25cf: \u25cf\u25cf- \u25cf\u25cf. the transgenic and knockout ko animals involving fgf23 have been highly informative in defining novel aspects of mineral metabolism but are limited by shortened lifespan inability of spatial temporal fgf23 control and infertility of the global ko to more finely test the role of systemic and genetic influences in fgf23 production a mouse was developed that carried a floxed f fgf23 allele exon 2 floxed which demonstrated in vivo recombination when bred to global cre transgenic mice eiia cre mice homozygous for the recombined allele \u03b4 had undetectable serum intact fgf23 elevated serum phosphate p 0 05 and increased kidney cyp27b1 mrna p 0 05 similar to global fgf23 ko mice to isolate cellular fgf23 responses during phosphate challenge fgf23 \u03b4 f mice were mated with early osteoblast type i\u03b11 collagen 2 3 kb promoter cre mice col2 3 cre and the late osteoblast early osteocyte dentin matrix protein 1 cre dmp1 cre fgf23 \u03b4 f col2 3 cre and fgf23 \u03b4 f dmp1 cre exhibited reduced baseline serum intact fgf23 versus controls after challenge with high phosphate diet cre mice had 2 1 fold to 2 5 fold increased serum fgf23 p 0 01 but col2 3 cre mice had no significant increase and dmp1 cre mice had only a 37 increase p 0 01 despite prevailing hyperphosphatemia in both models the fgf23 \u03b4 f col2 3 cre was bred onto the hyp murine x linked hypophosphatemia xlh model genetic background to test the contribution of osteoblasts and osteocytes to elevated fgf23 and hyp disease phenotypes whereas hyp mice maintained inappropriately elevated fgf23 considering their marked hypophosphatemia hyp fgf23 \u03b4 f col2 3 cre mice had serum fgf23 4 of hyp p 0 01 and this targeted restriction normalized serum phosphorus and ricketic bone disease in summary deleting fgf23 within early osteoblasts and osteocytes demonstrated that both cell types contribute to baseline circulating fgf23 concentrations and that targeting osteoblasts osteocytes for fgf23 production can modify systemic responses to changes in serum phosphate concentrations and rescue the hyp genetic syndrome 2016 american society for bone and mineral research incidence and prevalence estimates of acromegaly in the united states us are limited most existing reports are based on european data sources the objective of this study was to estimate the annual incidence and prevalence of acromegaly in a large us managed care population overall and stratified by age sex and geographic region using data from 2008 to 2012 using administrative claims data commercial health plan enrollees were identified with acromegaly if they had two or more medical claims with an acromegaly diagnosis code icd 9 cm 253 0 \xd7) or one medical claim with an acromegaly diagnosis code in combination with one other claim for a pituitary tumor or pituitary procedure the first date for an acromegaly related claim set the index year incidence rates for each year were calculated by dividing the number of new acromegaly cases by the calculated person time at risk annual prevalence estimates were calculated by dividing the number with any evidence of acromegaly by the total number of health plan enrollees enrolled for at least 1 day during each calendar year incidence and prevalence estimates were stratified by age 0 17 18 44 45 64 65 years sex male female and us geographic region of the health plan midwest northeast south west overall annual incidence rates of acromegaly were relatively constant across 2008 2012 with 11 cases per million person years pmpy rates increased with age ranging from 3 8 cases pmpy among children aged 0 17 years old to 9 18 cases pmpy among adults aged 65 and older females had 12 cases pmpy on average compared to 10 cases pmpy among men on average the midwest had the lowest incidence rates 7 cases pmpy compared to the northeast south and west 14 12 and 10 cases pmpy respectively the overall annual prevalence of acromegaly was relatively constant across the 5 years from 2008 to 2012 with approximately 78 cases per million each year annual prevalence estimates increased with age ranging from 29 37 cases per million among children aged 0 17 years old to 148 182 cases per million among adults aged 65 years and older males and females were similarly affected each with approximately 77 cases per million each year the northeast and south had the highest prevalence estimates 92 and 89 cases per million respectively while the estimates for the west and midwest were lower 65 and 57 cases per million respectively each year this study examined 5 years of recent data to estimate the incidence and prevalence of acromegaly in a large geographically diverse managed care population the incidence rates were higher on average than published rates outside the us 11 vs 3 3 pmpy but prevalence estimates were consistent with previous reports incidence and prevalence both increased by age did not differ for males and females and varied slightly by us geographic region the age and sex distribution of the selected population matched the known epidemiology of the disease using a claims based approach this analysis only captured acromegaly cases with an acromegaly related medical claim as a result these estimates may underestimate the incidence and prevalence of acromegaly in us commercial health plans as they did not include individuals who were undiagnosed in remission undertreated or not monitored during the study period at the same time these estimates may be viewed as an upper bound on the incidence of acromegaly in the us as the estimates did not include individuals who were in other health plans or uninsured during the study period additional evaluations are needed to identify the full extent of acromegaly in the us lymphovascular invasion lvi is a histopathological feature that is associated with an increased risk for micrometastasis the aim of this study was to determine the prognostic and staging value of lvi among patients with esophageal squamous cell carcinoma escc undergoing esophagectomy a prospective database of patients with escc was used to retrospectively analyze 666 cases to identify the relationship between lvi and survival and to evaluate predictive accuracy of prognosis after combining lvi and the tumor node and metastasis tnm system pathological slides were reassessed by gastrointestinal pathologists according to the strict criteria 1000 bootstrap resampling was used for internal validation and 222 cases from an independent multicenter database were used for external validation lvi was present in 33 8 of patients and the proportion increased with advancing t and n classification lvi was an independent predictor of unfavorable disease specific survival dss hazard ratio 1 59 95 confidence interval 1 30 1 94 and disease free survival dfs hazard ratio 1 62 95 confidence interval 1 32 1 98 after t classification among node negative patients lvi and t classification were two independent predictors of dss and dfs p 0 001 the risk score model combing lvi and t classification improved the predictive accuracy of the tnm system for dss and dfs by 3 5 and 4 8 respectively p 0 001 the external validation showed congruent results the dss of txn0mo disease with lvi was similar to the dss of txn1m0 both p 0 05 in contrast lvi was not associated with dss or dfs among node positive patients the independent prognostic significance of lvi existed only in node negative patients with escc and the combination of lvi and the tnm system enhanced the predictive accuracy of prognosis after confirmation node negative patients with lvi might be considered for upstaging in pathological staging to evaluate the effect and safety of using thermo sensitive matrigel as artificial ascites on minimizing thermal injury to the nearby structures in a rat model of radiofrequency rf ablation of the liver in this research the morphological characterization of matrigel was observed at different temperatures in vitro in vivo study was conducted by using 42 sd rats in matrigel saline and control groups of 14 rats each artificial ascites with 10 ml of matrigel or saline was produced under ultrasound guidance before rf in the experimental groups using a 0 7 cm exposed 17 g rf electrode for 5 minutes 90 2 \u2103, 41 hepatic ablations was performed abutting the diaphragm abdominal wall and stomach the 41 rats were sacrificed at 24 h and necropsy was performed gross and histopathologic examinations were performed to compare the frequency and extent of thermal injury to the nearby organs the animal status was followed up to achieve long term safety evaluation of matrigel matrigel was in liquid formation at 0 4 \u2103, but was not moving in vials at temperature 37 in 1 min presenting gel formation in vivo experiment the artificial fluid thickness of matrigel in site was significant larger than that of saline group especially at 5 min of ablation 8 1 1 1 mm vs 2 4 0 8 mm p 0 01 thermal injury to the nearby structures was found in 12 of 13 cases in control group 8 of 14 cases p 0 037 in saline group and 1 of 14 cases p 0 01 in matrigel group the sizes of the ablation zone of the liver did not differ among the three groups there was no difference in the incidence of operation related complications among the three groups there was no significant difference in body weight and health related parameters between matrigel and saline group during 60 days of follow up using thermo sensitive matrigel as artificial ascites may be a safe and useful technique and help to further reduce the frequency and severity of collateral thermal injury to the nearby structures compare to conventional saline during rf ablation of subcapsular hepatic tumors to determine whether intramural administration of rapamycin rpm loaded polylactic polyglycolic acid plga nanoparticles nps can reduce intimal thickening and affect the mrna expressions of matrix metalloproteinase mmp 2 tissue inhibitor of metalloproteinase timp 2 and p27 kipl in a coronary injury stenosis model of minipigs twenty eight minipigs were randomly separated into four groups saline group n 7 blank plga nps group 5 0 mg ml n 7 rpm group 1 0 mg ml n 7 and rpm plga nps 5 0 mg ml group n 7 respectively different treatments were intracoronary locally delivered via a dispatch catheter for 10 minutes serial angiography was performed pre and post modeling 30 days and the percent stenosis degree was assessed hematoxylin eosin he staining weigert s resorcin fuchsin staining and picric acid sirius red staining were used for morphometric analysis immunohistochemistry was performed to assess the levels of proliferating cell nuclear antigen pcna mmp 2 and timp 2 at early and late time points respectively the expression of p27 kip1 mrna was detected by in situ hybridization staining data from 21 minipigs had been collected at the end of the experiment with 6 4 5 and 6 from the former mentioned 4 groups respectively for the instant injury index there was no significant difference among the four groups the percent stenosis degree of rpm plga nps group was significantly lower than that of the other three groups respectively all p 0 05 the neointima area net external elastic lamina area to external elastic laminal area ratio and proliferative index of rpm plga nps group were significantly less than those of the other three groups with all the p values less than 0 05 the mean value of integral optical density of p27 kip1 mrna expression of rpm plga group was 0 35 0 06 higher than that of blank plga nps group 0 12 0 05 p 0 01 saline group 0 16 0 03 p 0 05 and rpm group 0 15 0 03 p 0 05 respectively the mmp 2 timp 2 ratio and the positive expression index of pcna in rpm plga group were lower than that of the other groups p 0 05 locally delivered rapamycin loaded plga nps significantly reduces mmp 2 timp 2 ratio and pcna expression increases p27 kip1 mrna expression and significantly relieves percent stenosis degree and shows excellent acute procedural results in the minipig interventional coronary artery oversized balloon injury model the results from minipig model further support that this approach could be a potential clinical procedure for vascular proliferative disease to evaluate the clinical value of swallow tail appearance in detecting the patient with parkinson s disease at 3 0 t mri a total of 42 patients with clinical diagnosis of parkinson s disease pd and 27 age matched normal controls underwent the brain mr examination with conventional and e swan sequences patients were divided into 4 groups based on hoehn yahr stage and 2 groups according the treatment condition treated untreated substantia nigra sn was selected as region of interest roi and observed the swallow tail appearance on magnitude imagines of e swan sequence nonparametric test was used for comparison between patients groups and normal controls there was statistically difference if the p value was lower than 0 05 the swallow tail appearance lost was significantly correlated with parkinson s disease p 0 000 the swallow tail appearance lost was not correlated with the usage of drugs p 0 833 and hoehn yahr stage p 0 189 the sensitivity of diagnosis of pd by using the swallow tail disappearance was 95 5 42 44 the specificity was 83 3 25 30 the accuracy was 90 5 67 74 assessing the substantia nigra on e swan for the typical swallow tail appearance has potential to become a new and easy applicable 3 0 t mri diagnostic tool for pd however it was meaningless for prognosis and staging to explore the effect of brain atrophy on the cognition in patients with subcortical ischemic vascular disease sivd a total of 116 sivd patients were enrolled from the department of neurology first affiliated hospital anhui medical university between september 2013 and december 2014 lobar atrophy leukoaraiosis la lacunar infarcts li and vascular risk factors were analyzed in the 116 sivd patients who were divided into three groups according to the diagnostic criteria non cognitive impairment group sivd nci mild cognitive impairment group sivd mci and dement group sivd vad all patients underwent magnetic resonance imaging mri with a 3 0 t system the cognitive functions were evaluated by mini metal state examination mmse the cambridge cognitive examination chinese version camcog c etc a widely used visual atrophy rating method 0 to 3 was adopted to rate the severity of frontal parietal and temporal lobe atrophy the degree of la and the numbers of li in 4 brain regions frontal parieto occipital temporal and basal ganglia were evaluated meanwhile firstly both the sivd mci and sivd vad groups showed significantly higher total scores of atrophy higher frontal lobe atrophy scores higher la scores and larger li numbers than sivd nci h 6 138 p 0 013 h 45 845 p 0 000 h 36 818 p 0 000 h 37 46 p 0 000 there were no significant differences in temporal lobe atrophy scores between sivd nci group and sivd mci group parietal lobe atrophy scores also showed no differences among the three groups secondly as well as total numbers of li total scores of atrophy and la were negatively correlated with sivd cognition especially frontal lobe atrophy scores parieto occipital la scores and basal ganglia li numbers had a remarkable negative correlation with mmse scores camcog c scores and partial subitems in camcog c scores p 0 005 however temporal li numbers was absence of correlation with mmse scores camcog c scores and subitems in camcog c scores p 0 005 thirdly education or 0 787 p 0 009 total scores of la or 1 201 p 0 036 and total numbers of li or 1 221 p 0 011 remained to be associated with cognition after controlling for sex age education hypertension diabetes smoking while after adjusting atrophy scores total scores of la had no significant association with cognition atrophy scores total numbers of li and education still showed significant association with cognition particularly frontal lobe atrophy scores or 16 082 p 0 000 but not temporal and parietal lobe atrophy scores brain atrophy may be a new and independent predictive index of cognitive impairment in sivd further the effect of brain atrophy the numbers of li and degree of la on cognitive decline is independent and decreases in turn to explore the clinical characteristics of iga nephropathy igan with severe chronic periodontitis and aggressive periodontitis a total of 436 hospitalized patients who underwent renal needle biopsy in the department of nephrology of china japan friendship hospital from november 2013 to december 2014 were recruited in the study and blindly had periodontal examination the patients were divided into igan group and non igan group according to the renal pathology the patients with igan were further categorized as non periodontitis chronic periodontitis and aggressive peridontitis group by haas classification the chronic periodontitis group was continually divided into mild moderate and severe periodontitis group the levels of interleukin il 1\u03b2 and il 6 in gingival crevicular fluid were analyzed by enzyme linked immunosorbent assays the prevalence of periodontitis in the study was 88 3 385 436 the prevalence of chronic periodontitis and aggressive periodontitis were higher in patients with igan than those with non igan p 0 05 degree of chronic periodontitis was correlated with pathologic grading of igan r 0 48 p 0 001 compared with igan patients with other types of periodontitis those with severe chronic and aggressive periodontitis had more severe pathology more frequent recurrent gross hematuria higher levels of 24 h proteinuria serum triglyceride and uric acid higher periodontal probing depth and clinical attatchment level as well as higer levels of il 1\u03b2 and il 6 but had lower creatinine clearance rate all p 0 05 the prevalence of severe chronic and aggressive periodontitis was higher in patients with igan chronic periodontitis is correlated with the onset and development of igan patients with igan have worse condition with the aggravation of periodontitis to analyse the prevalence of hypothyroidism in rheumatoid arthritis ra patients and to elucidate its correlation with disease activity a total of 52 ra patients were enrolled in this study all patients were assessed fully clinically and underwent routine laboratory investigation including thyroid function testing hypothyroidism defined as having a tsh level 4 20 \u03bciu ml was observed in 20 52 38 4 erythrocyte sedimentation rates esr were found significantly elevated in patients with hypothyroidism compared to those without 36 3 24 2 vs 24 6 9 0 mm h disease activity parameters such as das 28 esr tender joint count vas scores were also significantly higher in the former a significant correlation with serum tsh levels was observed with esr and das 28 esr thyroid function test should be included in clinical evaluation of ra patients systemic sclerosis ssc related interstitial lung disease ild has phenotypic similarities to lung involvement in idiopathic interstitial pneumonia iip we aimed to assess whether genetic susceptibility loci recently identified in the large iip genome wide association studies gwass were also risk loci for ssc overall or severity of ild in ssc a total of 2571 ssc patients and 4500 healthy controls were investigated from the us discovery gwas and additional us replication cohorts thirteen iip related selected single nucleotide polymorphisms snps were genotyped and analyzed for their association with ssc we found an association of ssc with the snp rs6793295 in the lrrc34 gene or 1 14 ci 95 1 03 to 1 25 p value 0 009 and rs11191865 in the obfc1 gene or 1 09 ci 95 1 00 to 1 19 p value 0 043 in the discovery cohort additionally rs7934606 in muc2 or 1 24 ci 95 1 01 to 1 52 p value 0 037 was associated with ssc ild defined by imaging however these associations failed to replicate in the validation cohort furthermore snps rs2076295 in dsp \u03b2 2 29 ci 95 3 85 to 0 74 p value 0 004 rs17690703 in sppl2c \u03b2 2 04 ci 95 0 21 to 3 88 p value 0 029 and rs1981997 in mapt \u03b2 2 26 ci 95 0 35 to 4 17 p value 0 02 were associated with percent predicted forced vital capacity fvc even after adjusting for the anti topoisomerase ata positive subset however these associations also did not replicate in the validation cohort our results add new evidence that ssc and ssc related ild are genetically distinct from iip although they share phenotypic similarities the determinants of renal shape are not well established the purpose of this study was to investigate the relationship between the renal shape as measured by ultrasound and the clinical characteristics in chronic kidney disease ckd patients the study included 121 ckd patients who had undergone kidney biopsy the renal shape was defined by 1 the renal shape index renal length renal width renal thickness and 2 the renal width length iga nephritis patients excluding patients with diabetes comprised the largest subgroup n 49 and were analyzed separately the correlation analyses and two sample student s t test results showed that age egfr bmi cortex volume fraction measured by mri cortex volume renal volume percentage of global sclerosis weight sex hypertension and diabetes were significantly correlated with the renal shape in both kidneys in a stepwise multiple linear regression analysis old age and high bmi were independently associated with plump kidney as for the left renal shape index low cortex volume fraction was also independently associated with plump kidney in the iga nephritis patient subgroup the cortex volume fraction was the most significant factor contributing to the left renal shape index r 0 50 p 0 01 and the width length r 0 47 p 0 01 age and bmi were stronger determinants of renal shape than renal function in ckd patients the left renal cortex volume fraction was also an independent determinant and a more important factor in iga nephritis patients the cholinergic nucleus basalis of meynert which is important for memory functions shows neuronal activation up phase during the early stages of alzheimer s disease and neurodegeneration down phase in later stages of alzheimer s disease microrna 132 mir 132 and the transcription factor early growth response 1 egr1 were proposed as possible candidate molecules regulating such an up down activity pattern of the nucleus basalis of meynert during the course of alzheimer s disease as they both show this up down pattern of expression in the prefrontal cortex during the course of alzheimer s disease not only do these two molecules stimulate synaptic activity and plasticity they are also involved in alzheimer s disease pathology and might in addition affect cholinergic function in the nucleus basalis of meynert we investigated the expression of mir 132 and egr1 along the entire course of alzheimer s disease forty nine post mortem nucleus basalis of meynert samples were studied ranging from non demented controls braak stage 0 to late alzheimer s disease patients braak stage vi and from clinical reisberg scale 1 to 7 each braak stage contained seven samples that were all well matched for confounding factors i e age range 58 91 sex post mortem delay cerebrospinal fluid ph as a measure for agonal state apoe genotype clock time of death tissue fixation time and tissue storage time the alterations of these two molecules were studied over the course of alzheimer s disease in relation to the expression of 4g8 stained amyloid \u03b2 hyperphosphorylated tau stained by antibody at8 neuronal fibrillary tangles and neuropil threads stained by silver and in relation to alterations in choline acetyltransferase we found that the expression of mir 132 and egr1 in the nucleus basalis of meynert was quite stable during the early stages of alzheimer s disease and decreased significantly only during late alzheimer s disease stages in addition mir 132 and egr1 showed a significant positive correlation with choline acetyltransferase expression r 0 49 p 0 001 and r 0 61 p 0 001 while choline acetyltransferase expression showed a significantly negative correlation with hyperphosphorylated tau r 0 33 p 0 021 but no correlation with 4g8 stained amyloid \u03b2 from the functional changes of mir 132 and egr1 along the course of alzheimer s disease we conclude i that these two molecules may play a role in keeping the cholinergic function intact in early alzheimer s disease stages and ii that these molecules may contribute to the late neurodegeneration of this cholinergic nucleus splanchnic artery aneurysms saas are uncommon and standards for surveillance and intervention are lacking the goal of this study was to review our 20 year experience with managing saas the research patient data registry at the massachusetts general hospital was queried and all patients with saas identified by axial imaging from 1994 to 2014 were included aneurysms were stratified into two cohorts those that underwent early intervention 6 months after lesion discovery and those that received surveillance primary study end points included aneurysm growth or rupture during surveillance and patient 30 day morbidity or mortality after aneurysm repair there were 264 saas identified in 250 patients in 166 patients 176 saas 66 6 were placed into the surveillance cohort 38 saas 21 6 did not have subsequent axial imaging and were considered lost to follow up mean aneurysm size in the surveillance cohort at first imaging study was 16 28 mm 8 41 mm and mean surveillance time was 36 1 months 2 155 months 126 saas 91 3 remained stable in size over time and 8 saas 5 8 required intervention for aneurysm growth after a mean of 24 months there were no ruptures in the surveillance cohort there were 88 saas 33 3 repaired early mean size of saas that were repaired early was 31 1 mm 10 140 mm for intact saas 30 day morbidity and mortality rates after repair were 13 and 3 respectively in the early repair cohort 13 saas 14 7 were ruptured at presentation the 30 day morbidity and mortality rates after rupture were 54 and 8 respectively five ruptured saas 38 were anatomically located in the pancreaticoduodenal arcade on univariate analysis pancreaticoduodenal aneurysms were strongly associated with rupture p 0002 small saas \u226425 mm are not prone to significant expansion and do not require frequent surveillance imaging imaging every 3 years for small saas is adequate aneurysms of the pancreaticoduodenal arcade and gastroduodenal aneurysms are more likely to rupture and therefore warrant a more aggressive interventional approach thoracoabdominal aortic aneurysm taaa repair remains a challenging clinical pathology endovascular technology in particular the evolution of fenestrated and branched f b endografts used in endovascular aneurysm repair evar has provided a less invasive method of treating these complex aneurysms this study evaluated the technical and clinical outcomes of f b evar for extensive type ii and iii taaa data from 354 high risk patients enrolled in a physician sponsored investigational device exemption trial 2004 2013 undergoing f b evar for type ii and iii taaa were evaluated technical success perioperative clinical outcomes and midterm outcomes 36 months for branch patency reintervention aneurysm related death and all cause mortality were analyzed data are presented as mean standard deviation and were assessed using kaplan meier univariate and multivariate analysis f b evars incorporating 1305 fenestration branches were implanted with 96 of target vessels successfully stented completion aortography showed 2 8 patients had a type i or iii endoleak procedure duration 6 0 1 7 vs 5 5 1 6 hours p 01 and hospital stay 13 1 10 1 vs 10 2 7 4 days p 01 were longer for type ii taaa perioperative mortality was greater in type ii repairs 7 0 vs 3 5 p 001 permanent spinal cord ischemia occurred in 4 and renal failure requiring hemodialysis occurred in 2 8 of patients twenty seven branches 7 6 required reintervention for stenosis or occlusion and celiac artery superior mesenteric artery and renal artery secondary patency at 36 months was 96 95 confidence interval ci 0 93 0 99 98 95 ci 0 97 1 0 and 98 95 ci 0 96 1 0 respectively eighty endoleak repairs were performed in 67 patients including 55 branch related endoleaks 4 type ia 5 type ib and 15 type ii endoleaks at 36 months freedom from aneurysm related death was 91 95 ci 0 88 0 95 and freedom from all cause mortality was 57 95 ci 0 50 0 63 the treatment of type ii taaa p 01 age p 01 and chronic obstructive pulmonary disease p 05 negatively affected survival f b evar is a robust treatment option for patients at increased risk for conventional repair of extensive taaas technical success and branch patency are excellent but some patients will require reintervention for branch related endoleak aneurysm extent portends a higher risk of perioperative and long term morbidity and mortality additional efforts are needed to improve outcomes and understand the utility of this treatment option in the general taaa population mycobacterium tuberculosis mtb infects one third of the world s population and in 2013 accounted for 1 5 million deaths fluoroquinolone antibacterials which target dna gyrase are critical agents used to halt the progression from multidrug resistant tuberculosis to extensively resistant disease however fluoroquinolone resistance is emerging and new ways to bypass resistance are required to better explain known differences in fluoroquinolone action the crystal structures of the wt mtb dna gyrase cleavage core and a fluoroquinolone sensitized mutant were determined in complex with dna and five fluoroquinolones the structures ranging from 2 4 to 2 6 \xe5 resolution show that the intrinsically low susceptibility of mtb to fluoroquinolones correlates with a reduction in contacts to the water shell of an associated magnesium ion which bridges fluoroquinolone gyrase interactions surprisingly the structural data revealed few differences in fluoroquinolone enzyme contacts from drugs that have very different activities against mtb by contrast a stability assay using purified components showed a clear relationship between ternary complex reversibility and inhibitory activities reported with cultured cells collectively our data indicate that the stability of fluoroquinolone dna interactions is a major determinant of fluoroquinolone activity and that moieties that have been appended to the c7 position of different quinolone scaffolds do not take advantage of specific contacts that might be made with the enzyme these concepts point to new approaches for developing quinolone class compounds that have increased potency against mtb and the ability to overcome resistance brain norepinephrine ne plays an important role in the modulation of stress response and neuroinflammation recent studies indicate that in alzheimer s disease ad the tau neuropathology begins in the locus coeruleus lc which is the main source of brain ne therefore we investigated the changes in brain ne system and also the immune status under basal and stress conditions in transgenic rats over expressing the human truncated tau protein brainstem catecholaminergic cell groups lc a1 and a2 and forebrain subcortical nucleus basalis of meynert hippocampal cornu ammonis dentate gyrus and neocortical areas frontal and temporal association cortices were analyzed for ne and interleukin 6 il 6 mrna levels in unstressed rats and also in rats exposed to single or repeated immobilization moreover gene expression of ne biosynthetic enzyme tyrosine hydroxylase th and several pro and anti inflammatory mediators were determined in the lc it was found that tauopathy reduced basal ne levels in forebrain areas while the gene expression of il 6 was increased in all selected areas at the same time the differences between wild type and transgenic rats in brain ne and il 6 mrna levels were observed in stressed animals as well tauopathy increased also the gene expression of th in the lc in addition the lc exhibited exaggerated expression of pro and anti inflammatory mediators il 6 tnf\u03b1 inducible nitric oxide synthases 2 inos2 and interleukin 10 il 10 in transgenic rats suggesting that tauopathy affects also the immune background in lc positive correlation between ne and il 6 mrna levels in cornu ammonis in stressed transgenic animals indicated the reduction of anti inflammatory effect of ne our data thus showed that tauopathy alters the functions of lc further leading to the reduction of ne levels and exaggeration of neuroinflammation in forebrain these findings support the assumption that tau related dysfunction of lc activates the vicious circle perpetuating neurodegeneration leading to the development of ad to explore the concentration response relationship between ambient concentration of pm2 5 and daily total hospital emergency room visits in beijing during 2012 and 2013 this study also examined the effects of ambient pm2 5 during heavy polluted days on emergency room visits compared with the light polluted days we collected the daily meteorological factors monitoring data and concentrations of air pollutants in beijing during october 1 2012 to december 31 2013 we also collected the daily emergency room visits from a tertiary hospital in beijing in the same time period generalized additive model was fitted to estimate the association between the ambient pm2 5 and the hospital emergency room visits by using the smooth function to adjust long term trend of time public holidays and day of week in addition constrained piecewise linear function was then used to estimate the excess risk for different segment of concentration response function the annual average concentration of pm2 5 was 90 9 \xb5g m 3 during october 1 2012 and december 31 2013 there were total 64 260 cases for total emergency room visits of which respiratory disease had 9 849 cases and cardiovascular disease had 11 168 cases pm2 5 was positive related with pm10 no2 and so2 the corresponding correlation coefficients were 0 87 0 78 and 0 62 respectively p 0 05 and pm2 5 was positively related with relative humidity with correlation coefficient 0 45 p 0 05 but pm2 5 was negatively related with mean temperature r 0 17 p 0 05 and wind speed 0 32 p 0 05 in the single polluted model after adjusting the effects of temperature relative humidity and wind every 10 \xb5g m 3 increase of concentration of ambient pm2 5 the corresponding excess risk of daily emergency room visits was 0 25 95 ci 0 07 0 43 in the two pollutant model pm2 5 so2 and pm2 5 no2 every 10 \xb5g m 3 increase of concentration of ambient pm2 5 the corresponding excess risk of daily emergency room visits were 1 07 95 ci 0 83 1 30 and 0 56 95 ci 0 32 0 80 respectively which were higher than the effect in single pollutant model average concentration of ambient particulate matters pm2 5 was 204 16 \xb5g m 3 during heavy pollution higher than control period 85 24 \xb5g m 3 when pm2 5 as the primary air pollutants during heavy polluted days we observed a significant increase in emergency room visits and the odd ratios was 1 16 95 ci 1 09 1 22 there were positive correlation between high concentration of ambient particulate matters pm2 5 and increasing daily emergency room visits especially during the heavy polluted days the effects of elevated concentration of pm2 5 on hospital emergency room visits were much larger to investigate the status of exclusive breastfeeding ebf and possible influencing factors during 0 7 days postpartum in china during 2011 to 2013 healthy mothers and neonates who were in the period of 0 7 days postpartum from 8 provinces across different regions of china were recruited to take the questionnaire investigations and physical examinations information about socio economic pregnant and delivery status infant healthy situation and feeding indicators was collected to calculate the rate of exclusive breastfeeding during 0 7 days postpartum and analyze the influencing factors a total of 1 882 pairs of mothers and neonates were covered by this study the rate of ebf was 13 3 250 cases during 0 7 days postpartum bottle feeding or 0 08 95 ci 0 05 0 12 the mothers themselves mixed fed at their 0 4 months old or 0 22 95 ci 0 08 0 58 the mothers who had used methods to stimulate milk secretion or 0 58 95 ci 0 35 0 94 might decrease the ebf rate compared with the mothers who believed that their breast milk was not enough for their infants the mothers who believed breastmilk was enough may increase the ebf rate or 6 04 95 ci 3 34 10 94 comparing to the ebf rate of beijing yunnan or 0 10 95 ci 0 04 0 24 and gansu or 0 03 95 ci 0 01 0 08 had lower ebf rate during 0 7 days postpartum what s more the ebf rate increased with the increasing neonates age or 1 33 95 ci 1 16 1 53 the ebf rate during 0 7 days postpartum is still low in china and had significant differences in different regions suboptimal feeding knowledge and practices affected the ebf rate significantly to evaluate the validity and reliability of diabetes self management knowledge attitude and behavior assessment scale dskab we selected 460 patients with diabetes in the community used the scale which was after two rounds of the delphi method and pilot study investigators surveyed the patients by the way of face to face by draw lots we selected 25 community diabetes randomly for repeating investigations after one week the validity analyses included face validity content validity construct validity and discriminant validity the reliability analyses included cronbach s \u03b1 coefficient \u03b8 coefficient \u03c9 coefficient split half reliability and test retest reliability this study distributed a total of 460 questionnaires reclaimed 442 qualified 432 the score of the scale was 254 59 28 90 the scores of the knowledge attitude behavior sub scales were 82 44 11 24 63 53 5 77 and 108 61 17 55 respectively it had excellent face validity and content validity the correlation coefficient was from 0 71 to 0 91 among three sub scales and the scale p 0 001 the common factor cumulative variance contribution rate of the scale and three sub scales was from 57 28 to 67 19 which achieved more than 50 of the approved standard there was 25 common factors 91 items of the total 98 items held factor loading \u22650 40 in its relevant common factor it had good construct validity the scores of high group and low group in three sub scales were knowledge 91 12 3 62 and 69 96 11 20 attitude 68 75 4 51 and 58 79 4 87 behavior 129 38 8 53 and 89 65 11 34 mean scores of three sub scales were apparently different which compared between high score group and low score group the t value were 19 45 16 24 and 30 29 respectively p 0 001 and it had good discriminant validity the cronbach s \u03b1 coefficient of the scale and three sub scales was from 0 79 to 0 93 the \u03b8 coefficient was from 0 86 to 0 95 the \u03c9 coefficient was from 0 90 to 0 98 split half reliability was from 0 89 to 0 95 test retest reliability of the scale was 0 51 the three sub scales was from 0 46 to 0 52 p 0 05 the validity and reliability of the diabetes self management knowledge attitude and behavior assessment scale are excellent which is a suitable instrument to evaluate the self management for patients with diabetes to develop a brief version scale with good validity and reliability to evaluate self management knowledge attitude and behavior kab of diabetes patients in a shorter time 20 authority experts who specialized in the field of diabetes clinical and non communicable disease self management and familiar with the relevant content of diabetes self management were selected face to face and email consultation methods were applied in two rounds delphi expert consultations to choose items from the diabetes self management knowledge attitude and behavior assessment scale dskab total scale 98 items in the first round of expert consultation experts were asked to select the core items from every dimension and score the extent of familiarity and basis of judgment in the second round of expert consultation the significance of the core items which were selected by experts in first round were graded the items which entered into the brief scale were determined by harmonious condition of expert opinions two rounds of consultation reclaimed 16 and 15 responses respectively positive coefficients of experts were 80 and 94 respectively and both authoritative coefficients were 0 90 in the first round of consultation experts selected 44 3 6 2 items on average 42 items were selected according to the integrity of the scale for measuring dimension and content at last in the second round of consultation experts thought that the 42 items could measure the important contents of each dimension comprehensive and representative the item importance scores of knowledge attitude and behavior subscale were 8 42 1 17 8 61 1 24 8 61 1 02 respectively and the coordination coefficients of the three subscale were 0 36 0 20 0 49 \u03c7 2 were 89 74 11 13 96 03 p 0 05 the total coordination coefficient was 0 38 \u03c7 2 199 36 p 0 001 which indicated the concentration of experts opinion was acceptable showed the brief scale with good face validity and content validity the brief scale could evaluate diabetes self management kab scale rapidly and relatively comprehensive in groups or individuals diabetes with good face validity and content validity to develop the diabetes self management knowledge attitude and behavior scale dskab with chinese population social culture character in a good validity and reliability after delphi method and pilot study this study based on former knowledge attitude and behavior questionnaires an index list was established through literature search group discussion and expert in depth interviews then we identified the core indexes and developed a primary scale through the delphi we selected 24 experts who specialized in the field of diabetes related clinical medicine non communicable diseases self management non communicable diseases control and prevention and public health the consultation tables were delivered by ems and email all the experts were asked to grade the evaluation indexes based on overall consideration finality scientificity importance applicability and to explain the extent of similarity and the basis of judgment the core indexes of the scale were determined through the positive coefficient the degree of concentration the harmonious coefficient the authoritative coefficient we selected 27 diabetes patients from the community and interviewed them face to face after finishing the field survey we organized the staff who investigated the patients to participate the panel discussion to modify and adjust the items formed the scale knowledge attitude behavior of self management for patients with diabetes mellitus two rounds of delphi both reclaimed 20 experts responses the positive coefficients were 83 and 100 respectively the authoritative coefficients were 0 85 0 10 and 0 87 0 09 the harmonious coefficients were 0 16 and 0 23 \u03c7 2 were 283 49 and 398 00 p 0 001 respectively we identified 75 core indexes through two round delphi 86 30 63 75 indexes had the importance of full marks than in 0 50 above it developed the primary scale which included 100 items based on the pilot study we increased 2 items deleted 4 items recomposed 2 items and reserved 96 items the scale consisted of 98 items that were made of three subscales which were the knowledge subscale the attitude subscale and the behavior subscale for dskab through delphi method and pilot study the active coefficients the authoritative coefficients the harmonious coefficients fulfilled the scientific requires it also laid the foundation for the good performance of the scale to investigate the correlation between obesity in children and diabetes in adults from a cohort study and further more to explore the necessity of preventing diabetes by controlling obesity in children in 1987 3 198 children and adolescents aged 6 18 were recruited from 6 elementary schools and 6 high schools located in 3 districts chaoyang haidian and xicheng of beijing using stratified cluster sampling design the physical examination process included physical development test blood pressure measurement and questionnaire investigation all children were invited to participate in the study except for those who had history of congenital heart disease chronic kidney disease and limb disability a total of 1 225 adults were enrolled in a prospective follow up study from march 2010 to july 2012 anthropometric measures and blood sample were obtained the obesity was defined by the following criteria for children aged 6 the age and the gender specific 95th percentile of bmi from the us centre for disease control and prevention growth charts 2000 as the baseline for children age 7 18 recommendation from working group on obesity in china wgoc as the standard for adults bmi \u226528 kg m 2 as the diagnosis standard diabetes was defined based on fasting plasma glucose fpg \u22657 0 mmol l or 2 hours postprandial blood glucose 2 h pg \u226511 1 mmol l or glycosylated hemoglobin hba1c \u22656 5 or current using blood glucose lowering agents or current using insulin logistic regression was used to analyze the association obesity in children with diabetes in adults the prevalence of diabetes diagnosed by fpg and 2 h pg in adults who were obese children 16 2 18 111 was higher than those who were non obese children 5 6 62 1 114 \u03c7 2 18 76 p 0 001 the prevalence of diabetes diagnosed by hba1c in adults who were obese children 18 1 20 111 was higher than those who were non obese children 6 9 77 1 114 \u03c7 2 16 66 p 0 001 with multi factor logistic regression analysis we found that after controlling follow up age genders and lifestyle smoking alcohol consuming dietary and sleeping in comparison with those non obese from childhood to adulthood those obese only in childhood or only in adulthood did not predict any risk of diabetes diagnosed by blood glucose in adults or 95 ci were 1 90 0 86 4 19 1 71 0 50 5 79 respectively those obese both in childhood and in adulthood increased the risk of diabetes diagnosed by blood glucose in adults or 95 ci was 4 50 2 22 9 14 with multi factor logistic regression analysis we found that after controlling age sex and lifestyle smoking alcohol consuming dietary and sleeping in comparison with those non obese from childhood to adulthood those obese only in childhood or only in adulthood did not increase the risk of diabetes diagnosed by hba1c in adults or 95 ci were 1 42 0 71 2 86 3 13 0 83 11 75 respectively those obese both in childhood and in adulthood increased the risk of diabetes diagnosed by hba1c in adults or 95 ci was 5 93 3 06 11 49 obesity in children even sustained to adulthood was a risk factor for diabetes in adulthood it is necessary to control obesity in children to prevent diabetes in adults scale is the basis and quality assurance of investigation research and a rigorous process is needed to develop a scale the establishment of the item pool is the first step then screening these items by using delphi expert consultation method or statistical methods to establish the scale at last the acceptability validity reliability and sensitivity of scale should be evaluated a scale can be widely applied only if it has a good acceptability validity reliability and sensitivity china national center for chronic and non communicable disease control and prevention chinese center for disease control and prevention have developed the diabetes self management knowledge attitude and behavior assessment scale dskab and the brief version of diabetes self management knowledge attitude and behavior assessment scale dskab sf these scales provide a set of scientific evaluation tools to diabetes self management of type 2 diabetes with excellent reliability validity sensitivity and acceptability cardiovascular diseases are the major threat to human health and underlie almost half of all deaths in china even more serious obesity and cardiometabolic risk factors have emerged to be prevalent in children and adolescents of some affluent regions as scientific knowledge emerges on the role of nutritional factors and exposures to environmental risk factors in the developmental origins of health and disease evidence suggests that it is imperative to create and implement early effective prevention strategies including optimisation of nutrition at first 1 000 days in life course and reduction of risk factors of obesity exposures during whole childhood to suppress the rising trend of cardiovascular disease otherwise the future costs of diagnosis and treatment are likely to be unaffordable anorexia nervosa an is a complex psychiatric disease with a moderate to strong genetic contribution in addition to conventional genome wide association gwa studies researchers have been using machine learning methods in conjunction with genomic data to predict risk of diseases in which genetics play an important role in this study we collected whole genome genotyping data on 3940 an cases and 9266 controls from the genetic consortium for anorexia nervosa gcan the wellcome trust case control consortium 3 wtccc3 price foundation collaborative group and the children s hospital of philadelphia chop and applied machine learning methods for predicting an disease risk the prediction performance is measured by area under the receiver operating characteristic curve auc indicating how well the model distinguishes cases from unaffected control subjects logistic regression model with the lasso penalty technique generated an auc of 0 693 while support vector machines and gradient boosted trees reached auc s of 0 691 and 0 623 respectively using different sample sizes our results suggest that larger datasets are required to optimize the machine learning models and achieve higher auc values to our knowledge this is the first attempt to assess an risk based on genome wide genotype level data future integration of genomic environmental and family based information is likely to improve the an risk evaluation process eventually benefitting an patients and families in the clinical setting patients receiving stereotactic body radiotherapy for stage i non small cell lung cancer are typically staged clinically with positron emission tomography computed tomography currently limited data exist for the detection of occult hilar peribronchial n1 disease we hypothesize that positron emission tomography computed tomography underestimates spread of cancer to n1 lymph nodes and that future stereotactic body radiotherapy patients may benefit from increased pathologic evaluation of n1 nodal stations in addition to n2 nodes a retrospective study was performed of all patients with clinical stage i t1 2an0 non small cell lung cancer american joint committee on cancer 7th edition by positron emission tomography computed tomography at our institution from 2003 to 2011 with subsequent surgical resection and lymph node staging findings on positron emission tomography computed tomography were compared to pathologic nodal involvement to determine the negative predictive value of positron emission tomography computed tomography for the detection of n1 nodal disease an analysis was conducted to identify predictors of occult spread a total of 105 patients with clinical stage i non small cell lung cancer were included in this study of which 8 7 6 patients were found to have occult n1 metastasis on pathologic review yielding a negative predictive value for n1 disease of 92 4 no patients had occult mediastinal nodes the negative predictive value for positron emission tomography computed tomography in patients with clinical stage t1 versus t2 tumors was 72 96 of 75 versus 25 83 of 30 respectively p 03 and for peripheral versus central tumor location was 77 98 of 78 versus 20 74 of 27 respectively p 0001 the negative predictive values for peripheral t1 and t2 tumors were 98 and 100 respectively while for central t1 and t2 tumors the rates were 85 and 64 respectively occult lymph node involvement was not associated with primary tumor maximum standard uptake value histology grade or interval between positron emission tomography computed tomography and surgery our results support pathologic assessment of n1 lymph nodes in patients with stage inon small cell lung cancer considered for stereotactic body radiotherapy with the greatest benefit in patients with central and t2 tumors diagnostic evaluation with endoscopic bronchial ultrasound should be considered in the evaluation of stereotactic body radiotherapy candidates previous studies have suggested a close correlation between gastroesophageal reflux disease gerd and various respiratory disorders however the association between gerd and tuberculosis tb remains unexplored using data retrieved from taiwan s national health insurance research database from 2000 to 2009 this longitudinal nationwide cohort study included a total of 63 930 patients with gerd and controls matched by age sex and comorbidities risk factors associated with the development of pulmonary tb ptb were investigated active ptb was documented in 65 0 20 patients with gerd and 41 0 13 matched cohorts within 1 year of gerd diagnosis the incidence rate of ptb in the gerd group and the matched cohort was respectively 24 1 and 15 2 cases per 10 000 person years in multivariate analysis gerd was an independent risk factor for ptb adjusted hr 1 63 95 ci 1 10 2 40 p 0 015 among patients with gerd independent predictors for ptb included older age male sex chronic obstructive pulmonary disease asthma and exposure to proton pump inhibitors ppis patients with gerd have a significantly increased risk of ptb within 1 year of gerd diagnosis exposure to ppis is an independent predictor for ptb among patients with gerd to investigate the incidence of ethambutol emb induced optic neuropathy prescribed at a relatively low dose of 15 mg kg day for the treatment of tuberculosis tb or mycobacterium avium complex mac lung disease patients diagnosed with tb or mac lung disease received multidrug regimens including emb at a single institution from august 2003 to july 2009 visual monitoring was performed at baseline and at regular follow up the incidence of emb induced visual disturbances was evaluated of the 415 patients included in the study three 0 7 developed toxic optic neuropathy over the 6 year period of the 289 patients prescribed a dose of 15 mg kg day emb only one 0 3 developed toxic optic neuropathy the incidence of emb induced optic neuropathy among koreans is estimated to be 0 7 and can be reduced with lower doses of emb anaemia commonly complicates both human immunodeficiency virus hiv infection and tuberculosis tb contributing substantially to morbidity and mortality the mechanisms underlying anaemia and corresponding treatments in co infected patients are poorly defined to determine the relative contributions of anaemia of chronic disease acd and iron deficiency to anaemia in patients with hiv associated tb consecutively recruited hospitalised n 102 and matched ambulatory patients n 51 with microbiologically confirmed hiv associated tb in cape town south africa were included haemoglobin levels iron status markers hepcidin and pro inflammatory cytokines in blood were measured we determined the prevalence of acd and iron deficiency anaemia ida using seven different published definitions of ida more than 80 of enrolled hiv associated tb patients were anaemic and anaemia was more severe among in patients over 95 of anaemic hiv associated tb patients had acd whereas the proportion with ida using a range of seven different definitions was low overall median 3 range 0 32 6 in both patient groups the proportion with ida and hepcidin concentration 20 0 ng ml predictive of responsiveness to oral iron supplementation was also very low median 3 range 0 15 1 acd was the predominant cause underlying anaemia in hiv associated tb patients and ida was very uncommon in this setting the majority of anaemic hiv associated tb patients were unlikely to benefit from oral iron supplementation a referral hospital for tuberculosis tb in irkutsk the russian federation to describe disease characteristics treatment and hospital outcomes of tb hiv human immunodeficiency virus observational cohort of hiv infected patients admitted for anti tuberculosis treatment over 6 months a total of 98 patients were enrolled with a median cd4 count of 147 cells mm 3 and viral load of 205 943 copies ml among patients with drug susceptibility testing dst results 29 64 were multidrug resistant mdr including 12 without previous anti tuberculosis treatment nineteen patients were on antiretroviral therapy art at admission and 10 13 art na\xefve were started during hospitalization barriers to timely art initiation included death in patient treatment interruption and patient refusal of 96 evaluable patients 21 22 died 14 15 interrupted treatment and 10 10 showed no microbiological or radiographic improvement patients with a cavitary chest x ray aor 7 4 95 ci 2 3 23 7 p 0 001 or central nervous system disease aor 6 5 95 ci 1 2 36 1 p 0 03 were more likely to have one of these poor outcomes high rates of mdr tb treatment interruption and death were found in an hiv infected population hospitalized in irkutsk there are opportunities for integration of hiv and tb services to overcome barriers to timely art initiation increase the use of anti tuberculosis regimens informed by second line dst and strengthen out patient diagnosis and treatment networks the world health organization recommends adding bedaquiline or delamanid to multidrug resistant tuberculosis mdr tb regimens for which four effective drugs are not available and delamanid for patients at high risk of poor outcome to identify patients at risk of unfavourable outcomes who may benefit from the new drugs retrospective cohort study of treatment outcomes involving four to five effective drugs for 15 24 months in programmes in uzbekistan georgia armenia swaziland and kenya between 2001 and 2011 of 1433 patients 48 5 had body mass index bmi 18 5 kg m 2 72 9 had a high bacillary load 16 7 were resistant to two injectables 2 9 were resistant to ofloxacin ofx and 3 0 had extensively drug resistant tb xdr tb treatment success ranged from 59 7 no second line resistance to 27 0 xdr tb xdr tb aor 8 16 95 ci 3 22 20 64 resistance to two injectables aor 1 90 95 ci 1 00 3 62 or ofx aor 5 56 95 ci 2 15 14 37 past incarceration aor 1 88 95 ci 1 11 3 2 history of second line treatment aor 3 24 95 ci 1 53 6 85 low bmi aor 2 22 95 ci 1 56 3 12 and high bacillary load aor 2 32 95 ci 1 15 4 67 were associated with unfavourable outcomes patients started on capreomycin rather than kanamycin were more likely to have an unfavourable outcome aor 1 54 95 ci 1 04 2 28 in our cohort patients who may benefit from bedaquiline and delamanid represented up to two thirds of all mdr tb patients on detecting a high prevalence of multidrug resistant tuberculosis tb in djibouti 32 mycobacterium tuberculosis isolates of patients hospitalised in the tb referral centre of the capital were genotyped a high variety of m tuberculosis lineages including lineage 1 indo oceanic lineage 2 east asian lineage 3 east african indian and lineage 4 euro american were detected laparoscopic sleeve gastrectomy lsg has established popularity as a weight loss procedure based on its success however lsg s effect on gastroesophageal reflux disease gerd is unknown to analyze the incidence of gerd after lsg and to compare the results in patients with preexisting and de novo gerd tertiary medical center the authors performed a retrospective review of primary lsg from 2005 to 2013 and compared patients with pre existing and de novo gerd who underwent lsg a total of 919 patients underwent lsg gerd was present in 38 4 of the lsg cohort we identified 2 groups group a consisted of 25 3 patients with de novo gerd and group b consisted of 13 1 patients with pre existing gerd diagnosis of gerd in both groups was determined by symptoms and history of proton pump inhibitor ppi treatment upper gastrointestinal endoscopy esophagogastroduodenoscopy and ph manometry in group a 1 4 patient was managed with over the counter drugs 17 68 patients were treated with low dose ppi 6 24 patients were treated with high dose ppi and 1 4 patient was lost to follow up group b consisted of 9 69 patients treated with low dose ppi and 4 31 patients treated with high dose ppi medical treatment failed in 4 patients 10 5 who subsequently required conversion to laparoscopic roux en y gastric bypass lrygb in group a 1 patient 4 required lrygb and in group b 3 patients 23 required lrygb the outcome of conversion for group a was incomplete resolution of symptoms in the 1 patient whereas in group b all 3 patients 100 had complete resolution of gerd symptoms after lrygb in this study 3 of patients developed de novo gerd but most responded to either low or high dose ppi with 4 requiring conversion to lrygb patients with epileptic spasms are at high risk for learning and memory impairment later in life we examined whether synaptic plasticity is affected in the adult hippocampus a structure responsible for learning and memory using an animal model of epileptic spasms of unknown cause we produced a rat model of n methyl d aspartate nmda induced spasms combined with prenatal betamethasone administration in 6 to 11 week old rats we evaluated the long term potentiation ltp and general properties of synaptic transmission in pyramidal neurons in the ca1 area of the hippocampus in brain slices the magnitude of ltp by theta burst stimulation was significantly larger in adult rats with a history of infantile nmda injections than in control rats and rats that received additional adrenocorticotropic hormone acth treatment the frequency of spontaneous excitatory transmission but not inhibitory transmission was smaller in adult rats with a history of infantile nmda injections this study is the first to provide a basis for the alteration of synaptic plasticity and transmission in a model of epileptic spasms of unknown cause postnatal nmda treatment causing epileptic spasms like aberrant episodes in the early stage of life in rats has a latent influence on various forms of synaptic plasticity in the hippocampus our results provide a novel insight into cognitive impairment that appears later in life in patients with a history of epileptic spasms significant advances have been performed in cutaneous adverse reactions leading to primary prevention strategy and implication of new signaling pathways histological features of dress and methotrexate toxicity are detailed new emerging infectious agents are reported including zika virus an arbovirus which can be confused with dengue or chikungunya a new cowpox virus transmitted by domestic cat leading to lymphadenitis spirurina type x larva transmitted in japan by eating raw squid or fish malignancies in pemphigus and pemphigoid are emphasized expert recommandations are developped on definitions diagnosis and disease activity of mucous membrane pemphigoid bubllous pemphigoid and pemphigus psoriasis and cardiometabolic association are discussed this risk association appears higher in hidradenitis suppurativa which seems more frequent in patients of african ancestry igg4 related disease is an immune mediated entity characterized by fibroinflammatory lesions often misdiagnosed pruritus heat sensations numbness could be recognized as a small fiber neuropathy symptoms burden impact in common dermatosis is demonstrated and should be integrated in our daily practice limited information is available on the non influenza etiology and epidemiology of influenza like illness ili in china from april 2011 to march 2014 we collected oropharyngeal swabs from children less than 5 years of age with symptoms of ili who presented to the outpatient departments of suzhou university affiliated children s hospital sch we used reverse transcription polymerase chain reaction rt pcr or pcr to detect 11 respiratory viruses among 3 662 enrolled ili patients 1 292 35 3 tested positive for at least one virus influenza virus 16 9 was detected most frequently influenza a 7 4 influenza b 9 5 followed by respiratory syncytial virus rsv 5 6 parainfluenza virus piv types 1 4 4 8 human bocavirus hbov 3 8 human metapneumovirus hmpv 3 5 and adenovirus adv 3 0 co infections were identified in 108 2 9 patients influenza virus predominantly circulated in january march and june july the 2013 2014 winter peaks of rsv and influenza overlapped compared with other virus positive cases influenza positive cases were more likely to present with febrile seizure and rsv positive cases were more likely to present with cough and wheezing and were most frequently diagnosed with pneumonia these data provide a better understanding of the viral etiology of ili among children less than 5 years of age in suzhou china influenza is not only the most frequently identified pathogen but it is also the only vaccine preventable illness among the 11 pathogens tested such findings suggest the potential value of exploring value of influenza vaccination among this influenza vaccination target group j med virol 88 1334 1340 2016 2016 wiley periodicals inc the spinocerebellar ataxias scas form an ever growing group of neurodegenerative disorders causing dysfunction of the cerebellum and loss of motor control in patients currently 41 different genetic causes have been identified with each mutation affecting a different gene interestingly these diverse genetic causes all disrupt cerebellar function and produce similar symptoms in patients in order to understand the disease better and define possible therapeutic targets for multiple scas the field has been searching for common ground among the scas in this review we discuss the physiology of climbing fibers and the possibility that climbing fiber dysfunction is a point of convergence for at least a subset of scas one attractive pharmacological strategy for alzheimer s disease ad is to design small peptides to interact with amyloid \u03b2 a\u03b2 protein reducing its aggregation and toxicity starting from clinical observations indicating that patients coding a mutated a\u03b2 variant a\u03b2a2v in the heterozygous state do not develop ad we developed a\u03b2a2v synthetic peptides as well as a small peptide homologous to residues 1 6 these hindered the amyloidogenesis of a\u03b2 and its neurotoxicity in vitro suggesting a basis for the design of a new small peptide in d isomeric form linked to the arginine rich tat sequence a\u03b21 6a2v tat d to allow translocation across biological membranes and the blood brain barrier a\u03b21 6a2v tat d was resistant to protease degradation stable in serum and specifically able to interfere with a\u03b2 aggregation in vitro reducing the appearance of toxic soluble species and protecting transgenic c elegans from toxicity related to the muscular expression of human a\u03b2 these observations offer a proof of concept for future pharmacological studies in mouse models of ad providing a foundation for the design of a\u03b2a2v based peptidomimetic molecules for therapeutic purposes protocatechuic acid pca plays a critical role in nutritional metabolism it is a major metabolite of anthocyanins which are flavonoids with a range of health benefits pca has a variety of biological activities including anti oxidant antiinflammatory anti apoptosis and anti microbial activities however the pharmacological effect of pca especially on osteoclastogenesis remains unknown we examined the effect of pca on receptor activator of nf \u03bab ligand rankl induced osteoclast differentiation and bone resorption pca dose dependently inhibited rankl induced osteoclast differentiation in mouse bone marrow macrophages bmms and suppressed the bone resorbing activity of mature osteoclasts at the molecular level pca suppressed rankl induced phosphorylation of jnk among mapks only without significantly affecting the early signaling pathway pca also suppressed rankl stimulated expression of c fos and nuclear factor of activated t cells c1 nfatc1 at the mrna and protein levels without altering c fos mrna expression additionally pca down regulated the expression of downstream osteoclastogenesis related genes including \u03b23 integrin dc stamp oc stamp atp6v0d2 ctr and ctsk mice treated with pca efficiently recovered from lipopolysaccharide induced bone loss in vivo thus pca inhibits rankl induced osteoclast differentiation and function by suppressing jnk signaling c fos stability and expression of osteoclastic marker genes these results suggest that pca could be useful in treatment of inflammatory bone disorders recent studies suggest that hyperuricemia is a potential risk factor for cardiovascular disease cvd hyperuricemia is highly heritable and is associated with sex and body weight previous genome wide association studies have found that the abcg2 single nucleotide polymorphism snp rs2231142 is an important genetic factor for increased uric acid ua levels and the degree of association between rs2231142 and hyperuricemia is affected by both sex and ethnicity this investigation aimed to analyze the association between abcg2 polymorphisms and ua levels as well as their interactions with sex and obesity'
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