Bisphenol A and the risk of cardiometabolic disorders: a systematic review with meta-analysis of the epidemiological evidence.

Published onlineResearch Support, Non-U.S. Gov'tBisphenol A (BPA) is suspected to be associated with several chronic metabolic diseases. The aim of the present study was to review the epidemiological literature on the relation between BPA exposure and the risk of cardiometabolic disorders. PubMed and Embase databases were searched up to August 2014 by two independent investigators using standardized subject terms. We included observational studies (cohort, case-control and cross-sectional studies) carried out in children or adults, measuring urinary BPA (uBPA), including at least 100 participants and published in English. The health outcomes of interest were diabetes, hyperglycemia, measures of anthropometry, cardiovascular disease (CVD) and hypertension. Data were extracted and meta-analyzed when feasible, using a random-effects model. Thirty-three studies with sample size ranging from 239 to 4811 met the inclusion criteria, including five with a prospective design. Twelve studies reported on diabetes or hyperglycemia, 16 on anthropometry, 6 on CVD and 3 on hypertension. Evidence for a positive association between uBPA concentrations and diabetes, overweight, obesity, elevated waist circumference (WC), CVD and hypertension was found in 7/8, 2/7, 6/7, 5/5, 4/5 and 2/3 of the cross-sectional studies, respectively. We were able to conduct outcome-specific meta-analyses including 12 studies. When comparing the highest vs. the lowest uBPA concentrations, the pooled ORs were 1.47 (95% CI: 1.21-1.80) for diabetes, 1.21 (95% CI: 0.98-1.50) for overweight, 1.67 (95% CI: 1.41-1.98) for obesity, 1.48 (95% CI: 1.25-1.76) for elevated WC, and 1.41 (95% CI: 1.12-1.79) for hypertension. Moreover, among the five prospective studies, 3 reported significant findings, relating BPA exposure to incident diabetes, incident coronary artery disease, and weight gain. To conclude, there is evidence from the large body of cross-sectional studies that individuals with higher uBPA concentrations are more likely to suffer from diabetes, general/abdominal obesity and hypertension than those with lower uBPA concentrations. Given the potential importance for public health, prospective cohort studies with proper adjustment for dietary characteristics and identification of critical windows of exposure are urgently needed to further improve knowledge about potential causal links between BPA exposure and the development of chronic disease.This study was funded by the National Health and Medical Research Council, Australia (NHMRC grant APP1022923). Support for FR was provided by a postdoctoral grant from CORDDIM (field of major interest of the Île-de-France Regional Council “Cardiovascular/Obesity/Kidney/Diabetes”), the French Endocrine Disruptor Research Programme (PNRPE grant) and the Scientific Mobility Program of the Embassy of France in Australia (2014). JGL is supported by National Heart Foundation of Australia/NHMRC postgraduate scholarship [586739] and the Cardiac Society of Australia and New Zealand. This work was supported in part by the Victorian Government’s OIS Program

Weekend admission and mortality for gastrointestinal disorders across England and Wales

BACKGROUND: Little has been reported on mortality following admissions at weekends for many gastrointestinal (GI) disorders. The aim was to establish whether GI disorders are susceptible to increased mortality following unscheduled admission on weekends compared with weekdays. METHODS: Record linkage was undertaken of national administrative inpatient and mortality data for people in England and Wales who were hospitalized as an emergency for one of 19 major GI disorders. RESULTS: The study included 2 254 701 people in England and 155 464 in Wales. For 11 general surgical and medical GI disorders there were little, or no, significant weekend effects on mortality at 30 days in either country. There were large consistent weekend effects in both countries for severe liver disease (England: 26·2 (95 per cent c.i. 21·1 to 31·6) per cent; Wales: 32·0 (12·4 to 55·1 per cent) and GI cancer (England: 21·8 (19·1 to 24·5) per cent; Wales: 25·0 (15·0 to 35·9) per cent), which were lower in patients managed by surgeons. Admission rates were lower at weekends than on weekdays, most strongly for severe liver disease (by 43·3 per cent in England and 51·4 per cent in Wales) and GI cancer (by 44·6 and 52·8 per cent respectively). Both mortality and the weekend mortality effect for GI cancer were lower for patients managed by surgeons. DISCUSSION: There is little, or no, evidence of a weekend mortality effect for most major general surgical or medical GI disorders, but large weekend effects for GI cancer and severe liver disease. Lower admission rates at weekends indicate more severe cases. The findings for severe liver disease may suggest a lack of specialist hepatological resources. For cancers, reduced availability of end-of-life care in the community at weekends may be the cause

Higher glomerular filtration rate is related to insulin resistance but not to obesity in a predominantly obese non-diabetic cohort

Correction to this article published https://doi.org/10.1038/srep4696

Developing cardiac and skeletal muscle share fast-skeletal myosin heavy chain and cardiac troponin-I expression

Skeletal muscle derived stem cells (MDSCs) transplanted into injured myocardium can differentiate into fast skeletal muscle specific myosin heavy chain (sk-fMHC) and cardiac specific troponin-I (cTn-I) positive cells sustaining recipient myocardial function. We have recently found that MDSCs differentiate into a cardiomyocyte phenotype within a three-dimensional gel bioreactor. It is generally accepted that terminally differentiated myocardium or skeletal muscle only express cTn-I or sk-fMHC, respectively. Studies have shown the presence of non-cardiac muscle proteins in the developing myocardium or cardiac proteins in pathological skeletal muscle. In the current study, we tested the hypothesis that normal developing myocardium and skeletal muscle transiently share both sk-fMHC and cTn-I proteins. Immunohistochemistry, western blot, and RT-PCR analyses were carried out in embryonic day 13 (ED13) and 20 (ED20), neonatal day 0 (ND0) and 4 (ND4), postnatal day 10 (PND10), and 8 week-old adult female Lewis rat ventricular myocardium and gastrocnemius muscle. Confocal laser microscopy revealed that sk-fMHC was expressed as a typical striated muscle pattern within ED13 ventricular myocardium, and the striated sk-fMHC expression was lost by ND4 and became negative in adult myocardium. cTn-I was not expressed as a typical striated muscle pattern throughout the myocardium until PND10. Western blot and RT-PCR analyses revealed that gene and protein expression patterns of cardiac and skeletal muscle transcription factors and sk-fMHC within ventricular myocardium and skeletal muscle were similar at ED20, and the expression patterns became cardiac or skeletal muscle specific during postnatal development. These findings provide new insight into cardiac muscle development and highlight previously unknown common developmental features of cardiac and skeletal muscle. © 2012 Clause et al

The Evolution of a High Copy Gene Array in Arabidopsis

Local gene duplication is a prominent mechanism of gene copy number expansion. Elucidating the mechanisms by which local duplicates arise is necessary in understanding the evolution of genomes and their host organisms. Chromosome one of Arabidopsis thaliana contains an 81-gene array subdivided into 27 triplet units (t-units), with each t-unit containing three pre-transfer RNA genes. We utilized phylogenetic tree reconstructions and comparative genomics to order the events leading to the array’s formation, and propose a model using unequal crossing-over as the primary mechanism of array formation. The model is supported by additional phylogenetic information from intergenic spacer sequences separating each t-unit, comparative analysis to an orthologous array of 12 t-units in the sister taxa Arabidopsis lyrata, and additional modeling using a stochastic simulation of orthologous array divergence. Lastly, comparative phylogenetic analysis demonstrates that the two orthologous t-unit arrays undergo concerted evolution within each taxa and are likely fluctuating in copy number under neutral evolutionary drift. These findings hold larger implications for future research concerning gene and genome evolution

Simple rules can guide whether land or ocean based conservation will best benefit marine ecosystems

Coastal marine ecosystems can be managed by actions undertaken both on the land and in the ocean. Quantifying and comparing the costs and benefits of actions in both realms is therefore necessary for efficient management. Here, we quantify the link between terrestrial sediment run-off and a downstream coastal marine ecosystem, and contrast the cost-effectiveness of marine and land-based conservation actions. We use a dynamic land- and sea-scape model to determine whether limited funds should be directed to one of four alternative conservation actions – protection on land, protection in the ocean, restoration on land, or restoration in the ocean – to maximise the extent of light-dependent marine benthic habitats, across decadal time-scales. We apply the model to a case study seagrass meadow in Australia. We find that marine restoration is the most cost-effective action over decadal time-scales in this system, based on a conservative estimate of the rate at which seagrass can expand into new habitat. The optimal decision will vary in different social-ecological contexts, but some basic information can guide optimal investments to counteract land and ocean based stressors: (1) marine restoration should be prioritised if the rates of marine ecosystem decline and expansion are similar and low; (2) marine protection should take precedence if the rate of marine ecosystem decline is high, or if the adjacent catchment is relatively intact and has a low rate of vegetation decline; (3) land-based actions are optimal when the ratio of marine ecosystem expansion to decline is >1.4, with terrestrial restoration typically the most cost effective; and (4) land protection should be prioritised if the catchment is relatively intact, but the rate of vegetation decline is high. These rules-of-thumb illustrate how cost-effective conservation outcomes for connected land-ocean systems can proceed without complex modelling

Long term extension of a randomised controlled trial of probiotics using electronic health records

Most randomised controlled trials (RCTs) are relatively short term and, due to costs and available resources, have limited opportunity to be re-visited or extended. There is no guarantee that effects of treatments remain unchanged beyond the study. Here, we illustrate the feasibility, benefits and cost-effectiveness of enriching standard trial design with electronic follow up. We completed a 5-year electronic follow up of a RCT investigating the impact of probiotics on asthma and eczema in children born 2005-2007, with traditional fieldwork follow up to two years. Participants and trial outcomes were identified and analysed after five years using secure, routine, anonymised, person-based electronic health service databanks. At two years, we identified 93% of participants and compared fieldwork with electronic health records, highlighting areas of agreement and disagreement. Retention of children from lower socio-economic groups was improved, reducing volunteer bias. At 5 years we identified a reduced 82% of participants. These data allowed the trial's first robust analysis of asthma endpoints. We found no indication that probiotic supplementation to pregnant mothers and infants protected against asthma or eczema at 5 years. Continued longer-term follow up is technically straightforward

Composition of Human Skin Microbiota Affects Attractiveness to Malaria Mosquitoes

The African malaria mosquito Anopheles gambiae sensu stricto continues to play an important role in malaria transmission, which is aggravated by its high degree of anthropophily, making it among the foremost vectors of this disease. In the current study we set out to unravel the strong association between this mosquito species and human beings, as it is determined by odorant cues derived from the human skin. Microbial communities on the skin play key roles in the production of human body odour. We demonstrate that the composition of the skin microbiota affects the degree of attractiveness of human beings to this mosquito species. Bacterial plate counts and 16S rRNA sequencing revealed that individuals that are highly attractive to An. gambiae s.s. have a significantly higher abundance, but lower diversity of bacteria on their skin than individuals that are poorly attractive. Bacterial genera that are correlated with the relative degree of attractiveness to mosquitoes were identified. The discovery of the connection between skin microbial populations and attractiveness to mosquitoes may lead to the development of new mosquito attractants and personalized methods for protection against vectors of malaria and other infectious diseases

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty