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

Dynamic phenotypic heterogeneity and the evolution of multiple RNA subtypes in Hepatocellular Carcinoma: the PLANET study

Intra-tumor heterogeneity (ITH) is a key challenge in cancer treatment, but previous studies have focused mainly on the genomic alterations without exploring phenotypic (transcriptomic and immune) heterogeneity. Using one of the largest prospective surgical cohorts for Hepatocellular Carcinoma (HCC) with multi-region sampling, we sequenced whole genomes and paired transcriptomes from 67 HCC patients (331 samples). We found that while genomic ITH was rather constant across TNM stages, phenotypic ITH had a very different trajectory and quickly diversified in stage II patients. Most strikingly, 30% patients were found to contain more than one transcriptomic subtype within a single tumor. Such phenotypic ITH was found to be much more informative in predicting patient survival than genomic ITH and explains the poor efficacy of single-target systemic therapies in HCC. Taken together, we not only revealed an unprecedentedly dynamic landscape of phenotypic heterogeneity in HCC, but also highlighted the importance of studying phenotypic evolution across cancer types

Important park features for encouraging park visitation, physical activity and social interaction among adolescents: A conjoint analysis

Little is known about what park features adolescents perceive as most important for encouraging them to visit and be active and social in parks. This study examined the relative importance of park features for encouraging these behaviours among adolescents and explored differences according to gender and frequency of visitation. Adolescents were recruited from secondary schools in diverse areas of Melbourne, Australia. In Phase 1 (2018–2019), participants [n = 222; 14.0 years (SD 1.1); 46% female] rated photographs of 40 park features in an online survey, indicating the degree to which each feature encouraged them to visit, and be active and social in the park. In Phase 2 (2019–2020), the top ten-rated features from Phase 1 for each outcome (overall and by gender and frequency of visitation) were presented in Adaptive Choice-Based Conjoint tasks to another sample of participants [n = 244; 14.7 years (SD 1.3); 46% female]. The most important feature for encouraging visitation was large swings; for physical activity was sports courts; and for social interaction was a café. Grassy open space was important for all behaviours, and preferred park features varied among sub-groups. The results highlight which park features park planners and designers should prioritise to support active and social park use among adolescents