Plasma organochlorine concentrations and bone ultrasound measurements: a cross-sectional study in peri-and postmenopausal Inuit women from Greenland

BACKGROUND: Inuit women are highly exposed through their traditional seafood based diet to organochlorine compounds, some of them displaying endocrine disrupting properties. We hypothesized that this exposure might be related to bone characteristics that are altered in osteoporosis, because hormone deficiency is a known risk factor for the disease. METHODS: We measured quantitative ultrasound parameters (QUS) at the right calcaneum of 153 peri- and postmenopausal Inuit women (49–64 year old) from Nuuk, Greenland, and investigated the relation between these parameters and plasma organochlorine concentrations. We used high-resolution gas chromatography with electron capture detection to analyze plasma samples for 14 polychlorinated biphenyls (PCB) congeners and 11 chlorinated pesticides and metabolites. We analysed morning urine samples for cadmium, a potential confounder, by atomic absorption spectrometry. We used a validated questionnaire to document dietary and lifestyle habits as well as reproductive and medical histories. RESULTS: Concentrations of PCB 153, a surrogate of exposure to most organochlorines present in plasma samples, were inversely correlated to QUS parameters in univariate analyses (p < 0.001). However, PCB 153 concentrations were not associated with QUS values in multivariate analyses that comprised potential confounding factors such as age, body weight, former oral contraceptive use and current hormone replacement therapy (HRT) use, which were all significant predictors of bone stiffness (total R(2 )= 0.39; p < 0.001). CONCLUSION: Overall we found little evidence that organochlorines exposure is related to osteoporosis in Greenlandic Inuit women, but the hypothesis that exposure to dioxin-like compounds might be linked to decreased bone quality and osteoporosis deserves further attention

Integrated genomic characterization of pancreatic ductal adenocarcinoma

We performed integrated genomic, transcriptomic, and proteomic profiling of 150 pancreatic ductal adenocarcinoma (PDAC) specimens, including samples with characteristic low neoplastic cellularity. Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS, TP53, CDKN2A, SMAD4, RNF43, ARID1A, TGFβR2, GNAS, RREB1, and PBRM1. KRAS wild-type tumors harbored alterations in other oncogenic drivers, including GNAS, BRAF, CTNNB1, and additional RAS pathway genes. A subset of tumors harbored multiple KRAS mutations, with some showing evidence of biallelic mutations. Protein profiling identified a favorable prognosis subset with low epithelial-mesenchymal transition and high MTOR pathway scores. Associations of non-coding RNAs with tumor-specific mRNA subtypes were also identified. Our integrated multi-platform analysis reveals a complex molecular landscape of PDAC and provides a roadmap for precision medicine

Maternal Exposure to Drinking-water Chlorination By- products and Small-for-gestational-age Neonates

Background: There is concern about possible effects of disinfection by-products on reproductive outcomes. The purpose of this study was to evaluate the association between maternal exposure to chlorination by-products and the risk of delivering a small forgestational-age (SGA) neonate. Methods: We conducted a population-based case-control study in the Québec City (Canada) area. Term newborn cases with birth weights Ͻ10th percentile (n ϭ 571) were compared with 1925 term controls with birth weights Ն10th percentile. Concentrations of trihalomethanes and haloacetic acids in the water-distribution systems of participants were monitored during the study period, and a phone interview on maternal habits was completed within 3 months after childbirth. We estimated chlorination by-products ingestion during the last trimester of pregnancy and trihalomethanes doses resulting from inhalation and dermal exposure. We evaluated associations between chlorination by-products in utero exposure and SGA by means of unconditional logistic regression with control of potential confounders. Results: When total trihalomethanes and the 5 regulated haloacetic acids concentrations were divided into quartiles, no clear doseresponse relationship was found with SGA. However, increased risk was observed when haloacetic concentrations were above the fourth quartile and when either trihalomethanes or haloacetic acids concentrations were above current water standards (adjusted ORϭ 1.5 ͓95% confidence interval ϭ 1.1-1.9͔ and 1.4 ͓1.1-1.9͔, respectively). Inhalation and dermal absorption of trihalomethanes did no

Les territoires de la culture scientifique

Les changements culturels, sociaux et économiques accélérés, si caractéristiques de notre modernité, déstabilisent les activités traditionnelles de la culture scientifique et technologique (CST). Ils nourrissent et amplifient un doute sur leur légitimité et nécessité. Nous proposons d'amorcer une réflexion en vue d'anticiper les développements prévisibles dans ce domaine ainsi que leurs impacts sur les pratiques actuelles et futures. L'objectif est de repérer les nouveaux espaces de communication qui s'ouvrent à la CST. Il est donc question d'enjeux, d'acteurs, d'institutions interpellées ou mobilisées, et de processus de dissémination dans le social. En arrière-plan, nous souhaitons susciter une prise de conscience des modalités émergente de socialisation, d'acculturation et de représentation des sciences et des technologies en réaction à ce qui nous semble être un ajustement structurel du champ de la CST. Nous souhaitons que cette démarche contribue à une compréhension des nouveaux modes de régulation entre les acteurs et les institutions et, par conséquent, des nouveaux rapports au savoir en voie de constitution

Pancreatic cancer genomes reveal aberrations in axon guidance pathways genes

Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n5142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis