Femoral and tibial bone torsions associated with medial femoro-tibial osteoarthritis. Index of cumulative torsions

AbstractFrontal plane varus deviation is one of the mechanisms hypothesized to be involved in the pathogenesis of medial compartment osteoarthritis of the knee. But only a few authors have suggested a role for tibial and femoral torsion. In the current study, CT scan was used to measure bone torsion. The torsional morphology of the lower limb was defined by the “index of cumulative torsions” (ICT). The resulting values were compared to the frontal angular deviation data. The effects of tibial and femoral torsion on the position of the lower limb during the stance phase of walking and the consequences for the knee are discussed

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers

Médecine de précision : un rendez-vous à ne pas manquer pour l’interniste généraliste [Precision medicine : a required approach for the general internist]

The general internist cannot be a passive bystander of the anticipated medical revolution induced by precision medicine. This latter aims to improve the predictive and/or clinical course of an individual by integrating all biological, genetic, environmental, phenotypic and psychosocial knowledge of a person. In this article, national and international initiatives in the field of precision medicine are discussed as well as the potential financial, ethical and limitations of personalized medicine. The question is not to know if precision medicine will be part of everyday life but rather to integrate early the general internist in multidisciplinary teams to ensure optimal information and shared-decision process with patients and individuals

Structure of an extracellular polysaccharide produced by Lactobacillus rhamnosus strain C83

International audienc

La restauration écologique comme nouveau paradigme d’aménagement ? Regards croisés sur l’environnement fluvio estuarien Garonne Gironde

National audienceAlthough land management policies have improved the overall control of rivers, they have also resulted in considerable disturbance and deterioration in a range of different environments. New approaches to the restoration of wetlands are now being tried in south-western France, on the Garonne River and in the Gironde estuary. Such changes primarily involve allowing storm-induced ooding of marshlands (depolderisation). Further upstream, in the mid-Garonne-Toulouse region, consideration is currently being given to restoring areas of standing water or creating ood expansion zones. Our article uses a multidisciplinary approach to analyze the emergence of this new paradigm from a geo-historical, geochemical, ecological and sociological perspective.Bien que les politiques aménagistes aient permis d’améliorer la maîtrise globale des fleuves, elles ont également généré de nombreuses perturbations et altérations. Aujourd’hui, la restauration des cours d’eau fait l’objet de nouvelles expérimentations. Dans le sud-ouest de la France, sur le fleuve Garonne et dans l’estuaire de la Gironde, elles se traduisent notamment par des remises en eau des marais, liées au passage de tempêtes (dynamique de dépoldérisation). Plus en amont, dans la moyenne Garonne toulousaine, les réflexions en cours concernent la réouverture de bras morts ou la création de zones d’expansion de crues. Nous proposons d’examiner l’émergence de ce nouveau paradigme, dans une perspective pluridisciplinaire, par une évaluation géohistorique, géochimique, écologique et sociologique