Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk.

Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10(-14), odds ratio = 0.86, 95% confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression

Cardiovascular risk associated with co-morbid insomnia and sleep apnoea (COMISA) in type 2 diabetics

Objective: In the general population, co-morbid insomnia and sleep apnoea (COMISA) is associated with higher risk of cardiovascular diseases (CVD). However, despite a high prevalence of COMISA in type 2 diabetics, no study has investigated its potential implication in the negative cardiovascular outcome of this particular subpopulation. The aim of this study was therefore to examine the risk of CVD associated with COMISA in type 2 diabetics. Methods: Data from 471 type 2 diabetics recruited from the clinical database of the Erasme Hospital sleep laboratory were analysed. Only type 2 diabetics with SCORE index ≥5% were included in the group at high risk of CVD. Logistic regression analyses were conducted to examine the risk of CVD associated with COMISA in type 2 diabetics. Results: A high risk of CVD was present in 32.9% of type 2 diabetics. After adjustment for the main confounding factors associated with cardiovascular risk, multivariate logistic regression analysis revealed that unlike obstructive sleep apnoea syndrome or insomnia alone, only COMISA was associated with higher risk of CVD in type 2 diabetics. Discussion: In our study, we have demonstrated that unlike its components alone, only COMISA was associated with higher risk of CVD in type 2 diabetics, which highlights the importance of the central role played by the negative synergistic effect of COMISA on the cardiovascular outcome in this particular subpopulation. Thus, given these elements, more systematic research and adequate therapeutic management of COMISA seem to be necessary to allow better cardiovascular prevention in type 2 diabetics

Candidate locus analysis of the TERT-CLPTM1L cancer risk region on chromosome 5p15 identifies multiple independent variants associated with endometrial cancer risk.

Several studies have reported associations between multiple cancer types and single-nucleotide polymorphisms (SNPs) on chromosome 5p15, which harbours TERT and CLPTM1L, but no such association has been reported with endometrial cancer. To evaluate the role of genetic variants at the TERT-CLPTM1L region in endometrial cancer risk, we carried out comprehensive fine-mapping analyses of genotyped and imputed SNPs using a custom Illumina iSelect array which includes dense SNP coverage of this region. We examined 396 SNPs (113 genotyped, 283 imputed) in 4,401 endometrial cancer cases and 28,758 controls. Single-SNP and forward/backward logistic regression models suggested evidence for three variants independently associated with endometrial cancer risk (P = 4.9 × 10(-6) to P = 7.7 × 10(-5)). Only one falls into a haplotype previously associated with other cancer types (rs7705526, in TERT intron 1), and this SNP has been shown to alter TERT promoter activity. One of the novel associations (rs13174814) maps to a second region in the TERT promoter and the other (rs62329728) is in the promoter region of CLPTM1L; neither are correlated with previously reported cancer-associated SNPs. Using TCGA RNASeq data, we found significantly increased expression of both TERT and CLPTM1L in endometrial cancer tissue compared with normal tissue (TERT P = 1.5 × 10(-18), CLPTM1L P = 1.5 × 10(-19)). Our study thus reports a novel endometrial cancer risk locus and expands the spectrum of cancer types associated with genetic variation at 5p15, further highlighting the importance of this region for cancer susceptibility.This work was supported by the NHMRC Project Grant (ID#1031333). This work was also supported by Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692)This is the published version. It first appeared at http://link.springer.com/article/10.1007%2Fs00439-014-1515-4

Restricted Attentional Capacity within but Not between Sensory Modalities: An Individual Differences Approach

Background Most people show a remarkable deficit to report the second of two targets when presented in close temporal succession, reflecting an attentional blink (AB). An aspect of the AB that is often ignored is that there are large individual differences in the magnitude of the effect. Here we exploit these individual differences to address a long-standing question: does attention to a visual target come at a cost for attention to an auditory target (and vice versa)? More specifically, the goal of the current study was to investigate a) whether individuals with a large within-modality AB also show a large cross-modal AB, and b) whether individual differences in AB magnitude within different modalities correlate or are completely separate. Methodology/Principal Findings While minimizing differential task difficulty and chances for a task-switch to occur, a significant AB was observed when targets were both presented within the auditory or visual modality, and a positive correlation was found between individual within-modality AB magnitudes. However, neither a cross-modal AB nor a correlation between cross-modal and within-modality AB magnitudes was found. Conclusion/Significance The results provide strong evidence that a major source of attentional restriction must lie in modality-specific sensory systems rather than a central amodal system, effectively settling a long-standing debate. Individuals with a large within-modality AB may be especially committed or focused in their processing of the first target, and to some extent that tendency to focus could cross modalities, reflected in the within-modality correlation. However, what they are focusing (resource allocation, blocking of processing) is strictly within-modality as it only affects the second target on within-modality trials. The findings show that individual differences in AB magnitude can provide important information about the modular structure of human cognition

Etude de l’impact de l’indice de masse corporelle sur les paramètres polysomnographiques chez les patients avec une plainte du sommeil ou de la vigilance -- Psychiatrie

Introduction: L’objectif de cette étude est de permettre la réalisation d’un premier diagnostic de probabilité chez les patients se présentant en consultation pour des plaintes du sommeil ou de la veille en se basant sur l’IMC et l’ESS qui sont deux valeurs simples à obtenir, rapides et peu coûteuse.Méthodes: Nous avons étudié de manière rétrospective les données de 188 patients ayant bénéficié d’une polysomnographie à de l’hôpital Erasme au cours de l’année 2012. Les patients ont été répartis, indépendamment de leur pathologie du sommeil, en 4 groupes selon l’IMC (groupe 1 :18kg/m²≤ IMC <25kg/m², groupe 2 :25kg/m²≤ IMC <30kg/m², groupe 3 :30kg/m²≤ IMC <35kg/m² et groupe 4 :IMC ≥35kg/m²) et en 2 groupes selon l’ESS (groupe A :ESS <10 et groupe B :ESS ≥10). A l’aide du logiciel SPSS, nous avons réalisé une analyse multivariée pour rechercher une interaction entre l’IMC et l’ESS au niveau des différents paramètres de sommeil.Résultats: Une interaction significative a été mise en évidence entre l’IMC et l’ESS au niveau de l’index d’apnée (p=0.010) et de l’index de désaturation (p=0.032) lorsque l’IMC est ≥35kg/m² et l’ESS est ≥10. Ces critères ont une sensibilité de 89%, une spécificité de 60%, une VPP de 60% et une VPN 90% pour le diagnostic de SAS.Conclusion: En cas d’IMC ≥35kg/m², avoir un ESS ≤10 permet d’exclure la présence d’un SAS. Cependant, en cas de score d’ESS ≥10, il n’est pas possible de poser le diagnostic de SAS avec certitude en raison de la faible spécificité et VPP de ces critères.info:eu-repo/semantics/nonPublishe

Application de la thérapie cognitivo-comportementale de l’insomnie chez un sujet déprimé majeur en rémission avec insomnie résiduelle -- Certificat d’Université en Traitements cognitivo-comportementaux de l’Insomnie (ULB)

L’insomnie résiduelle chez le sujet déprimé majeur en rémission est un facteur de risque bien identifié de rechute dépressive. Or, la TCCI semble permettre une amélioration voire même une rémission de cette plainte d’insomnie résiduelle chez le sujet déprimé majeur en rémission. L’efficacité de ce traitement chez ces sujets ouvre de nouvelles possibilités thérapeutiques pour la prévention des rechutes dépressives et l’amélioration de leur qualité de vie. De plus, le fait d’avoir suivi le patient avant sa TCCI dans le cadre de la prise en charge de son épisode dépressif majeur semble avoir eu un effet très positif sur la compliance et l’adhérence du patient à la thérapie. En effet, dès le début de la TCCI, le patient était très réceptif aux différentes consignes car une relation de confiance solide s’était déjà créée lors de ce suivi préalable ce qui confirme l’importance du contact humain dans la réussite de ce type de thérapie.info:eu-repo/semantics/nonPublishe

La vaccination: Entre intox et réalité

SCOPUS: ed.jinfo:eu-repo/semantics/publishe