Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci.

Bone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown. We used a novel genetic pleiotropy-informed conditional False Discovery Rate (FDR) method to identify single nucleotide polymorphisms (SNPs) associated with BMD by leveraging cardiovascular disease (CVD) associated disorders and metabolic traits. By conditioning on SNPs associated with the CVD-related phenotypes, type 1 diabetes, type 2 diabetes, systolic blood pressure, diastolic blood pressure, high density lipoprotein, low density lipoprotein, triglycerides and waist hip ratio, we identified 65 novel independent BMD loci (26 with femoral neck BMD and 47 with lumbar spine BMD) at conditional FDR < 0.01. Many of the loci were confirmed in genetic expression studies. Genes validated at the mRNA levels were characteristic for the osteoblast/osteocyte lineage, Wnt signaling pathway and bone metabolism. The results provide new insight into genetic mechanisms of variability in BMD, and a better understanding of the genetic underpinnings of clinical comorbidity

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Statins and metformin in digestive tract cancers : pattern of use and its association with disease progression

With the increasing life expectancy, the incidence of cancers is expected to rise worldwide. Consequently, cancer is thought to become the most important barrier to life expectancy in the future. Research on affordable and efficient alternatives to increase diagnosed individuals’ survival are required. The present thesis illustrates how linkage between a cancer registry and administrative databases can lead to high-quality epidemiological studies aiming to assess the association between commonly prescribed drugs and cancers survival. At the Belgian population level, the present work has shown a protective association between statins and metformin in esophageal as well as gastric cancers, respectively. Despite such encouraging results, the present work has also highlighted poor adherence to the two selected drugs despite a high volume of prescriptions.(MED - Sciences médicales) -- UCL, 202

Surface modification of calcium carbonate nanofillers by fluoro- and alkyl-alkoxysilane: Consequences on the morphology, thermal stability and gas barrier properties of polyvinylidene fluoride nanocomposites

International audienceNano-sized precipitated silica coated calcium carbonate fillers (PCC-Si) were modified by an alkyl- and a fluoro-alkoxysilane derivative, respectively. PCC-Si surface modification was characterized by elemental analysis, Fourier transform infrared analysis and X-ray photoelectron spectroscopy. The modification conditions used for surface treatment led to a similar grafting density (around 3.2 mu mol m(-2)) for the two alkoxysilane derivatives. A significant decrease of filler hydrophilicity was observed after the alkoxysilane treatment. Nanocomposites prepared by melt mixing the modified fillers (10 wt.%) with polyvinylidene fluoride (PVDF) depicted no color change, an enhanced filler dispersion state with an homogeneous dispersion of very small filler aggregates (less than 150 nm diameter size), an increase of the thermal stability at high temperature and no change of the PVDF crystalline morphology. The oxygen permeability decrease measured on the nanocomposite prepared from the perfluorooctyltriethoxysilane modified filler was in good agreement with Maxwell law. The permeability increase evidenced for the nanocomposite based on the octyltriethoxysilane modified PCC suggested the formation of weak interfaces in this system

Beta-blocker use and mortality following ovarian cancer diagnosis: a population-based study.

BACKGROUND: Preclinical studies suggest that β-blockers could exhibit anticancer properties in ovarian cancer. Similar effects have also been reported in observational studies, but their results remain inconsistent and could be impaired by methodological limitations. This study aimed to investigate whether β-blocker use is associated with improved survival in ovarian cancer patients at the Belgian population level. METHODS: We conducted a population-based study by linking data of the Belgian Cancer Registry with medical claims data of the health insurance companies for patients diagnosed with ovarian cancer between 2004 and 2014. Information on ovarian-cancer-specific deaths was retrieved from mortality records collected by regional governments. Use of β-blockers was modelled as a time-varying covariate in Cox regression models to calculate adjusted hazards ratios (HRs) and 95% confidence intervals (95%CIs) for the association between postdiagnostic β-blocker exposure and overall or cancer-specific survival (OS and CSS, respectively). Adjustments were made for age at diagnosis, year of diagnosis, comorbidities, cancer stage, and cancer treatments. RESULTS: In our population of 6197 patients, 2373 patients (38%) had at least one prescription of β-blockers in the 5 years following diagnosis. Postdiagnostic exposure to β-blockers was associated with a significant decrease in OS (adjusted HR, 1.21, 95%CI 1.12;1.30, p < 0.001) and CSS (adjusted HR, 1.17, 95%CI 1.07;1.29, p < 0.001). Moreover, this association remained similar in dose-response analyses, in subgroup analyses (including by β-blocker selectivity types), and in sensitivity analyses. CONCLUSION: In this large nationwide cohort of ovarian cancer patients, β-blocker users had reduced survival

Impact of metformin on gastric adenocarcinoma survival: A Belgian population based study

Background: Preclinical studies have shown anticancer activities of metformin in gastric cancer and a recent epidemiological study showed a decrease in recurrence and mortality of gastric cancer in metformin users. This study aimed to assess the impact of metformin on gastric cancer survival in diabetic patients at a Belgian population level. Methods: We conducted an observational, population-based study by linking data of the Belgian Cancer Registry with medical claims data coming from the health insurance companies for patients diagnosed with stage I to III gastric adenocarcinoma between 2006 and 2012. Information on gastric cancer-specific deaths was retrieved from mortality records collected by regional governments. Time-dependent Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CI) for overall survival (OS) and cancer-specific mortality (CSS). Results: In our population of 371 patients, a reduction in all-cause mortality was observed in metformin users (adjusted HR=0.73, 95% CI: [0.52; 1.01], p=0.06) but not for cancer specific mortality (adjusted HR=0.86, 95% CI: [0.56; 1.33], p=0.50). Pre-diagnosis exposure to metformin was associated with a significant improvement in OS (adjusted HR=0.75, 95% CI: [0.57; 0.98], p=0.04) that was not significant for CSS (adjusted HR=0.89, 95% CI: [0.62; 1.28], p=0.52). Moreover, no dose-response relationship between metformin use and either all-cause or cancer-specific mortality was observed. Conclusion: In the first population based study of metformin use in gastric cancer adenocarcinoma patients with previous diabetes, our findings suggest that metformin use might improve overall mortality. However, no such association was found for cancer-specific survival. Additional studies in other populations are required

Statin use after diagnosis is associated with an increased survival in esophageal cancer patients: a Belgian population-based study

PURPOSE: Preclinical studies have shown that statins reduce proliferation in esophageal cancer. Three recent observational studies have shown encouraging results but suffered from limitations. This work aimed to assess at the Belgian population level whether statin usage was associated with a decreased mortality in esophageal cancer patients. METHODS: We conducted an observational, population-based study by linking data of the Belgian Cancer Registry (BCR) with medical claims data coming from health insurance companies and mortality records collected by regional governments for patients diagnosed with esophageal cancer between 2004 and 2014. Using time-dependent Cox regression models, hazard ratios (HRs) and 95% confidence intervals (CI) for overall and cancer-specific mortality were calculated. RESULTS: Of 6,238 patients with stage I-III esophageal cancer, post-diagnostic use of statins was found in 1,628 (26%) patients. Statins use after diagnosis was associated with a reduction in overall mortality (adjusted HR = 0.84, 95% CI [0.77; 0.92]) and cancer-specific mortality (adjusted HR = 0.87, 95% CI [0.78; 0.97]). Similar association were also seen for pre-diagnostic statin use in overall (adjusted HR = 0.83, 95% CI [0.76-0.91]) and cancer-specific analysis (adjusted HR = 0.86, 95% CI [0.77-0.96]). CONCLUSIONS: In this large cohort of Belgian patients with esophageal cancer, statins use after diagnosis was associated with a decreased mortality

Statin use is associated with improved survival in ovarian cancer: A retrospective population-based study

<div><p>Background</p><p>Preclinical in vitro and in vivo studies suggest that statins could exhibit anticancer properties in ovarian cancer. Similar effects have also been reported in observational studies but their results remain inconsistent and could be impaired by methodological limitations. This study aimed to investigate whether statin use is associated with improved survival in ovarian cancer patients at the Belgian population-level.</p><p>Methods</p><p>All patients with invasive epithelial ovarian cancer diagnosed between 2004 and 2012 were identified from the Belgian Cancer Registry. Vital statuses were obtained from the Crossroads Bank for Social Security and ovarian cancer-specific deaths were identified from death certificates provided by regional administrations. Information on cancer treatments and statin use were retrieved from health insurance databases. Statin use was modelled as a time-varying covariate in Cox regression models to calculate adjusted hazards ratios (HR) and 95% confidence intervals (95%CI) for the association between postdiagnostic exposure to statins and overall- or ovarian cancer-specific mortality within three years after diagnosis. Adjustments were made for age at diagnosis, year of diagnosis, comorbidities, cancer stage, and cancer treatments.</p><p>Results</p><p>A total of 5,416 patients with epithelial ovarian cancer met the inclusion criteria. Of these 1,255 (23%) had at least one statin prescription within three years after diagnosis. Postdiagnostic use of statins was associated with a reduced risk of overall mortality (adjusted HR = 0.81, 95%CI:0.72–0.90, p<0.001). In analyses by statin type, this association was only significant for simvastatin (adjusted HR = 0.86, 95%CI:0.74–0.99, p = 0.05) or rosuvastatin (adjusted HR = 0.71, 95%CI:0.55–0.92, p = 0.01). In subgroup analyses by statin prediagnostic use, the protective association for postdiagnostic statin use was only observed in patients who were also using statins before diagnosis (adjusted HR = 0.73, 95%CI:0.64–0.83, p<0.001). Similar results were observed for ovarian cancer-specific mortality.</p><p>Conclusion</p><p>In this large nation-wide cohort of ovarian cancer patients postdiagnostic use of statins was associated with improved survival.</p></div

Évaluation du descripteur 10 « Déchets marins » en France métropolitaine. Rapport scientifique pour l’évaluation 2024 au titre de la DCSMM.

The descriptor D10 considers macro- and micro- litter in several compartments in marine environment (on the coastline, in the surface layer of the water column and on the seafloor) and their impacts (ingestion, entanglement) on marine species (northern fulmar, loggerhead sea turtle, common shag) at marine sub-region scale (MSR) in Channel-North Sea (CNS), Celtic Seas (CS), Bay of Biscay (BoB) and Western Mediterranean (WM). For the indicator “litter (excluding micro-litter) on the coastline” related with the criterion D10C1, the achievement of Good Environmental Status (GES) is defined by the assessment of the achievement of the threshold of 20 litter/100m. For the other indicators of criteria D10C1 and D10C2, and in the absence of a baseline and threshold (currently being defined by the TG ML), the trends "total quantity of floating litter", "total quantity of seabed litter" and "total quantity of floating micro-litter" are used to qualify the status of the parameter. When this trend expresses an improvement (decrease in litter pollution), a stable level (no change) or an "unknown" trend (statistical reason), it does not allow to conclude on the realization of the parameter, which is then considered as "unknown". When the trend expresses an increase in litter pollution (significant increase), then the parameter is "not achieved", in accordance with the DCSMM principle of non-deterioration of the state. In the absence of rules of integration, the achievement of GES is established at indicator’s level as recommended in the review of the Guidance Document related to the Article 8 of the MSFD (European Commission, 2022). For the MSFD cycle 3, the results for each indicator are filled in the Table 1. The criterion D10C3, indicator “litter ingested by marine turtles” has been evaluated. But, in the absence of threshold value and rules of integration, the status of indicator has been filled « unknown » as recommended in the revision of Art. 8. The criterion D10C4 could not be assessed, because the associated indicators are still in development. However, a “candidate indicator” form has been suggested for “Litter in Cormoran’s nest”.Le descripteur D10 considère les macro- et les micro-déchets dans plusieurs compartiments de l’environnement marin (sur le littoral, en surface et sur les fonds marins) ainsi que leurs impacts (ingestion, étranglements et emmêlements) sur les organismes marins (fulmar boréal, tortue caouanne, cormoran huppé) à l’échelle des Sous-Régions-Marines (SRM) Manche Mer du Nord (MMN), Mers Celtiques (MC), Golfe de Gascogne (GdG) et Méditerranée Occidentale (MO). Pour l’indicateur “déchets (hors micro-déchets)” sur le littoral associé au critère D10C1, l’atteinte du Bon État Écologique (BEE) est définie par l’évaluation de l’atteinte du seuil de 20 déchets/100m. Pour les autres indicateurs des critères D10C1 et D10C2 et en l’absence de niveau de base et de seuil (en cours de définition par le TG ML), les tendances « quantité totale de déchets flottants », « quantité totale de déchets sur les fonds » et « quantité totale de micro-déchets flottants » sont utilisées pour qualifier le statut du paramètre. Lorsque cette tendance exprime une amélioration (diminution de la pollution par les déchets), un niveau stable (pas de changement) ou une tendance « inconnue » (raison statistique), elle ne permet pas de conclure sur la réalisation du paramètre qui est alors considéré comme « inconnu ». Lorsque la tendance exprime une augmentation de la pollution par les déchets (augmentation significative) alors le paramètre est « non atteint », conformément au principe DCSMM de non-détérioration de l'État. En l’absence de règles d’intégration, l’atteinte du BEE se fait au niveau des indicateurs comme préconisé dans la révision du document guide relatif à l’Article 8 de la DCSMM (Commission Européenne, 2022). Pour le cycle 3, les résultats pour chaque indicateur sont renseignés dans le Tableau 1 : Le critère D10C3, indicateur « déchets ingérés par les tortues » a fait l’objet d’une évaluation, cependant en l’absence de seuil et de règle d’intégration des paramètres, le statut de l’indicateur a été renseigné en « inconnu » comme préconisé dans la révision du document guide relatif à l’Art. 8. Le critère D10C4 n’a pas pu faire l’objet d’une évaluation, puisque les indicateurs associés sont en cours de développement. Cependant, une fiche « indicateur candidat » a été proposée pour l’indicateur « Macro-déchets dans les nids de Cormorans huppés »

Flowchart of patients.

<p>NSSN stands for the National Social Security Number in Belgium.</p