Vitamin D and Bone Health; Potential Mechanisms

Osteoporosis is associated with increased morbidity, mortality and significant economic and health costs. Vitamin D is a secosteriod hormone essential for calcium absorption and bone mineralization which is positively associated with bone mineral density [BMD]. It is well-established that prolonged and severe vitamin D deficiency leads to rickets in children and osteomalacia in adults. Sub-optimal vitamin D status has been reported in many populations but it is a particular concern in older people; thus there is clearly a need for effective strategies to optimise bone health. A number of recent studies have suggested that the role of vitamin D in preventing fractures may be via its mediating effects on muscle function (a defect in muscle function is one of the classical signs of rickets) and inflammation. Studies have demonstrated that vitamin D supplementation can improve muscle strength which in turn contributes to a decrease in incidence of falls, one of the largest contributors to fracture incidence. Osteoporosis is often considered to be an inflammatory condition and pro-inflammatory cytokines have been associated with increased bone metabolism. The immunoregulatory mechanisms of vitamin D may thus modulate the effect of these cytokines on bone health and subsequent fracture risk. Vitamin D, therefore, may influence fracture risk via a number of different mechanisms

The handbook for standardized field and laboratory measurements in terrestrial climate change experiments and observational studies (ClimEx)

1. Climate change is a world‐wide threat to biodiversity and ecosystem structure, functioning and services. To understand the underlying drivers and mechanisms, and to predict the consequences for nature and people, we urgently need better understanding of the direction and magnitude of climate change impacts across the soil–plant–atmosphere continuum. An increasing number of climate change studies are creating new opportunities for meaningful and high‐quality generalizations and improved process understanding. However, significant challenges exist related to data availability and/or compatibility across studies, compromising opportunities for data re‐use, synthesis and upscaling. Many of these challenges relate to a lack of an established ‘best practice’ for measuring key impacts and responses. This restrains our current understanding of complex processes and mechanisms in terrestrial ecosystems related to climate change. 2. To overcome these challenges, we collected best‐practice methods emerging from major ecological research networks and experiments, as synthesized by 115 experts from across a wide range of scientific disciplines. Our handbook contains guidance on the selection of response variables for different purposes, protocols for standardized measurements of 66 such response variables and advice on data management. Specifically, we recommend a minimum subset of variables that should be collected in all climate change studies to allow data re‐use and synthesis, and give guidance on additional variables critical for different types of synthesis and upscaling. The goal of this community effort is to facilitate awareness of the importance and broader application of standardized methods to promote data re‐use, availability, compatibility and transparency. We envision improved research practices that will increase returns on investments in individual research projects, facilitate second‐order research outputs and create opportunities for collaboration across scientific communities. Ultimately, this should significantly improve the quality and impact of the science, which is required to fulfil society's needs in a changing world

Régulation de l'expression du gène codant la protéine ribosomique L20 chez la bactérie Escherichia coli

La protéine ribosomique L20 d Escherichia coli est une protéine essentielle. Elle a deux fonctions. Elle est indispensable à l étape précoce de l assemblage du ribosome; et elle réprime l expression du gène rpmI. La région de l ARNm nécessaire à ce contrôle est appelée opérateur traductionnel. Il a été montré que la protéine L20 pouvait se fixer à deux sites de cet opérateur. Les deux sites sont essentiels au contrôle. Le mécanisme de ce contrôle peut être divisé en deux étapes: la fixation de la protéine L20 à l ope rateur et l effet de cette fixation sur l expression du gène. Nous avons montré qu une seule molécule de protéine L20 se fixait à l ARNm, et ce malgré la présence des deux sites de fixation. Nous avons également montré que le contrôle était basé sur un mécanisme de compétition. Nous nous sommes également intéressés au double rôle que joue la protéine dans l assemblage et dans le contrôle en y introduisant des mutations.PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Apical four-chamber longitudinal left ventricular strain in patients with aortic stenosis and preserved left ventricular ejection fraction analysis related with flow/gradient pattern and association with outcome

International audienceAims - To evaluate the prognostic value of apical four-chamber (A4-C) longitudinal strain (LS) in patients with aortic stenosis (AS). Methods and results - In a multicentre cohort, 582 patients (74.3 ± 10.9 years) with moderate or severe AS and preserved left ventricular (LV) ejection fraction (≥50%) were included in this retrospective study. Patients with severe AS were classified in four subgroups according to flow and gradient: low flow (LF) was defined as a stroke volume index <35 mL/m2 compared with normal flow (NF); low-gradient (LG) as a mean gradient <40 mmHg compared with high gradient (HG). The end point was all-cause of mortality. A4-C LS was measured by two-dimensional speckle tracking and was feasible in all patients. The degree of A4-C LV longitudinal dysfunction increased according to the severity and subgroups of severe AS: from the least to the most impaired: moderate AS, NF/HG, NF/LG, LF/HG, and LF/LG AS (P < 0.001). During a mean follow-up of 2.6 ± 0.2 years, 58(10%) patients died. The 2-year survival was 76.8% in patients with LF/LG vs. 89.3% in patients with other groups. The best threshold of A4-C LS associated with overall mortality was an absolute cut-off value of |13.75%|. According to this cut-off, the 2-year survival was higher both in patients with moderate AS (96.3 vs. 70%, P = 0.02) and those with severe AS (92.9 vs. 80.9%, P = 0.005). However when dichotomized according to flow/gradient patterns, the association was only statistically significant in the subgroup of patients with NF/HG. By multivariable cox regression analysis, A4-C LS <|13.75| remained independently associated with overall mortality (hazard ratio: 1.8; P = 0.045). Conclusion - A4-C LS is independently associated with death in patients with AS and preserved LVEF, however the flow/gradient pattern should also be considered as an important parameter. The management of these patients may use A4-C LS as a new parameter of evaluation of LV function and prognosis

Coronary events complicating infective endocarditis

International audienceOBJECTIVE: Acute coronary syndromes (ACS) are a rare complication of infective endocarditis (IE). Only case reports and small studies have been published to date. We report the largest series of ACS in IE. The aim of our study was to describe the incidence and mechanisms of ACS associated with IE, to assess their prognostic impact and to describe their management. METHODS: In a bicentre prospective observational cohort study, all patients with a definite diagnosis of IE were prospectively included. The incidence, mechanism and prognosis of patients with ACS were studied. RESULTS: Among 1210 consecutive patients with definite IE, 26 patients (2.2%) developed an ACS. Twenty-three patients (88%) had a coronary embolism. Two patients had coronary compression by an abscess or a pseudoaneurysm and one patient had an obstruction of his bioprosthesis and left coronary ostium by a large vegetation. Nineteen (73%) patients with ACS developed heart failure and this complication was 2.5 times more frequent than in patients without ACS (p\textless0.0001). In the ACS population, mortality rate was twice than the population without ACS. CONCLUSIONS: ACS is a rare complication of IE but is associated with an increased risk of heart failure and high mortality rate

Targeted panel sequencing in adult patients with left ventricular non-compaction reveals a large genetic heterogeneity

International audienceLeft ventricular non-compaction (LVNC) is a cardiomyopathy that may be of genetic origin; however, few data are available about the yield of mutation, the spectrum of genes and allelic variations. The aim of this study was to better characterize the genetic spectrum of isolated LVNC in a prospective cohort of 95 unrelated adult patients through the molecular investigation of 107 genes involved in cardiomyopathies and arrhythmias. Fifty-two pathogenic or probably pathogenic variants were identified in 40 patients (42%) including 31 patients (32.5%) with single variant and 9 patients with complex genotypes (9.5%). Mutated patients tended to have younger age at diagnosis than patients with no identified mutation. The most prevalent genes were TTN, then HCN4, MYH7, and RYR2. The distribution includes 13 genes previously reported in LVNC and 10 additional candidate genes. Our results show that LVNC is basically a genetic disease and support genetic counseling and cardiac screening in relatives. There is a large genetic heterogeneity, with predominant TTN null mutations and frequent complex genotypes. The gene spectrum is close to the one observed in dilated cardiomyopathy but with specific genes such as HCN4. We also identified new candidate genes that could be involved in this sub-phenotype of cardiomyopathy

Whole Exome Sequencing Reveals a Large Genetic Heterogeneity and Revisits the Causes of Hypertrophic Cardiomyopathy

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Diagnosis of Infective Endocarditis After TAVR

International audienc

Personal and psychosocial impacts of clinical fracture in men

Background : Little is known about the personal burden of fracture across the age spectrum, particularly in men. This study aimed to document the impact of clinical fracture on men\u27s participation in employment, sports and outdoor recreation, mobility, handiwork, activities of daily living, home modification, and utilisation of community and health services.Methods : This prospective study followed 196 men with incident fracture identified from radiology reports at the Geelong Hospital during the period July 2006 to December 2007 and examined personal and psychosocial impacts 12 months post-fracture, using a self-report questionnaire.Results : Of all men identified with fracture, 40% took time off work. All fractures, except those to the upper limbs, had considerable impact on mobility. Inability to drive was associated with all fractures, but was most common with ankle fractures and most prolonged with hip fractures. Loss of confidence was reported by over one-third of all fracture cases, even 12 months after the fracture event. All fractures affected activities of daily living, and this was generally most prolonged for fractures of the hip. Similarly, all men with fracture utilised community and health services, even for the relatively minor fractures of the finger/thumb.Conclusions : This study supports previous reports of the personal impact of hip fracture, and presents data about the consequences of upper and lower limb fractures and the generally poorly described sequelae of fractures of the finger/thumb and foot/toe. These observations have important implications for post-fracture care and rehabilitation in men