Measure of health-related quality of life in interventional studies aiming at the management of sarcopenia: results from a systematic literature review

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Predictors of 8-year survival in nursing homes: results from the SENIOR cohort

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Investigation of the relationships between frailty, nutritional status and muscle strength and the incidence and severity of Covid-19 among the residents of nursing homes. Results from the SENIOR cohort

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High pressure and high temperature in situ X-ray diffraction studies in the Paris-Edinburgh cell using a laboratory X-ray source

International audienceWe have developed a new laboratory experimental set-up to study in situ the pressure-temperature phase diagram of a given pure element or compound, its associated phase transitions, or the chemical reactions involved at high pressure and high temperature (HP-HT) between different solids and liquids. This new tool allows laboratory studies before conducting further detailed experiments using more brilliant synchrotron X-ray sources or before kinetic studies. This device uses the diffraction of X-rays produced by a quasi-monochromatic micro-beam source operating at the silver radiation (λ(Ag)Kα1,2 ≈ 0.56Å). The experimental set-up is based on a VX Paris-Edinburgh cell equipped with tungsten carbide or sintered diamond anvils and uses standard B-epoxy 5 or 7mm gaskets. The diffracted signal coming from the compressed (and heated) sample is collected on an image plate. The pressure and temperature calibrations were performed by diffraction, using conventional calibrants (BN, NaCl and MgO) for determination of the pressure, and by crossing isochores of BN, NaCl, Cu or Au for the determination of the temperature. The first examples of studies performed with this new laboratory set-up are presented in the article: determination of the melting point of germanium and magnesium under HP-HT, synthesis of MgB2 or C-diamond and partial study of the P, T phase diagram of MgH2

The interconnection between Covid-19, sarcopenia and lifestyle

peer reviewedIn March 2020, Covid-19 was declared a global pandemic by the World Health Organization. Infection with Sars-Cov-2, the virus responsible for Covid-19, can have a wide range of consequences, the severity of which depends on the individual [1]. Moreover, this vulnerability is increased by the presence of comorbidities such as chronic respiratory disease, diabetes, hypertension and other pathologies affecting immunity [2]. Also, musculoskeletal disorders, and particularly sarcopenia, have recently been suggested to be either a consequence of [3] or a risk factor for [4] Covid-19. For example, studies have reported muscle damage in patients hospitalized for Covid-19 and greater loss of muscle function in older women living independently during the pandemic [5], [6]. Some studies, but not all, have also highlighted that low skeletal muscle mass and reduced muscle strength are associated with higher severity of Covid-19 [7], [8], [9]. Very recently, histopathological changes in muscle, such as muscle atrophy, have also been identified in patients complaining of long-term Covid-19 symptoms, including fatigue and weakness [10]. In addition, results from a meta-analysis highlighted a twofold greater risk of getting severe complications and of mortality due to Covid-19 for sarcopenic people compared with non-sarcopenic ones [4]

Huntingtin proteolysis releases non-polyQ fragments that cause toxicity through dynamin 1 dysregulation

Cleavage of mutant huntingtin (HTT) is an essential process in Huntington's disease (HD), an inherited neurodegenerative disorder. Cleavage generates N-ter fragments that contain the polyQ stretch and whose nuclear toxicity is well established. However, the functional defects induced by cleavage of full-length HTT remain elusive. Moreover, the contribution of non-polyQ C-terminal fragments is unknown. Using time- and site-specific control of full-length HTT proteolysis, we show that specific cleavages are required to disrupt intramolecular interactions within HTT and to cause toxicity in cells and flies. Surprisingly, in addition to the canonical pathogenic N-ter fragments, the C-ter fragments generated, that do not contain the polyQ stretch, induced toxicity via dilation of the endoplasmic reticulum (ER) and increased ER stress. C-ter HTT bound to dynamin 1 and subsequently impaired its activity at ER membranes. Our findings support a role for HTT on dynamin 1 function and ER homoeostasis. Proteolysis-induced alteration of this function may be relevant to disease. Synopsis The development of a time and site-specifically controlled cleavage of the mutant huntingtin protein reveals a pathogenic mechanism induced by the non-polyQ-containing fragments that are generated upon proteolysis during disease progression. Huntingtin proteolysis generates N-ter fragments that contain the toxic polyQ stretch but also the corresponding C-ter fragments. N-ter to C-ter intramolecular interactions present in full-length huntingtin are abrogated by sequential cleavages. Whereas the N-ter polyQ fragments translocate into the nucleus, the non-polyQ C-ter huntingtin fragments remain in the cytoplasm and cause ER dilation, stress and cell death. C-ter huntingtin fragments bind and inactivate dynamin 1 at the ER thus causing ER dilation and toxicity. Site-specifically controlled cleavage of the mutant huntingtin protein reveals a pathogenic mechanism induced by non-polyQ-containing fragments that are generated upon proteolysis during disease progression.</p

Efficacy of osteoporosis pharmacological treatments in men: a systematic review and meta-analysis.

peer reviewed[en] INTRODUCTION: The objective of this systematic review and meta-analysis is to systematically identify and review the efficacy of pharmacological treatments in men with osteoporosis. METHODS: Medline (via Ovid) and Cochrane CENTRAL were searched up to May 2023 for any randomized controlled trial (RCT) evaluating the efficacy of osteoporotic treatment on the evolution of Bone Mineral Density (BMD) and incidence of fractures of men suffering from primary osteoporosis. If at least two studies used the same pharmacological treatment and evaluated the same outcome, a random effect model meta-analysis was applied to reported pooled mean difference (MD) and 95% confidence interval (CI). RESULTS: From the 1,061 studies identified through bibliographic search, 21 RCTs fitted the inclusion criteria. Bisphosphonates (k = 10, n = 2992 men with osteoporosis) improved all three BMD sites compared to placebo; lumbar spine: MD + 4.75% (95% CI 3.45, 6.05); total hip: MD + 2.72% (95% CI 2.06; 3.37); femoral neck: MD + 2.26% (95% CI 1.67; 2.85). Denososumab (k = 2, n = 242), Teriparatide (k = 2, n = 309) and Abaloparatide (k = 2, n = 248) also produced significant improvement of all sites BMD compared to placebo. Romosozumab was only identified in one study and was therefore not meta-analysed. In this study, Romosozumab increased significantly BMD compared to placebo. Incident fractures were reported in 16 RCTs but only four reported fractures as the primary outcome. Treatments were associated with a lower incidence of fractures. CONCLUSIONS: Medications used in the management of osteoporosis in women appear to provide similar benefits in men with osteoporosis. Therefore, the algorithm for the management of osteoporosis in men could be similar to the one previously recommended for the management of osteoporosis in women

Association of circulating hsa-miRNAs with sarcopenia: the SarcoPhAge study.

peer reviewed[en] OBJECTIVE: To identify a microRNA signature associated to sarcopenia in community-dwelling older adults form the SarcoPhAge cohort. METHODS: In a screening phase by next generation sequencing (NGS), we compared the hsa-miRome expression of 18 subjects with sarcopenia (79.6 ± 6.8 years, 9 men) and 19 healthy subjects without sarcopenia (77.1 ± 6 years, 9 men) at baseline. Thereafter, we have selected eight candidate hsa-miRNAs according to the NGS results and after a critical assessment of previous literature. In a validation phase and by real-time qPCR, we then analyzed the expression levels of these 8 hsa-miRNAs at baseline selecting 92 healthy subjects (74.2 ± 10 years) and 92 subjects with sarcopenia (75.3 ± 6.8 years). For both steps, the groups were matched for age and sex. RESULTS: In the validation phase, serum has-miRNA-133a-3p and has-miRNA-200a-3p were significantly decreased in the group with sarcopenia vs controls [RQ: relative quantification; median (interquartile range)]: -0.16 (-1.26/+0.90) vs +0.34 (-0.73/+1.33) (p < 0.01) and -0.26 (-1.07/+0.68) vs +0.27 (-0.55/+1.10) (p < 0.01) respectively. Has-miRNA-744-5p was decreased and has-miRNA-151a-3p was increased in the group with sarcopenia vs controls, but this barely reached significance: +0.16 (-1.34/+0.79) vs +0.44 (-0.31/+1.00) (p = 0.050) and  +0.35 (-0.22/+0.90) vs  +0.03 (-0.68/+0.75) (p = 0.054). CONCLUSION: In subjects with sarcopenia, serum hsa-miRNA-133a-3p and hsa-miRNA-200a-3p expression were downregulated, consistent with their potential targets inhibiting muscle cells proliferation and differentiation