Effect of exercise training on respiration and reactive oxygen species metabolism in eel red muscle.

International audienceThis paper deals with the effects of exercise training on oxygen consumption (MO(2)) and ROS metabolism in the red muscle of trained and untrained female silver eels. Their critical swimming speed (U(crit)) was determined before and after a 4-day training (10h of swimming at 70% of U(crit) and 14 h at 50%, every day). The U(crit) of trained eels increased significantly (by about 7%). The in vitro MO(2) and ROS production by the red fibres were higher (not significant) in trained than in untrained eels, but the ROS production/MO(2) ratio was alike in both groups. The antioxidant-enzyme activities and lipoperoxidation index in trained eels were both lower than those of the untrained ones. These biochemical changes related to the increase in U(crit) suggest that such a training session could maintained or even increased aerobic power of the red muscle without deleterious impact by ROS. These regulations could play a role in the eel's swimming performance efficiency

In vitro aerobic and anaerobic muscle capacities in the European eel, Anguilla anguilla: effects of a swimming session.

International audienceIn order to have a general view of metabolic requirements during swimming, in vitro aerobic and anaerobic fluxes were measured in red and white muscles from silver eels and yellow eels which differ in activity levels and nutritional states. These measurements were performed in control eels and after a 4 day swimming session (70% U(crit) in yellow eels, 80% U(crit) in silver eels). A swimming session significantly increases U(crit) from 12% to 18%, depending on the stage, with a significantly higher in vitro energy cost during the yellow stage at the muscle level. In vitro, the swimming session brings about a gain in anaerobic capacities rather than in aerobic ones. Some in vivo hypotheses are proposed

Sanatoriums en France : patrimoine minoritaire ?

Les sanatoriums sont aujourd’hui des lieux en friches pour la plupart, héritiers d’une localisation périphérique, invisibilisée autant qu’ils sont le témoin d’une pensée architecturale, géographique et médicale du rapport au paysage en contemplation comme moyen thérapeutique. Ils constituent aujourd’hui un patrimoine rarement mis en valeur même lorsqu’ils sont inscrits à un inventaire national, régional ou départemental. Parfois détruit, parfois reconverti en Epahd, ou autre-lieu c’est autant leur gigantisme que la charge mémorielle liée à la contagiosité de la tuberculose et donc à la mort qui les met à l’écart et perdure à en faire des marges.Les sanatoriums en France sont construits tardivement par rapport à d’autres territoires et pour nombre d’entre eux ils n’ont auront été en activité de soin contre la tuberculose que quelques années. Ils auront également abrité toute forme de détournement médical et économique (accueil de silicosés dans les services de traitement contre la tuberculose). Les sanatoriums sont donc à la fois un révélateur de l’empreinte spatiale de politiques d’aménagement et de santé passés et celui d’un déni de patrimonialisation

Assessment of Takayasu's arteritis activity by ultrasound localization microscopy

International audienceBackground: Ultrasound localization microscopy (ULM) based on ultrafast ultrasound imaging of circulating microbubbles (MB) can image microvascular blood flows in vivo up to the micron scale. Takayasu arteritis (TA) has an increased vascularisation of the thickened arterial wall when active. We aimed to perform vasa vasorum ULM of the carotid wall and demonstrate that ULM can provide imaging markers to assess the TA activity.Methods: Patients with TA were consecutively included with assessment of activity by the National Institute of Health criteria: 5 had active TA (median age 35.8 [24.5-46.0] years) and 11 had quiescent TA (37.2 [31.7-47.3] years). ULM was performed using a 6.4 MHz probe and a dedicated imaging sequence (plane waves with 8 angles, frame rate 500 Hz), coupled with the intravenous injection of MB. Individual MB were localised at a subwavelength scale then tracked, allowing the reconstruction of the vasa vasorum flow anatomy and velocity.Findings: ULM allowed to show microvessels and to measure their flow velocity within the arterial wall. The number of MB detected per second in the wall was 121 [80-146] in active cases vs. 10 [6-15] in quiescent cases (p = 0.0005), with a mean velocity of 40.5 [39.0-42.9] mm.s-1 in active cases.Interpretation: ULM allows visualisation of microvessels within the thickened carotid wall in TA, with significantly greater MB density in active cases. ULM provides a precise visualisation in vivo of the vasa vasorum and gives access to the arterial wall vascularisation quantification.Funding: French Society of Cardiology. ART (Technological Research Accelerator) biomedical ultrasound program of INSERM, France

Sanatoriums en France : patrimoine minoritaire ?

Les sanatoriums sont aujourd’hui des lieux en friches pour la plupart, héritiers d’une localisation périphérique, invisibilisée autant qu’ils sont le témoin d’une pensée architecturale, géographique et médicale du rapport au paysage en contemplation comme moyen thérapeutique. Ils constituent aujourd’hui un patrimoine rarement mis en valeur même lorsqu’ils sont inscrits à un inventaire national, régional ou départemental. Parfois détruit, parfois reconverti en Epahd, ou autre-lieu c’est autant leur gigantisme que la charge mémorielle liée à la contagiosité de la tuberculose et donc à la mort qui les met à l’écart et perdure à en faire des marges.Les sanatoriums en France sont construits tardivement par rapport à d’autres territoires et pour nombre d’entre eux ils n’ont auront été en activité de soin contre la tuberculose que quelques années. Ils auront également abrité toute forme de détournement médical et économique (accueil de silicosés dans les services de traitement contre la tuberculose). Les sanatoriums sont donc à la fois un révélateur de l’empreinte spatiale de politiques d’aménagement et de santé passés et celui d’un déni de patrimonialisation

Women Specific Characteristics and 1-Year Outcome Among Patients Hospitalized for Peripheral Artery Disease: A Monocentric Cohort Analysis in a Tertiary Center

International audienceAlthough women have lower age-standardized cardiovascular disease incidence, prevalence, and death-related rates than men, there are also reports indicating that women with cardiovascular disease receive less care, fewer investigations, and have poorer outcomes after a coronary event. The aims of this study were to compare the characteristics of men and women hospitalized for peripheral artery disease (PAD), their cardiovascular and limb outcomes, and their 1-year mortality. The study is a prospective registry collecting data about all consecutive patients hospitalized for PAD within the vascular department of the tertiary center Georges-Pompidou European Hospital (Paris, France). Patients were required to have one of three inclusion criteria: previous revascularization of the lower limb or any lower limb artery occlusion due to an atherosclerotic vascular disease or hemodynamic evidence of PAD. Exclusion criteria were patients with lower extremity arterial occlusion due to another cause. All patients were followed-up for at least 12 months after the initial hospitalization. Among the 235 patients included, there were 61 women (26%), older than men with a median age of 75.6 and 68.3 years, respectively. Main cardiovascular risk factors and comorbidities were similar for men and women except more former or current smokers [145 (83.4%) vs. 33 (54.1%)] and more history of coronary heart disease [42 (24.1%) vs. 7 (11.5%)] in men. Most patients [138 (58.8%)] had critical limb ischemia and 97 (41.3%) had claudication, with no difference for sex. After discharge, 218 patients received an antithrombotic therapy (93.2%), 195 a lipid-lowering drug (83.3%), 185 an angiotensin converting enzyme inhibitor or angiotensin-receptor blocker (78.9%), similarly between sex. At 1-year, overall mortality, major adverse cardiovascular events, major adverse limb events did not differ with 23 (13.2%), 11 (6.3%) and 32 (18.4%) in men, and 8 (13.1%), 3 (4.9%), 15 (24.6%) in women, respectively, despite the difference in age. Overall mortality, cardiovascular outcomes, limb revascularization or amputation did not differ between men and women, 1-year after hospitalization for PAD although the latter were older, less smoker and had less coronary artery disease. Due to the small size of this cohort, larger studies and future research are needed to better understand sex-specific mechanisms in the pathophysiology and natural history of PAD

Carotid Plaque Vulnerability Assessed by Combined Shear Wave Elastography and Ultrafast Doppler Compared to Histology

International audienceUltrafast ultrasound imaging (UUI) provides an estimation of carotid plaque stiffness by shear wave elastography (SWE) and the quantification of wall shear stress (WSS) by ultrafast Doppler. We aimed to evaluate the combined criteria of plaque stiffness and WSS applied on the plaque as potential biomarkers of plaque vulnerability assessed by histology. We included patients for whom carotid endarterectomy had been decided by a multidisciplinary team. UUI was performed within 48 h before surgery, and acquisitions were obtained on a carotid longitudinal view. After endarterectomy, gross examination and histological analysis were performed on each removed plaque. Forty-six plaques with SWE data and 29 with WSS data were analyzed. Histological analysis revealed 29 vulnerable and 17 stable plaques. Gray-scale median analysis by B-mode, mean, and standard deviation of stiffness by SWE did not differ between vulnerable and stable plaques. SWE analysis revealed that the percentage of stiffness range of 3-5 m/s was significantly increased in vulnerable plaques (p = 0.048). WSS alone showed no difference between stable and vulnerable plaques regardless of the segment of the plaque which was analyzed. A multiparametric score using maximal WSS at the peak of the plaque associated with SWE texture analysis parameters was calculated by stepwise regression, leading to a score with a sensitivity of 80% and a specificity of 78%. Area under the receiver operating characteristics curve was 0.85. A multiparameter scoring system including plaque stiffness and flow analysis using UUI allows to effectively identify histologically vulnerable carotid plaques. ClinicalTrials.gov Identifier: NCT03234257

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old