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Duchenne muscular dystrophy (DMD) is characterized by progressive muscle wasting following repeated muscle damage and inadequate regeneration. Impaired myogenesis and differentiation play a major role in DMD as well as intracellular calcium (Ca2+) mishandling. Ca2+ release from the sarcoplasmic reticulum is mostly mediated by the type 1 ryanodine receptor (RYR1) that is required for skeletal muscle differentiation in animals. The study objective was to determine whether altered RYR1-mediated Ca2+ release contributes to myogenic differentiation impairment in DMD patients. The comparison of primary cultured myoblasts from six boys with DMD and five healthy controls highlighted delayed myoblast differentiation in DMD. Silencing RYR1 expression using specific si-RNA in a healthy control induced a similar delayed differentiation. In DMD myotubes, resting intracellular Ca2+ concentration was increased, but RYR1-mediated Ca2+ release was not changed compared with control myotubes. Incubation with the RYR-calstabin interaction stabilizer S107 decreased resting Ca2+ concentration in DMD myotubes to control values and improved calstabin1 binding to the RYR1 complex. S107 also improved myogenic differentiation in DMD. Furthermore, intracellular Ca2+ concentration was correlated with endomysial fibrosis, which is the only myopathologic parameter associated with poor motor outcome in patients with DMD. This suggested a potential relationship between RYR1 dysfunction and motor impairment. Our study highlights RYR1-mediated Ca2+ leakage in human DMD myotubes and its key role in myogenic differentiation impairment. RYR1 stabilization may be an interesting adjunctive therapeutic strategy in DMD.

International audience; Introduction: Patients with right stroke lesion have postural and balance disorders, including weight-bearing asymmetry, more pronounced than patients with left stroke lesion. Spatial cognition disorders post-stroke, such as misperceptions of subjective straight-ahead and subjective longitudinal body axis, are suspected to be involved in these postural and balance disorders. Prismatic adaptation has showed beneficial effects to reduce visuomotor disorders but also an expansion of effects on cognitive functions, including spatial cognition. Preliminary studies with a low level of evidence have suggested positive effects of prismatic adaptation on weight-bearing asymmetry and balance after stroke. The objective is to investigate the effects of this intervention on balance but also on postural disorders, subjective straight-ahead, longitudinal body axis and autonomy in patients with chronic right stroke lesion.Methods and analysis: In this multicentre randomised double-blind sham-controlled trial, we will include 28 patients aged from 18 to 80 years, with a first right supratentorial stroke lesion at chronic stage (≥12 months) and having a bearing ≥60% of body weight on the right lower limb. Participants will be randomly assigned to the experimental group (performing pointing tasks while wearing glasses shifting optical axis of 10 degrees towards the right side) or to the control group (performing the same procedure while wearing neutral glasses without optical deviation). All participants will receive a 20 min daily session for 2 weeks in addition to conventional rehabilitation. The primary outcome will be the balance measured using the Berg Balance Scale. Secondary outcomes will include weight-bearing asymmetry and parameters of body sway during static posturographic assessments, as well as lateropulsion (measured using the Scale for Contraversive Pushing), subjective straight-ahead, longitudinal body axis and autonomy (measured using the Barthel Index).Ethics and dissemination: The study has been approved by the ethical review board in France. Findings will be submitted to peer-reviewed journals relative to rehabilitation or stroke.Trial registration number: NCT03154138.

International audience; High-intensity interval training (HIIT) and linseed oil (LO) supplementation are effective strategies to reduce obesity-induced oxidative stress. Our aim was to determine whether the HIIT + LO combination prevents obesity-induced oxidative stress in high fat diet (HFD)-fed rats. HFD-fed 8-week-old, male, Wistar rats were subdivided in four groups: HFD, LO (2% of sunflower oil replaced with 2% of LO in the HFD), HIIT (4 days/week for 12 weeks), and HIIT + LO. Wistar rats fed a low-fat diet (LFD) were used as controls. Epididymal and subcutaneous adipose tissue, gastrocnemius muscle, liver, and plasma samples were collected to measure oxidative stress markers (AOPP, oxLDL), antioxidant (SOD, CAT, and GPx activities) and pro-oxidant (NOx and XO) enzyme activities. Compared with the LFD, the HFD altered the pro/antioxidant status in different tissues (increase of AOPP, oxLDL, SOD and catalase activities in plasma, and SOD activity increase in liver and decrease in adipose tissues) but not in gastrocnemius. LO upregulated CAT activity and decreased NOx in liver. HIIT alleviated HFD negative effects in liver by reducing SOD and NOx activities. Moreover, the HIIT + LO combination potentiated SOD activity upregulation in subcutaneous tissue. HIIT and LO supplementation have independent beneficial effects on the pro/antioxidant balance. Their association promotes SOD activity in subcutaneous adipose tissue.

Despite their unprecedented success in relapsed/refractory (R/R) large B-cell lymphoma (LBCL), anti-CD19 CAR T cells are associated with significant toxicity, and more than half of patients relapse. As monocytes emerged as key players in CAR therapy, we sought to evaluate the evolution of HLA-DR expression on monocytes (mHLA-DR) before and after commercial anti-CD19 CAR T-cell infusion in a large cohort (n = 103) of patients with R/R LBCL and its association with adverse events and treatment response. Cy-Flu-based lymphodepletion (LD) upregulated mHLA-DR in 79% of the cases, whereas in 2l% of cases (15 patients), the mHLA-DR level decreased after LD, and this decrease was associated with poorer outcome. Low mHLA-DR at day minus 7 (D−7) (

International audience; Hydroxyurea (HU) is commonly used as a treatment for patients with sickle cell disease (SCD) to enhance fetal hemoglobin production. This increased production is expected to reduce anemia (which depresses oxygen transport) and abnormal Hb content alleviating clinical symptoms such as vaso-occlusive crisis and acute chest syndrome. The effects of HU on skeletal muscle bioenergetics in vivo are still unknown. Due to the beneficial effects of HU upon oxygen delivery, improved skeletal muscle energetics and function in response to a HU treatment have been hypothesized. Muscle energetics and function were analyzed during a standardized rest-exercise-recovery protocol, using 31P-magnetic resonance spectroscopy in Townes SCD mice. Measurements were performed in three groups of mice: one group of 2-mo-old mice (SCD2m, n = 8), another one of 4-mo-old mice (SCD4m, n = 8), and a last group of 4-mo-old mice that have been treated from 2 mo of age with HU at 50 mg/kg/day (SCD4m-HU, n = 8). As compared with SCD2m mice, SCD4m mice were heavier and displayed a lower acidosis. As lower specific forces were developed by SCD4m compared with SCD2m, greater force-normalized phosphocreatine consumption and oxidative and nonoxidative costs of contraction were also reported. HU-treated mice (SCD4m-HU) displayed a significantly higher specific force production as compared with untreated mice (SCD4m), whereas muscle energetics was unchanged. Overall, our results support a beneficial effect of HU on muscle function.

International audience; On-chip study of blood flow has emerged as a powerful tool to assess the contribution of each component of blood to its overall function. Blood has indeed many functions, from gas and nutrient transport to immune response and thermal regulation. Red blood cells play a central role therein, in particular through their specific mechanical properties, that directly influence pressure regulation, oxygen perfusion, or platelet and white cells segregation towards endothelial walls. As the bloom of in-vitro studies has led to the apparition of various storage and sample preparation protocols, we address the question of the robustness of the results involving cell mechanical behavior against this diversity. The effects of three conservation media (EDTA, citrate and glucose-albumin-sodium-phosphate) and storage time on the red blood cell mechanical behavior are assessed under different flow conditions: cell deformability by ektacytometry, shape recovery of cells flowing out of a microfluidic constriction, and cell flipping dynamics under shear flow. The impact of buffer solutions (phosphate-buffered saline and density-matched suspension using iodixanol/Optiprep) are also studied by investigating individual cell flipping dynamics, relative viscosity of cell suspensions and cell structuration under Poiseuille flow. Our results reveal that storing blood samples up to seven days after withdrawal and suspending them in adequate density-matched buffer solutions has in most experiments a moderate effect on the overall mechanical response, with a possible rapid evolution in the first three days after sample collection. SIGNIFICANCE Blood is in intimate contact with all organs in the body, supplying oxygen, nutrients and drugs while removing waste. It carries cells involved in immune response, wound repair and tumor dissemination. Blood is easily collected, revealing the presence of disease through biomarker analysis. It is storable and transfusable. Thus, blood is the subject of many in-vitro studies for research and medical purposes. Guidelines associated to sample preparation or storage conditions have been established, but these may affect its mechanical behavior. In this collaborative study, we provide new guidelines to minimize the impact of specific experimental requirements (e.g. density matching, blood freshness) by focusing on the single or collective motion of red blood cells in a large range of flow conditions.

Background: Scientific evidence and public health reports keep highlighting the continuous and alarming worldwide progression of physical inactivity and sedentary behaviors in children and adolescents. The present paper summarizes findings from the 2022 French Report Card (RC) on physical activity for children and youth and compares them to the 2016, 2018, and 2020 RCs. Methods: The 2022 edition of the French RC follows the standardized methodology established by the Active Healthy Kids Global Matrix. Ten physical activity indicators have been evaluated and graded based on the best available evidence coming from national surveys, peer-reviewed literature, government and nongovernment reports, and online information. The evaluation was also performed in children and adolescents with disabilities. Indicators were graded from A (high level of evidence) to F (very low level of evidence) or INC for incomplete. Results: The evaluated indicators received the following grades: overall physical activity: D−; organized sport participation and physical activity: C; active play: F; active transportation: C; sedentary behaviors: D−; family and peers: D; physical fitness: C; school: C−; community and the built environment: F; government: B. Conclusions: While this 2022 French RC shows progression for 7 out of the 10 indicators considered, it also underlines the continuous need for actions at the local, regional, and national levels to develop better surveillance systems and favor a long-term improvement of youth movement behaviors.

International audience; Objectives: The aim of the present study was to investigate the level of cardiorespiratory fitness and neuromuscular function of ICU survivors after COVID-19 and to examine whether these outcomes are related to ICU stay/mechanical ventilation duration.Design: Prospective nonrandomized study.Setting: Patients hospitalized in ICU for COVID-19 infection.Patients: Sixty patients hospitalized in ICU (mean duration: 31.9 ± 18.2 d) were recruited 4-8 weeks post discharge from ICU.Interventions: None.Measurements and main results: Patients visited the laboratory on two separate occasions. The first visit was dedicated to quality of life questionnaire, cardiopulmonary exercise testing, whereas measurements of the knee extensors neuromuscular function were performed in the second visit. Maximal oxygen uptake (V o2 max) was 18.3 ± 4.5 mL·min -1 ·kg -1 , representing 49% ± 12% of predicted value, and was significantly correlated with ICU stay/mechanical ventilation (MV) duration ( R = -0.337 to -0.446; p < 0.01 to 0.001), as were maximal voluntary contraction and electrically evoked peak twitch. V o2 max (either predicted or in mL· min -1 ·kg -1 ) was also significantly correlated with key indices of pulmonary function such as predicted forced vital capacity or predicted forced expiratory volume in 1 second ( R = 0.430-0.465; p ≤ 0.001) and neuromuscular function. Both cardiorespiratory fitness and neuromuscular function were correlated with self-reported physical functioning and general health status.Conclusions: V o2 max was on average only slightly above the 18 mL·min -1 ·kg -1 , that is, the cut-off value known to induce difficulty in performing daily tasks. Overall, although low physical capacities at admission in ICU COVID-19 patients cannot be ruled out to explain the association between V o2 max or neuromuscular function and ICU stay/MV duration, altered cardiorespiratory fitness and neuromuscular function observed in the present study may not be specific to COVID-19 disease but seem applicable to all ICU/MV patients of similar duration.

International audience; Introduction:Motor imagery (MI) can be defined as a “dynamic state during which one simulates an action mentally without any body movement” [1]. The aim of MI is to optimise learning (e.g., in athletic training) or re-learning (e.g., in motor rehabilitation after stroke) by mastering the technique of new motor skills, but also through attentional focus [2] thanks to brain plasticity mechanisms. Indeed, similarities exist between MI and motor execution with regards to the solicitation of certain brain networks and regions, including premotor, parietal, and somatosensory regions [3]. Current BCI protocols targeting MI consist in positively reinforcing the maximum modulation of sensorimotor rhythms (SMRs) from baseline levels. This suggests that we consider that the growing expertise in the MI task will be associated with a higher desynchronisation of neurons in the sensorimotor cortices [4]. Yet, experiments investigating the neural efficiency hypothesis have shown that experts happen to have a reduced modulation of neural activity in comparison to novices [5], which can be attributed to a more efficient resource distribution. This efficiency would take form of reinforced temporal and spatial stability during MI tasks [6,7]. Thus, our questions are as follows: Q1. Does expertise modify the brain patterns associated with a MI task? Q2. If so, are those modifications elicited exclusively during MI of mastered movements? Or do these modifications reflect the acquisition of a generic skill (whatever the imagined movement)? Q3. Is maximising the percentage of desynchronisation a relevant objective? If not, what metrics of performance should be used in order to optimise the training of users/patients to self-regulate their brain activity? In order to investigate those different questions, we will recruit athletes who can be considered as an expert population in MI because of their frequent mental training use (to prevent overtraining or during rehabilitation but also as warm-up routines and rehearsal technique). Material and Methods:We will recruit 48 participants who will be divided into three groups: “basketball experts” (G1exp), “dance experts” (G2exp) and “novices” (G3) [16 participants per group, 8 men, 8 women]. All participants will perform 20 MI trials lasting 10s each for all four of the following movements: a simple reaching action (T1 – for which all participants are experts), a complex novel drawing task (T2 – for which none are expert), a basketball free throw (T3 – expertise of G1exp only) and a short pre-defined dancing choreography (T4 – expertise of G2exp only). EEG activity will be recorded during trials. This paradigm will enable us to compare MI-related brain patterns between experts and novices (G1exp/G2exp vs. G3) (Q1). It will also enable us to assess the extent to which the potential modifications of brain patterns due to expertise are specific to expert movements or generic (for G1exp and G2exp: T3 vs. T4; for all, control: T1 vs. T2) (Q2). From those results, we will investigate which performance metrics seem the most relevant to use in MI-based BCI/NF paradigms (Q3).Discussion:This study will enable us to acquire new knowledge regarding the neural efficiency hypothesis. If our results comfort this hypothesis, it will be important to identify, implement and evaluate new metrics of performance to guide BCI/NF users during their training (i.e., instead of ERD%). Following the neural efficiency hypothesis, we expect experts to show brain patterns that are more spatially and temporally stable than those of novices [6,7]. In other terms, in experts, we expect the modulations of brain activity during MI to be circumscribed to sensorimotor cortices (provided that they perform kinaesthetic MI) and to be highly stable across trials in terms of location and frequency. In addition, we hypothesise that those modulations will represent a general skill. In other terms, we expect the same patterns to be elicited for experts when doing MI of a mastered technique from their discipline, but also when doing MI of a novel movement of similar nature (in our case a different physical activity). Indeed, we believe that a transfer of neural efficiency exists. However, this phenomenon might only happen to a certain extent and not be identifiable for MI of a complex novel task or of a simple everyday life action. To our knowledge, this last hypothesis hasn’t been tested in the current literature and will therefore require an exploratory approach.References:[1] Guillot, A. and Collet, C. (2008). Construction of the Motor Imagery Integrative Model in Sport: A review and theoretical investigation of motor imagery use. IRSEP 1, 31–44[2] Budnik-Przybylska, D. et al. (2021). Neural Oscillation During Mental Imagery in Sport: An Olympic Sailor Case Study. Frontiers in Human Neuroscience 15, 669422.[3] Hardwick, R. M. et al. (2018). Neural Correlates of Action: Comparing Meta-Analyses of Imagery, Observation, and Execution. Neuroscience & Biobehavioral Reviews 94, 31‑44.[4] Ono, T. et al. (2013). Daily Training with Realistic Visual Feedback Improves Reproducibility of Event-Related Desynchronisation Following Hand Motor Imagery. Clinical Neurophysiology 124(9), 1779 86.[5] Li, L. and Smith, D. M. (2021). Neural Efficiency in Athletes: A Systematic Review. Frontiers in Behavioral Neuroscience 15.[6] Del Percio, C. et al. (2009). “Neural Efficiency” of Athletes’ Brain for Upright Standing: A High-Resolution EEG Study. Brain Research Bulletin 79(3), 193‑200.[7] Kraeutner, S. N. et al. (2018). Experience Modulates Motor Imagery-Based Brain Activity. EJN 47, no. 10: 1221–29.

International audience; Introduction: Originally developed for astronauts, lower body positive pressure treadmills (LBPPTs) are increasingly being used in sports and clinical settings because they allow for unweighted running. However, the neuromuscular adjustments to unweighted running remain understudied. They would be limited for certain lower limb muscles and interindividually variable. This study investigated whether this might be related to familiarization and/or trait anxiety. Methods: Forty healthy male runners were divided into two equal groups with contrasting levels of trait anxiety (high, ANX+, n = 20 vs. low, ANX−, n = 20). They completed two 9-min runs on a LBPPT. Each included three consecutive 3-min conditions performed at 100%, 60% (unweighted running), and 100% body weight. Normal ground reaction force and electromyographic activity of 11 ipsilateral lower limb muscles were analyzed for the last 30 s of each condition in both runs. Results: Unweighted running showed muscle- and stretch-shortening cycle phase-dependent neuromuscular adjustments that were repeatable across both runs. Importantly, hamstring (BF, biceps femoris; STSM, semitendinosus/semimembranosus) muscle activity increased during the braking (BF: +44 ± 18%, p < 0.001) and push-off (BF: +49 ± 12% and STSM: +123 ± 14%, p < 0.001 for both) phases, and even more so for ANX+ than for ANX−. During the braking phase, only ANX+ showed significant increases in BF (+41 ± 15%, p

International audience; Motor imagery (MI) is widely used in sports, in particular for motor learning and anxiety management [1]. Indeed, athletes consistently report using MI for rehearsing technique, maintaining arousal or enhancing self-confidence [2]. However, optimal gains are limited by the fact that they receive no feedback and cannot assess their performance. This can have detrimental effects on their motivation to diligently practice MI. Therefore, using Neurofeedback (NF) appears to be an adapted solution, allowing athletes to know if they are correctly performing the task. This addition also makes it possible to objectify performance and quantify progression throughout the sessions. In fact, three recent meta-analysis testify that NF improves the ability to self-regulate brain activity and sport performance [3, 4, 5]. The number of papers using MI-NF protocols has increased in the past few years. However, their efficiency has been shown to depend on various factors such as expertise in the imagined task [6], personality traits [7], MI ability [8] or NF acceptability [9]. Some of these factors can be assessed using validated questionnaires [10,11,12] but items are generally focused on questioning the current use of MI or thoughts on NF. An issue, as we know that practice can sometimes differ from real needs and expectations. To our knowledge, no previous work has investigated sports field actors’ preferences with the aim of designing specific NF tools, perfectly fitted to their profile, goals and expectations. Therefore, based on pre-existing questionnaires, we will build and broadcast an online questionnaire for athletes where personality, MI use, NF acceptability and NF preferences will be assessed. This method will enable us to personalise MI-NF trainings to fit each athlete’s needs. A longitudinal study will then require that athletes follow a personalised procedure to investigate how it impacts their MI and NF performances as well as their acceptability levels.[1] Guillot, A., & Collet, C. (2008). Construction of the Motor Imagery Integrative Model in Sport : A review and theoretical investigation of motor imagery use. International Review of Sport and Exercise Psychology, 1.[2] Munroe, K. J., Giacobbi Jr., P. R., Hall, C., & Weinberg, R. (2000). The Four Ws of Imagery Use : Where, When, Why, and What. Sport Psychologist, 14(2), 119.[3] Mirifar, A., Beckmann, J., & Ehrlenspiel, F. (2017). Neurofeedback as supplementary training for optimizing athletes’ performance: A systematic review with implications for future research. Neuroscience & Biobehavioral Reviews, 75, 419 432. [4] Xiang, M.-Q., Hou, X.-H., Liao, B.-G., Liao, J.-W., & Hu, M. (2018). The effect of neurofeedback training for sport performance in athletes: A meta-analysis. Psychology of Sport and Exercise, 36, 114 122.[5] Gong, A., Gu, F., Nan, W., Qu, Y., Jiang, C., & Fu, Y. (2021). A Review of Neurofeedback Training for Improving Sport Performance From the Perspective of User Experience. Frontiers in Neuroscience, 15.[6] Kraeutner, S. N., McWhinney, S. R., Solomon, J. P., Dithurbide, L., & Boe, S. G. (2018). Experience modulates motor imagery-based brain activity. European Journal of Neuroscience, 47(10), 1221 1229.[7] Jeunet, C., N’Kaoua, B., Subramanian, S., Hachet, M., & Lotte, F. (2015). Predicting Mental Imagery-Based BCI Performance from Personality, Cognitive Profile and Neurophysiological Patterns. PLOS ONE, 10(12), e0143962.[8] Guillot, A., Collet, C., Nguyen, V. A., Malouin, F., Richards, C., & Doyon, J. (2008). Functional neuroanatomical networks associated with expertise in motor imagery. NeuroImage. [9] Morone, G., Pisotta, I., Pichiorri, F., Kleih, S., Paolucci, S., Molinari, M., Cincotti, F., Kübler, A., & Mattia, D. (2015). Proof of principle of a brain-computer interface approach to support poststroke arm rehabilitation in hospitalized patients: Design, acceptability, and usability. Archives of Physical Medicine and Rehabilitation, 96(3 Suppl), S71-78. [10] Hall, C. R., Rodgers, W. M., & Barr, K. A. (1990). The Use of Imagery by Athletes in Selected Sports. The Sport Psychologist, 4(1), 1 10.[11] Plaisant, O., Courtois, R., Réveillère, C., Mendelsohn, G. A., & John, O. P. (2010). Validation par analyse factorielle du Big Five Inventory français (BFI-Fr). Analyse convergente avec le NEO-PI-R. Annales Médico-psychologiques, revue psychiatrique, 168(2), 97 106. [12] Grevet, E., Forge, K., Tadiello, S., Izac, M., Amadieu, F., Brunel, L., Pillette, L., Py, J., Gasq, D., & Jeunet-Kelway, C. (2023). Modeling the acceptability of BCIs for motor rehabilitation after stroke: A large scale study on the general public. Frontiers in Neuroergonomics, 3.

International audience; Low back pain represents a major economic and societal challenge due to its high prevalence. Lumbar orthoses are one of the recommended treatments. Even if previous results showed their clinical effects, the detailed mode of action is still poorly known, making the device design difficult. A renewed instrumentation and experimental protocol should bring better insight into the lumbar brace–trunk mechanical interaction. This instrumentation should give detailed information on the basic physical or geometrical parameters: the pressure applied on the trunk, the body shape and the strain in the belt. The principal objective of this study was to propose and validate a new measurement protocol, based on pressure mapping systems and full-field shape and strain measurement. The feasibility of the protocol was tested along with its validity and repeatability. The influence of various parameters, which could cause changes in the measurements, was tested with six different belt configurations on one subject. Measurements were also performed to study the impact of posture on pressure and strain. Both pressure and strain appeared to be asymmetric from left to right. The pressure applied by the lumbar belt on the back varies with breathing and with posture. This study showed that full-field measurements were necessary to render the high variability of pressure or strain around the trunk, under recommendations of their use to guarantee a satisfying repeatability.

International audience; (1) Background: Transcutaneous oxygen pressure (TcpO(2)) is used to determine the severity of lower extremity arterial disease (LEAD). Many authors used a ratio of limb to chest TcpO(2), also called the regional perfusion index (RPI), which should be independent of variations in oxygen delivery and reflective of local limb oxygen supply. The relevance of a reference probe-positioned TcpO(2) electrode is debated. We aimed to review the relevance of the reference probe in previous studies using rest TcpO(2). (2) Methods: We searched Medline and the Cochrane Central Register of Controlled Trials on 22 September 2022 using keywords related to TcpO(2), reference probe and LEAD. (3) Results/Discussion: Fifteen studies were included in the review. Nine studies investigated LEAD severity (n = 9), amputation healing predication (n = 4), surgical outcome prediction (n = 2), therapeutic effect (n = 3) and difference according to diabetic status (n = 1). Four studies investigated more than 1 indication. Among 12 (16.7%) studies using RPI, only two authors found a benefit of using RPI instead of absolute TcpO(2). Using only univariate analysis, one author reported that RPI was significantly related to viability at 1 year, while distal TcpO(2) was not, on 13 limbs. The following year, the same author published a new study including 118 limbs that reported that RPI and absolute TcPO2 were both prognostic factors for limb viability at 1 year using a multivariate model. (4) Conclusions: Only one study firmly supporting the use of RPI, calculated using a reference probe on the arm, to predict BKA healing. Prospective studies are needed to validate this result; for other indications there is insufficient data supporting the use of a TcpO(2) reference probe at rest.

Cancer patients at advanced stages experience a severe depletion of skeletal muscle compartment together with a decrease in muscle function, known as cancer cachexia. Cachexia contributes to reducing quality of life, treatment efficiency, and lifespan of cancer patients. However, the systemic nature of the syndrome is poorly documented. Here, we hypothesize that glucocorticoids would be important systemic mediators of cancer cachexia.To explore the role of glucocorticoids during cancer cachexia, biomolecular analyses were performed on several tissues (adrenal glands, blood, hypothalamus, liver, and skeletal muscle) collected from ApcTwenty-three-week-old Apc mice recapitulated important features of cancer cachexia including body weight loss (-16%, P 0.0001), muscle atrophy (gastrocnemius muscle: -53%, P 0.0001), and weakness (-50% in tibialis anterior muscle force, P 0.0001), increased expression of atrogens (7-fold increase in MuRF1 transcript level, P 0.0001) and down-regulation of Akt-mTOR pathway (3.3-fold increase in 4EBP1 protein content, P 0.0001), together with a marked transcriptional rewiring of hepatic metabolism toward an increased expression of gluconeogenic genes (Pcx: +90%, Pck1: +85%), and decreased expression of glycolytic (Slc2a2: -40%, Gk: -30%, Pklr: -60%), ketogenic (Hmgcs2: -55%, Bdh1: -80%), lipolytic/fatty oxidation (Lipe: -50%, Mgll: -60%, Cpt2: -60%, Hadh: -30%), and lipogenic (Acly: -30%, Acacb: -70%, Fasn: -45%) genes. The hypothalamic pituitary-adrenal axis was activated, as evidenced by the increase in the transcript levels of genes encoding corticotropin-releasing hormone in the hypothalamus (2-fold increase, P 0.01), adrenocorticotropic hormone receptor (3.4-fold increase, P 0.001), and steroid biosynthesis enzymes (Cyp21a1, P 0.0001, and Cyp11b1, P 0.01) in the adrenal glands, as well as by the increase in corticosterone level in the serum (+73%, P 0.05), skeletal muscle (+17%, P 0.001), and liver (+24%, P 0.05) of cachectic 23-week-old Apc mice. A comparative transcriptional analysis with dexamethasone-treated C57BL/6J mice indicated that the activation of the hypothalamic-pituitary-adrenal axis in 23-week-old ApcThese findings highlight the role of the hypothalamic-pituitary-adrenal-glucocorticoid pathway in the transcriptional regulation of skeletal muscle catabolism and hepatic metabolism during cancer cachexia. They also provide the paradigm for the design of new therapeutic strategies.

International audience; High-altitude exposure results in a hyperventilatory-induced respiratory alkalosis followed by renal compensation (bicarbonaturia) to return arterial blood pH (pHa) toward sea-level values. However, acid-base balance has not been comprehensively examined in both lowlanders and indigenous populations-where the latter are thought to be fully adapted to high altitude. The purpose of this investigation was to compare acid-base balance between acclimatizing lowlanders and Andean and Sherpa highlanders at various altitudes (∼3,800, ∼4,300, and ∼5,000 m). We compiled data collected across five independent high-altitude expeditions and report the following novel findings: 1) at 3,800 m, Andeans (n = 7) had elevated pHa compared with Sherpas (n = 12; P < 0.01), but not to lowlanders (n = 16; 9 days acclimatized; P = 0.09); 2) at 4,300 m, lowlanders (n = 16; 21 days acclimatized) had elevated pHa compared with Andeans (n = 32) and Sherpas (n = 11; both P < 0.01), and Andeans had elevated pHa compared with Sherpas (P = 0.01); and 3) at 5,000 m, lowlanders (n = 16; 14 days acclimatized) had higher pHa compared with both Andeans (n = 66) and Sherpas (n = 18; P < 0.01, and P = 0.03, respectively), and Andean and Sherpa highlanders had similar blood pHa (P = 0.65). These novel data characterize acid-base balance acclimatization and adaptation to various altitudes in lowlanders and indigenous highlanders.NEW & NOTEWORTHY Lowlander, Andean, and Sherpa arterial blood data were combined across five independent high-altitude expeditions in the United States, Nepal, and Peru to assess acid-base status at ∼3,800, ∼4,300, and ∼5,000 m. The main finding was that Andean and Sherpa highlander populations have more acidic arterial blood, due to elevated arterial carbon dioxide and similar arterial bicarbonate compared with acclimatizing lowlanders at altitudes ≥4,300 m.

International audience; OBJECTIVE: Admission in the intensive care unit of the old patient with coronavirus disease 19 raises an ethical question concerning the scarce resources and their short-term mortality. METHODS: Patients aged over 60 from 7 different intensive care units admitted between March 1, 2020 and May 6, 2020, with a diagnosis of coronavirus disease 19 were included in the cohort. Twenty variables were collected during the admission, such as age, severity (Simplified Acute Physiology Score [SAPS] II), several data on physiological status before intensive care unit comorbidities, evaluation of autonomy, frailty, and biological variables. The objective was to model the 30-day mortality with relevant variables, compute their odds ratio associated with their 95% CI, and produce a nomogram to easily estimate and communicate the 30-day mortality. The performance of the model was estimated with the area under the receiving operating curve. RESULTS: We included 231 patients, among them 60 (26.0%) patients have died on the 30th day. The relevant variables selected to explain the 30-day mortality were Instrumental Activities of Daily Living (IADL) score (0.82 [0.71-0.94]), age 1.12 (1.07-1.18), SAPS II 1.05 (1.02-1.08), and dementia 6.22 (1.00-38.58). A nomogram was computed to visually represent the final model. Area under the receiving operating curve was at 0.833 (0.776-0.889). CONCLUSIONS: Age, autonomy, dementia, and severity at admission were important predictive variables for the 30-day mortality status, and the nomogram could help the physician in the decision-making process and the communication with the family.

Hydroxyurea (HU) is a ribonucleotide reductase inhibitor most commonly used as a therapeutic agent in sickle cell disease (SCD) with the aim of reducing the risk of vaso-occlusion and improving oxygen transport to tissues. Previous studies suggest that HU may be even beneficial in mild anemia. However, the corresponding effects on skeletal muscle energetics and function have never been reported in such a mild anemia model. Seventeen mildly anemic HbAA Townes mice were subjected to a standardized rest-stimulation (transcutaneous stimulation)-protocol while muscle energetics using 31Phosphorus magnetic resonance spectroscopy and muscle force production were assessed and recorded. Eight mice were supplemented with hydroxyurea (HU) for 6 weeks while 9 were not (CON). HU mice displayed a higher specific total force production compared to the CON, with 501.35 ± 54.12 N/mm3 and 437.43 ± 57.10 N/mm3 respectively (+14.6%, p < 0.05). Neither the total rate of energy consumption nor the oxidative metabolic rate were significantly different between groups. The present results illustrated a positive effect of a HU chronic supplementation on skeletal muscle function in mice with mild anemia.

Background The growing interest of the scientific community in trail running has highlighted the acute effects of practice at the time of these races on isolated aspects of physiological and structural systems; biological, physiological, cognitive, and muscular functions; and the psychological state of athletes. However, no integrative study has been conducted under these conditions with so many participants and monitoring of pre-, per-, and postrace variables for up to 10 days over a distance close to 100 miles. Objective The aim of this study was to evaluate the kinetics of the performance parameters during a 156 km trail run and 6000 m of elevation gain in pre-, per-, and postrace conditions. The general hypothesis is based on significant alterations in the psychological, physiological, mechanical, biological, and cognitive parameters. Methods The Trail Scientifique de Clécy took place on November 11, 2021. This prospective experimental study provides a comprehensive exploration of the constraints and adaptations of psychophysiological and sociological variables assessed in real race conditions during a trail running of 156 km on hilly ground and 6000 m of elevation gain (D+). The study protocol allowed for repeatability of study measurements under the same experimental conditions during the race, with the race being divided into 6 identical loops of 26 km and 1000 m D+. Measurements were conducted the day before and the morning of the race, at the end of each lap, after a pit stop, and up to 10 days after the race. A total of 55 participants were included, 43 (78%) men and 12 (22%) women, who were experienced in ultra–trail-running events and with no contraindications to the practice of this sport. Results The launch of the study was authorized on October 26, 2021, under the trial number 21-0166 after a favorable opinion from the Comité de Protection des Personnes Ouest III (21.09.61/SIRIPH 2G 21.01586.000009). Of the 55 runners enrolled, 41 (75%) completed the race and 14 (25%) dropped out for various reasons, including gastric problems, hypothermia, fatigue, and musculoskeletal injuries. All the measurements for each team were completed in full. The race times (ie, excluding the measurements) ranged from 17.8206 hours for the first runner to 35.9225 hours for the last runner. The average time to complete all measurements for each lap was 64 (SD 3) minutes. Conclusions The Trail Scientifique de Clécy, by its protocol, allowed for a multidisciplinary approach to the discipline. This approach will allow for the explanation of the studied parameters in relation to each other and observation of the systems of dependence and independence. The initial results are expected in June 2022. International Registered Report Identifier (IRRID) RR1-10.2196/38027

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International audience; Introduction: The gastrointestinal (GI) tract is a frequent site of bleeding in patients receiving anticoagulant therapy for venous thromboembolism (VTE). At-risk patients have not been consistently identified yet. Methods: We used the RIETE registry to assess the clinical characteristics of patients developing major GI bleeding during the course of anticoagulation. Then, we built a predictive score based on multivariable analysis, aiming to identify patients at increased risk for major GI bleeding. Results: We included 87,431 patients with acute VTE. During the course of anticoagulation, 778 (0.89%) suffered major GI bleeding, 815 (0.93%) non-major GI bleeding and 1462 (1.67%) had major bleeding outside the GI tract. During the first 30 days after major GI bleeding, 7.6% of patients re-bled, 3.9% had VTE recurrences and 33% died. On multivariable analysis, male sex, age >= 70 years, initial VTE presentation as pulmonary embolism, active cancer, prior VTE, recent major bleeding in the GI tract, esophageal varicosities, anemia, abnormal prothrombin time, renal insufficiency and use of corticosteroids were associated to an increased risk for major GI bleeding. Using the predictive score, 39,591 patients (45%) were at low risk; 36,602 (42%) at intermediate-risk; 9315 (11%) at high-risk; and 1923 (2.2%) at very high risk. Their rates of major GI bleeding were: 0.21%, 0.96%, 2.41% and 6.08%, respectively. The c-statistics was 0.771 (95%CI. 0.755-0.786). Conclusions: We have developed a score which has the potential to identify patients at increased risk for GI bleeding, but needs to be externally validated."

International audience; Dynamic 31P MRS was performed during a standardized exercise of the lower leg, in patients with chronic fatigue enrolled in 2 clinical studies: multiple sclerosis patients and COVID19 patients that were hospitalized in intensive care unit and requiring respiratory assistance. In this work, we also revisit certain assumptions on the metabolite T1 and question shortcuts often made to shorten 31P protocol for a better patient's compliance.

Sex differences in muscle fiber-type composition have been documented in several muscle groups while the hamstring muscle fiber-type composition has been poorly characterized. This study aimed to compare the semitendinosus muscle composition between men and women. Biopsy samples were obtained from the semitendinosus muscle of twelve men and twelve women during an anterior cruciate ligament reconstruction. SDH and ATPase activities as well as the size and the proportion of muscle fibers expressing myosin heavy chain (MyHC) isoforms were used to compare muscle composition between men and women. The proportion of SDH-positive muscle fibers was significantly lower (37.4 ± 11.2% vs. 49.3 ± 10.6%, p 0.05), and the percentage of fast muscle fibers (i.e., based on ATPase activity) was significantly higher (65.8 ± 10.1% vs. 54.8 ± 8.3%, p 0.05) in men versus women. Likewise, men muscles exhibited a lower percentage of the area that was occupied by MyHC-I labeling (35.6 ± 10.1% vs. 48.7 ± 8.9%; p 0.05) and a higher percentage of the area that was occupied by MyHC-IIA (38.3 ± 6.7% vs. 32.5 ± 6.5%; p 0.05) and MyHC-IIX labeling (26.1 ± 9.6% vs. 18.8 ± 8.5%; p = 0.06) as compared with women muscles. The cross-sectional area of MyHC-I, MyHC-IIA, and MyHC-IIX muscle fibers was 31%, 43%, and 50% larger in men as compared with women, respectively. We identified sex differences in semitendinosus muscle composition as illustrated by a faster phenotype and larger muscle size in men as compared with women. This sexual dimorphism might have functional consequences.

International audience; Red blood cells (RBCs) can act as carriers for therapeutic agents and can substantially improve the safety, pharmacokinetics, and pharmacodynamics of many drugs. Maintaining RBCs integrity and lifespan is important for the efficacy of RBCs as drug carrier. We investigated the impact of drug encapsulation by hypotonic dialysis on RBCs physiology and integrity. Several parameters were compared between processed RBCs loaded with l-asparaginase (“eryaspase”), processed RBCs without drug and non-processed RBCs. Processed RBCs were less hydrated and displayed a reduction of intracellular content. We observed a change in the metabolomic but not in the proteomic profile of processed RBCs. Encapsulation process caused moderate morphological changes and was accompanied by an increase of RBCs-derived Extracellular Vesicles release. Despite a decrease in deformability, processed RBCs were not mechanically retained in a spleen-mimicking device and had increased surface-to-volume ratio and osmotic resistance. Processed RBCs half-life was not significantly affected in a mouse model and our previous phase 1 clinical study showed that encapsulation of asparaginase in RBCs prolonged its in vivo half-life compared to free forms. Our study demonstrated that encapsulation by hypotonic dialysis may affect certain characteristics of RBCs but does not significantly affect the in vivo longevity of RBCs or their drug carrier function.

The purpose of this study was to evaluate the influence of the menstrual cycle phases on the movement patterns of sub-elite women soccer players during competitive matches over three consecutive seasons. Individual movement data were analyzed and compared in eight players from the second French League at the early follicular (EF), late follicular (LF) and mid-luteal (ML) phases of their menstrual cycle, determined by the calendar method. The movement patterns, expressed as meters per minute, were recorded during competitive matches using devices placed on the player’s ankle. Our results showed significantly lower distances covered at moderate and high velocity in the EF phase than in the LF and ML phases (Cohen’s d effect size = 1.03 and 0.79, respectively). The total distance covered during matches and the number of sprints also were reduced during EF compared with LF (d = 0.78 and 0.7, respectively). Overall, the total distance and distance covered at low velocity were significantly lower during the second half-time of the matches (d = 1.51), but no menstrual cycle phase × game period interaction was noted. In conclusion, our study suggests that EF may impact the movement pattern of sub-elite women soccer players during competitive matches, without any modulation of this effect by the playing time. Despite the low sample size, these results can be useful for coaches and support staff to modulate training loads and player rotation during soccer games.

International audience; High altitude exposes humans to hypobaric hypoxia, which induces various physiological and molecular changes. Recent studies point toward interaction between circadian rhythms and the hypoxic response, yet their human relevance is lacking. Here, we examine the effect of different high altitudes in conjunction with time of day on human whole-blood transcriptome upon an expedition to the highest city in the world, La Rinconada, Peru, which is 5,100 m above sea level. We find that high altitude vastly affects the blood transcriptome and, unexpectedly, does not necessarily follow a monotonic response to altitude elevation. Importantly, we observe daily variance in gene expression, especially immune-related genes, which is largely altitude dependent. Moreover, using a digital cytometry approach, we estimate relative changes in abundance of different cell types and find that the response of several immune cell types is time- and altitude dependent. Taken together, our data provide evidence for interaction between the transcriptional response to hypoxia and the time of day in humans.

PurposeTo determine associations between thermal responses, medical events, performance, heat acclimation and health status during a World Athletics Championships in hot-humid conditions.MethodsFrom 305 marathon and race-walk starters, 83 completed a preparticipation questionnaire on health and acclimation. Core (Tcore; ingestible pill) and skin (Tskin; thermal camera) temperatures were measured in-competition in 56 and 107 athletes, respectively. 70 in-race medical events were analysed retrospectively. Performance (% personal best) and did not finish (DNF) were extracted from official results.ResultsPeak Tcore during competition reached 39.6°C±0.6°C (maximum 41.1°C). Tskin decreased from 32.2°C±1.3°C to 31.0°C±1.4°C during the races (pcore was not related to DNF (25% of starters) or medical events (p≥0.150), whereas Tskin, Tskin rate of decrease and Tcore-to-Tskin gradient were (p≤0.029). A third of the athletes reported symptoms in the 10 days preceding the event, mainly insomnia, diarrhoea and stomach pain, with diarrhoea (9% of athletes) increasing the risk of in-race medical events (71% vs 17%, pcore (39.4°C±0.4°C vs 39.8°C±0.7°C, p=0.044) and larger in-race decrease in Tskin (−1.4°C±1.0°C vs −0.9°C±1.2°C, p=0.060), than non-acclimated athletes. Although not significant, they also showed lower DNF (19% vs 30%, p=0.273) and medical events (19% vs 32%, p=0.179).ConclusionTskin, Tskin rate of decrease and Tcore-to-Tskin gradient were important indicators of heat tolerance. While heat-acclimated athletes ranked better, recent diarrhoea represented a significant risk factor for DNF and in-race medical events.

International audience; This study investigated the effects of marker placement (skin- vs shoe-mounted) on metatarsophalangeal joint (MTP) kinematics and kinetics during running. Fifteen trained men ran on a 15-m track at 10 and 13 km/h with three (low, standard and high stiffness) shoe longitudinal bending stiffnesses (LBS). Reflective markers were fixed on the shoe upper, and on the skin using holes cut in the shoe. Three-dimensional marker positions and ground reaction forces were recorded at 200 and 2000 Hz, respectively. Kinematic and kinetic parameters were analyzed using one-dimensional metrics (statistical parametric mapping). MTP joint was less dorsiflexed at midstance ([57% to 100%] of braking phase and [0% to 48%] of pushing phase), and the MTP joint plantarflexion moment was higher ([22% to 55%] of pushing phase) with the shoe markerset in comparison with the skin markerset. The effect of LBS on MTP angle was found to be significant for a larger percentage of each stride using the shoe markerset compared to the skin markerset. However, the effect of LBS on plantarflexion moment was significant with the shoe markerset only. The effect of running speed on MTP angle was significant for a larger percentage of each stride with the skin markerset. This study demonstrates that the placement of markers influences the measurement of MTP kinematics and kinetics and that these effects are mediated by other variables such as LBS or running speed. It is concluded that the shoe markerset does not fully reflect the movement of the MTP joint.

Aims A unique Andean population lives in the highest city of the world (La Rinconada, 5100 m, Peru) and frequently develops a maladaptive syndrome, termed chronic mountain sickness (CMS). Both extreme altitude and CMS are a challenge for the cardiovascular system. This study aims to evaluate cardiac remodelling and pulmonary circulation at rest and during exercise in healthy and CMS highlanders. Methods and results Highlanders living permanently at 3800 m (n = 23) and 5100 m (n = 55) with (n = 38) or without CMS (n = 17) were compared with 18 healthy lowlanders. Rest and exercise echocardiography were performed to describe cardiac remodelling, pulmonary artery pressure (PAP), and pulmonary vascular resistance (PVR). Total blood volume (BV) and haemoglobin mass were determined in all people. With the increase in the altitude of residency, the right heart dilated with an impairment in right ventricle systolic function, while the left heart exhibited a progressive concentric remodelling with Grade I diastolic dysfunction but without systolic dysfunction. Those modifications were greater in moderate–severe CMS patients. The mean PAP was higher both at rest and during exercise in healthy highlanders at 5100 m. The moderate–severe CMS subjects had a higher PVR at rest and a larger increase in PAP during exercise. The right heart remodelling was correlated with PAP, total BV, and SpO2. Conclusion Healthy dwellers at 5100 m exhibit both right heart dilatation and left ventricle concentric remodelling with diastolic dysfunction. Those modifications are even more pronounced in moderate–severe CMS subjects and could represent the limit of the heart's adaptability before progression to heart failure.

International audience; Interface pressure applied by compression bandages is the therapeutic action of the treatment of some venous or lymphatic pathologies. The so-called Static Stiffness Index, which quantifies the pressure increase from supine to standing position, is usually used to differentiate compression bandages. It was hypothesized that this pressure increase was the consequence of a change in leg geometry (blood and muscle falling down) and a change in calf soft tissue mechanical properties (muscles contraction). Calf soft tissue global stiffness of both legs of 25 patients was characterized in a sitting and standing position. This characterization was combined with interface pressure measurements applied by six different bandages. Though soft tissue mechanical properties significantly increased from sitting to standing position, no correlation was observed with the corresponding pressure increase. Thus, pressure increase is mainly attributed to a change in leg geometry.

Intermittent hypoxia (IH) is a landmark of obstructive sleep apnea (OSA) at the core of the cardiovascular consequences of OSA. IH triggers oxidative stress, a major underlying mechanism for elevated blood pressure (BP) and increased infarct size. L-citrulline is an amino acid that has been demonstrated to be protective of the cardiovascular system and exert pleiotropic effects. Therefore, we tested the impact of citrulline supplementation on IH-induced increase in BP and infarct size. Four groups of rats exposed to normoxia (N) or IH [14 days (d), 8 h/day, 30 s-O2 21%/30 s-O2 5%] and were supplemented or not with citrulline (1 g·kg−1·d−1). After 14 d, BP was measured, and hearts were submitted to global ischemia-reperfusion to measure infarct size. Histological and biochemical analyses were conducted on hearts and aorta to assess oxidative stress. Citrulline significantly reduced BP (–9.92%) and infarct size (–18.22%) under IH only. In the aorta, citrulline supplementation significantly decreased superoxide anion and nitrotyrosine levels under IH and abolished the IH-induced decrease in nitrite. Citrulline supplementation significantly decreased myocardial superoxide anion levels and xanthine oxidase enzyme activity under IH. Citrulline shows a cardioprotective capacity by limiting IH-induced pro-oxidant activity. Our results suggest that citrulline might represent a new pharmacological strategy in OSA patients with high cardiovascular risk.

Background Cancer-related fatigue (CRF) is the most common side effect of cancer and cancer treatment. CRF prevalence is up to 50% in breast cancer patients and can continue several years after cancer remission. This persistent subjective sense of exhaustion is multifactorial. Numerous parameters have been evidenced to be related to CRF across biological, physical, psychological, social and/or behavioral dimensions. Although CRF has been studied for many years, the majority of previous studies focused on only one dimension, i.e., physical function. Moreover, few studies investigated CRF longitudinally with repeated measures. These are the two main obstacles that limit the understanding of CRF mechanisms. The purpose of this study is to create a biopsychosocial model of CRF with simultaneous and longitudinal anthropometric, clinical, biological, physical, psychological and sociological parameters. Methods BIOCARE FActory is a multicentric prospective study that will consist of an 18-month follow-up of 200 women diagnosed with breast cancer. Four visits will be scheduled at diagnosis, after treatments, and 12 and 18 months after diagnosis. The same procedure will be followed for each visit. Each session will be composed of anthropometric data collection, a semi-structured interview, cognitive tests, postural control tests, neuromuscular fatigability tests and a cardiorespiratory fitness test. Clinical and biological data will be collected during medical follow-ups. Participants will also complete questionnaires to assess psychological aspects and quality of life and wear an actigraphy device. Using a structural equation modeling analysis (SEM), collected data will build a biopsychosocial model of CRF, including the physiological, biological, psychological, behavioral and social dimensions of CRF. Discussion This study aims to highlight the dynamics of CRF and its correlates from diagnosis to post treatment. SEM analysis could examine some relations between potential mechanisms and CRF. Thus, the biopsychosocial model will contribute to a better understanding of CRF and its underlying mechanisms from diagnosis to the aftermaths of cancer and its treatments. Trial registration This study is registered at ClinicalTrials.gov (NCT04391543), May 2020.

Background The Unilateral Seated Shot-Put Test (USSPT) consists of pushing an overweight ball as far as possible to assess upper extremity power unilaterally and bilateral symmetry. Literature however reports various body positions and upper limb pushing patterns to perform USSPT, demanding to provide additional guideline to achieve overweight ball push. This study therefore aimed at assessing the reliability and agreement of USSPT outcome measures when pushing an overweight ball in a horizontal direction. Methods Twenty-seven healthy male athletes performed two sessions, one week apart, of three unilateral pushes per upper limb using a 3-kg medicine ball, for which the distances were measured. The intraclass correlation coefficient (ICC), standard error of measurement (SEM), minimum detectable change at a 95 % confidence level (MDC95 %) and coefficient of variation (CV) were assessed for the pushing distances based on one, two or three trials per side to produce two outcome measures: the pushing distance per limb and USSPT Limb Symmetry Index (LSI) when dividing pushing distance of the dominant side by that of the non-dominant side. Results The most reliable pushing distance per limb was obtained when averaging three pushing distances, normalized by body mass with the exponent 0.35. The mean USSPT LSI was 1.09 ± 0.10 for the first session and 1.08 ± 0.10 for the second session, highlighting good reliability and agreement (ICC = 0.82; SEM = 0.045; MDC95 % = 0.124; CV = 5.02 %). Conclusions When the overweight ball is pushed in a horizontal direction, averaging the distances of three trials for both the dominant and non-dominant limbs is advised to provide the most reliable USSPT distance per limb and USSPT LSI.

Le déconditionnement musculaire se produit suite à l'inactivité (vols spatiaux, sédentarité). Les changements apparaissant les premiers jours seraient déterminants pour mettre au point des méthodes de prévention. Une expérience d'immersion sèche de 5 jours a été menée au CNES. Dix-huit volontaires ont été divisés en groupe « témoin » et groupe avec une contremesure vasculaire, un brassard de cuisse ou « cuffs ». Des biopsies musculaires ont été réalisées sur le vaste latéral. La force de contraction du genou (MVC) diminue de 17% et la section transversale des fibres musculaires de 22%. L'équilibre protéique est altéré (activation réduite de la voie mTOR), ainsi que la capacité oxydative (diminution des niveaux de PGC1-α). L'utilisation des cuffs n'a pas empêché le déconditionnement. Ces résultats devraient permettre une meilleure compréhension de la fonte musculaire lors des maladies musculaires, du vieillissement etc... Muscle deconditioning is a major consequence of a wide range of conditions from spaceflight to a sedentary lifestyle, and occurs as a result of muscle inactivity, leading to a rapid decrease in muscle strength, mass, and oxidative capacity. The early changes that appear in the first days of inactivity must be studied to determine effective methods for the prevention of muscle deconditioning. To evaluate the mechanisms of muscle early changes and the vascular effect of a thigh cuff, a five-day dry immersion (DI) experiment was conducted by the French Space Agency at the MEDES Space Clinic (Rangueil, Toulouse). Eighteen healthy males were recruited and divided into a control group and a thigh cuff group, who wore a thigh cuff at 30 mmHg. All participants underwent five days of DI. Prior to and at the end of the DI, the lower limb maximal strength was measured and muscle biopsies were collected from the vastus lateralis muscle. Five days of DI resulted in muscle deconditioning in both groups. The maximal voluntary isometric contraction of knee extension decreased significantly. The muscle fiber cross-sectional area decreased significantly by 21.8%, and the protein balance seems to be impaired, as shown by the reduced activation of the mTOR pathway. Measurements of skinned muscle fibers supported these results and potential changes in oxidative capacity were highlighted by a decrease in PGC1-α levels. The use of the thigh cuff did not prevent muscle deconditioning or impact muscle function. These results suggest that the major effects of muscle deconditioning occur during the first few days of inactivity, and countermeasures against muscle deconditioning should target this time period. These results are also relevant for the understanding of muscle weakness induced by muscle diseases, aging, and patients in intensive care. 22;21

Introduction: The design of uncemented femoral stems for use in total hip arthroplasty has evolved. Several uncemented short stems have been developed with different bone fixations, shapes, or stem lengths. The literature analyzing the biomechanical performance of short to standard stem lengths is limited. The aim was to compare the stress repartition on a standard uncemented stem and a shortened uncemented femoral stem with the same design features. Material and methods: This finite element analysis assessed the stress repartition on two femoral components with the same design (uncemented, collared, proximal trapezoidal cross-section, and a tapered quadrangular distal stem) but with two different lengths. The shortened stem was shorter by 40 mm compared to the standard stem. The stress repartition was analysed according to the Von Mises criterion. Results: The stress repartition was similar for the standard and shorter stem without significant difference (p = 0.94). The mean Von Mises stress was 58.1 MPa [0.2; 154.1] for the standard stem and 57.2 MPa [0.03; 160.2] for the short stem. The distal part of the standard stem, which was removed in the short stem, had mean stress of 3.7 MPa [0.2; 7.0]. Conclusion: The finite element analysis found similar stress repartitions between a standard uncemented collared stem and a short, collared stem with the same design. A clinical study assessing the clinical outcomes and the bone remodelling with a collared short stem would be interesting to confirm these first promising results.

International audience; Covert speech is accompanied by a subjective multisensory experience with auditory and kinaesthetic components. An influential hypothesis states that these sensory percepts result from a simulation of the corresponding motor action that relies on the same internal models recruited for the control of overt speech. This simulationist view raises the question of how it is possible to imagine speech without executing it. In this perspective, we discuss the possible role(s) played by motor inhibition during covert speech production. We suggest that considering covert speech as an inhibited form of overt speech maps naturally to the purported progressive internalization of overt speech during childhood. We further argue that the role of motor inhibition may differ widely across different forms of covert speech (e.g., condensed vs. expanded covert speech) and that considering this variety helps reconciling seemingly contradictory findings from the neuroimaging literature.

Objective To compare old patients hospitalized in ICU for respiratory distress due to COVID-19 with old patients hospitalized in ICU for a non-COVID-19-related reason in terms of autonomy and quality of life. Design Comparison of two prospective multi-centric studies. Setting This study was based on two prospective multi-centric studies, the Senior-COVID-Rea cohort (COVID-19-diagnosed ICU-admitted patients aged over 60) and the FRAGIREA cohort (ICU-admitted patients aged over 70). Patients We included herein the patients from both cohorts who had been evaluated at day 180 after admission (ADL score and quality of life). Interventions None. Measurements and main results A total of 93 COVID-19 patients and 185 control-ICU patients were included. Both groups were not balanced on age, body mass index, mechanical ventilation, length of ICU stay, and ADL and SAPS II scores. We modeled with ordered logistic regression the influence of COVID-19 on the quality of life and the ADL score. After adjustment on these factors, we observed COVID-19 patients were less likely to have a loss of usual activities (aOR [95% CI] 0.47 [0.23; 0.94]), a loss of mobility (aOR [95% CI] 0.30 [0.14; 0.63]), and a loss of ADL score (aOR [95% CI] 0.30 [0.14; 0.63]). On day 180, 52 (56%) COVID-19 patients presented signs of dyspnea, 37 (40%) still used analgesics, 17 (18%) used anxiolytics, and 14 (13%) used antidepressant. Conclusions COVID-19-related ICU stay was not associated with a lower quality of life or lower autonomy compared to non-COVID-19-related ICU stay.

International audience; Background: Left ventricular (LV) remodeling, characterized by increased LV hypertrophy and depressed function, is observed in strength-trained athletes who use anabolic-androgenic steroids (AAS). Previous studies reported an increase in cardiac fibrosis in these athletes, which could promote intraventricular dyssynchrony. In this context, this study evaluated LV dyssynchrony in strength-trained athletes using AA; hypothesizing that the use of AAS leads to an increase in LV dyssynchrony with an increase in post-systolic shortening.Methods: Forty-four participants (aged 20-40 years) were divided into three age-matched groups: strength-trained athletes using AAS (users, n=14) and those who were not (non-users, n=15), and healthy sedentary men (controls, n=15),. After completing a survey, each participant was assessed with 2D-strain echocardiography. Left ventricular dyssynchrony was quantified using the standard deviation of the time to peak for longitudinal strains (SD), the longitudinal strain delay index (LSDI) and the segmental post-systolic index (PSI).Results: Users exhibited a greater LV mass index and higher systolic and diastolic functions than both controls and non-users. The decrease in LV strains in users was predominantly observed at the interventricular segments. The SD, LSDI and PSI, calculated on the basal inferoseptal, basal anteroseptal and basal inferolateral segments, were higher in users.Conclusion: The results strongly support that the specific LV remodeling observed in young AAS users was associated with an increase in LV dyssynchrony. The correlations with ejection fraction suggested that wasted energy, due to post-systolic shortenings, contributed in part to the decrease in LV function in strength-trained athletes using AAS.

International audience; Sickle cell disease (SCD) is the most common hemoglobinopathy worldwide. It is characterized by an impairment of shear stress-mediated vasodilation, a pro-coagulant, and a pro-adhesive state orchestrated among others by the depletion of the vasodilator nitric oxide, by the increased phosphatidylserine exposure and tissue factor expression, and by the increased interactions of erythrocytes with endothelial cells that mediate the overexpression of adhesion molecules such as VCAM-1, respectively. Extracellular vesicles (EVs) have been shown to be novel actors involved in SCD pathophysiological processes. Medium-sized EVs, also called microparticles, which exhibit increased plasma levels in this pathology, were shown to induce the activation of endothelial cells, thereby increasing neutrophil adhesion, a key process potentially leading to the main complication associated with SCD, vaso-occlusive crises (VOCs). Small-sized EVs, also named exosomes, which have also been reported to be overrepresented in SCD, were shown to potentiate interactions between erythrocytes and platelets, and to trigger endothelial monolayer disruption, two processes also known to favor the occurrence of VOCs. In this review we provide an overview of the current knowledge about EVs concentration and role in SCD.

International audience; This study focused on a coagulation assessment based on the novel technique of blood-impedance-magnitude measurement. With the impedance characterization of recalcified human blood, it was possible to identify two significative biomarkers (i.e., measurable indicators) related to fibrin formation (1st marker) and clot retraction (2nd marker). The confocal microscopy of clotting blood provided a complete visual analysis of all the events occurring during coagulation, validating the significance of the impedance biomarkers. By analyzing the impedance phase angle (Φ) of blood during coagulation, as well as those of the clot and serum expelled after retraction, it was possible to further clarify the origin of the 2nd marker. Finally, an impedance-magnitude analysis and a rotational thromboelastometry test (ROTEM®) were simultaneously performed on blood sampled from the same donor; the results pointed out that the 1st marker was related to clotting time. The developed technique gives rise to a comprehensive and evolutive insight into coagulation, making it possible to progressively follow the whole process in real time. Moreover, this approach allows coagulation to be tested on any materials’ surface, laying the ground for new studies related to contact coagulation, meaning, thrombosis occurring on artificial implants. In a near future, impedance spectroscopy could be employed in the material characterization of cardiovascular prostheses whose properties could be monitored in situ and/or online using effective biomarkers.