Search

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.

Objective To investigate the effects of focal muscle fatigue induced by electromyostimulation (EMS) on Anticipatory Postural Adjustments (APAs) during arm flexions performed at maximal velocity. Methods Fifteen healthy subjects performed self-paced arm flexions at maximal velocity before and after the completion of fatiguing electromyostimulation programs involving the medial and anterior deltoids and aiming to degrade movement peak acceleration. APA timing and magnitude were measured using surface electromyography. Results Following muscle fatigue, despite a lower mechanical disturbance evidenced by significant decreased peak accelerations (−12%, p p >.11 for all analyses). Conclusion The fatigue signals evoked by externally-generated contractions seem to be gated by the Central Nervous System and result in postural strategy changes which aim to increase the postural safety margin. Significance EMS is widely used in rehabilitation and training programs for its neuromuscular function-related benefits. However and from a motor control viewpoint, the present results show that the use of EMS can lead to acute inaccuracies in predictive motor control. We propose that clinicians should investigate the chronic and global effects of EMS on motor control.

AB Introduction: Prolonged and strenuous exercise (PSE) induces transient left ventricular (LV) dysfunction. Although a consensus exists regarding the decrease in diastolic function, the existence of a decrease in systolic function by a PSE remains controversial, probably due to the transient tachycardia and changes in loading conditions observed upon the completion of exercise. Therefore, the objective was to evaluate LV systolic function before and after a PSE using two-dimensional speckle tracking echocardiography not only at rest but also during incremental tests to adjust heart rates (HR). Methods and Results: Sixteen healthy young men (23 +/- 3 yr old) performed a 3-h period of intensity-controlled upright cycling. LV strain (S), systolic strain rate (SR), rotation, and systolic rotational rate were evaluated by two-dimensional speckle tracking echocardiography before and after a 3-h period of PSE at rest and during incremental tests. Posttest evaluation was performed once the HR had returned to the pretest value. Under resting conditions, parameters of systolic function were either unchanged or increased after the PSE. However, during the incremental test, all LV systolic SR and apical rotational rates were decreased after PSE (radial SR at workload 3 (W3): 2.21 +/- 0.12.s-1 vs 1.87 +/- 0.10.s-1, P < 0.01 and apical rotational rate at W3: 128 +/- 28 deg.s-1 vs 105 +/- 26 deg.s-1, P < 0.05). Regression analyses between LV systolic SR and HR showed lower y-intercepts without differences in slopes, suggesting a decrease of both global and regional systolic functions irrespective of HR after the PSE. Conclusion: Our findings based on LV S and SR data during incremental tests demonstrate that the 3-h period of PSE induces LV systolic dysfunction

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.

article i nfo Background: The variability of peroneal reaction time measurements is a major problem when using this parameter to control rehabilitation or proprioceptive training processes. In order to control peroneal reaction time values, some extrinsic factors should be considered. The purpose of this study was to measure peroneal reaction time in unipodal stance for two different destabilization axes. Methods: The peroneal reaction time of 10 healthy subjects was measured from kinematic and electromyograhic data in an experimental study using an ankle destabilization device. Findings: Inapreliminaryanalysis,resultsshowedthatthedestabilizationaxisorientationdidnotaffectperoneal reaction time values (68.5 ms, standard deviation=9.5 ms and 71.5 ms, standard deviation=8 ms for destabilizations in the frontal plane and around the Henke's axis, respectively). However, the inter-trial variance of inversion velocity peaks explained between 40% and 49% of the peroneal reaction time variance. When trials were selected on the basis of homogeneous inversion velocity peaks, results showed that peroneal reaction time values for the peroneus brevis were shorter during inversion movements performed around the physiological Henke's tilting axis (63 ms, standard deviation=9 ms vs. 71 ms, standard deviation=8 ms). Interpretation: Our findings evidenced that tilting axis orientation must be considered as an extrinsic factor that may influence peroneal reaction time. Moreover it also seems necessary to consider inversion speed values to adequately compare peroneal reaction time values.

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.

The study investigated the effects of an unilateral ankle muscle fatigue onto independent postural control parameters including the trajectories of the estimated resultant CoP (CoPres) and his components: the centre of gravity (CG) and CoP–CG trajectories. Nine healthy men realized series of 10 toe-lift immediately followed by 10 knee flexions until exhaustion with one (Ex) leg. Maximal isometric voluntary contractions, postural sway measures of each leg, and muscular activities of the ankle muscles were recorded before and immediately after the fatiguing exercise. As expected, the latter induced a decrease in maximal voluntary peak force associated with a greater variability of the relative contribution of each leg on the CoPres, enhanced all postural parameters of the non-exercised leg. A significant decreased of the tibialis anterior EMG activity for the Ex leg and an increased one for the NoEx leg. Finally, following unilateral fatigue, the body sway destabilisation seemed to occur only along the medio-lateral (ML) axis. The enhanced and greater variability of the variance along ML axis might be explained by the recourse at the loading–unloading strategy choice and suggests a central attempt to compensate for pain sensation.

The main objective of this study was to examine whether static and dynamic signals from a non-fatigued reference ankle can differently improve the movement accuracy of a fatigued ankle. To address this question, subjects performed an ankle-matching task in a control condition and in a condition of local fatigue induced in the right tibialis anterior, in two matching conditions. In a bilateral condition, the matching task was completed with the two ankles simultaneously. In a unilateral condition subjects had to match the exact target position with the left non-fatigued ankle first and then tried to match the target position with the right fatigued ankle. Results showed that the final accuracy of the right fatigued ankle was degraded when matched with both ankles simultaneously while, for the unilateral condition, the final accuracy remained constant whether the ankle was fatigued or not. In addition, the EMG activity of the right tibialis increased significantly in the acceleration portion of the ankle movement for the unilateral condition. These results suggest that the CNS was able to integrate the correct static positional signals originating from the left reference ankle, to improve the movement accuracy of the controlateral fatigued ankle. This compensation of lateralized fatigue is operated in a feedforward manner.

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; BACKGROUND: Transcranial magnetic stimulation (TMS) is a widely-used investigative technique in motor cortical evaluation. Recently, there has been a surge in TMS studies evaluating lower-limb fatigue. TMS intensity of 120-130% resting motor threshold (RMT) and 120% active motor threshold (AMT) and TMS intensity determined using stimulus-response curves during muscular contraction have been used in these studies. With the expansion of fatigue research in locomotion, the quadriceps femoris is increasingly of interest. It is important to select a stimulus intensity appropriate to evaluate the variables, including voluntary activation, being measured in this functionally important muscle group. This study assessed whether selected quadriceps TMS stimulus intensity determined by frequently employed methods is similar between methods and muscles. METHODS: Stimulus intensity in vastus lateralis, rectus femoris and vastus medialis muscles was determined by RMT, AMT (i.e. during brief voluntary contractions at 10% maximal voluntary force, MVC) and maximal motor-evoked potential (MEP) amplitude from stimulus-response curves during brief voluntary contractions at 10, 20 and 50% MVC at different stimulus intensities. RESULTS: Stimulus intensity determined from a 10% MVC stimulus-response curve and at 120 and 130% RMT was higher than stimulus intensity at 120% AMT (lowest) and from a 50% MVC stimulus-response curve (p < 0.05). Stimulus intensity from a 20% MVC stimulus-response curve was similar to 120% RMT and 50% MVC stimulus-response curve. Mean stimulus intensity for stimulus-response curves at 10, 20 and 50% MVC corresponded to approximately 135, 115 and 100% RMT and 180, 155 and 130% AMT, respectively. Selected stimulus intensity was similar between muscles for all methods (p > 0.05). CONCLUSIONS: Similar optimal stimulus intensity and maximal MEP amplitudes at 20 and 50% MVC and the minimal risk of residual fatigue at 20% MVC suggest that a 20% MVC stimulus-response curve is appropriate for determining TMS stimulus intensity in the quadriceps femoris. The higher selected stimulus intensities at 120-130% RMT have the potential to cause increased coactivation and discomfort and the lower stimulus intensity at 120% AMT may underestimate evoked responses. One muscle may also act as a surrogate in determining optimal quadriceps femoris stimulation intensity.

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.

International audience; Sickle cell anemia (SCA) is a disease characterized by abnormal red blood cell rheology. Because of their effects on HbS polymerization and red blood cell deformability, alpha-thalassemia and the residual HbF level are known genetic modifiers of the disease. The aim of our study was to determine if the number of HbF quantitative trait loci (QTL) would also favor a specific sub-phenotype of SCA as it is the case for alpha-thalassemia. Our results confirmed that alpha-thalassemia protected from cerebral vasculopathy but increased the risk for frequent painful vaso-occlusive crises. We also showed that more HbF-QTL may provide an additional and specific protection against cerebral vasculopathy but only for children with alpha-thalassemia (-α/αα or -α/-α genotypes).

Context:Isokinetic assessment of shoulder internal- (IR) and external-rotator (ER) strength is commonly used with many different postures (sitting, standing, or supine) and shoulder positions (frontal or scapular plane with 45° or 90° of abduction).Objective:To conduct a systematic review to determine the influence of position on the intersession reliability of the assessment of IR and ER isokinetic strength, to identify the most reliable position, and to determine which isokinetic variable appears to be most stable in intersession reliability.Evidence Acquisition:A systematic literature search through MEDLINE and Pascal Biomed databases was performed in October 2009. Criteria for inclusion were that studies be written in English or French, describe the isokinetic evaluation methods, and describe statistical analysis.Evidence Synthesis:Sixteen studies meeting the inclusion criteria were included. Variable reliability of ER and IR peak torque (PT) were generally reported for all assessment positions; intraclass correlation coefficients were .44–.98 in the seated position with 45° of shoulder abduction, .09–.77 in the seated position with 90° of shoulder abduction, .86–.99 (coefficient of variation: 7.5–29.8%) in the supine position with 90° of shoulder abduction, .82–.84 in the supine position with 45° of shoulder abduction, and .75–.94 in standing. The ER:IR ratio reliability was low for all positions.Conclusions:The seated position with 45° of shoulder abduction in the scapular plane seemed the most reliable for IR and ER strength assessment. The standing position or a shoulder posture with 90° of shoulder abduction or in the frontal plane must be used with caution given the low reliability for peak torque. Good reliability of ER and IR PT was generally reported, but ER:IR ratio reliability was low.

International audience

Background Rapid discrete goal-directed movements are characterized by a well known coordination pattern between the gaze and the hand displacements. The gaze always starts prior to the hand movement and reaches the target before hand velocity peak. Surprisingly, the effect of the target size on the temporal gaze-hand coordination has not been directly investigated. Moreover, goal-directed movements are often produced in a reciprocal rather than in a discrete manner. The objectives of this work were to assess the effect of the target size on temporal gaze-hand coordination during fast 1) discrete and 2) reciprocal pointings. Methods Subjects performed fast discrete (experiment 1) and reciprocal (experiment 2) pointings with an amplitude of 50 cm and four target diameters (7.6, 3.8, 1.9 and 0.95 cm) leading to indexes of difficulty (ID = log2[2A/D]) of 3.7, 4.7, 5.7 and 6.7 bits. Gaze and hand displacements were synchronously recorded. Temporal gaze-hand coordination parameters were compared between experiments (discrete and reciprocal pointings) and IDs using analyses of variance (ANOVAs). Results Data showed that the magnitude of the gaze-hand lead pattern was much higher for discrete than for reciprocal pointings. Moreover, while it was constant for discrete pointings, it decreased systematically with an increasing ID for reciprocal pointings because of the longer duration of gaze anchoring on target. Conclusion Overall, the temporal gaze-hand coordination analysis revealed that even for high IDs, fast reciprocal pointings could not be considered as a concatenation of discrete units. Moreover, our data clearly illustrate the smooth adaptation of temporal gaze-hand coordination to terminal accuracy requirements during fast reciprocal pointings. It will be interesting for further researches to investigate if the methodology used in the experiment 2 allows assessing the effect of sensori-motor deficits on gaze-hand coordination.

Cancer-related fatigue can continue long after curative cancer treatment. The aim of this study was to investigate sleep and rest–activity cycles in fatigued and non-fatigued cancer survivors. We hypothesized that sleep and rest–activity cycles would be more disturbed in people experiencing clinically-relevant fatigue, and that objective measures of sleep would be associated with the severity of fatigue in cancer survivors. Cancer survivors (n = 87) completed a 14-day wrist actigraphy measurement to estimate their sleep and rest–activity cycles. Fatigue was measured using the Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-F). Participants were dichotomised into two groups using a previously validated score (fatigued n = 51 and non-fatigued n = 36). The participant’s perception of sleep was measured using the Insomnia Severity Index (ISI). FACIT-F score was correlated with wake after sleep onset (r = −0.28, p = 0.010), sleep efficiency (r = 0.26, p = 0.016), sleep onset latency (r = −0.31, p = 0.044) and Insomnia Severity Index (ISI) score (r = −0.56, p &lt, 0.001). The relative amplitude of the rest–activity cycles was lower in the fatigued vs. the non-fatigued group (p = 0.017, d = 0.58). After treatment for cancer, the severity of cancer-related fatigue is correlated with specific objective measures of sleep, and there is evidence of rest–activity cycle disruption in people experiencing clinically-relevant fatigue.

BACKGROUND Soft tissue surgery to address in-toeing gait in young cerebral palsy (CP) patients may be an alternative in some cases to femoral derotation osteotomy (FDO), which is the currently accepted treatment. The relative contribution of muscular contracture, spasticity and bone deformity is still controversial. In this study, we determined the outcomes of soft tissue surgery on hip internal rotation (HIR) when femoral anteversion was less than 45° and the soft tissues were identified as being the cause. METHODS This prospective study included select adolescent patients who were operated in the context of single-event multilevel surgery. The soft tissues' contribution to the HIR was identified beforehand. The surgical procedures focused on the hamstrings, adductor magnus and gluteus minimus muscles. RESULTS Over a 6-year period, 21 patients (mean age 14 years) and 25 lower limbs were treated. The HIR improved by an average of 17.4°±4.8° (95% CI). The gait deviation index and gait profile score also improved significantly. At a mean follow-up of 36 months, no loss of correction had occurred. DISCUSSION In-toeing gait in CP patents is due to the action of retracted and/or spastic muscles and the presence of excessive bone torsion. When femoral anteversion

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.

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.

Chronic Ankle Instability sprain causes are unclear and many factors or mechanisms may contribute to recurrence of this injury. The aim of the study was to investigate how an ankle destabilization device affects the EMG patterns of the ankle muscles during ankle stabilization against inversion. The left foot was equipped with a mechanical device mounted under the heel of the shoe. This mechanical device induces subtalar joint destabilization necessitating the control of ankle muscles. Surface electrodes were placed over the tibialis anterior, the peroneus longus, the peroneus brevis, the gastrocnemius lateral, and the gastrocnemius medial. Nine healthy subjects (mean age 37+/-12 yr; mean mass 68+/-17 kg; mean height 1.73+/-0.7 m) were instructed to walk normally along a tape fixed on the floor. The ankle destabilization device altered the walking pattern of all subjects. More specifically, the walking pattern is disturbed resulting in higher amplitude of the EMG activity of the peroneal muscles and the Tibialis Anterior and anticipatory reactions in the peroneal muscles. The results suggest that the ankle destabilization device could be beneficial for rehabilitation programs especially during the training of walking. Using this material may help to a specific reinforcement of muscles involved in anti-inversion ankle movement.

International audience; Background Laparoscopy is nowadays considered as the standard approach for hepatic left lateral sectionectomy (LLS), but its value in the prevention of incisional hernia (IH) has not been demonstrated. Methods Between 2012 and 2017, patients undergoing laparoscopic (LLLS) or open LLS (OLLS) in 8 centers were compared. Patients undergoing a simultaneous major abdominal procedure were excluded. The incidence of IH was assessed clinically and morphologically on computed tomography (CT) using inverse probability of treatment weighting (IPTW) and multivariable regression analysis. Results After IPTW, 84 LLLS were compared to 48 OLLS. Compared to OLLS, LLLS patients had reduced blood loss (100 [IQR: 50-200] ml vs. 150 [IQR: 50-415] ml,p = 0.023) and shorter median hospital stay (5 [IQR: 4-7] days vs. 7 [6-9] days,p < 0.001), but experienced similar rate of postoperative complications (mean comprehensive complication index: 12 +/- 19 after OLLS versus 13 +/- 20 after LLLS,p = 0.968). Long-term radiological screening was performed with a median follow-up of 27.4 (12.1-44.9) months. There was no difference between the two groups in terms of clinically relevant IH (10.7% [n = 9] after LLLS, 8.3% [n = 4] after OLLS,p = 0.768). The rate of IH detected on computed tomography was lower after LLLS than after OLLS (11.9% [n = 10] versus 29.2% [n = 14],p = 0.013). On multivariable analysis, the laparoscopic approach was the only independent factor influencing the risk of morphological IH (OR = 0.290 [95% CI: 0.094-0.891],p = 0.031). The 2 preferential sites for specimen extraction after LLLS were Pfannenstiel and midline incisions, with rates of IH across the extraction site of 2.3% [n = 1/44] and 23.8% [n = 5/21], respectively (p = 0.011). Conclusion The laparoscopic approach for LLS decreases the risk of long-term IH as evidenced on morphological examinations, with limited clinical impact. Pfannenstiel's incision should be preferred to midline incision for specimen extraction after LLLS.

International audience; Purpose: Ultramarathon running includes two main types of events: single-stage race (SSR) and multistage races (MSR). Direct comparison of neuromuscular fatigue and recovery after SSR versus MSR race of comparable distance and elevation has never been performed. The aim of this study was to assess neuromuscular fatigue and recovery after two ultramarathons of equal distance performed either (i) in a single stage or (ii) in four successive days.Methods: Thirty-one runners participated in the study: 17 ran 169 km in a single-stage race and 14 performed around 40 km·d over 4 d. The two races were performed on the same course. Neuromuscular function was tested before (PRE), after (POST), and 2 (D + 2), 5 (D + 5) and 10 (D + 10) days after the races. Neuromuscular function was evaluated on both knee extensors (KE) and plantar flexors (PF) with voluntary and evoked contractions using electrical (femoral and tibial, respectively) nerve stimulation.Results: Reduction of voluntary activation measured in the KE was greater (i.e., central fatigue) for SSR than MSR directly after the race (-23% vs -7%), P < 0.01). Reductions in evoked mechanical KE and PF responses on relaxed muscle (i.e., peripheral fatigue) of both KE and PF took longer to recover in MSR than in SSR.Conclusions: Performing prolonged running exercise over several days, each separated by rest, elicits more prolonged impairments in contractile function compared with single-stage ultramarathon, whereas single-stage mountain ultramarathon ran on the same course is associated with greater central fatigue.

Healthy young subjects were instructed to modify their weight-bearing asymmetry when standing on a double-seesaw device. The results indicated decreased and unchanged amplitudes in the center-of-pressure movements under the unloaded and loaded legs, respectively. In addition, a concomitant increased contribution of the more loaded leg and a decreased contribution of the pressure distribution mechanism along the mediolateral axis were observed in the production of the resultant center of pressure, its amplitude remaining constant. Thus, contrary to what was previously reported for stance control on solid ground, one of the main characteristics of a double-seesaw device, by preventing increased amplitudes on the loaded side during weight-bearing asymmetry, would be to facilitate a greater independency of the feet in the stance control process.

International audience; Capillary network of skeletal muscle has a crucial role in oxygen supply and is strongly associated with the phenotype and metabolic profile of muscle fibers. Abundant literature has explored capillarization of skeletal muscle in different populations and in response to different interventions. Capillary and fiber type identification techniques have considerably evolved over the last decades, but to the best of our knowledge, no validated immunohistochemical method has yet been developed to simultaneously identify capillaries (using CD31), the three different muscle fiber types, and basal lamina. Nine human muscle biopsies of vastus lateralis were stained using 5 different methods to test: the reliability of different CD31 antibodies for capillary identification, the reliability between single-section or serial-section methods, and the intra-experimenter reproducibility in visual detection of capillaries. High reliability for the different antibodies directed against capillaries was observed for capillary contacts (CC) measurements (intra-class correlations (ICC) [ICC95%] of 0.89 [0.72; 0.96] for type I fibers, 0.93 [0.81; 0.97] for type IIA fibers, 0.88 [0.71; 0.96] for type IIX fibers, 0.95 [0.86; 0.98] for all fiber types) as well as a high level of similarity between single and serial sections methods. A strong similarity in capillary analysis between the different methods was obtained for each sample measurements. Analysis of Lin's concordance correlation coefficients and Bland and Altman's graphics showed a strong intra-experimenter reproducibility. This article proposes two time- and tissue-sparing immunohistochemical methods to accurately assess a complete fiber typing (type I, IIA, and IIX) along with muscle capillarization on a single muscle section.

New findings What is the central question of this study? What are the effects of repeated subclinical vaso-occlusions on nuclear factor erythroid 2 related factor 2 (Nrf2) and oxidative stress balance regulation in the kidney of transgenic SAD mice? What is the main finding and its importance? In response to hypoxia-reoxygenation, nuclear Nrf2 protein expression decreased in the kidney of SAD mice while haem oxygenase transcripts were increased. This suggest that in SAD mice, other transcription factors than Nrf2 could be involved in renal antioxidant gene regulation in response to hypoxia-reoxygenation. Abstract Hypoxia-reoxygenation (H/R) stress is known to increase oxidative stress in transgenic sickle mice and can cause organ failure. Here we described the effects of H/R on nuclear factor erythroid 2-related factor 2 (Nrf2) as a putative regulator of redox status in the kidneys of SAD mice investigating Nrf2-regulated antioxidant enzymes. Transgenic SAD mice and healthy C57Bl/6J mice were exposed to 4 h of hypoxia followed by various times of reoxygenation at ambient air (2 or 6 h). Regardless of the conditions (i.e. normoxia or H/R), SAD mice expressed higher renal oxidative stress levels. Nuclear Nrf2 protein expression decreased after 2 h post-hypoxia only in the medulla region of the kidney and only in SAD mice. Simultaneously, haem oxygenase transcripts were affected by H/R stimulus with a significant enhancement after 2 h post-hypoxia. Similarly, hypoxia inducible factor-1α staining increased after 2 h post-hypoxia in SAD mice in both cortex and medulla areas. Our data confirm that the kidneys are organs that are particularly sensitive to H/R stimuli in sickle cell SAD mice. Also, these results suggest an effect of the duration of recovery period (short vs. long) and specific responses according to kidney areas, medulla vs. cortex, on Nrf2 expression in response to H/R stimuli in SAD mice.

Resume Introduction Les lesions musculaires des ischiojambiers sont une problematique importante chez les sportifs du fait de leur frequence, de leur taux de recidive et de leur impact. Leur incidence ne cesse de croitre malgre la multiplication des etudes scientifiques sur ce sujet. L’objectif principal de notre etude etait d’evaluer les connaissances et les attitudes des medecins pouvant y etre confrontes. Methodes Nous avons realise une etude observationnelle, descriptive, transversale, declarative aupres de medecins francais confrontes a la prise en charge des patients presentant une lesion musculaire des ischiojambiers, par le biais d’un questionnaire electronique. Une analyse descriptive a ete faite dans un premier temps. Puis une analyse comparative a ete effectuee entre les medecins ayant ou non beneficie d’une formation specifique en medecine du sport. Resultats Les donnees de 559 questionnaires ont ete inclus dans l’analyse. Il y avait 402 medecins sans formation en medecine du sport (NFMDS) et 157 medecins avec formation (FMDS). Les medecins FMDS semblaient plus souvent confrontes a la prise en charge de lesion musculaire des ischiojambiers que ceux NFMDS. La note moyenne d’auto-evaluation des connaissances par les medecins etait de 4,8 ± 2,2 sur 10 ; elle etait superieure dans le groupe FMDS par rapport au groupe NFMDS. Les principaux facteurs de risque et les moyens de les prevenir etaient connus de la plupart des medecins, surtout par le groupe FMDS. Concernant la prise en charge initiale, le protocole POLICE (Protection Optimal Loading Ice Contention Elevation) etait bien integre par les medecins. La prescription d’anti-inflammatoires non steroidiens etait acceptee par les medecins NFMDS et refutee par les FMDS. L’imagerie etait plebiscitee par une majorite de medecins surtout l’echographie, a visee pronostique principalement. Les grands principes de la reeducation etaient connus majoritairement par les medecins FMDS. Les medecins NFMDS s’accordaient a laisser le soin au kinesitherapeute d’organiser la reeducation. Enfin, les medecins interroges acceptaient l’ensemble des parametres cliniques proposes pour determiner le retour au sport et refutaient l’interet de l’imagerie a ce sujet. Conclusion Les grands principes de la prise en charge des lesions musculaires des ischiojambiers semblent integres par les medecins y faisant face. Ces lesions sont plus frequemment rencontrees par les medecins ayant beneficie d’une formation en medecine du sport dont les connaissances a ce sujet sont plus en adequation avec les donnees de la science.

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.

Background Artificial intelligence (AI) is defined as the study of algorithms that allow machines to reason and perform cognitive functions such as problem-solving, objects, images, word recognition, and decision-making. This study aimed to review the published articles and the comprehensive clinical relevance of AI-based tools used before, during, and after knee arthroplasty. Methods The search was conducted through PubMed, EMBASE, and MEDLINE databases from 2000 to 2021 using the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol (PRISMA). Results A total of 731 potential articles were reviewed, and 132 were included based on the inclusion criteria and exclusion criteria. Some steps of the knee arthroplasty procedure were assisted and improved by using AI-based tools. Before surgery, machine learning was used to aid surgeons in optimizing decision-making. During surgery, the robotic-assisted systems improved the accuracy of knee alignment, implant positioning, and ligamentous balance. After surgery, remote patient monitoring platforms helped to capture patients’ functional data. Conclusion In knee arthroplasty, the AI-based tools improve the decision-making process, surgical planning, accuracy, and repeatability of surgical procedures.

International audience; Prototype of monogenic disorder, sickle cell disease (SCD) is caused by a unique single mutation in the β-globin gene, leading to the production of the abnormal hemoglobin S (HbS). HbS polymerization in deoxygenated condition induces the sickling of red blood cells (RBCs), which become less deformable and more fragile, and thus prone to lysis. In addition to anemia, SCD patients may exhibit a plethora of clinical manifestations ranging from acute complications such as the frequent and debilitating painful vaso-occlusive crisis to chronic end organ damages. Several interrelated pathophysiological processes have been described, including impaired blood rheology, increased blood cell adhesion, coagulation, inflammation and enhanced oxidative stress among others. During the last two decades, it has been shown that extracellular vesicles (EVs), defined as cell-derived anucleated particles delimited by a lipid bilayer, and comprising small EVs (sEVs) and medium/large EVs (m/lEVs); are not only biomarkers but also subcellular actors in SCD pathophysiology. Plasma concentration of m/lEVs, originated mainly from RBCs and platelets (PLTs) but also from the other blood cell types, is higher in SCD patients than in healthy controls. The concentration and the density of externalized phosphatidylserine of those released from RBCs may vary according to clinical status (crisis vs. steady state) and treatment (hydroxyurea). Besides their procoagulant properties initially described, RBC-m/lEVs may promote inflammation through their effects on monocytes/macrophages and endothelial cells. Although less intensely studied, sEVs plasma concentration is increased in SCD and these EVs may cause endothelial damages. In addition, sEVs released from activated PLTs trigger PLT-neutrophil aggregation involved in lung vaso-occlusion in sickle mice. Altogether, these data clearly indicate that EVs are both biomarkers and bio-effectors in SCD, which deserve further studies.

Background Active participation in high-fidelity simulation remains stressful for residents. Increased stress levels elicited during such simulation impacts performance. We tested whether relaxing breathing, paired or not with cardiac biofeedback, could lead to enhanced performance of residents during simulation. Methods This randomized pilot study involved the fifth-year anesthesiology and critical care residents who participated in high-fidelity at Lyon medical simulation center in 2019. Residents were randomized into three parallel interventions: relaxing breathing, relaxing breathing paired with cardiac biofeedback, and control. Each intervention was applied for five minutes immediately after the scenario briefing. The primary endpoint was the overall performance during the simulation rated by two blinded independent investigators. The secondary endpoints included component scores of overall performance and changes in psychological states. Results Thirty-four residents were included. Compared to the control group, residents in the relaxing breathing (+ 7%, 98.3% CI: 0.3 to 13.7, P = 0.013) and relaxing breathing paired with cardiac biofeedback (+ 8%, 98.3% CI: 0.82 to 14.81, P = 0.009) groups had a higher overall performance score. Following the interventions, compared to the control group, stress level was lower when participants had performed relaxing breathing alone (P = 0.029) or paired with biofeedback (P = 0.035). The internal relaxation level was higher in both the relaxing breathing alone (P = 0.016) and paired with biofeedback groups (P = 0.035). Conclusions Performing five minutes of relaxing breathing before the scenario resulted in better overall simulation performance. These preliminary findings suggest that short breathing interventions are effective in improving performance during simulation. Trial registration The study protocol was retrospectively registered on clinicaltrials.gov (NCT04141124, 28/10/2019).

International audience; Champigneulle, Benoit, Ivan Hancco, Richard Renan, Stéphane Doutreleau, Emeric Stauffer, Aurélien Pichon, Julien V. Brugniaux, Hélène Péré, Pierre Bouzat, David Veyer, and Samuel Verges. High-altitude environment and COVID-19: SARS-CoV-2 seropositivity in the highest city in the world. High Alt Med Biol. 22: 000-000, 2021. Background: A reduced coronavirus disease 2019 (COVID-19) diffusion has been suggested in high-altitude areas but remained questionable. Aims of this study were to estimate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seropositivity as well as the risk factors associated in La Rinconada, the highest city in the world (5,100-5,300 m), a gold-mining town located in southeastern Peru where >50,000 dwellers live in precarious sanitary conditions. Materials and Methods: We performed a cross-sectional study during a 1-week period in October 2020, using point-of-care lateral flow serological assays allowing detection of antibodies directed against SARS-CoV-2 among voluntary dwellers in La Rinconada. Participants were also questioned about potential occupational and environmental risk factors of COVID-19 occurrence. Results: In a sample of 159 dwellers tested in La Rinconada, 48.4% [95% confidence interval, CI: 40.5-56.4] were seropositive for the SARS-CoV-2. Occurrence of at least one symptom compatible with the COVID-19 over the past 6 months remained the only significant factor associated with SARS-CoV-2 seropositivity (adjusted odds ratio: 3.27; [95% CI: 1.70-6.44]; p < 0.001). Conclusions: The high rate of SARS-CoV-2 seropositivity observed in this small sample of highlanders does not support a protective effect of high-altitude against the COVID-19 spread and demonstrates its large dissemination in vulnerable populations. Clinical Trial Registration number: NCT04604249.

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.

Introduction: Women have been shown to experience less neuromuscular fatigue than men in knee extensors (KE) and less peripheral fatigue in plantar flexors (PF) after ultratrail running, but it is unknown if these differences exist for shorter trail running races and whether this may impact running economy. The purpose of this study was to characterize sex differences in fatigability over a range of running distances and to examine possible differences in the postrace alteration of the cost of running (Cr). Methods: Eighteen pairs of men and women were matched by performance after completing different races ranging from 40 to 171 km, divided into SHORT versus LONG races (100 km, respectively). Neuromuscular function and Cr were tested before and after each race. Neuromuscular function was evaluated on both KE and PF with voluntary and evoked contractions using electrical nerve (KE and PF) and transcranial magnetic (KE) stimulation. Oxygen uptake, respiratory exchange ratio, and ventilation were measured on a treadmill and used to calculate Cr. Results: Compared with men, women displayed a smaller decrease in maximal strength in KE (−36% vs −27%, respectively, P < 0.01), independent of race distance. In SHORT only, women displayed less peripheral fatigue in PF compared with men (Δ peak twitch: −10% vs −24%, respectively, P < 0.05). Cr increased similarly in men and women. Conclusions: Women experience less neuromuscular fatigue than men after both “classic” and “extreme” prolonged running exercises but this does not impact the degradation of the energy Cr. Refereed/Peer-reviewed

The term ‘stiffness’ is commonly used in the literature to refer to various components of ‘hyperresistance’ by which spastic muscles oppose to their passive lengthening, especially in children with cerebral palsy (CP). Originally, stiffness consists of mechanical resistance to passive movement in the absence of any muscle activation. Increased muscle stiffness in CP therefore refers to alterations to the mechanical properties of the tissue. It is closely linked to muscle shortening, yet the two phenomena are not equivalent. Both increased stiffness and shortening are present early in childhood in the plantarflexor muscles of children with spastic CP. This narrative review provides a comprehensive overview of the literature on passive stiffness of the plantarflexor muscles measured at the joint, muscles, fascicles, and fiber level in children with CP. Articles were searched through the Pub’Med database using the keywords “cerebral palsy” AND “stiffness”. The ambiguous use of the term ‘stiffness’ has been supported by discrepancies in available results, influenced by heterogeneity in materials, methodologies and characteristics of the participants among studies. Increased stiffness at the joint and muscle belly level may be explained by altered structural properties at the microscopic level. This thorough investigation of the literature suggests that the pathophysiology and the time course of the development of stiffness and contracture remain to be elucidated. A consideration of both morphological and mechanical measurements in children with CP is important when describing the alterations in their plantarflexors.

Whether muscle stiffness is influenced by fatigue remains unclear. Classical methods used to assess muscle stiffness provide a global measure at the joint level. As fatigue may selectively affect specific muscles, a joint-level approach may not be sensitive enough to detect potential changes in muscle stiffness. Taking advantage of ultrasound shear wave elastography, this study aimed to determine the influence of a fatiguing protocol involving intermittent submaximal isometric contractions on muscle shear modulus (an index of stiffness).Shear modulus was measured on either the vastus lateralis (n = 9) or the abductor digiti minimi (n = 10) before and after 15 min of intermittent submaximal isometric contractions at 60% of maximal voluntary contraction (MVC) (4 s ON, 4 s OFF). An index of active muscle stiffness was estimated PRE- and POST-fatigue as the slope of the linear regression established between shear modulus and absolute joint force up to 60% MVC.After the fatiguing exercise, MVC was significantly decreased by 22% ± 7% and 32% ± 15% for knee extension and little finger abduction, respectively (P0.001). When compared to PRE-fatigue, the index of active muscle stiffness was 12% ± 15% lower for the vastus lateralis (P0.031) and 44% ± 19% lower for the abductor digiti minimi (P0.001) POST-fatigue.Although the present results cannot clearly determine the involved mechanisms, they demonstrate a decreased active muscle stiffness after a fatiguing task involving intermittent submaximal isometric contractions. Further studies should now determine whether this change in stiffness affects performance and risk of injury.

Videofluoroscopic Swallow studies (VFSS) are useful radiological examinations to explore swallowing disorders but which require ionizing radiation. The aim of our study was to evaluate the comparability of pediatric VFSS at 15 frames per second (fps) with 30 fps. Fifty-five loops including 190 swallowings of VFSS at 30 fps performed on 32 consecutive pediatric patients in a University Hospital Center were retrospectively modified by a software to delete one image out of two to obtain secondary loops with a frame rate of 15 fps. An otorhinolaryngologist-phonatrician and a radiologist reviewed all swallowings blindly and randomly using the penetration and aspiration scale (PAS). In case of discordance, they concluded a consensual interpretation. Fifteen girls and seventeen boys were included. The median age was 4 years and 8 months (range = 4 months-16 yr.). 144 swallowings were normal. Swallowing disorder was confirmed in 46 swallowings, (23 supraglottic penetrations and 23 aspirations). Considering each swallowing at 15 fps, sensitivity and specificity were, respectively, 93% (CI 0.82-0.98) and 98% (CI 0.94-0.99). The Cohen'Kappa coefficient between each interpretation at 15 and 30 fps was "almost perfect" (κ = 0.95; CI 0.88-0.99). Considering each loop, conclusion was identical. Reducing frame rate at 15 fps during pediatric VFSS seemed to be acceptable with comparable diagnostic performances without clinical impact compared to 30 fps, while being an efficient way to reduce the ionizing radiation exposition in children. We would suggest reconsidering the possibility of using VFSS with a 15 fps in a pediatric population.

Resume Objectif Realiser un etat des lieux des connaissances actuelles concernant la prevention des blessures chez le skieur alpin de competition, âge de 14 a 19 ans, en suivant la sequence de prevention des blessures en 4 etapes de van Mechelen et al. (1992). Methode Une revue systematique a ete effectuee en novembre 2018 en utilisant deux moteurs de recherche (« Pub Med » et « Science Direct ») et les mots cles suivants : « Injury », « Sports injuries », « Young », « Adolescent », « Epidemiology », « Risk factor », « Prevention », « Alpine skiing » et « Alpine ski » pour inclure les articles traitant de l’epidemiologie, l’identification de facteurs de risque, la mise en place et/ou l’evaluation des programmes de prevention des blessures du skieur alpin de competition âge de 14 a 19 ans. Resultats Cinq etudes rapportaient des resultats concernant l’epidemiologie des blessures du skieur alpin de competition âge de 14 a 19 ans ; ces blessures etaient majoritairement localisees au genou concernant les ligaments et la blessure la plus frequente etait la lesion du ligament croise anterieur (LCA). Deux etudes identifiaient l’asymetrie de force entre les muscles flechisseurs et extenseurs du rachis, ainsi que l’asymetrie de performance au one leg hop test comme facteurs de risque de lesion du LCA. Une etude a rapporte qu’un programme de prevention base sur l’amelioration du controle neuromusculaire des membres inferieurs et le renforcement des muscles du rachis limitait le nombre de lesions du LCA. Discussion et conclusion Les lesions du LCA etaient les plus frequentes chez le skieur alpin de competition âge de 14 a 19 ans;un faible controle neuromusculaire ainsi qu’une asymetrie de musculature du tronc seraient predictifs de cette lesion, et il semblerait que la mise en place d’un programme de prevention puisse diminuer la survenue de cette blessure. Cependant, d’autres etudes longitudinales cherchant a identifier les facteurs de risque potentiels, leur evolution dans le temps et leur modification par des programmes de prevention sont necessaires. Niveau de preuve 4.

Introduction Variations in the length of lateral extra-articular reconstruction (LER) have been widely investigated during knee flexion but there is no information about length changes during pivot shift. This study sought to assess the changes in LER tension during weightbearing knee flexion in a normal knee and in a computer-simulated pivot-shift scenario. Hypothesis Placing the femoral tunnel posterior and proximal to the lateral femoral epicondyle allows the LER to tighten early in the flexion range during weightbearing (squatting motion) and simulated pivot-shift. Material and methods A computer model was used to simulate weightbearing knee flexion and pivot shift scenarios. Changes in LER tension were calculated in both scenarios by estimating the distance between six femoral attachment sites (posterior and proximal to the lateral femoral epicondyle) and two tibial tunnel locations: Gerdy's tubercle (GT) and the anterolateral ligament (ALL) anatomic attachment site. Results Independent of the location of the femoral and tibial tunnels, the LER tightened by up to 22% of its resting length during the early portion of weightbearing knee flexion and then relaxed from 40° to 60° of knee flexion. The ALL tibial tunnel position allowed complete LER relaxation at 60° flexion whereas LER using the GT tibial tunnel position remained tighter. In the simulated pivot-shift test, and for all femoral tunnel locations, the LER tightened by 20% to 34% of its resting value for the GT tibial tunnel position and by 11% to 26% for the ALL tibial tunnel position. Discussion During weightbearing knee flexion, placing the femoral tunnel proximal and posterior to the femoral epicondyle was associated with LER tightening in the early degrees of flexion and LER relaxation between 40 and 60° flexion. LER tightening occurred during a simulated pivot-shift test supporting the concept that a posterior and proximal femoral LER tunnel position is most effective during weightbearing knee flexion and altered knee kinematics.

International audience

ObjectiveCarotid atherosclerotic plaques are a source of emboli for stroke. ‘Unstable’ carotid atherosclerotic plaques may have intraplaque haemorrhages, neovessels, prevalent macrophages, excessive calcium deposits, a large lipid core and a thin fibrous cap. Regular physical activity (PA) may lower the risk of plaques becoming unstable. We evaluated the association of both PA and sedentary behaviour (SB) with carotid plaque histopathology.Methods90 asymptomatic patients who were undergoing carotid endarterectomy for carotid artery narrowing identified on ultrasound reported their PA and SB by questionnaires. We calculated PA intensity in MET (metabolic equivalent of task)-min/week. For analysis, the population was divided into tertiles according to PA (T1PA: the less PA patients; T2PA: the intermediate PA patients; T3PA: the most physically active patients) (T1PAResultsIntraplaque haemorrhage was less frequent in the most physically active tertile (T3PA, 48%) versus T1PA (74%) and in the least sedentary tertile T1SB (50%) versus T3SB (71%). The intraplaque haemorrhage was less frequent in those who exercised more than 900 MET-min/week (59% vs 47% for >900 and ConclusionIn this cross-sectional study of asymptomatic patients who underwent endarterectomy (i) higher reported PA, (ii) intensity of PA and (iii) lower reported SB were associated with lower prevalence of intraplaque haemorrhage. This could be a mechanism whereby PA protects against cerebrovascular disease (stroke) and death.

The hip is the joint most exposed to orthopaedic complications in cerebral palsy (CP), which is the main cause of spasticity in paediatric patients. The initial immaturity of the hip allows the forces applied by the spastic and retracted muscles to displace the femoral head, eventually causing it to dislocate. The risk of hip dislocation increases with the severity and extent of CP, exceeding 70% in the most severe cases. Hip dislocation causes pain in up to 30% of cases, carries a risk of orthopaedic and cutaneous complications and hinders patient installation and nursing care. These adverse outcomes warrant routine screening, which has been proven effective in lessening the frequency and severity of hip displacement. Preventive techniques including physical therapy, orthoses and treatments to alleviate spasticity are strongly recommended in every case. The beneficial effects of treating spasticity, if needed via neurosurgical procedures, have been convincingly established. Orthopaedic surgery is required when prevention fails. Soft-tissue release is designed to correct the asymmetry in the forces applied by the muscles. Femoral osteotomy creates the possibility for spontaneous correction of secondary acetabular dysplasia. Progress has been made in standardising the use of multilevel surgery involving the soft tissues, femur and pelvis, which is often effective in correcting the morphological abnormalities and stabilising the joint. When hip pain or alterations are severe, hip resection or total hip arthroplasty are highly effective in alleviating the pain and improving patient comfort. The spastic hip is a complex condition in which currently available screening protocols and treatment strategies have been proven effective in benefitting patient outcomes.

To compare the effects of local-vibration and active warm-up on knee extensors muscle stiffness and neuromuscular performance.Experimental crossover study.Thirteen participants performed three 15-min warm-up protocols of control (CON), active (ACT) and local-vibration (LV) in separate testing session. Passive stiffness of vastus lateralis (VL) and vastus medialis (VM) by shear wave elastography and neuromuscular performance were assessed before and 2-min after each condition.A decrease in muscle stiffness was reported after ACT for VL (-16.0±6.6%; p0.001) and VM (-10.2±8.7%; p=0.03) while no changes were reported after CON (p=0.46 and p=0.34 for VL and VM, respectively) and LV (p=0.07 and p=0.46 for VL and VM, respectively). Maximal jump performances increased during squat (+8.5±6.6%; p0.001) and countermovement jump (+5.2±5.8%; p0.001) after ACT while no changes were reported after CON and LV during squat (p=0.16 and p=0.81, respectively) and countermovement jump (p=0.18 and p=0.31, respectively). We further report that each condition was ineffective to inducing changes in maximal voluntary isometric contraction force (p=0.18), rate of force development (p=0.92), twitch parameters (p0.05) as well as central modulations as reported by the unchanged voluntary activation level (p=0.24) and maximal electromyography (EMG) recorded from the VL (p=0.44).The active warm-up acutely reduced muscle stiffness and increased muscle performance during maximal dynamic tasks. With regard to LV, further studies are required to determine optimal parameters (frequency, amplitude, duration) to significantly increase muscle performance.

Background The variation of the anterolateral ligament (ALL) length during knee motion is still unclear, and the knee position in which a reconstruction graft should be tensioned remains controversial. The objective of this study was to determine the variation of the ALL length during knee motion using a three-dimensional optoelectronic system. Methods Kinematic analyses of 20 cadaveric knees were performed using a Motion Analysis® system. The variability of the measurements made during the five acquisition cycles was studied. Reliability was evaluated by two separate measurement sessions, with complete system reinstallation, using different cadavers and a new operator. The ALL length was analysed from extension to full flexion in three rotational conditions. Findings When analysing the reliability of the five cycles, 82% of the measurements we found to have an Intra Class Correlation (ICC) >0.85. The reproducibility of inter-sessional measures by different operators and different cadavers was either good (ICC >0.75) or excellent (ICC >0.85). The ALL length was maximum in full internal rotation with the knee at 25° of flexion. Interpretation This three-dimensional optoelectronic protocol allowed us to analyse the variation of the ALL length during intact knee motion with good reliability and the required accuracy to analyse this variable. The maximal length and highest tension of the ALL was reported at 25° of knee flexion in internal rotation, suggesting this as the optimal position for the knee joint when tensioning an ALL reconstruction.