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International audience; Sirtuin 1 (SIRT1), a NAD +-dependent protein deacetylase, has emerged as a main determinant of whole body homeostasis in mammals by regulating a large spectrum of transcriptional regulators in metabolically relevant tissue such as liver, adipose tissue and skeletal muscle. Sterol regulatory element binding protein (SREBP)-1c is a transcription factor that controls the expression of genes related to fatty acid and triglyceride synthesis in tissues with high lipid synthesis rates such as adipose tissue and liver. Previous studies indicate that SIRT1 can regulate the expression and function of SREBP-1c in liver. In the present study, we determined whether SIRT1 regulates SREBP-1c expression in skeletal muscle. SREBP-1c mRNA and protein levels were decreased in the gastrocnemius muscle of mice harboring deletion of the catalytic domain of SIRT1 (SIRT1 Dex4/Dex4 mice). By contrast, adenoviral expression of SIRT1 in human myotubes increased SREBP-1c mRNA and protein levels. Importantly, SREBP-1c promoter transactivation, which was significantly increased in response to SIRT1 overexpression by gene electrotransfer in skeletal muscle, was completely abolished when liver X receptor (LXR) response elements were deleted. Finally, our in vivo data from SIRT1 Dex4/Dex4 mice and in vitro data from human myotubes overexpressing SIRT1 show that SIRT1 regulates LXR acetylation in skeletal muscle cells. This suggests a possible mechanism by which the regulation of SREBP-1c gene expression by SIRT1 may require the deacetylation of LXR transcription factors.

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; There is evidence that pulmonary arterial hypertension plays a major role in the occurrence of high altitude pulmonary edema (HAPE). We tested the hypothesis that the pulmonary arterial systolic pressure response to a challenge associated with hypoxia and mild exercise may be considered a predictive factor of HAPE. Pulmonary arterial systolic pressure was measured by Doppler echocardiography in 8 HAPE susceptible (HAPE-S) subjects and 8 HAPE resistant mountaineers (HAPE-R) during a hypoxic exercise challenge established by the French Association for Sport Medicine (Richalet's test). Pulmonary arterial systolic pressure during hypoxic exercise allowed a significant discrimination between the groups, although an overlap of values was observed. When expressed as individual variations from baseline to hypoxic exercise level however, we found a highly significant difference. No overlap was observed between HAPE-R (range: 6.7-18.5 mmHg) and HAPE-S (range: 19.2-30.4 mmHg) groups, with a cut-off value at 19 mmHg. Plasma Vascular Endothelial growth factor (VEGF) and malondialdehyde (MDA) increased in response to hypoxic exercise only in HAPE-S group. Individual increases in pulmonary arterial systolic pressure during hypoxic exercise from basal resting normoxic values seem relevant to estimate HAPE susceptibility when measured during the Richalet's test.

International audience; We investigated the physiological consequences of one of the most extreme exercises realized by humans in race conditions: a 166-km mountain ultra-marathon (MUM) with 9500 m of positive and negative elevation change. For this purpose, (i) the fatigue induced by the MUM and (ii) the recovery processes over two weeks were assessed. Evaluation of neuromuscular function (NMF) and blood markers of muscle damage and inflammation were performed before and immediately following (n = 22), and 2, 5, 9 and 16 days after the MUM (n = 11) in experienced ultra-marathon runners. Large maximal voluntary contraction decreases occurred after MUM (235% [95% CI: 228 to 242%] and 239% [95% CI: 232 to 246%] for KE and PF, respectively), with alteration of maximal voluntary activation, mainly for KE (219% [95% CI: 27 to 232%]). Significant modifications in markers of muscle damage and inflammation were observed after the MUM as suggested by the large changes in creatine kinase (from 144694 to 13,633612,626 UI L 21), myoglobin (from 32622 to 1,43261,209 mg L 21), and C-Reactive Protein (from ,2.0 to 37.7626.5 mg L 21). Moderate to large reductions in maximal compound muscle action potential amplitude, high-frequency doublet force, and low frequency fatigue (index of excitation-contraction coupling alteration) were also observed for both muscle groups. Sixteen days after MUM, NMF had returned to initial values, with most of the recovery process occurring within 9 days of the race. These findings suggest that the large alterations in NMF after an ultra-marathon race are multi-factorial, including failure of excitation-contraction coupling, which has never been described after prolonged running. It is also concluded that as early as two weeks after such an extreme running exercise, maximal force capacities have returned to baseline.

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

International audience

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.

Autosomal dominant centronuclear myopathy (AD-CNM) is due to mutations in the gene encoding dynamin 2 (DNM2) involved in endocytosis and intracellular membrane trafficking. To understand the pathomechanisms resulting from a DNM2 mutation, we generated a knock-in mouse model expressing the most frequent AD-CNM mutation (KI-Dnm2R465W). Heterozygous (HTZ) mice developed a myopathy showing a specific spatial and temporal muscle involvement. In the primarily and prominently affected tibialis anterior muscle, impairment of the contractile properties was evidenced at weaning and was progressively associated with atrophy and histopathological abnormalities mainly affecting mitochondria and reticular network. Expression of genes involved in ubiquitin–proteosome and autophagy pathways was up-regulated during DNM2-induced atrophy. In isolated muscle fibers from wild-type and HTZ mice, Dnm2 localized in regions of intense membrane trafficking (I-band and perinuclear region), emphasizing the pathophysiological hypothesis in which DNM2-dependent trafficking would be altered. In addition, HTZ fibers showed an increased calcium concentration as well as an intracellular Dnm2 and dysferlin accumulation. A similar dysferlin retention, never reported so far in congenital myopathies, was also demonstrated in biopsies from DNM2-CNM patients and can be considered as a new marker to orientate direct genetic testing. Homozygous (HMZ) mice died during the first hours of life. Impairment of clathrin-mediated endocytosis, demonstrated in HMZ embryonic fibroblasts, could be the cause of lethality. Overall, this first mouse model of DNM2-related myopathy shows the crucial role of DNM2 in muscle homeostasis and will be a precious tool to study DNM2 functions in muscle, pathomechanisms of DNM2-CNM and developing therapeutic strategies.

International audience; Although it is well established that chronic hypoxia leads to an inexorable loss of skeletal muscle mass in healthy subjects, the underlying molecular mechanisms involved in this process are currently unknown. Skeletal muscle atrophy is also an important systemic consequence of chronic obstructive pulmonary disease (COPD), but the role of hypoxemia in this regulation is still debated. Our general aim was to determine the molecular mechanisms involved in the regulation of skeletal muscle mass after exposure to chronic hypoxia and to test the biological relevance of our findings into the clinical context of COPD. Expression of positive and negative regulators of skeletal muscle mass were explored 1) in the soleus muscle of rats exposed to severe hypoxia (6,300 m) for 3 wk and 2) in vastus lateralis muscle of nonhypoxemic and hypoxemic COPD patients. In rodents, we observed a marked inhibition of the mammalian target of rapamycin (mTOR) pathway together with a strong increase in regulated in development and DNA damage response 1 (REDD1) expression and in its association with 14-3-3, a mechanism known to downregulate the mTOR pathway. Importantly, REDD1 overexpression in vivo was sufficient to cause skeletal muscle fiber atrophy in normoxia. Finally, the comparative analysis of skeletal muscle in hypoxemic vs. nonhypoxemic COPD patients confirms that hypoxia causes an inhibition of the mTOR signaling pathway. We thus identify REDD1 as a negative regulator of skeletal muscle mass during chronic hypoxia. Translation of this fundamental knowledge into the clinical investigation of COPD shows the interest to develop therapeutic strategies aimed at inhibiting REDD1.

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.

mTor, acting mainly via mTORC1, controls dystrophin transcription in a raptor- and rictor-independent mechanism., Mammalian target of rapamycin (mTOR) is a key regulator of cell growth that associates with raptor and rictor to form the mTOR complex 1 (mTORC1) and mTORC2, respectively. Raptor is required for oxidative muscle integrity, whereas rictor is dispensable. In this study, we show that muscle-specific inactivation of mTOR leads to severe myopathy, resulting in premature death. mTOR-deficient muscles display metabolic changes similar to those observed in muscles lacking raptor, including impaired oxidative metabolism, altered mitochondrial regulation, and glycogen accumulation associated with protein kinase B/Akt hyperactivation. In addition, mTOR-deficient muscles exhibit increased basal glucose uptake, whereas whole body glucose homeostasis is essentially maintained. Importantly, loss of mTOR exacerbates the myopathic features in both slow oxidative and fast glycolytic muscles. Moreover, mTOR but not raptor and rictor deficiency leads to reduced muscle dystrophin content. We provide evidence that mTOR controls dystrophin transcription in a cell-autonomous, rapamycin-resistant, and kinase-independent manner. Collectively, our results demonstrate that mTOR acts mainly via mTORC1, whereas regulation of dystrophin is raptor and rictor independent.

Muscular fatigue is known to impair motor performance and to catalyse the development of upper limb musculoskeletal disorders. In order to delay the deleterious effects of muscular fatigue, the central nervous system (CNS) employs compensatory strategies. The cognitive cost of such compensatory strategies was assessed in 10 male subjects who alternatively performed two dual-task protocols before and immediately after an exhaustion procedure specific to upper arm abductor musculature. The main motor tasks were an isometric force-matching and a rapid multi-joint pointing. A secondary probe reaction time (RT) task was performed during both protocols and served as an indicator of attentional demands. Overall motor task performance was maintained despite fatigue. Kinematic and electromyographic data revealed that subjects used motor reorganization during the pointing task when fatigued. The RT increased with fatigue in both dual-task protocols, but this increase was significantly higher during the pointing task than during the force-matching task. The results highlight that the motor reorganization used by the CNS under muscular fatigue states require higher attentional demands than the initial motor organization. Finally, the capacity to delay the deleterious effects of muscular fatigue seems to depend on the proportion of cognitive resources available to plan the compensatory motor strategy.

International audience; The purpose of this study was to examine the physiological and biomechanical changes occurring in a subject after running 8,500 km in 161 days (i.e. 52.8 km daily). Three weeks before, 3 weeks after (POST) and 5 months after (POST+5) running from Paris to Beijing, energy cost of running (Cr), knee flexor and extensor isokinetic strength and biomechanical parameters (using a treadmill dynamometer) at different velocities were assessed in an experienced ultra-runner. At POST, there was a tendency toward a 'smoother' running pattern, as shown by (a) a higher stride frequency and duty factor, and a reduced aerial time without a change in contact time, (b) a lower maximal vertical force and loading rate at impact and (c) a decrease in both potential and kinetic energy changes at each step. This was associated with a detrimental effect on Cr (+6.2%) and a loss of strength at all angular velocities for both knee flexors and extensors. At POST+5, the subject returned to his original running patterns at low but not at high speeds and maximal strength remained reduced at low angular velocities (i.e. at high levels of force). It is suggested that the running pattern changes observed in the present study were a strategy adopted by the subject to reduce the deleterious effects of long distance running. However, the running pattern changes could partly be linked to the decrease in maximal strength.

Net metabolic cost of walking normalized by body mass ( CW·BM−1; in J·kg−1·m−1) is greater in obese than in normal-weight individuals, and biomechanical differences could be responsible for this greater net metabolic cost. We hypothesized that, in obese individuals, greater mediolateral body center of mass (COM) displacement and lower recovery of mechanical energy could induce an increase in the external mechanical work required to lift and accelerate the COM and thus in net CW·BM−1. Body composition and standing metabolic rate were measured in 23 obese and 10 normal-weight adolescents. Metabolic and mechanical energy costs were assessed while walking along an outdoor track at four speeds (0.75–1.50 m/s). Three-dimensional COM accelerations were measured by means of a tri-axial accelerometer and gyroscope and integrated twice to obtain COM velocities, displacements, and fluctuations in potential and kinetic energies. Last, external mechanical work (J·kg−1·m−1), mediolateral COM displacement, and the mechanical energy recovery of the inverted pendulum were calculated. Net CW·BM−1was 25% higher in obese than in normal-weight subjects on average across speeds, and net CW·BM−67(J·kg−0.67·m−1) was significantly related to percent body fat ( r2= 0.46). However, recovery of mechanical energy and the external work performed (J·kg−1·m−1) were similar in the two groups. The mediolateral displacement was greater in obese subjects and significantly related to percent body fat ( r2= 0.64). The mediolateral COM displacement, likely due to greater step width, was significantly related to net CW·BM−67( r2= 0.49). In conclusion, we speculate that the greater net CW·BM−67in obese subjects may be partially explained by the greater step-to-step transition costs associated with wide gait during walking.

We investigated whether acute hypoxic exposures could modify the pro-oxidant/antioxidant balance in elite endurance athletes, known to have efficient antioxidant status. Forty-one elite athletes were subjected to two hypoxic tests: one at an altitude of 4 800 m during 10-min of mild exercise (4 800 m test) and the second at rest for 3 h at an altitude of 3 000 m (3 000 m test). Plasma levels of advanced oxidation protein products (AOPP), malondialdehydes (MDA), ferric reducing antioxidant power (FRAP) and lipid-soluble antioxidants were measured before and immediately after the 4 800 m test and at the end of the 3 000 m test. The 4 800 m and the 3 000 m tests induced a significant increase in the level of MDA and AOPP (+7.1% and +71.7% for 4 800 m test and +8.6% and +40.9% for 3 000 m test). The changes in plasma MDA and arterial oxygen saturations were significantly correlated (r=0.35) during the 3 000 m test. FRAP values (-13%) and alpha-tocopherol (-21%) were decreased following the 3 000 m test. However, following the 4 800 m test, only alpha-tocopherol was decreased (-16%). These results provide evidence that the highly-trained athletes do not have the antioxidant buffering capacity to counterbalance free radical over-production generated by acute hypoxic exposure, with or without mild exercise.

Background and Purpose— To analyze the postural behavior of standing stroke patients: (1) To differentiate between postural impairment attributable to the neurological condition (deficits attributable to the cerebral lesion) and postural impairment attributable to new mechanical constraints caused by body weight asymmetry; (2) To assess the involvement of each limb in the postural impairment; (3) To better understand which clinical deficits underlie the postural impairment. Methods— The posturographic characteristics of each limb in 41 stroke patients (first hemispheric stroke: 16 left, 25 right cerebral lesions) required to stand in their preferred posture were compared to those in 40 matched healthy individuals required to stand asymmetrically. Results— Compared to normal individuals in a similar asymmetrical posture, stroke patients were more unstable. The weight bearing asymmetry and the lateral postural instability were mainly related to spatial neglect. The paretic limb was unable to bring into play a normal longitudinal pattern of the center of pressure, which reflects an impaired stabilization control. Overall postural instability occurred when the strong limb was unable to compensate for the postural impairment of the paretic limb. Conclusions— The weight bearing asymmetry of standing stroke patients is not the primary cause of their postural imbalance, which is rather the consequence of impaired control of postural stabilization involving both limbs. Weight bearing asymmetry may not be the principle target of rehabilitation programs aiming at restoring standing balance after stroke. Instead it is suggested that more account should be taken of the compensatory role of the strong limb.

National audience

The aim was to investigate the effects of acute exercise under hypoxic condition and the repetition of such exercise in a 'living low-training high' training on the antioxidant/prooxidant balance.Randomized, repeated measures design.Faculté de Médecine, Clermont-Ferrand, France.Fourteen runners were randomly divided into two groups. A 6-week endurance training protocol integrated two running sessions per week at the second ventilatory threshold into the usual training.A 6-week endurance training protocol integrated two running sessions per week at the second ventilatory threshold into the usual training. The first hypoxic group (HG, n=8) carried out these sessions under hypoxia (3000 m simulated altitude) and the second normoxic group (NG, n=6) in normoxia. In control period, the runners were submitted to two incremental cycling tests performed in normoxia and under hypoxia (simulated altitude of 3000 m). Plasma levels of advanced oxidation protein products (AOPP), malondialdehydes (MDA) and lipid oxidizability, ferric-reducing antioxidant power (FRAP), lipid-soluble antioxidants (alpha-tocopherol and beta-carotene) normalized for triacyglycerols and cholesterol were measured before and after the two incremental tests and at rest before and after training.No significant changes of MDA and AOPP level were observed after normoxic exercise, whereas hypoxic exercise induced a 56% rise of MDA and a 44% rise of AOPP. Plasma level of MDA and arterial oxygen hemoglobin desaturations after the acute both exercises were highly correlated (r=0.73). alpha-Tocopherol normalized for cholesterol and triacyglycerols increased only after hypoxic exercise (10-12%, P0.01). After training, FRAP resting values (-21%, P0.05) and alpha-tocopherol/triacyglycerols ratio (-24%, P0.05) were diminished for HG, whereas NG values remained unchanged.Intense exercise and hypoxia exposure may have a cumulative effect on oxidative stress. As a consequence, the repetition of such exercise characterizing the 'living low-training high' model has weakened the antioxidant capacities of the athletes.International Olympic Committee and the Direction Régionale de la Jeunesse et des Sports de la Région Auvergne.

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

To investigate the capacity of the central nervous system to integrate and differentiate two different muscular fatigue states, the present study examines the changes on multi-joint movement organization following muscular fatigue of elbow extensor muscles (triceps brachii) induced by voluntary versus electrically induced contractions. Twenty right-handed male volunteers performed throws in the horizontal plane before and after two fatiguing procedures. First, success rate of throws was not affected by fatigue neither after voluntary contractions, nor after electrically induced contractions. Despite similar reductions of the maximal voluntary isometric force and the median frequency of the electromyographic signal following both fatiguing protocols, voluntary contractions induced greater changes in muscle activation, kinematics and kinetics during throws than electrically induced contractions. The changes observed following voluntary contractions are interpreted as a compensatory strategy involving a greater contribution of the wrist. In contrast, the greater activation of the triceps brachii could compensate the weakness of this muscle induced by fatigue without any modification of the initial multi-joint movement organization.

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.

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.

Hypoxia is defined as any combination of reduced barometric pressure (PB) and/or a reduced inspired fraction of oxygen (FiO2), which ultimately results in an inspired partial pressure of oxygen (PiO2) less than 150 mmHg ([6][1]). Pathophysiological responses to hypoxia or adaptations to hypoxic

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.

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.

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.

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).

Running and various team sports generate transient vibrations in the soft tissues of the lower limb at each impact between the foot and the ground. These impacts and vibrations can generate significant mechanical stress, which increases the risk of overuse injury when not properly managed. The first objective of the thesis was devoted to the development of signal processing and statistical analysis methods to better characterize the impacts and vibrations encountered by athletes. The second objective was to define the external factors, such as practices, sports equipment, or neuromuscular fatigue, that modify the vibratory behavior in ecological practice. With the development of signal processing methods (continuous wavelet transform) and statistical methods (Statistical Parametric Mapping), we highlighted that soft tissue vibration was different from muscle vibration. Thus, accelerometers allow only a salient characterization of the muscle vibration compared to an ultrafast ultrasound. Besides, increasing running speed and sport specific tasks generated higher impact amplitude and frequency, as well as greater soft tissue vibration compared to in-line running. Among the sports equipment evaluated, only a sliding sports surface reduced the amplitude of the impact on the ground. An identification of the type of movement was made possible thanks to the measurement of the impacts and a convolutional neural network, allowing to cross the first step in the evaluation of the vibratory dose undergone by an athlete. Finally, a study carried out during the UTMB races put forward a strategy of protection of the neuromuscular system after trail-type efforts by decreasing the amplitude and the frequency of the vibrations of the most solicited muscles. It is now necessary to improve the characterization of muscle vibration with accelerometers fixed to the skin and to determine the effect of repetitive exposure to transient vibrations on the neuromuscular and musculoskeletal system.; La course à pied et les différentes pratiques sportives induisent des chocs et des vibrations transitoires au niveau des tissus mous à chaque impact. Ces impacts et vibrations peuvent générer un stress mécanique important, qui accroit le risque de fatigue et de blessure de sur-sollicitation. Le premier objectif de la thèse était consacré au développement de méthodes de traitement du signal d’accélération et d’analyse statistique afin de mieux caractériser les impacts et vibrations subies par le sportif. Le second objectif était de définir les facteurs externes, tels que le type de mouvement, le matériel sportif, ou la fatigue neuromusculaire, qui faisaient varier le comportement vibratoire en pratique écologique. Avec le développement de méthodes de traitement du signal (transformée en ondelettes continue) et statistiques (Statistical Parametric Mapping), nous avons montré que la vibration des tissus mous était différente de la vibration musculaire. Ainsi, les accéléromètres ne permettaient de caractériser que partiellement la vibration du muscle par rapport à une échographe ultra rapide. De plus, l’augmentation de la vitesse de course et les mouvements effectués lors de la pratique de sports collectifs génèrent des impacts à plus grande amplitude et à plus haute fréquence, ainsi que des vibrations des tissus mous plus amples que la course en ligne droite. Parmi le matériel sportif évalué, seul un revêtement sportif coulissant a permis de réduire l’amplitude de l’impact au sol. Une identification du type de mouvement a été rendu possible grâce à la mesure des impacts et l’usage d’un réseau de neurones convolutifs, permettant de franchir une première étape dans l’évaluation de la dose vibratoire subie par un sportif lors de sa pratique. Enfin, une étude réalisée lors des courses de l’UTMB a permis d’observer une stratégie de protection de l’organisme après des efforts de type trail en diminuant l’amplitude et la fréquence des vibrations des muscles les plus sollicités. Il reste nécessaire d’améliorer la caractérisation de la vibration musculaire avec des accéléromètres fixés sur la peau et de déterminer l’effet de l’exposition répétée à des vibrations transitoires sur le système neuromusculaire et musculo-squelettique.