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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.

]) and endurance performance of previously non-acclimatized subjects, Fulco et al. (3) provided sets of datahighlighting the potential differences in physiological mecha-nisms of acclimatization and exercise between hypobaric hyp-oxia (HH) and normobaric hypoxia (NH).The authors are to be commended for the consistency (e.g.,investigators’ team, subject characteristics, assessment protocols,targetaltitude)amongdozensofstudies(mostofthemconductedat Pikes Peaks Laboratory, Colorado, 4300 m) within two deca-des, which enabled a robust comparison of benefits and effec-tiveness of different HH versus NH preacclimatization strategies.Their conclusions are convincing enough to recommendHH instead of NH for preacclimatization because of the moredeveloped ventilatory acclimatization and lesser decrease in per-formance when assessed at 4300 m.However,stricto sensus, the review by Fulco et al. (3) did notclarify if the differences observed between HH and NH (4,6)are clinically relevant and lead to a higher severity of acutemountain sickness (AMS) in HH than in NH, a topic highlydebated (Millet et al. (4) vs Schommer et al. (7)) where, todate, there is no well-controlled comparative crossover study.To our view, the most striking and novel finding arising fromFulco et al. (3) is the very low (or lack of) transfer of the bene-fits induced by the NH acclimatization to the HH condition.When transported to 4300 m (HH), subjects who were pre-acclimatized in NH had a minimal benefit (e.g., no or

Purpose To identify genetic, systemic, and biological factors associated with the occurrence of sickle cell maculopathy (SCM). To evaluate microvascular macular alterations using optical coherence tomography angiography (OCTA) in sickle cell disease (SCD). Design Cross-sectional study. Methods One hundred fifty-one eyes of 78 adult SCD patients (43 HbSS, 30 HbSC, 4 S/β+, and 1 HbS Lepore) and 40 eyes of 20 healthy controls underwent spectral-domain optical coherence tomography (SDOCT) and OCTA using Spectralis HRA+OCT (Heidelberg Engineering, Heidelberg, Germany). We analyzed the occurrence of SCM, the foveal avascular zone (FAZ) area, and the severity of macular ischemia and studied their relationships with genetic, systemic, and biological parameters using multivariate logistic regression analysis. Results Maculopathy occurred in 66 eyes (44%), and more frequently in HbSS patients (71%, P = .004). Multivariate analysis identified HbSS genotype and lower prothrombin ratio (PR) as independently associated with SCM (P = .01). Proliferative sickle cell retinopathy was also associated with SCM (P = .02). FAZ enlargement was associated with higher lactate dehydrogenase level (P = .02). Macular ischemia was more severe in patients with lower hemoglobin level (P = .004) and lower PR (P = .01). No flow areas were identified with OCTA even in eyes with no macular thinning (36 eyes, 42%) and appeared more frequently in the temporal superior subfield (36%). Conclusions HbSS genotype, abnormal coagulation and hemolysis increase the risk of SCM. OCTA provides valuable criteria to identify potential risk factors of SCM. OCTA also improves detection of early microvascular changes before the onset of macular thinning.

Atherosclerosis is a chronic systemic inflammatory disease, inducing cardiovascular and cerebrovascular acute events. A role of neuroinflammation is suspected, but not yet investigated in the gyrencephalic brain and the related activity at blood−brain interfaces is unknown. A non-human primate model of advanced atherosclerosis was first established using longitudinal blood samples, multimodal imaging and gene analysis in aged animals. Non-human primate carotid lesions were compared with human carotid endarterectomy samples. During the whole-body imaging session, imaging of neuroinflammation and choroid plexus function was performed. Advanced plaques were present in multiple sites, premature deaths occurred and downstream lesions (myocardial fibrosis, lacunar stroke) were present in this model. Vascular lesions were similar to in humans: high plaque activity on PET and MRI imaging and systemic inflammation (high plasma C-reactive protein levels: 42 ± 14 µg/ml). We also found the same gene association (metabolic, inflammatory and anti-inflammatory markers) as in patients with similar histological features. Metabolic imaging localized abnormal brain glucose metabolism in the frontal cortex. It corresponded to cortical neuro-inflammation (PET imaging) that correlated with C-reactive protein level. Multimodal imaging also revealed pronounced choroid plexus function impairment in aging atherosclerotic non-human primates. In conclusion, multimodal whole-body inflammation exploration at the vascular level and blood−brain interfaces identified high-risk aging atherosclerosis. These results open the way for systemic and central inflammation targeting in atherosclerosis in the new era of immunotherapy., Elevated cortical inflammation and defective choroid plexus activity associate with high-risk atherosclerosis in cynomolgus monkeys. Using diet-induced atherosclerosis, in-vivo imaging and gene analysis, Di Cataldo et al. showed (i) monkeys exhibit similar atherosclerosis features and vulnerable plaques-associated genes as patients, (ii) brain imaging demonstrated frontal cortex neuroinflammation and neurovascular signs., Graphical Abstract Graphical Abstract

to the editor: We thank the authors of the comments (see Ref. [1][1]) who contributed their thoughts to this debate ([3][2], [5][3]). Many additional interesting arguments were provided, and most of the comments are in line with our view that hypobaric hypoxia induces different physiological

Background Carbohydrates (CHOs), branched-chain amino acids (BCAAs) and caffeine are known to improve running performance. However, no information is available on the effects of a combination of these ingredients on performance and neuromuscular function during running. Methods The present study was designed as a randomized double-blind cross-over placebo-controlled trial. Thirteen trained adult males completed two protocols, each including two conditions: placebo (PLA) and Sports Drink (SPD: CHOs 68.6 g.L-1, BCAAs 4 g.L-1, caffeine 75 mg.L-1). Protocol 1 consisted of an all-out 2 h treadmill run. Total distance run and glycemia were measured. In protocol 2, subjects exercised for 2 h at 95% of their lowest average speeds recorded during protocol 1 (whatever the condition). Glycemia, blood lactate concentration and neuromuscular function were determined immediately before and after exercise. Oxygen consumption (V˙O2), heart rate (HR) and rate of perceived exertion (RPE) were recorded during the exercise. Total fluids ingested were 2 L whatever the protocols and conditions. Results Compared to PLA, ingestion of SPD increased running performance (p = 0.01), maintained glycemia and attenuated central fatigue (p = 0.04), an index of peripheral fatigue (p = 0.04) and RPE (p = 0.006). Maximal voluntary contraction, V˙O2, and HR did not differ between the two conditions. Conclusions This study showed that ingestion of a combination of CHOs, BCAAs and caffeine increased performance by about 2% during a 2-h treadmill run. The results of neuromuscular function were contrasted: no clear cut effects of SPD were observed. Trial registration ClinicalTrials.gov, http://www.clinicaltrials.gov, NCT00799630

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.

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.

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.

Shoulder performance and sensorimotor control assessments help to identify shoulder instabilities and document the rehabilitation progress. Testing seated subjects in a position of hand prehension requires less controlled adjustments to maintain body balance in a clinically relevant situation. The objective of this work was to determine the test–retest repeatability of a novel shoulder stability test in seated subjects with the ipsi-lateral hand in prehension during four arm loading conditions. Able-bodied subjects were seated on a rigid chair fixed to a force plate. A horizontally and posteriorly directed force was applied to the hand for four 4 loading conditions ranging from 0 to 3 kg. Ten postural balance parameters were calculated from the center of pressure displacements and its corresponding free moments. Intra-class correlation coefficients were calculated for three consecutive trials and for four loading conditions. Generally, the intra-class correlations values increased gradually with the load and varied from 0.727 to 0.948. Tz values increased non-linearly with the applied load. The test–retest reliability of a new shoulder stability test in seated able-bodied subjects was high with sufficient loading (3 kg) and 3 trials.

Aims Peripheral neuropathy (PN) in patients with diabetes can lead to changes in the distribution of plantar pressure during walking, which can be recorded with pedobarography. Compared to traditional spatial data reduction analysis, the pedobarographic Statistical Parametric Mapping (pSPM) allows comparison of the footprints with the advantage that sub-regions do not need to be defined a priori. Aim of the study was to test the potential of pSPM in identifying specific distribution of spatial pressure in different stages of PN. Methods PN was defined according to usual tools (i.e., tendon reflexes and sensory tests). Four groups were compared: patients with diabetes without PN (n = 24; 239 steps); with signs of mild PN (n = 12; 117 steps); with signs of severe PN (n = 6; 52 steps) and a control group without diabetes (n = 12; 124 steps). Traditional spatial data reduction and pSPM were performed to compare plantar pressures in the different groups. Results In patients with PN, traditional spatial data reduction analysis showed lower plantar pressures with PN severity. pSPM analysis is able to better define the initial changes: mild PN patients presents higher pressures on the anterior side of the metatarsal heads compared to patients without neuropathy. Patients with severe PN are characterised by higher pressures under the medial foot arch compared to other groups. Conclusions pSPM may identify specific features of plantar pressure distribution during walking in patients with mild PN and may become a useful screening tool for a timely identification of this complication.

Traditionally in total knee arthroplasty (TKA), a post-operative neutral alignment was the gold standard. This principle has been contested as functional outcomes were found to be inconsistent. Analysis of limb alignment in the non-osteoarthritic population reveals variations from neutral alignment and consideration of a personalized or patient-specific alignment in TKA is challenging previous concepts. The aim of this review was to clarify the variations of current personalized alignments and to report their results. Current personalized approaches of alignment reported are: kinematic, inverse kinematic, restricted kinematic, and functional. The principle of “kinematic alignment” is knee resurfacing with restitution of pre-arthritic anatomy. The aim is to resurface the femur maintaining the native femoral joint line obliquity. The flexion and extension gaps are balanced with the tibial resection. The principle of the “inverse kinematic alignment” is to resurface the tibia with similar medial and lateral bone resections in order to keep the native tibial joint line obliquity. Gap balancing is performed by adjusting the femoral resections. To avoid reproducing extreme anatomical alignments there is “restricted kinematic alignment” which is a compromise between mechanical alignment and true kinematic alignment with a defined safe zone of alignment. Finally, there is the concept of “functional alignment” which is an evolution of kinematic alignment as enabling technology has progressed. This is obtained by manipulating alignment, bone resections, soft tissue releases, and/or implant positioning with a robotic-assisted system to optimize TKA function for a patient’s specific alignment, bone morphology, and soft tissue envelope. The aim of personalizing alignment is to restore native knee kinematics and improve functional outcomes after TKA. A long-term follow-up remains crucial to assess both outcomes and implant survivorship of these current concepts.

The quadriceps-intermittent-fatigue (QIF) test assesses knee extensors strength, endurance and performance fatigability in isometric condition. We aimed to assess reliability and agreement for this test in dynamic conditions and with the use of transcranial magnetic stimulation. On two separate sessions, 20 young adults (25 ± 4 yr, 10 women) performed stages of 100 knee extensors concentric contractions at 120°/s (60° range-of-motion) with 10% increments of the initial maximal concentric torque until exhaustion. Performance fatigability across the test was quantified as maximal isometric and concentric torque loss, and its mechanisms were investigated through the responses to transcranial magnetic and electrical stimulations. Reliability and agreement were assessed using ANOVAs, coefficients of variation (CVs) and intra-class correlation coefficients (ICCs) with 95% CI. Good inter-session reliability and high agreement were found for number of contractions [489 ± 75 vs. 503 ± 95; P = 0.20; ICC = 0.85 (0.66; 0.94); CV = 5% (3; 7)] and total work [11,285 ± 4,932 vs. 11,792 ± 5838 Nm.s; P = 0.20; ICC = 0.95 (0.87; 0.98); CV = 8% (5; 11)]. Poor reliability but high agreement were observed for isometric [–33 ± 6 vs. −31 ± 7%; P = 0.13; ICC = 0.47 (0.05; 0.75); CV = 6% (4;8)] and concentric [−20 ± 11% vs. −19 ± 9%; P = 0.82; ICC = 0.26 (−0.22; 0.63); CV = 9% (6; 12)] torque loss. The dynamic QIF test represents a promising tool for neuromuscular evaluation in isokinetic mode.

International audience; Objective: To analyse the rates of lower limb muscle injuries in athletics disciplines requiring different running velocities during international athletics championships.Design: Prospective total population study.Methods: During 13 international athletics championships (2009–2019) national medical teams and local organizing committee physicians daily reported all newly incurred injuries using the same study design, injury definition and data collection procedures. In-competition lower limb muscle injuries of athletes participating in disciplines involving running (i.e. sprints, hurdles, jumps, combined events, middle distances, long distances, and marathon) were analysed.Results: Among the 12,233 registered athletes, 344 in-competition lower limb muscle injuries were reported (36% of all in-competition injuries). The proportion, incidence rates and injury burden of lower limb muscles injuries differed between disciplines for female and male athletes. The most frequently injured muscle group was hamstring in sprints, hurdles, jumps, combined events and male middle distances runners (43–75%), and posterior lower leg in female middle distances, male long distances, and female marathon runners (44–60%). Hamstring muscles injuries led to the highest burden in all disciplines, except for female middle distance and marathon and male long distance runners. Hamstring muscles injury burden was generally higher in disciplines requiring higher running velocities, and posterior lower leg muscle injuries higher in disciplines requiring lower running velocities.Conclusions: The present study shows discipline-specific injury location in competition context. Our findings suggest that the running velocity could be one of the factors that play a role in the occurrence/location of muscle injuries.

International audience; The presence of modifier genes is now well recognized in severe liver disease outcome associated with alpha-1-antitrypsin deficiency (A1ATD) but their identification remains to be fully elucidated. To address this goal, we performed a candidate gene study with the SORL1 gene, already identified as risk gene in early-onset Alzheimer Disease families. A particular SORL1 micro-haplotype constituted with 3 SNPs (wild-type form TTG) was genotyped on 86 ZZ A1ATD children issued from 66 families. Interestingly, the mutated forms of this micro-haplotype (CAT most of the time) were associated with lower occurrence of severe liver disease and in cellulo studies showed that SORL1 influences Z-A1ATD cellular toxicity and biogenesis. These data suggest that the mutated CAT form of SORL1 micro-haplotype may partly prevent from severe liver disease in A1ATD children. Overall, these findings support a replication study on an independent cohort and additional in cellulo studies to confirm these promising results.Trial registration: ClinicalTrials.gov NCT01862211.

Non-invasive methods still need to better estimate scapular kinematics because of soft tissue artifact issue. This study aimed to develop and assess new procedures to estimate scapular kinematics by combining closed kinematic chain optimization and double calibration. Sixteen healthy volunteers performed static postures mimicking analytical and daily living movements. Scapulo-thoracic angles were computed either with a scapula locator (Ref), or with a closed-loop multibody kinematic optimization (Ell) or with double calibration involving linear (DClin), exponential (DCexp) or logarithmic (DClog) correction. Double calibration corrections enforced scapulo-thoracic angles to be the same than those measured with Ref at the end of the movement performed. DClin and DClog significantly (p < 0.01) reduced scapulo-thoracic misorientation for at least the second third of the movement with averaged improvement ranging from 9° to 32°. Moreover, for arm elevation in the sagittal plane, internal rotations and mimicking hair combing, the beneficial effect of DClin and DClog propagates up to half of the movement. To conclude, when a kinematic chain is required, coupling double calibration (using either linear or logarithmic correction), to a closed-loop multibody kinematic optimization is an efficient and fast method in regard with improvement in scapular kinematic estimates in healthy population.

Resume Introduction Mieux comprendre les consequences psychologiques d’une blessure et l’influence de celle-ci sur les modifications de comportement et la realisation d’un programme de prevention semble pertinent pour la prise en charge therapeutique et dans une optique de prevention. Ainsi, l’objectif de cette presente etude a donc ete (1) d’analyser la perception des blessures par les athletes, et (2) d’analyser l’influence de celles-ci sur la realisation de mesures de prevention. Methodes Nous avons conduit une etude observationnelle quantitative retrospective nationale de recueil du ressenti des athletes de competition licencies a la Federation francaise d’athletisme vis-a-vis de leurs antecedents de blessures, leur perception de la blessure et les programmes de prevention des blessures, par un questionnaire informatique envoye aux athletes au printemps 2020. Resultats Au total, 7712 reponses d’athletes ont ete incluses dans cette analyse, incluant 37 % de femmes et 63 % d’hommes, âges de 37,9 ± 14,8 ans (de 18 a 87 ans), allant de niveau international a departemental, couvrant toutes les disciplines de l’athletisme. Soixante-dix pour cent des athletes n’avaient jamais realise de programme de prevention des blessures durant leur carriere, alors que 30 % estimaient en avoir suivi un de maniere partielle ou totale. Quatre-vingt dix pour cent des athletes avaient eu au moins une blessure depuis le debut de leur pratique. Les sportifs rapportaient qu’une blessure engendrait une tristesse, une frustration, un degout et une preoccupation de se refaire mal au meme endroit. Ils etaient conscients qu’une mauvaise prise en charge pouvait entrainer une recidive ou une nouvelle blessure. Les athletes avec antecedent de blessure realisaient significativement plus un programme de prevention des lesions que ceux ne s’etant jamais blesses. Ceux s’etant deja blesses croyaient en l’efficacite des programmes de prevention, davantage que ceux sans antecedent de blessure. En revanche, il n’y avait pas de difference de perception de l’interet de mesures preventives telles que l’hygiene de vie, l’ecoute de son corps, de ses douleurs et de sa fatigue entre les athletes avec et sans antecedent de blessures. Conclusion Une blessure peut entrainer des consequences psychologiques non negligeables pour l’athlete. Ses repercussions sont importantes a prendre en compte dans la prise en charge globale des lesions.

Among the treatments recommended in Chronic Obstructive Pulmonary Disease (COPD), respiratory rehabilitation has shown undeniable effectiveness in reducing dyspnea and improving quality of life. However, the most severe patients do not have the possibility to make sufficient effort to induce physiological adaptation. The addition of noninvasive ventilation (NIV) during efforts, allows increasing exercise endurance and decreasing dyspnea. Its use during respiratory rehabilitation allows an increase of the training load. However, the selection of patients who can benefit the most from NIV during exercise remains empirical.The question is therefore to discriminate the patients who improve the most during an effort with NIV using a simple test achievable in current practice and to seek after a relationship between the NIV-induced prevention of post-exercise quadriceps fatigue and the training load during the PR program with the adjunct of noninvasive ventilation.In a first study, using a simple test of knee extension maintenance against resistance carried out after a cycling exercise, we showed that the application of NIV during exercise reduced quadriceps muscle fatigue. We also found that one third of the patients did not show an improvement in muscle fatigue with NIV, suggesting that this test could be used to discriminate between patients who could benefit from NIV training.In a second study, we trained severe COPD patients with ventilatory effort limitation with NIV to show a link between training load and the effectiveness of NIV in improving quadriceps endurance. We confirmed the initial results of the first study and showed that training with NIV increased the duration of effort with or without inspiratory support and that the prevention effect of post-exercise fatigue with NIV persisted after training. We did not find a relationship between NIV effectiveness and training load.Our work suggests that the decrease in respiratory work with NIV during exercise has an effect on peripheral muscle performance and that this effect persists after respiratory rehabilitation.; Parmi les traitements recommandés dans la Broncho pneumopathie Chronique obstructive, la réhabilitation respiratoire a montré une efficacité indéniable pour diminuer la dyspnée et améliorer la qualité de vie. Pourtant, les patients les plus sévères n'ont pas la possibilité de réaliser un effort suffisant pour induire une adaptation physiologique. L'ajout d'une ventilation non invasive (VNI) pendant les efforts, permet d’augmenter l’endurance à l’exercice, de diminuer la dyspnée. Son utilisation au cours d'une réhabilitation respiratoire permet une augmentation de la charge d'entrainement. Cependant la sélection des patients pouvant bénéficier le plus de la VNI à l’exercice reste empirique.La question est donc de discriminer les patients qui s'améliorent le plus lors d'un effort avec la VNI en utilisant un test simple, réalisable en pratique courante et de chercher un lien potentiel entre efficacité de la VNI et augmentation de la charge de travail pendant la réhabilitation.Dans une première étude, à l'aide du test simple de maintien d’une extension du genou contre résistance réalisé après un exercice de pédalage, nous avons montré que l'application d'une VNI au cours de l'effort permettait de diminuer la fatigue musculaire du quadriceps. Nous avons également trouvé qu'un tiers des patients ne présentaient pas d'amélioration de la fatigue musculaire avec VNI, suggérant que ce test pouvait servir à discriminer les patients pouvant bénéficier de l'entrainement avec VNI.Dans une deuxième étude, nous avons entrainé avec une VNI, des patients BPCO sévères présentant une limitation ventilatoire à l'effort afin de montrer un lien entre charge d'entrainement et efficacité de la VNI pour améliorer l’endurance du quadriceps. Nous avons confirmé les premiers résultats de la première étude et montré que l'entrainement avec VNI permettait d'augmenter la durée des efforts avec ou sans aide inspiratoire et que l'effet de prévention de la fatigue post-exercice avec VNI persistait après entraînement. Nous n'avons pas retrouvé de relation entre efficacité de la VNI et charge d'entrainement.Nos travaux suggèrent que la diminution du travail respiratoire avec VNI à l’exercice a un effet sur la performance des muscles périphériques et que cet effet persiste après réhabilitation respiratoire.

International audience

International audience; Context: Strength-endurance mainly depends on the power output, which is often expressed relative to the individual’s maximal power capability (Pmax). However, an individual can develop the same power, but in different combinations of force and velocity (force-velocity condition). Also, at matched power output, changing the force-velocity condition results in a change of the velocity-specific relative power (Pmaxv), associated with a change in the power reserve. So far, the effect of these changing conditions on strength-endurance remains unclear.Purpose: We aimed to test the effects of force-velocity condition and power output on strength-endurance.Methods: Fourteen sportsmen performed (i) force- and power-velocity relationships evaluation in squat jumps and (ii) strength-endurance evaluations during repeated squat jump tests in 10 different force-velocity-power conditions, individualized based on the force- and power-velocity relationships. Each condition was characterized by different (i) relative power (%Pmax), (ii) velocity-specific relative power (%Pmaxv), and (iii) ratio between force and velocity (RFv). Strength-endurance was assessed by the maximum repetitions (SJRep), and the cumulated mechanical work (Wtot) performed until exhaustion during repeated squat jump tests. Intra and inter-day reliability of SJRep were tested in one of the 10 conditions. The effects of %Pmax, %Pmaxv, and RFv on SJRep and Wtot were tested via stepwise multiple linear regressions and two-way ANOVAs.Results: SJRep exhibited almost perfect intra- and inter-day reliability (ICC=0.94 and 0.92, respectively). SJRep and Wtot were influenced by %Pmaxv and RFv (R2 = 0.975 and 0.971; RSME=0.243 and 0.234, respectively; both p < 0.001), with the effect of RFv increasing with decreasing %Pmaxv (interaction effect, p = 0.03). %Pmax was not considered as a significant predictor of strength-endurance by the multiple regressions analysis. SJRep and Wtot were higher at lower %Pmaxv and in low force-high velocity conditions (i.e., lower RFv).Conclusion: Strength-endurance was almost fully dependent on the position of the exercise conditions relative to the individual force-velocity and power-velocity relationships (characterized by %Pmaxv and RFv). Thus, the standardization of the force-velocity condition and the velocity-specific relative power should not be overlooked for strength-endurance testing and training, but also when setting fatiguing protocols.

NEW FINDINGS What is the central question of this study? Is neuromuscular fatigability interrelated between different muscle groups from the same individual during isometric all-out exercise? What is the main finding and its importance? Although the average decrease can vary between muscles, an individual demonstrates interrelated fatigability aetiology regardless of the muscle group tested. The inter-individual variability provides evidence of different profiles common between muscles, which can be regarded as an individual characteristic. ABSTRACT Neuromuscular fatigability is commonly attributed to central and peripheral origins. However, there is strong evidence of interactions between these two mechanisms. According to the idea that peripheral fatigability might be centrally regulated, one can hypothesize that neuromuscular fatigability would be correlated between different muscle groups at the individual level. Thirty-two healthy participants (16 women and 16 men) completed two 5 min fatiguing exercises [60 isometric maximal voluntary contractions (MVCs)] with finger flexors (FFs) and ankle plantar flexors (PFs) in two randomized sessions. Neuromuscular testing was conducted before, during (every six MVCs) and directly after the fatigue procedure. The force asymptote (FA ) was calculated as the asymptote of the force-time relationship. Changes (post- vs. pre-fatigue) in the exercise-evoked force (ΔDb100 ), voluntary activation (ΔVA) and central activation ratio (∆CAR) were also investigated. Significant correlations were found between FFs and PFs for FA , ΔDb100 and ΔVA (r = 0.65, r = 0.63 and r = 0.50, respectively). A significant negative correlation between ∆CAR and ∆Db100 was evidenced for both PFs (r = -0.82) and FFs (r = -0.57). Neuromuscular fatigability is correlated between different muscle groups at the individual level. The results support the idea that a restrained motor drive prevents large peripheral perturbations and that individuals exhibit correlated fatigability aetiology regardless of the muscle group tested. Widely different central/peripheral profiles can be found amongst individuals, and a part of the fatigability aetiology can be regarded as an individual characteristic.

To assess the effects of (1) rugby union practice, (2) history of injury managed nonoperatively, and (3) history of injury managed operatively on shoulder functional status in male rugby union players.Cross sectional study.Clinical.86 male athletes were assigned into four groups: multisport athletes, rugby union players without shoulder problems, with history of shoulder injury managed nonoperatively and with history of shoulder injury managed operatively.SI-RSI questionnaire, maximal isometric glenohumeral internal and external rotator strength, unilateral seated shot put test, upper quarter Y balance test.Healthy players presented higher internal (p = 0.03) and external (p = 0.04) rotator strength than multisport athletes. History of shoulder injury managed nonoperatively did not impair physical abilities but limited player's psychological readiness (p 0.001). After 4.5-months, shoulder stabilization surgery impaired maximal muscle strength and upper quarter body stability and mobility (p 0.001 for all).The shoulder functional status in rugby union player presented increased glenohumeral rotator strength when compared to non-collision sport athletes. In rugby union players, psychological concerns remained in the long-term after a shoulder injury managed nonoperatively, and psychological and physical readiness seemed not be reached at 4.5 months postoperatively to respond to rugby union practice demand.

Background: General agreement exists upon the importance of acquiring laparoscopic skills outside the operation room. During the past two decades, simulation-based training and simulators have been more extensively used in surgeons’ training. Nevertheless learning through simulation-based systems is hindered by several flaws. High-fidelity simulators are cost-prohibitive which limits training opportunities. Their use also elicits a high cognitive load. Low-fidelity simulators lack in haptic, direct and summative feedback. Our goal is to develop a new low fidelity simulator integrating effective learning features as a new assessment variable while limiting the associated costs. We also aim at assessing its primary validity. Methods: We engineered a low fidelity simulator for teaching basic laparoscopic skills taking into account psychomotor skills, direct and summative feedback and engineering key features (haptic feedback and complementary assessment variables). Afterward, 77 participants with 4 different surgical skill levels (17 experts; 12 intermediates; 28 inexperienced interns and 20 novices) tested the simulator. We checked the content validity using a 10 point Likert scale. We also assessed the simulator discriminative power by comparing the 4 groups’ performance over two sessions. To do so, we used 3 variables: time, number of errors (collisions) and affine velocity. Results: The content validation mean value score was 7.57/10. The statistical analysis yielded performance discrepancies on the selected variables among the groups (pConclusion: We developed an affordable and validated simulator for testing and learning basic laparoscopic skills. The results exhibit three levels of performance on the selected variables. Experts and intermediates outperformed the inexperienced interns who in turn outperformed the novices. Results show that the embedded evaluation variables are complimentary and provide realistic results. The inclusion of a new variable and, meanwhile, haptic, direct and summative feedback is innovative regarding low-fidelity simulators. Limitations and implementation conditions of the simulator in the surgical curricula are discussed.

International audience; Objective: A numerical 3D model of the human trunk was developed to study the biomechanical effects of lumbar belts used to treat low back pain. Methods: This model was taken from trunk radiographies of a person and simplified so as to make a parametric study by varying morphological parameters of the patient, characteristic parameters of the lumbar belt and mechanical parameters of body and finally to determine the parameters influencing the effects of low back pain when of wearing the lumbar belt. The loading of lumbar belt is modelled by Laplace's law. These results were compared with clinical study. Results: All the results of this parametric study showed that the choice of belt is very important depending on the patient's morphology. Surprisingly, the therapeutic treatment is not influenced by the mechanical characteristics of the body structures except the mechanical properties of intervertebral discs. Discussion: The numerical model can serve as a basis for more in-depth studies concerning the analysis of efficiency of lumbar belts in low back pain. In order to study the impact of the belt's architecture, the pressure applied to the trunk modelled by Laplace's law could be improved. This model could also be used as the basis for a study of the impact of the belt over a period of wearing time. Indeed, the clinical study shows that movement has an important impact on the distribution of pressure applied by the belt.; Objectif : Un modèle numérique 3D du tronc humain a été développé pour étudier les effets biomécaniques des ceintures lombaires utilisées pour traiter les lombalgies. Méthodes : Ce modèle a été pris à partir de radiographies du tronc d'une personne et simplifié de manière à faire une étude paramétrique en faisant varier les paramètres morphologiques du patient, les paramètres caractéristiques de la ceinture lombaire et les paramètres mécaniques du corps et enfin à déterminer les paramètres influençant les effets de la lombalgie lors du port de la ceinture lombaire. La charge de la ceinture lombaire est modélisée par la loi de Laplace. Ces résultats ont été comparés à ceux d'une étude clinique. Résultats : Tous les résultats de cette étude paramétrique ont montré que le choix de la ceinture est très important en fonction de la morphologie du patient. De façon surprenante, le traitement thérapeutique n'est pas influencé par les caractéristiques mécaniques des structures corporelles, à l'exception des propriétés mécaniques des disques intervertébraux. Discussion : Le modèle numérique peut servir de base à des études plus approfondies concernant l'analyse de l'efficacité des ceintures lombaires dans les lombalgies. Afin d'étudier l'impact de l'architecture de la ceinture, la pression appliquée sur le tronc modélisée par la loi de Laplace pourrait être améliorée. Ce modèle pourrait également servir de base à une étude de l'impact de la ceinture sur une période de port. En effet, l'étude clinique montre que le mouvement a un impact important sur la répartition de la pression appliquée par la ceinture.

Background While millions of people are living permanently at high altitude (>2,500 m) worldwide, the mechanisms underlying their tolerance to chronic hypoxia and those responsible for the occurrence of chronic mountain sickness (CMS) remain to be elucidated. Excessive erythrocytosis (EE) is thought to be the main mechanism responsible for CMS symptoms and is included in the definition of CMS, but the precise interplay between EE and symptoms of CMS requires further investigations. Methods The present study benefits from an exceptional dataset coming from 1,594 dwellers of La Rinconada, the highest city in the world (5,100-5,300 m). Based on individual clinical characteristics, subjects were categorized according to the presence of EE and CMS diagnosis, based on current guidelines. Results In this population of relatively young [32 (23; 39) years] highlanders residing in La Rinconada for only a few years [3 (2; 5) years], the internal prevalence of EE (44%) was high, whereas the internal prevalence of CMS (14%) was similar compared to previous reports in highlander populations living at lower altitude (∼4,000 m) in the Andes. Individuals with EE reported less symptoms compared to individuals with lower hematocrit values. Multivariable analysis revealed that age and sex are the main factors associated with EE, whereas age, hematocrit and number of years living at La Rinconada are factors associated with CMS symptoms. Conclusion In this specific population of La Rinconada, high hematocrit values were observed but were associated with limited symptoms. These results raise important questions regarding the definition of EE and CMS and their underlying mechanisms in high-altitude populations.

Resume Introduction Modifier les habitudes de vie vers plus d’activite physique des femmes atteintes de cancer du sein est aujourd’hui un objectif majeur des prises en charge. L’objectif de cette etude etait de tester de maniere exploratoire l’impact de l’evolution du profil d’activite quotidienne sur la qualite de vie aupres de ce public. Methodes Soixante patientes (18 a 75 ans) atteintes de cancer du sein non metastatique ont ete randomisees selon un ratio 2/1 (intervention en activite physique ; controle) dans le cadre de l’essai clinique randomise PASAPAS. Des analyses de regression lineaire multiples ont ete effectuees afin d’expliquer les scores de qualite de vie six mois apres le debut des traitements adjuvants. Variables explicatives retenues : score de qualite de vie en debut d’etude, trait d’anxiete, bras de randomisation, variations du temps passe dans differentes classes d’activite physique ([3-4[MET, [4-6[MET, ≥ 6 MET) et dans des comportements sedentaires. Resultats Seule la diminution du temps passe dans des comportements sedentaires est veritablement apparue comme un predicteur de la qualite de vie physique. La participation au groupe d’intervention est apparue comme un predicteur de la qualite de vie mentale. Discussion Les resultats plaident pour l’intensification de la lutte contre la sedentarite dans les objectifs de prise en charge des femmes atteintes de cancer du sein, ainsi que pour la mise place d’un accompagnement collectif encadre par des personnels competents. Ils suggerent egalement de s’interesser a l’effet de la dynamique d’evolution du profil d’activite quotidienne sur la qualite de vie.

Purpose: The aim of this study was to perform a systematic review of the literature to determine whether there are any clinical or radiological differences in mechanically aligned Total Knee Arthroplasty (TKA) compared with kinematically aligned TKA.Methods: This study included retrospective cohort studies, prospective randomized controlled trials (PRCTs) and prospective cohort studies comparing clinical and radiological outcomes, and complications in TKA with kinematic alignment (KA) and mechanical alignment (MA). All studies had a minimum follow-up of 2 years.Results: Five PRCTs published between 2014 and 2020 were included. These studies showed a low risk of bias and were of very high quality. We did not find a superiority of KA compared to MA technique for clinical and radiological outcomes, except in one study which showed a significant difference favoring KA between the two groups for all clinical scores.Conclusion: We found that KA in TKA achieved clinical and radiological results similar to those of MA. The complication rate was not increased for KA TKAs. Studies with longer follow-up and larger cohorts are required to prove any benefit of KA technique over MA technique.

New findings What is the central question of this study? Does progesterone reduce the effect of chronic intermittent hypoxia (CIH) on arterial blood pressure, respiratory control and oxidative stress in the central nervous system in ovariectomized rats? What is the main finding and its importance? Progesterone does not prevent the elevation of arterial blood pressure in rats exposed to CIH, but normalizes respiratory control, and reduces cerebral oxidative stress. This study draws focus to a potential role of progesterone and the consequences of sleep apnoea in menopausal women. Abstract We tested the hypothesis that progesterone (Prog) reduces the effect of chronic intermittent hypoxia (CIH) on arterial blood pressure, respiratory chemoreflexes and oxidative stress in the central nervous system. Ovariectomized female rats were implanted with osmotic pumps delivering vehicle (Veh) or Prog (4 mg kg-1 day-1 ). Two weeks following the surgery, rats were exposed to room air (Air) or CIH (7 days, 10% O2 , 10 cycles h-1 , 8 h day-1 ). We studied three groups: Veh-Air, Veh-CIH and Prog-CIH. After the CIH exposures, we measured the mean arterial pressure (MAP; tail cuff) and assessed the frequency of apnoeas at rest and ventilatory responses to hypoxia and hypercapnia (whole body plethysmography). The activities of the pro-oxidant enzyme NADPH oxidase (NOX) and antioxidant enzymes superoxide dismutase (SOD; in mitochondrial and cytosolic fractions) and glutathione peroxidase (GPx), as well as the concentration of malondialdehyde (MDA), a marker of lipid peroxidation, were measured in brain cortex and brainstem samples. CIH exposure increased the MAP, the frequency of apnoeas, and the respiratory frequency response to hypoxia and hypercapnia. Prog did not prevent the CIH-induced elevation in MAP, but it reduced the CIH-induced frequency of apnoeas and increased hypoxic and hypercapnic ventilatory responses. In the brain cortex, CIH increased NOX activity, and decreased the cytosolic and mitochondrial SOD activities. These effects were prevented by Prog. NOX activity was increased by CIH in the brainstem, and this was also blocked by Prog. The study draws focus to the links between ovarian hormones and the consequences of sleep apnoea in women.

Studies have suggested that older individuals are more fatigable than young adults when power loss, measured during single-joint contractions, is considered the fatigue index; however, age-related differences in fatigue considering power measurements during multi-joint movements (e.g., cycling) have not been fully elucidated yet. This study examined age-related differences in dynamic and isometric measures of fatigue in response to three cycling exercises. Ten young (27 ± 4 years) and ten old (74 ± 4 years) men performed exercises on different days, 30-s Wingate, 10-min at severe-intensity, and 90-min at moderate-intensity. Dynamic measures-maximal power, torque, and velocity-were assessed after cycling and during recovery (1-8 min post-exercise) through 7-s cycling sprints and isometric force and fatigue etiology (central and peripheral components) through isometric contractions. There were no age-related differences in the relative reduction of dynamic and isometric measures following the Wingate and moderate-intensity tasks. Maximal power, isometric force, and indices of peripheral function (e.g., high-frequency doublet) decreased more in young compared with older individuals after the severe-intensity exercise (all p .05). The only observed age-related difference in the recovery of NM fatigue was a slower recovery of power and torque from 1 to 8 min (p .05) and at 4 min (p = .015), respectively, in younger males after the Wingate. Age-related fatigue and recovery depend on the fatiguing exercise intensity and duration and on the fatigue assessment mode. This study provides novel information on age-related neuromuscular fatigue responses to multi-joint dynamic exercises performed at different intensities and durations.

International audience; Key points: Highlanders develop unique adaptative mechanisms to chronic hypoxic exposure, including substantial haemoglobin and haematocrit increases. However, a significant proportion of populations living permanently at high altitude develop maladaptive features known as chronic mountain sickness (CMS). This study aimed to assess the effects of permanent life at high altitude on clinical and haemorheological parameters (blood viscosity and red blood cell aggregation) and to compare clinical and haemorheological parameters of dwellers from the highest city in the world according to CMS severity. Blood viscosity increased with altitude, together with haemoglobin concentration and haematocrit. At 5100 m, highlanders with moderate-to-severe CMS had higher blood viscosity mainly at high shear rate and even at corrected haematocrit (40%), with a lower red blood cell aggregation. Blood viscosity may contribute to CMS symptomatology but the increased blood viscosity in CMS patients cannot solely be explained by the rise in haematocrit.Abstract: Chronic mountain sickness (CMS) is a condition characterised by excessive erythrocytosis (EE). While EE is thought to increase blood viscosity and subsequently to trigger CMS symptoms, the exact relationship between blood viscosity and CMS symptoms remains incompletely understood. We assessed the effect of living at high altitude on haemoglobin, haematocrit and haemorheological parameters (blood viscosity and red blood cell aggregation), and investigated their relationship with CMS in highlanders living in the highest city in the world (La Rinconada, Peru, 5100 m). Ninety-three men participated in this study: 10 Caucasian lowlanders, 13 Andean highlanders living at 3800 m and 70 Andean highlanders living at 5100 m (35 asymptomatic, CMS score ≤5; 15 with mild CMS, CMS score between 6 and 10; 20 with moderate-to-severe CMS, CMS score >10). Blood viscosity was measured at native and corrected haematocrit (40%). Haemoglobin concentration and haematocrit increased with the altitude of residency. Blood viscosity also increased with altitude (at 45 s-1 : 6.7 ± 0.9 mPa s at sea level, 14.0 ± 2.0 mPa s at 3800 m and 27.1 ± 8.8 mPa s at 5100 m; P < 0.001). At 5100 m, blood viscosity at corrected haematocrit was higher in highlanders with moderate-to-severe CMS (at 45 s-1 : 18.9 ± 10.7 mPa s) than in highlanders without CMS (10.2 ± 5.9 mPa s) or with mild CMS (12.1 ± 6.1 mPa s) (P < 0.05). In conclusion, blood viscosity may contribute to CMS symptomatology but the increased blood viscosity in CMS patients cannot solely be explained by the rise in haematocrit.

International audience; This study used wireless technology to investigate joint kinematic characteristics of the four alpine skiing disciplines. Knee and hip angles were measured in 20 national team alpine skiers during 253 ski runs under FIS regulation, including: 85 Slalom (SL), 123 Giant Slalom (GS), 29 Super Giant Slalom (SG), and 16 Downhill (DH). Data were analyzed by outside (OL, n = 2,087) and inside leg (IL, n = 2,015). The proportion of concentric and eccentric phases (extension and flexion respectively for the knee extensors) as well as the proportion of the quasi-isometric phase defined between ±20 • .s −1 depended on the discipline in interaction with the IL/OL (p < 0.001). The results showed a lower knee quasi-isometric duration on OL in SL (11%) than other disciplines (DH: 38%; SG: 42%; GS: 34%, p < 0.001, d > 1.8), suggesting a highly dynamic style. Quasi-isometric mode was significantly longer on OL than IL in GS (34 vs. 20%, p < 0.001, d = 1.16) and SG (42 vs. 28%, p < 0.001, d = 1.11) but was significantly longer on IL than OL in SL (19 vs. 11%, p < 0.001, d = 0.64). Thus, GS and SG showed similarities, with a significantly faster knee eccentric mean angular velocity on IL compared to OL (GS −58 vs. −54 • .s −1 , SG −52 vs. −45 • .s −1 , p < 0.001, d ≥ 0.22) whereas SL showed an opposite pattern (−72 vs. −89 • .s −1 , p < 0.001, d = 1.10). The quasi-isometric phase was overlooked in previous studies but is crucial to consider. The current data may be used to train the outside and inside leg specificities incorporating discipline-specific contraction modes and exercises.

Introduction: Distal Femoral Osteotomy (DFO) is a common procedure for correcting lower limb valgus deformity and lateral compartment overload. Low 20-year survivorship rate was reported with a consequent need for total knee arthroplasty (TKA). This study aims to review literature and to analyse the influence of a previous distal femoral osteotomy on outcomes of patients undergoing TKA.Methods: A systematic literature review was performed in PubMed/Medline and Embase in May 2020. Papers were selected based on the following criteria: patient with a previous distal femoral osteotomy; total knee replacement; Pre- and Postoperative outcomes; surgical outcomes: clinical scores, range of motion, radiographic evaluation and revisions for any cause; case series, retrospective studies, observational studies, open-label studies, randomized clinical trials; systematic reviews and meta-analyses were included to extract primitive studies.Results: 306 articles were found, of which five papers were considered eligible for this review. In every study included, postoperative clinical outcomes (Knee Society Score or Hospital for Special Surgery score) statistically improved from the preoperative. Complications were not uncommon; implant survivorship at the available follow-up seems to be similar to primary TKA, although being too short to draw any conclusions.Conclusions: Limited and highly heterogeneous evidence is currently available on the influence of DFO on outcomes after TKA. Knee replacement improves clinical middle-term outcomes in patients with previous distal femoral osteotomy. In this complex surgery, the use of technical tips and tricks could help surgeons to obtain an accurate knee balancing and better long-term results.

This thesis aims to demonstrate the central role of opioid system in developing and maintaining addiction in two behavioural addiction models: sport addiction and anorexia nervosa.It presents an original, multidisciplinary and transversal approach using modern and innovative tools, with a brain imagery using [11C]-diprenorphine PET-scan as main process. We attempt to get receptor density mapping using a SRTM model. Images obtained by this way were then exploited by voxel-based analysis using SPM12. Statistical parametric comparisons include several variables, covariables and regression parameters extracted from complementary exams (psychometric tests, anthropometric measurements, biological samplings especially peripheric circulating opioids assessment by ELISA technic).These analyses demonstrate the complexity of addictive mechanisms in these two models, with an indirect role of opioid system which seems to work by modulation of dopaminergic mesolimbic reward system. However, we also find several differences and inhomogeneities in these two behavioural addictions which indicate existence of various sensitivity and different mechanisms among subjects. This asks the question of phenotyping and genetics underlying these phenomena, needing new studies with a long-term perspective of clinical and therapeutic possibilities.; Le travail présenté dans cette thèse s’attache à démontrer le rôle central joué par le système opioïde dans le développement et le maintien de deux modèles d’addictions comportementales : l’anorexie mentale et l’addiction au sport.Il présente une approche originale, multidisciplinaire et transverse utilisant des techniques modernes et novatrices, avec pour procédé central une imagerie cérébrale TEP/TDM utilisant de la [11C]-diprénorphine comme traceur. Cherchant à obtenir une imagerie en densité de récepteurs opioïdes, une modélisation SRTM a été utilisée. Les images en densité de récepteurs ainsi obtenues ont été exploitées par analyse voxel à voxel sous SPM12. Ces comparaisons statistiques paramétriques ont également intégré plusieurs variables, covariables et paramètres de régressions issus d’analyses complémentaires (tests psychométriques, mesures anthropométriques et analyses biologiques, notamment des dosages d’opioïdes en circulation périphérique mesurés par une technique ELISA).Ces analyses ont démontré la complexité du mécanisme addictif dans ces deux modèles, avec un rôle indirect du système opioïde probablement par modulation du circuit dopaminergique de la boucle méso limbique du circuit de la récompense. Cependant les nombreuses divergences entre ces deux addictions comportementales et les hétérogénéités retrouvées entre les individus montre aussi l’existence d’une sensibilité et de mécanismes variables d’une personne à l’autre, posant la question du phénotypage et de la génétique, et ouvrant le champ à de nouvelles études, avec à terme de possibles répercussions cliniques voire thérapeutiques.

BACKGROUND Erythrocyte deformability is impaired in sickle cell disease (SCD). The regulation of cytoskeletal protein organization plays a key role in erythrocyte deformability. The activation of adenylyl cyclase (AC)/cAMP/Protein kinase A (PKA) signaling pathway was associated with increased deformability in healthy erythrocytes, however the role of this pathway in SCD is unknown. OBJECTIVE We evaluated mechanical responses of sickle red blood cells under physiological levels of shear stress and the possible link between their deformability and AC/cAMP/PKA signaling pathway. METHODS The shearing of sickle red blood cells at physiological level (5 Pa) and the measurement of deformability were performed by a laser assisted optical rotational cell analyzer (LORRCA). RESULTS Red blood cell deformability increased of 2.5-6.5% by blocking the activity of phosphodiesterase with Pentoxifylline (10μM) (p

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Introduction: Proficiency in the direct anterior approach (DAA) as with many surgical techniques is considered to be challenging. Added to this is the controversy of the benefits of DAA compared to other total hip arthroplasty (THA) approaches. Our study aims to assess the influence of experience on learning curve and clinical results when transitioning from THA via posterior approach in a lateral position to DAA in a supine position. Methods: A consecutive retrospective series of 525 total hip arthroplasty of one senior and six junior surgeons was retrospectively analysed from May 2013 to December 2017. Clinical results were analysed and compared between the two groups and represented as a learning curve. Mean follow up was 36.2 months ± 11.8. Results: This study found a significant difference in complications between the senior and junior surgeons for operating time, infection rate, and lateral femoral cutaneous nerve (LFCN) neuropraxia. A trainee’s learning curve was an average of 10 DAA procedures before matching the senior surgeon. Of note, the early complications correlated with intraoperative fractures increased with experience in both groups. Operating time for the senior equalised after 70 cases. Dislocation rate and limb length discrepancy were excellent and did not show a learning curve between the two groups. Conclusion: DAA is a safe approach to implant a THA. There is a learning curve and initial supervision is recommended for both seniors and trainees. Level of evidence: Retrospective, consecutive case series; level IV.

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Background:Reconstruction of the medial patellofemoral ligament (MPFL) is the gold standard treatment for recurrent patellar dislocation. Patella alta has been reported in about half of patients with recurrent patellofemoral instability.Hypothesis:MPFL reconstruction (MPFLr) has a beneficial role in the correction of patellar height in patients with mild patella alta (Caton-Deschamps index [CDI] between 1.20 and 1.40).Study Design:Case series; Level of evidence, 4.Methods:Skeletally mature patients, with no history of previous or concomitant knee surgical procedures, who underwent isolated MPFLr using hamstring autograft for recurrent patellar instability between 2005 and 2018, were included in this study. The authors calculated CDI, modified Insall-Salvati index (MISI), and Blackburne-Peel index (BPI) ratios. Measurements done by 2 independent observers were calculated and used to compare pre- and postoperative patellar height (patella alta: CDI >1.20).Results:A total of 89 patients (95 knees) were included in the study, with a mean age of 25.0 years (range, 15.0-45.0 years). There were 70% women and 30% men. We found patella alta in 35.8% of cases preoperatively. Among them, 79.4% had reduced patellar height indices, within normal limits, postoperatively (mean follow-up, 18.4 ± 12.0 months). All the ratios showed a significant reduction in patellar height after surgery (CDI: 0.19 [range, –0.05, 0.60]; MISI: 0.22 [–0.14, 0.76]; BPI: 0.18 [–0.08, 0.59]; P < .00001). The CDI of 79.4% of the study knees was reduced to within normal limits postoperatively. The CDI was maintained within normal limits postoperatively in 93.4% of the knees with normal patellar height and reduced to normal in 50% of the knees with severe patella alta before surgery . No patient reported patella infera before surgery, whereas this condition was found in 8.2% of study patients postoperatively. A moderate correlation was reported between preoperative radiographic indices and their reduction after surgery (CDI: P < .001, ρ = 0.39; MISI: P < .001, ρ = 0.39; BPI: P < .001, ρ = 0.48).Conclusion:The higher the preoperative patellar height, the more important is the lowering effect of MPFLr using the hamstring for patellar instability. Bony procedures should not be indicated in patients with patellar instability and a CDI between 1.20 and 1.40.

Blood rheology is a key determinant of blood flow and tissue perfusion. There are still large discrepancies regarding the effects of an acute running exercise on blood rheological properties and red blood cell (RBC) physiology. We investigated the effect of a 10 km running trial on markers of blood rheology and RBC physiology in endurance trained athletes. Blood was sampled before and after the exercise to measure lactate and glucose, hematological and hemorheological parameters (blood viscosity, RBC deformability, and aggregation), eryptosis markers (phosphatidylserine and CD47 exposure, RBC reactive oxygen species), RBC-derived microparticles (RBC-MPs), and RBC electrophysiological activity. Weight was measured before and after exercise. Peripheral oxygen saturation and heart rate were monitored before and during the trial. Blood lactate and glucose levels increased after exercise and subjects significantly lost weight. All athletes experienced a significant fall in oxygen saturation. Mean corpuscular volume (MCV) was increased from 95.1 ± 3.2 to 96.0 ± 3.3 and mean corpuscular hemoglobin concentration (MCHC) decreased after exercise suggesting a slight RBC rehydration. Exercise increased RBC deformability from 0.344 ± 0.04 to 0.378 ± 0.07, decreased RBC aggregates strength and blood viscosity, while hematocrit (Hct) remained unaffected. While RBC electrophysiological recording suggested a modulation in RBC calcium content and/or chloride conductance, eryptosis markers and RBC-MPs were not modified by the exercise. A 10 km acute running exercise had no effect on RBC senescence and membrane blebbing. In contrast, this exercise increased RBC deformability, probably through rehydration process which resulted in a decrease in blood viscosity.

Introduction: Total knee arthroplasty (TKA) remains the treatment of choice for severe osteoarthritis of the knee and nearly 60% of patients undergoing TKA are women. Females present three notable anatomic differences. Thus, gender-specific (GS) components were introduced to accommodate the females’ anatomic differences. No systematic review has been published since 2014. The aim of this study was to perform a recent systematic review of the literature to determine whether there is any clinical benefit of gender-specific implants compared to conventional unisex implants in total knee arthroplasty (TKA).Methods: This study included prospective randomized controlled trials (PRCTs) comparing clinical and radiological outcomes, and complications in TKA with gender-specific implants and conventional implants. All studies had a minimum follow-up of two years.Results: Three PRCTs published between 2010 and 2012 were included. These studies showed a low risk of bias and were of very high quality. We did not find superior clinical outcomes for gender-specific prostheses compared to conventional prostheses. However, gender-specific TKA reduced the number of patients with femoral component overhang compared to conventional TKA.Conclusion: In our systematic review, despite a lower overhang rate, gender-specific implants in female TKA showed no clinical benefit over standard unisex implants. Good clinical results with significant improvement were observed with both designs. There is a notable absence of new studies on this subject in recent years, and further research needs to be performed using various gender-specific implant designs to further define the role of gender-specific implants.Level of evidence: Systematic review, Level IV

Purpose: Motor outputs are governed by dynamics organized around stable states and spontaneous transitions: we seek to investigate the swimmers’ motor behavior flexibility as a function of speed and aquatic environment manipulations. Method: Eight elite male swimmers partook an eight-level incremental test (4% increment from 76% to 104% of their mean speed on 200 m front crawl) in a quasi-static aquatic environment (pool). Swimmers then partook another incremental test at similar effort in a dynamic aquatic environment (swimming flume) up to maximal speed. Stroke rate (SR), index of coordination (IdC) and intersegmental coupling of the upper limbs were computed from the inertial sensors located on the upper limbs and the sacrum. Results: With speed increase, SR values presented a steeper linear increase in the pool than in the flume. IdC values increased also in the pool but remained stable in the flume. Individual SR and IdC vs. speed increase displayed second-order polynomial dynamics, indicative of adaptive flexibility with a range of extremum values more restricted in the flume. Finally, a reduction of the in-phase coordination pattern was noted with flume speed increase. Conclusions: Action possibilities were strongly constrained in the flume at the highest speeds as the fluid flow led to discontinuity in the propulsive actions of the upper limbs and lack of in-phase inter-segmental coordination. This highlights that the behavioral flexibility was restricted in the flume in comparison to the pool, in which the exploitation of opportunities for action involved a larger number of degrees of freedom in the movement.

International audience; Vulnerable carotid atherosclerotic plaques are characterised by several risk factors, such as inflammation, neovascularization and intraplaque haemorrhage (IPH). Vulnerable plaques can lead to ischemic events such as stroke. Many studies reported a relationship between IPH, plaque rupture, and ischemic stroke. Histology is the gold standard to evaluate IPH, but it required carotid endarterectomy (CEA) surgery to collect the tissue sample. In this context, several imaging methods can be used as a non-invasive way to evaluate plaque vulnerability and detect IPH. Most imaging studies showed that IPH is associated with plaque vulnerability and stroke, with magnetic resonance imaging (MRI) being the most sensitive and specific to detect IPH as a predictor of ischemic events. These conclusions are however still debated because of the limited number of patients included in these studies; further studies are required to better assess risks associated with different IPH stages. Moreover, IPH is implicated in plaque vulnerability with other risk factors which need to be considered to predict ischemic risk. In addition, MRI sequences standardization is required to compare results from different studies and agree on biomarkers that need to be considered to predict plaque rupture. In these circumstances, IPH detection by MRI could be an efficient clinical method to predict stroke. The goal of this review article is to first describe the pathophysiological process responsible for IPH, its histological detection in carotid plaques and its correlation with plaque rupture. The second part will discuss the benefits and limitations of imaging the carotid plaque, and finally the clinical interest of imaging IPH to predict plaque rupture, focusing on MRI-IPH.

Highlights • Endurance training has beneficial effects on red blood cell aging and function. • Improved hemorheological effects are observed in endurance-untrained individuals after a 6-week running training. • A shift to more young red blood cells is observed after the training. • Physical performance and blood parameters increased after the training., Objective To examine the impact of a 6-week endurance training on red blood cell (RBC) aging and deformability of healthy participants to detect possible improved hemorheological and performance-related adaptations. Methods A total of 31 participants (17 females and 14 males) performed a 6-week moderate training protocol (three 1-h running sessions per week at 70% of maximal heart rate). Blood was sampled before and after the training. RBCs from each participant were fractioned according to density and age into 4 RBC subfractions. Subfractions were examined for changes of RBC properties, including aging distribution, RBC deformability, RBC microparticles, and phosphatidylserine concentrations. RBC and plasma nitrite levels were measured as indicators of nitric oxide metabolism. Results Aerobic performance, peak oxygen consumption, ventilatory thresholds, velocity at the aerobic–anaerobic threshold, and lactate at exhaustion improved after training. The relative amount of both young RBCs and old RBCs increased, and the amount of the main RBC fraction decreased. Phosphatidylserine externalization and RBC-derived microparticles decreased. Overall deformability expressed as shear stress required to achieve half-maximum deformation to theoretical maximal elongation index at infinite shear stress improved in unfractioned RBCs (p < 0.001). Nitrite decreased in total (p = 0.001), young (p < 0.001), main (p < 0.001), and old (p = 0.020) aged RBCs and in plasma (p = 0.002), but not in very old RBCs. Conclusion These results indicate that non-endurance-trained healthy participants benefit from a regular moderate running training program because performance-related parameters improve and a younger RBC population with improved RBC properties is induced, which might support oxygen supply in the microcirculation.

Purpose The purpose of this study was to investigate bone microarchitecture of cadaveric proximal femurs using ultra-high field (UHF) 7-Tesla magnetic resonance imaging (MRI) and to compare the corresponding metrics with failure load assessed during mechanical compression test and areal bone mineral density (ABMD) measured using dual-energy X-ray absorptiometry. Materials and methods ABMD of ten proximal femurs from five cadavers (5 women; mean age = 86.2 ± 3.8 (SD) years; range: 82.5–90 years) were investigated using dual-energy X-ray absorptiometry and the bone volume fraction, trabecular thickness, trabecular spacing, fractal dimension, Euler characteristics, connectivity density and degree of anisotropy of each femur was quantified using UHF MRI. The whole set of specimens underwent mechanical compression tests to failure. The inter-rater reliability of microarchitecture characterization was assessed with the intraclass correlation coefficient (ICC). Associations were searched using correlation tests and multiple regression analysis. Results The inter-rater reliability for bone microarchitecture parameters measurement was good with ICC ranging from 0.80 and 0.91. ABMD and the whole set of microarchitecture metrics but connectivity density significantly correlated with failure load. Microarchitecture metrics correlated to each other but did not correlate with ABMD. Multiple regression analysis disclosed that the combination of microarchitecture metrics and ABMD improved the association with failure load. Conclusion Femur bone microarchitecture metrics quantified using UHF MRI significantly correlated with biomechanical parameters. The multimodal assessment of ABMD and trabecular bone microarchitecture using UHF MRI provides more information about fracture risk of femoral bone and might be of interest for future investigations of patients with undetected osteoporosis.

Background To determine the influence of anterolateral ligament reconstruction (ALLR) on knee constraint through the analysis of knee abduction (valgus) moment when the knee is subjected to external translational (anterior) or rotational (internal) loads. Methods A knee computer model simulated from a three-dimensional computed tomography scan of healthy male was implemented for this study. Three groups were designed: (1) intact knee, (2) combined Anterior Cruciate Ligament (ACL) and Antero-Lateral Complex (ALC) deficient knee, and (3) combined ACL and Antero- lateral Ligament (ALL) reconstructed knee. The reconstructed knee group was subdivided into four groups according to attachment of reconstructed anterolateral ligament to the femoral epicondyle. Each group of simulated knees was placed at 0°, 10°, 20°, 30°, 40° and 50° of knee flexion. For each position an external anterior (drawer) 90-N force or a five-newton meter internal rotation moment was applied to the tibia. The interaction effect between the group of knees and knee flexion angle (0–50°) on knee kinematics and knee abduction moment under external loads was tested. Results When reconstructed knees were subjected to a 90-N anterior force or a five-newton meter internal rotation moment there was significant reduction in anterior translation and internal rotation compared with deficient knees. Only the ALLR procedure using posterior and proximal femoral attachment sites for graft fixation combined with ACL reconstruction allowed similar mechanical behavior to that observed in the intact knee. Conclusions Combined ACL and ALLR using a minimally invasive method in an anatomically reproducible manner prevents excessive anterior translation and internal rotation. Using postero-proximal femoral attachment tunnel for reconstruction of ALL does not produce overconstraint of the lateral tibiofemoral compartment.