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Background. For individuals with lateral postural imbalance after stroke, the decision to adopt a cane for walking often is not based on objective findings. Objective. The authors investigated the explanatory value of 2 posturographic criteria for lateral postural imbalance on the walking abilities of poststroke subjects. Methods. Indices of postural asymmetry (percentage of body weight on the less loaded lower limb) and instability (mediolateral variance of center-of-pressure displacements) were measured in 40 healthy individuals and 52 patients (mean 94.2 days after first hemispheric stroke), who stood still on a double force platform. Cut-off values (mean ± 2 standard deviations) were calculated and compared. The predictive value of both postural indices on walking abilities with or without a cane was analyzed. Results. Of the patients, 34.6% were unstable along the mediolateral axis (variance >7 mm2), and 44.2% were asymmetrical (body weight

PEYROT, N., D. THIVEL, L. ISACCO, J.-B. MORIN, A. BELLI, and P. DUCHE. Why Does Walking Economy Improve after Weight Loss in Obese Adolescents? Med. Sci. Sports Exerc., Vol. 44, No. 4, pp. 659–665, 2012. Purpose: This study tested the hypothesis that the increase in walking economy (i.e., decrease in net metabolic rate per kilogram) after weight loss in obese adolescents is induced by a lower metabolic rate required to support the lower body weight and maintain balance during walking. Methods: Sixteen obese adolescent boys and girls were tested before and after a weight reduction program. Body composition and oxygen uptake while standing and walking at four preset speeds (0.75, 1, 1.25, and 1.5 mIs j1 ) and at the preferred speed were quantified. Net metabolic rate and gross metabolic cost of walking–versus-speed relationships were determined. A three-compartment model was used to distinguish the respective parts of the metabolic rate associated with standing (compartment 1), maintaining balance and supporting body weight during walking (compartment 2), and muscle contractions required to move the center of mass and limbs (compartment 3). Results: Standing metabolic rate per kilogram (compartment 1) significantly increased after weight loss, whereas net metabolic rate per kilogram during walking decreased by 9% on average across speeds. Consequently, the gross metabolic cost of walking per unit of distance–versus-speed relationship and hence preferred walking speeds did not change with weight loss. Compartment 2 of the model was significantly lower after weight loss, whereas compartment 3 did not change. Conclusions: The model showed that the improvement in walking economy after weight loss in obese adolescents was likely related to the lower metabolic rate of the isometric muscular contractions required to support the lower body weight and maintain balance during walking. Contrastingly, the part of the total metabolic rate associated with muscle contractions required to move the center of mass and limbs did not seem to be related to the improvement in

Chronic hypoxia has been shown to promote a large number of pathologies such as hypertension, cardiovascular and metabolic disorders, and respiratory diseases. The oxidative stress that occurs during intermittent or continuous cellular hypoxia is likely involved in all these diseases. Indeed, the reactive species were demonstrated to inhibit active substances, modulate the signaling of intracellular pathways, and mediate enzymes activation, which are known to play a critical role in the geneses and/or the outcomes of these pathologies. The four review articles of this special issue describe the current knowledge regarding the role of oxidative stress in ischemic retinopathy, pulmonary diseases, and infertile testis and discuss a new model of yeast to study hypoxia-induced oxidative stress. In addition, the two original research articles presented in this issue further expand the understanding of the redox biology in the context of pulmonary arterial hypertension and impaired spermatogenesis induced by hypoxia. The review article by S.-Y. Li et al. presents the underlying mechanisms involved in the hypoxia/ischemia-induced oxidative damage in diabetic retinopathy and retinopathy of prematurity. In particular, the authors have discussed the effect of therapeutic strategies of antioxidants treatment such as administration of catalase and superoxide dismutase, vitamin E, and lutein and inhibition of NADPH oxidase or similar signaling pathways in these retinal ischemic diseases. The extensive review by O. F. Araneda and M. Tuesta reports recent in vitro and in vivo experimental evidence that shows the implied mechanisms in pulmonary redox state by hypoxia via the increase of ROS generation in mitochondria, as from activation of NADPH oxidase, xanthine oxidase/reductase, and nitric oxide synthase enzymes, as well as throughout inflammatory process. Then, the role and impact of enzymatic and nonenzymatic antioxidant in the modulation of the pathways involved in the physiopathological response to hypoxia are extensively discussed. In a last part, the authors report the evolution of the two most studied makers of oxidative stress (exhaled nitric oxide for humans and pulmonary content of malondialdehydes for animals) in the lung in response to hypoxic exposure. The paper of J. G. Reyes et al. synthesizes the current state of knowledge of the physiology of the testicles under pathologic hypoxic conditions that lead to reduced spermatogenesis. The molecular events triggered by all causes of hypoxia in the testis share common mechanistic pathways involving ROS generated by mitochondrial dysfunction and activation of enzymes such as xanthine oxidase or the inducible nitric oxide synthase. The recent results analyzed suggest that conditions such as germ cell apoptosis and DNA damage are common features in hypoxic testicles such as varicocele and testicular torsion. In addition, the oxidative damages present in hypoxia suggest the ROS play a role in the initiation stages of germ cell damage and apoptosis. In another review by M. I. G. Siso and M. E. Cerdan the yeast Kluyveromyces lactis K. is proposed as a respiratory eukaryote model, complementary to the fermentative S. cerevisiae, for the study of the pathways of hypoxia-induced oxidative stress. Although these two yeasts share homology between their acting proteins, the experimental studies described in this review reveal that there are many differences from a comparative perspective with respect to the signaling pathways and mechanisms of cells regulation including life span adjustment, programmed cell dead, autophagy, and mitophagy. The paper by A. Zepeda et al. tests the protective and antioxidant effects of a blueberry extract in testis of rats exposed to hypobaric hypoxia. The authors demonstrated that the decreased apoptosis of the testicles cells observed with such supplementation was probably driven by a reduced lipid peroxidation and increased antioxidant enzymes activities. This suggests that blueberry extract may have a high antioxidant capacity and that its regular ingestion could prevent the testicles disorders related to oxidative stress induced by hypoxia. Finally, M. Mata et al. address the relationship between the expression of the proliferator-activated receptor γ coactivator-1α (PGC-1α), the pulmonary vascular resistance, and the oxidative stress (cytochrome c and SOD expression) in patients with pulmonary arterial hypertension. The results suggest that PGC-1α likely modulates by oxidative mechanisms at the mitochondrial level of patients with pulmonary hypertension and could be used as a biomarker since it is not expressed healthy subjects. In conclusion, the growing body of evidence suggests that the paradoxical increase in ROS generation is at the heart of the pathologic mechanisms associated with the hypoxic feature. In this respect, we are convinced that the study of the underlying mechanisms increasing oxidative stress in the pathologies associated with hypoxia will be essential to develop the future therapies/treatments of these diseases.

Sickle cell disease (SCD) is a class of hemoglobinopathy in humans, which causes a disruption of the normal activities in different systems. Although this disease begins with the polymerization of red blood cells during its deoxygenating phase, it can erupt into a cascade of debilitating conditions such as ischemia-reperfusion injury, inflammation, and painful vaso-occlusion crises. The purpose of this review is to discuss how these phenomena can result in the formation of oxidative stress as well as limit nitric oxide (NO) bioavailability and decrease antioxidant status. The cumulative effects of these traits cause an increase in other forms of reactive oxygen species (ROS), which in turn intensify the symptoms of SCD and generate a vicious circle. Finally, we will discuss antioxidant therapeutic strategies that limit ROS generation and subsequently increase NO bioavailability with respect to endothelial protection in SCD.

Background Muscle atrophy associated with various pathophysiological conditions represents a major health problem, because of its contribution to the deterioration of patient status and its effect on mortality. Although the involvement of pro-inflammatory cytokines in this process is well recognized, the role of sphingolipid metabolism alterations induced by the cytokines has received little attention. Results We addressed this question both in vitro using differentiated myotubes treated with TNF-α, and in vivo in a murine model of tumor-induced cachexia. Myotube atrophy induced by TNF-α was accompanied by a substantial increase in cell ceramide levels, and could be mimicked by the addition of exogenous ceramides. It could be prevented by the addition of ceramide-synthesis inhibitors that targeted either the de novo pathway (myriocin), or the sphingomyelinases (GW4869 and 3-O-methylsphingomyelin). In the presence of TNF-α, ceramide-synthesis inhibitors significantly increased protein synthesis and decreased proteolysis. In parallel, they lowered the expression of both the Atrogin-1 and LC3b genes, involved in muscle protein degradation by proteasome and in autophagic proteolysis, respectively, and increased the proportion of inactive, phosphorylated Foxo3 transcription factor. Furthermore, these inhibitors increased the expression and/or phosphorylation levels of key factors regulating protein metabolism, including phospholipase D, an activator of mammalian target of rapamycin (mTOR), and the mTOR substrates S6K1 and Akt. In vivo, C26 carcinoma implantation induced a substantial increase in muscle ceramide, together with drastic muscle atrophy. Treatment of the animals with myriocin reduced the expression of the atrogenes Foxo3 and Atrogin-1, and partially protected muscle tissue from atrophy. Conclusions Ceramide accumulation induced by TNF-α or tumor development participates in the mechanism of muscle-cell atrophy, and sphingolipid metabolism is a logical target for pharmacological or nutritional interventions aiming at preserving muscle mass in pathological situations.

International audience; Trekking and military missions generally consist of carrying heavy loads for extreme durations. These factors have been separately shown to be sources of neuromuscular (NM) fatigue and locomotor alterations. However, the question of their combined effects remains unresolved, and addressing this issue required a representative context. PURPOSE: The aim was to investigate the effects of extreme-duration heavy load carriage on NM function and walking characteristics.METHODS: Ten experienced infantrymen performed a 21-h simulated military mission (SMM) in a middle-mountain environment with equipment weighing ∼27 kg during battles and ∼43 kg during marches. NM function was evaluated for knee extensors (KE) and plantar flexors (PF) pre- and immediately post-SMM using isometric maximal voluntary contraction (MVC) measurement, neural electrical stimulation and surface EMG. The twitch-interpolation method was used to assess central fatigue. Peripheral changes were examined by stimulating the muscle in the relaxed state. The energy cost, mechanical work and spatio-temporal pattern of walking were also evaluated pre-/post-SMM on an instrumented treadmill in three equipment conditions: Sportswear, Battle and March.RESULTS: After the SMM, MVC declined by -10.2±3.6% for KE (P\textless0.01) and -10.7±16.1% for PF (P = 0.06). The origin of fatigue was essentially peripheral for both muscle groups. A trend toward low-frequency fatigue was detected for KE (5.5%, P = 0.08). These moderate NM alterations were concomitant with a large increase in perceived fatigue from pre- (rating of 8.3±2.2) to post-SMM (15.9±2.1, P\textless0.01). The SMM-related fatigue did not alter walking energetics or mechanics, and the different equipment carried on the treadmill did not interact with this fatigue either.CONCLUSION: this study reports the first data on physiological and biomechanical consequences of extreme-duration heavy load carriage. Unexpectedly, NM function alterations due to the 21-h SMM were moderate and did not alter walking characteristics.CLINICAL TRIAL REGISTRATION: Name: Effect of prolonged military exercises with high load carriage on neuromuscular fatigue and physiological/biomechanical responses. Number: NCT01127191.

International audience; In the military context, soldiers carry equipments of total mass often exceeding 30%-40% of their body mass (BM) and complexly distributed around their body (backpack, weapons, electronics, protections, etc.), which represents severe load carrying conditions. Purpose: This study aimed to better understand the effects of load carriage on walking energetics and mechanics during military-type walking. Methods: Ten male infantrymen recently retired from the French Foreign Legion performed 3-min walking trials at a constant speed of 4 km[middle dot]h-1 on an instrumented treadmill, during which walking pattern spatiotemporal parameters, energy cost (CW), external mechanical work (Wext), and the work done by one leg against the other during the double-contact period (Wint,dc) were specifically assessed. Three conditions were tested: (i) light sportswear (SP, reference condition considered as unloaded), (ii) battle equipment (BT, ~22 kg, ~27% of subjects' BM, corresponding to a military intermediate load), and (iii) road march equipment (RM, ~38 kg, ~46% of subjects' BM, corresponding to a military high load). Results: Repeated-measures ANOVA showed that military equipment carriage significantly (i) altered the spatiotemporal pattern of walking (all P \textless 0.01), (ii) increased absolute gross and net CW (P \textless 0.0001), and (iii) increased both absolute and mass-relative Wext (P \textless 0.01) and Wint,dc (P \textless 0.0001) but did not alter the inverted pendulum recovery or locomotor efficiency. Conclusions: Military equipments carriage induced significant changes in walking mechanics and energetics, but these effects appeared not greater than those reported with loads carried around the waist and close to the center of mass. This result was not expected because the latter has been hypothesized to be the optimal method of load carriage from a metabolic standpoint.

International audience

International audience; PURPOSE OF REVIEW: Muscle wasting and impaired muscle oxidative metabolism are common extrapulmonary features of chronic respiratory failure (CRF) that significantly increase disease burden. This review aims to address the question whether hypoxia, an obvious consequence of this disease, actually plays a causal role in these muscle impairments. RECENT FINDINGS: In experimental models, a causal role for hypoxia in muscle atrophy and metabolic impairments has clearly been shown. Although the hypoxia-inducible factors and nuclear factor kappa B are putative mediators of these hypoxia-induced alterations, their true involvement remains to be proven. Molecular signatures of disrupted regulation of muscle mass and oxidative metabolism observed in these experimental models also have been shown in muscles of patients suffering from CRF, suggestive of but not conclusive for a causal role of hypoxia. Therapies, including but not restricted to those aimed at alleviating hypoxia, have been shown to partially but not completely restore muscle mass and oxidative capacity in CRF patients, which may imply an additive effect of nutritional modulation of substrate metabolism. SUMMARY: Although hypoxia clearly affects skeletal muscle maintenance, it remains to be confirmed whether and by which underlying molecular mechanisms hypoxia is causally involved in CRF-related muscle atrophy and impaired oxidative capacity.

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.

Background: Knowing the frequency and causes of dropouts in combined events seems relevant and helpful to develop strategies of injury prevention and to better define/understand the necessary qualities for decathletes. Objective: To determine the causes of dropouts and the frequency of injury in decathlon. Design: This pilot prospective study focused on 3 high-level decathlon competitions. Main outcome measures: Data concerning athlete’s participation (number of participating athletes listed on the start list, number of athletes in the final ranking), and the causes of dropouts were collected prospectively during the 3 high-level decathlon competitions. Results: 38% of decathletes did not complete these competitions. The causes of dropout were: injury (36%), loss of motivation (36%), tiredness (9%), and indeterminate (18%). 50% of injuries were acute hamstring injuries during explosive events on the first day (100-m and long jump). Conclusions: Musculoskeletal injury prevention and motivational aspects seem important to complete an entire decathlon and to aim at best performance. More detailed prospective studies are needed to determine the exact medical causes of dropouts in combined events.

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.

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.

International audience; Clinical manual tests refer to increased ankle stiffness in children immobilized due to hip osteochondritis. The aim of the present study was to investigate musculo-articular stiffness via different techniques in immobilized children to confirm or not and quantify these observations. Ankle stiffness was quantified monthly during the long immobilization period in three diseased children and compared to healthy age-matched children. Sinusoidal perturbations were used to evaluate musculo-articular (MA) stiffness of the ankle plantar-flexors. The stiffness index (SI(MA-EMG)) was the slope of the linear relationship between angular stiffness and plantar-flexion torque normalized with electromyographic activity of the triceps surae (TS). The stiffness of the ankle plantar-flexors was also indirectly evaluated using the TS electromechanical delay (EMD). SI(MA-EMG) was greater for diseased children, and this higher stiffness was confirmed by the higher EMD values found in these immobilized children. Furthermore, both parameters indicated that ankle stiffness continues to increase through immobilization period. This study gives a quantitative evaluation of ankle stiffness changes through the immobilization period imposed to children treated for hip osteochondritis. The use of EMD measurement to indirectly evaluate these stiffness changes is also validated. This study shed for the first time some light into the patterns of muscle modifications following immobilization in children.

International audience; In response to repetitive proprioceptive disturbances (vibration) applied to postural muscles, the evoked response has been shown to decrease in amplitude within the first few trials. The present experiment investigated whether this attenuation of the response to vibration stimulation (90Hz, 5s) was muscle specific or would be transferred to the antagonist muscles. Sixteen participants stood upright with eyes closed. One half of the participants practiced 15 tibialis vibrations followed by 15 calf vibrations (TIB-CALF order), while the other half practiced the opposite order (CALF-TIB order). Antero-posterior trunk displacements were measured at the level of C7 and centre of foot pressure (COP). EMG activity of the tibialis anterior (TA) and gastrocnemius lateralis (GL) was also measured. Results showed that evoked postural responses as well as EMG activity decreased with practice when vibration was applied to either calf or tibialis muscles. However, such attenuation of the response appeared muscle specific since it did not generalise when the same vibration stimulus was later applied onto the antagonist muscles.

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.

The aim of the present study was to examine the effect of fatigue (physiological, mechanical, and muscular parameters) induced by a sprint simulation on kinematic parameters (cycle, phases, and joints angles) of the double pole technique. Eight elite skiers were tested for knee extensor strength and upper body power both before and after a three-bout simulation of sprint racing. They were video analyzed during the final part of the test track of bouts 1 and 3 using a digital camera. Results showed that skiers were in a fatigue state (decrease of the knee extensors voluntary force (-10.4+/-10.4%) and upper body power output (-11.1+/-8.7%) at the end of the sprint. During bout 3, the final spurt and cycle velocities decreased significantly (-7.5+/-12.3%; -13.2+/-9.5%; both p

Myostatin, a member of the TGF-β family, has been identified as a master regulator of embryonic myogenesis and early postnatal skeletal muscle growth. However, cumulative evidence also suggests that alterations in skeletal muscle mass are associated with dysregulation in myostatin expression and that myostatin may contribute to muscle mass loss in adulthood. Two major branches of the Akt pathway are relevant for the regulation of skeletal muscle mass, the Akt/mammalian target of rapamycin (mTOR) pathway, which controls protein synthesis, and the Akt/forkhead box O (FOXO) pathway, which controls protein degradation. Here, we provide further insights into the mechanisms by which myostatin regulates skeletal muscle mass by showing that myostatin negatively regulates Akt/mTOR signaling pathway. Electrotransfer of a myostatin expression vector into the tibialis anterior muscle of Sprague Dawley male rats increased myostatin protein level and decreased skeletal muscle mass 7 d after gene electrotransfer. Using RT-PCR and immunoblot analyses, we showed that myostatin overexpression was ineffective to alter the ubiquitin-proteasome pathway. By contrast, myostatin acted as a negative regulator of Akt/mTOR pathway. This was supported by data showing that the phosphorylation of Akt on Thr308, tuberous sclerosis complex 2 on Thr1462, ribosomal protein S6 on Ser235/236, and 4E-BP1 on Thr37/46 was attenuated 7 d after myostatin gene electrotransfer. The data support the conclusion that Akt/mTOR signaling is a key target that accounts for myostatin function during muscle atrophy, uncovering a novel role for myostatin in protein metabolism and more specifically in the regulation of translation in skeletal muscle. Myostatin down-regulates Akt/mammalian target of rapamycin (mTOR) signaling pathway uncovering a novel role for myostatin in protein metabolism and more specifically in the regulation of translation in skeletal muscle.

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

International audience; In the mammalian olfactory system, oscillations related to odour representation have been described in field potential activities. Previous results showed that in olfactory bulb (OB) of awake rats engaged in an olfactory learning, odour presentation produced a decrease of oscillations in gamma frequency range (60-90 Hz) associated with a power increase in beta frequency range (15-40 Hz). This response pattern was strongly amplified in trained animals. The aim of this work was twofold: whether learning also induces similar changes in OB target structures and whether such OB response depends on its centrifugal inputs. Local field potentials (LFPs) were recorded through chronically implanted electrodes in the OB, piriform and enthorhinal cortices of freely moving rats performing an olfactory discrimination. Oscillatory activities characteristics (amplitude, frequency and time-course) were extracted in beta and gamma range by a wavelet analysis. First, we found that odour induced beta oscillatory activity was present not only in the OB, but also in the other olfactory structures. In each recording site, characteristics of the beta oscillatory responses were dependent of odour, structure and learning level. Unilateral section of the olfactory peduncle was made before training, and LFPs were symmetrically recorded in the two bulbs all along the acquisition of the learning task. Data showed that deprivation of centrifugal feedback led to an increase of spontaneous gamma activity. Moreover, under this condition olfactory learning was no longer associated with the typical large beta band. As a whole, learning modulation of the beta oscillatory response in olfactory structures may reflect activity of a distributed functional network involved in odour representation.

The spring-mass model, representing a runner as a point mass supported by a single linear leg spring, has been a widely used concept in studies on running and bouncing mechanics. However, the measurement of leg and vertical stiffness has previously required force platforms and high-speed kinematic measurement systems that are costly and difficult to handle in field conditions. We propose a new “sine-wave” method for measuring stiffness during running. Based on the modeling of the force-time curve by a sine function, this method allows leg and vertical stiffness to be estimated from just a few simple mechanical parameters: body mass, forward velocity, leg length, flight time, and contact time. We compared this method to force-platform-derived stiffness measurements for treadmill dynamometer and overground running conditions, at velocities ranging from 3.33 m·s–1to maximal running velocity in both recreational and highly trained runners. Stiffness values calculated with the proposed method ranged from 0.67% to 6.93% less than the force platform method, and thus were judged to be acceptable. Furthermore, significant linear regressions (p< 0.01) close to the identity line were obtained between force platform and sine-wave model values of stiffness. Given the limits inherent in the use of the spring-mass model, it was concluded that this sine-wave method allows leg and stiffness estimates in running on the basis of a few mechanical parameters, and could be useful in further field measurements.

International audience; The purpose of this study was to assess the influence of age and speed on the asymmetry of ground reaction forces (GRFs) and spatiotemporal parameters (STPs) during normal gait in 4- to 10-year-old children. Forty-seven children walked at three speeds on a treadmill dynamometer (ADAL; Tecmachine, Andrézieux Bouthéon, France). Thirty steps were recorded at each speed for each foot for each child. The GRF and stride parameters were normalized to body weight and to body height, respectively. A left-right symmetry index (SI) was calculated for each parameter. The influence of both age and speed on the different SI was examined with a two-way analysis of variance. GRF and STP were asymmetric (SI ranged from +/- 1.92% to +/- 45.05%). The SI of forces Fz1 and Fy1 are negative in children aged 4-6 years, indicating that left Fz1 and Fy1 are higher than right Fz1 and Fy1. The cross effect of age and speed on the asymmetries of gait parameters was not significant There was no significant effect of age on the asymmetries of vertical GRF and STP. The asymmetry of vertical propulsive force (Fz3) alone increased with the speed (P < 0.05). This study showed that the different tasks performed by the lower limbs could be responsible for the asymmetry of GRF and STP in children aged 4-6 years. It also shows that upper and lower limits of normal asymmetry of gait parameters are different. Therefore no single criterion value can be used to assess the symmetry of several gait parameters. The small values of upper and lower limits of symmetry indices of vertical forces and stride duration show that the symmetry indices of these variables are reliable measurements and should thus be used in symmetry analysis of gait in normal and disabled children.

International audience; The purpose of this study was to determine the effect of different methods of backpack carrying on gait kinetics in children, using a new treadmill that allowed three-dimensional measurement of right and left leg ground reaction forces (GRFs). Forty-one healthy children, with a mean age of 12 years, participated in this study. The mean height was 152 cm and the mean weight 40 kg. The three trials consisted of walking on the treadmill at the speed of 3.5 km/h, first without a backpack and then carrying a 10 kg school bag on the right shoulder or on both shoulders. For each carrying condition GRFs were recorded, averaged, and analyzed for 30 steps. Stride, stance, double stance, thirteen specific GRF parameters and the symmetry index were measured. The right leg produced higher propulsive fore-aft forces than the left one, whatever the walking conditions. For the two maximum peaks and the average vertical force during stance, a statistical difference was found between walking without a backpack and carrying a backpack on one or two shoulders (one or two shoulder carrying > no backpack) but never between one-shoulder and two-shoulder carrying. The children increased their stance and double stance when walking with a backpack compared with walking without a pack. The symmetry index increased with one-strap carrying (compared with no backpack and two-strap carrying) for the maximum force during the breaking phase (Fy1) when it decreased for the maximum propulsive horizontal force before taking-off (Fy2). Children should be advised to carry their backpack on two shoulders rather than use a one-strap backpack.

International audience; This study addressed the question of the possible functional relevance of two different oscillatory activities, beta and gamma (15-40 and 60-90 Hz, respectively) for perception and memory processes in olfactory areas of mammals. Local field potentials were recorded near relay olfactory bulb neurons while rats performed an olfactory discrimination task. Signals reflected the mass activity from this region and characteristics of oscillatory activities were used as an index of local synchrony. Beta and gamma oscillatory activities were quantified by time-frequency methods before during and after odour sampling. In rats early in their training, olfactory sampling was associated with a significant decrease in power in the gamma band in parallel with a weak but significant increase in the beta band (centred on 27 Hz). Several days later, in well-trained rats, the gamma oscillatory depression was significantly enhanced both in duration and amplitude. It appeared within the 500 ms time period preceding odour onset and was further reduced during the odour period. Concurrently the beta oscillatory response (now centred on 24 Hz) during odour sampling was amplified by a twofold factor. The beta band response was modulated according to the chemical nature of the stimuli and rat's behavioural response. This study showed for the first time that odour sampling in behaving animals is associated with a clear shift in the olfactory bulb neuronal activity from a gamma to a beta oscillatory regime. Moreover, the data stress the importance of studying the odour-induced beta activity and its relation to perception and memory.

International audience; The evoked potential recorded in the rat piriform cortex in response to electrical stimulation of the olfactory bulb is composed of an early component occasionally followed by a late component (60-70 ms). We previously showed that the late component occurrence was enhanced following an olfactory learning. In the present study carried out in naive rats, we investigated the precise conditions of induction of this late component, and its spatiotemporal distribution along the olfactory pathways. In the anaesthetized rat, a stimulating electrode was implanted in the olfactory bulb. Four recording electrodes were positioned, respectively, in the olfactory bulb, the anterior and posterior parts of the piriform cortex, and the entorhinal cortex. Simultaneous recording of signals evoked in the four sampled structures in response to stimulation of the olfactory bulb revealed that the late component was detected in anterior and posterior piriform cortex as well as in entorhinal cortex, but not in the olfactory bulb. The late component occurred reliably for a narrow range of low intensities of stimulation delivered at frequencies not exceeding 1 Hz. Comparison of late component amplitude and latency across the different recorded sites showed that this component appeared first and with the greatest amplitude in the posterior piriform cortex. In addition to showing a functional dissociation between anterior and posterior parts of the piriform cortex, these data suggest that the posterior piriform cortex could be the locus of generation of this late high amplitude synchronized activity, which would then propagate to the neighbouring regions.

International audience; BACKGROUND AND OBJECTIVES: A major limitation of dietary trials is that double blind design is not feasible. These trials are therefore prone to biases. The Lyon diet heart study is a single-blind secondary prevention trial to test the hypothesis that a Mediterranean-type of diet may prevent recurrences after a first myocardial infarction. A surprising 73% reduction of the risk of new major cardiac events was observed in the experimental group. For this reason, it is important to describe the methods used in the trial. We now report our techniques to randomize the patients, to change their diet and to control for possible bias, in particular any investigator or attending physician bias. DESIGN: In this dietary trial, a specific design was used to recruit and randomize the patients without informing them and their physicians that they were participating in a comparative trial. The attending physician bias was evaluated by studying drug usage and the investigator bias by constructing a questionnaire from which specific scores were used to evaluate (1) how the patients appreciated their participation in the study and (2) whether this participation resulted in significant changes in their way of living. SUBJECTS: 605 survivors of a first myocardial infarction were randomized into either a control or a Mediterranean group. RESULTS: The two randomized groups were similar for all the variables of prognosis. Drug usage was not significantly different between groups, suggesting that there was no major attending physician bias. Analyses of the appreciation scores and of the change score did not detect any significant investigator bias. CONCLUSIONS: Although the study cannot be completely shielded from minor biases, the data presented here provide evidence that the dietary modifications per se were protective, not other (including psychosocial) changes resulting from the participation to the trial.

Objectives: Previous uncontrolled studies have suggested an interaction between ticlopidine, a major antiplatelet agent, and cyclosporin in heart- and kidney-transplant recipients. The aims of this study were to examine in a randomised, double-blind fashion, the possible interaction between cyclosporin A and ticlopidine (250 mg per day) and the tolerability of this combination in heart-transplant recipients. Methods: Twenty heart-transplant recipients were randomised into either a treated or a placebo group. Blood samples were drawn for time-course evaluation of cyclosporin blood levels over a period of 12 h, following the morning intake of cyclosporin and, for platelet aggregation studies, before and after 14 days of ticlopidine administration. Twenty four-hour urine samples were collected for 6-β-hydroxycortisol measurements, before and after 14 days of ticlopidine. Results: Although given at half the recommended daily dosage, ticlopidine significantly reduced platelet aggregation. Pharmacokinetic parameters indicate that the bioavailability of cyclosporin A was not significantly modified by ticlopidine. However, one patient in the ticlopidine group was withdrawn because of a major fall in cyclosporin blood level within 3 days of treatment. Urinary excretion of 6-β-hydroxycortisol was augmented after treatment in the ticlopidine group compared with the placebo group, suggesting that induction of drug metabolism might have occurred. Data also show quite a large intra-individual variability in cyclosporin bioavailability in the placebo group, suggesting that poor absorption of the drug formulation and/or poor compliance might have contributed to the decreased cyclosporin blood levels in the patient withdrawn from this study and in previous uncontrolled studies. Conclusion: Cyclosporin bioavailability was not clearly modified by a half dosage of ticlopidine in this study. We, however, recommend closely monitoring cyclosporin blood levels when prescribing ticlopidine. Further studies will be needed with new formulations of cyclosporin or when using the full dosage of ticlopidine.

We introduce Sleep, a new Python open-source graphical user interface (GUI) dedicated to visualization, scoring and analyses of sleep data. Among its most prominent features are: (1) Dynamic display of polysomnographic data, spectrogram, hypnogram and topographic maps with several customizable parameters, (2) Implementation of several automatic detection of sleep features such as spindles, K-complexes, slow waves, and rapid eye movements (REM), (3) Implementation of practical signal processing tools such as re-referencing or filtering, and (4) Display of main descriptive statistics including publication-ready tables and figures. The software package supports loading and reading raw EEG data from standard file formats such as European Data Format, in addition to a range of commercial data formats. Most importantly, Sleep is built on top of the VisPy library, which provides GPU-based fast and high-level visualization. As a result, it is capable of efficiently handling and displaying large sleep datasets. Sleep is freely available (http://visbrain. org/sleep) and comes with sample datasets and an extensive documentation. Novel functionalities will continue to be added and open-science community efforts are expected to enhance the capacities of this module.