Search

International audience; Abstract The capacity to predict the heart rate (HR) and speed at the first (VT1) and second (VT2) ventilatory thresholds was evaluated during an incremental ski-mountaineering test using heart rate variability (HRV). Nine skiers performed a field test to exhaustion on an alpine skiing track. VT1 and VT2 were individually determined by visual analysis from gas exchanges (VT1V and VT2V) and time-varying spectral HRV analysis (VT1fH, VT2fH and VT2H). VT1 could not be determined with the HRV methods used. On the contrary, the VT2 was determined in all skiers. No significant difference between HR and speed at VT2H and VT2V was observed (174.3 ± 5.6 vs. 174.3 ± 5.3 bpm, and 6.3 ± 0.9 and 6.3 ± 0.9 km h-1, respectively). Strong correlations were obtained for HR (r = 0.91) and speed (r = 0.92) at VT2H and VT2V with small limits of agreement (±3.6 bpm for HR). Our results indicated that HRV enables determination of HR and speed at VT2 during a specific ski-mountaineering incremental test. These findings provide practical applications for skiers in order to evaluate and control specific training loads, at least when referring to VT2.

Introduction: In vitamin K antagonist (VKA)-treated patients with severe hemorrhage, guidelines recommend prompt VKA reversal with prothrombin complex concentrate (PCC) and vitamin K. The aim of this observational cohort study was to evaluate the impact of guideline concordant administration of PCC and vitamin K on seven-day mortality. Methods: Data from consecutive patients treated with PCC were prospectively collected in 44 emergency departments. Type of hemorrhage, coagulation parameters, type of treatment and seven-day mortality mortality were recorded. Guideline-concordant administration of PCC and vitamin K (GC-PCC-K) were defined by at least 20 IU/kg factor IX equivalent PCC and at least 5 mg of vitamin K performed within a predefined time frame of eight hours after admission. Multivariate analysis was used to assess the effect of appropriate reversal on seven-day mortality in all patients and in those with intracranial hemorrhage (ICH). Results: Data from 822 VKA-treated patients with severe hemorrhage were collected over 14 months. Bleeding was gastrointestinal (32%), intracranial (32%), muscular (13%), and “other” (23%). In the whole cohort, seven-day mortality was 13% and 33% in patients with ICH. GC-PCC-K was performed in 38% of all patients and 44% of ICH patients. Multivariate analysis showed a two-fold decrease in seven-day mortality in patients with GC-PCC-K (odds ratio (OR) = 2.15 (1.20 to 3.88); P = 0.011); this mortality reduction was also observed when only ICH was considered (OR = 3.23 (1.53 to 6.79); P = 0.002). Conclusions: Guideline-concordant VKA reversal with PCC and vitamin K within eight hours after admission was associated with a significant decrease in seven-day mortality.

Femoroacetabular impingement (FAI) is a pathomechanical process of the hip joint, which could lead to hip pain and functional disability. Aim of this thesis was to investigate hip muscle function in patients with a symptomatic FAI. Hip muscle function was first investigated before patients underwent any surgical treatment for managing FAI. It was shown that they present with reduced hip muscle strength (i.e., muscle weakness), probably due to hip muscle inhibition. Nevertheless, hip muscle weakness was not associated with exaggerated hip muscle fatigue. Hip muscle strength recovery was then evaluated in a series of patients after hip arthroscopy to treat FAI. These patients demonstrated a good recovery for all hip muscle groups, except for hip flexors. The case of a professional ice hockey player who underwent bilateral hip open surgeries for treating bilateral FAI was also documented. This report showed that iliotibial band dehiscence could occur after hip open surgery, thereby preventing hip abductor strength increase during rehabilitation and delaying the return to sport. In addition, the assessment of the rate of force development scaling factor for the hip muscles was evaluated in a group of healthy adults. This parameter seems to be promising for the evaluation of hip muscle inhibition. The testing protocol was feasible and reproducible for hip adductors, external rotators and flexors. Taken as a whole, these findings show that patients with symptomatic FAI demonstrate an impaired hip muscle function, which is however mainly resolved after surgical treatment.; Le conflit fémoro-acétabulaire (femoroacetabular impingement, FAI) est une pathologie mécanique de la hanche qui peut causer des douleurs et limitations fonctionnelles. Le but de cette thèse était d’étudier la fonction musculaire au niveau de la hanche chez des patients présentant un FAI symptomatique. La fonction musculaire de la hanche a été évaluée, dans un premier temps, chez des patients avant qu’ils ne subissent une opération. Ces patients démontraient un déficit de force qui pourrait être expliqué par de l’inhibition musculaire. Cependant, ce déficit de force n’était pas associé à une plus grande fatigabilité musculaire. Dans un deuxième temps, les altérations de force musculaire ont été évaluées chez des patients ayant subi une arthroscopie de la hanche. Après l’opération, les patients récupéraient un niveau de force normal au niveau de tous les groupes musculaires de la hanche excepté les fléchisseurs. Le cas d’un joueur de hockey sur glace ayant subi une chirurgie ouverte aux deux hanches pour traiter un FAI bilatéral a aussi été décrit. On a démontré que la déhiscence de la bandelette iléo-tibiale pouvait survenir après chirurgie, empêcher l’augmentation de force musculaire des abducteurs de la hanche, et retarder la reprise du sport. Enfin, un protocole d’évaluation du taux de développement de la force normalisé, variable permettant d’estimer l’inhibition musculaire de la hanche, a été proposé chez des sujets sains. La fiabilité et reproductibilité des résultats ont été montrées au niveau des adducteurs, rotateurs externes, et fléchisseurs de la hanche. Ces résultats montrent que ces patients ont une fonction musculaire altérée au niveau de la hanche, qui est toutefois récupéré après une opération.

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

International audience; BACKGROUND: Age and peak performance in ultra-endurance athletes have been mainly investigated in long-distance runners and triathletes, but not for long-distance swimmers. The present study investigated the age and swimming performance of elite ultra-distance swimmers competing in the 5-, 10- and 25-km Fédération Internationale de Natation (FINA) World Cup swimming events. METHODS: The associations of age and swimming speed in elite male and female swimmers competing in World Cup events of 5-, 10- and 25-km events from 2000 to 2012 were analysed using single and multi-level regression analyses. RESULTS: During the studied period, the swimming speed of the annual top ten women decreased significantly from 4.94 ± 0.20 to 4.77 ± 0.09 km/h in 5 km and from 4.60 ± 0.04 to 4.44 ± 0.08 km/h in 25 km, while it significantly increased from 4.57 ± 0.01 to 5.75 ± 0.01 km/h in 10 km. For the annual top ten men, peak swimming speed decreased significantly from 5.42 ± 0.04 to 5.39 ± 0.02 km/h in 5 km, while it remained unchanged at 5.03 ± 0.32 km/h in 10 km and at 4.94 ± 0.35 km/h in 25 km. The age of peak swimming speed for the annual top ten women remained stable at 22.5 ± 1.2 years in 5 km, at 23.4 ± 0.9 years in 10 km and at 23.8 ± 0.9 years in 25 km. For the annual top ten men, the age of peak swimming speed increased from 23.7 ± 2.8 to 28.0 ± 5.1 years in 10 km but remained stable at 24.8 ± 1.0 years in 5 km and at 27.2 ± 1.1 years in 25 km. CONCLUSION: Female long-distance swimmers competing in FINA World Cup races between 2000 and 2012 improved in 10 km but impaired in 5 and 25 km, whereas men only impaired in 5 km. The age of peak performance was younger in women (approximately 23 years) compared to men (about 25-27 years).

International audience; BackgroundRecent findings showed that elite Ironman triathletes competing in ‘Ironman Hawaii’ improved both split and overall race times. The present study investigated whether elite athletes also improved in transition time (i.e. time needed between disciplines for changing clothes and equipment).MethodsChanges in split times, overall race times and transition times (i.e. expressed in absolute and relative terms) in the annual fastest competing in ‘Ironman Hawaii’ were investigated using linear, non-linear and multi-level regression analyses. To detect a potential difference in transition times between different race distances, we compared transition times in ‘Ironman Hawaii’ to transition times in the World Championships ‘Ironman 70.3’ covering the half distance of the Ironman distance triathlon.ResultsIn ‘Ironman Hawaii’, transition times remained unchanged for the annual fastest women but increased linearly for the annual fastest men. For the annual ten fastest, transition times increased linearly for women and men in both absolute and relative terms. The sex difference in transition times remained unchanged for the annual fastest, but decreased linearly for the annual ten fastest. In ‘Ironman 70.3’, transition times remained unchanged for the annual fastest. For the annual ten fastest, transition times decreased linearly for both women and men in absolute and relative terms. The sex difference in transition times remained unchanged for both the annual fastest and the annual ten fastest. Transition times were faster in ‘Ironman 70.3’ for women in 2011 and for men in 2006, 2007, and 2010-2013. In relative terms, transition times were faster in ‘Ironman 70.3’compared to ‘Ironman Hawaii’ during 2006-2013. The sex difference in transition times remained unchanged.ConclusionsIn ‘Ironman Hawaii’, transition times increased for both women and men whereas the sex difference decreased. In ‘Ironman 70.3’, transition times decreased for both women and men whereas the sex difference remained unchanged. Generally, transition times were slower in ‘Ironman Hawaii’ compared to ‘Ironman 70.3’.

International audience; This study compared fatigue development of the triceps surae induced by two electrical stimulation protocols composed of constant and variable frequency trains (CFTs, VFTs, 450 trains, 30 Hz, 167 ms ON, 500 ms OFF and 146 ms ON, 500 ms OFF respectively). For the VFTs protocol a doublet (100 Hz) was used at the beginning of each train. The intensity used evoked 30% of a maximal voluntary contraction (MVC) and was defined using CFTs. Neuromuscular tests were performed before and after each protocol. Changes in excitation-contraction coupling were assessed by analysing the M-wave [at rest (M-max) and during MVC (M-sup)] and associated peak twitch (Pt). H-reflex [at rest (H-max) and during MVC (H-sup)] and the motor evoked potential (MEP) during MVC were studied to assess spinal and corticospinal excitability of the soleus muscle. MVC decrease was similar between the protocols (28%, P

Ischemia-reperfusion (IR) is a situation encountered in transplantation or during aortic surgery, which can result in renal damages, requiring sometimes transient or definitive dialysis. Mitochondria play a crucial role in the pathophysiology of IR causing cell death. Previous studies of cardiac IR highlighted the role of mitochondrial permeability transition pore (mPTP). Cyclosporin A (CsA) has been proposed as a treatment to protect the kidney from IR by the delay of the opening of the mPTP. However, CsA has acute renal hemodynamic effects and a long-term toxicity, requiring an experimental validation of its protection in the renal IR. In this work, we developed a mouse model of renal IR. In a first study, we showed that the post-conditioning with CsA and ischemic postconditioning improve renal function with a delay of the opening of the mPTP. In a second study, we showed that a high dose of CsA injected just before the ischemia improves renal function and leads to the delay of the opening of mPTP mediated by an increase of HSP70. Our results open new perspectives in renal protection, especially for reducing episodes of acute renal failure in aortic surgery or in renal transplantation, L'ischémie-reperfusion (IR) rénale entraîne des lésions de nécrose tubulaire aigue, nécessitant parfois une épuration extra rénale transitoire voir définitive. La mitochondrie joue un rôle important dans la physiopathologie de ces lésions d'IR en entrainant la mort cellulaire. L'étude de l'IR dans la cellule cardiaque a permis de mettre en évidence le rôle central du pore de transition de perméabilité mitochondriale (mPTP) dans le déclenchement de cette mort cellulaire. La ciclosporine (CsA) a été proposée comme thérapeutique pour protéger la cellule des lésions d'IR en retardant l'ouverture de ce mPTP. Cependant la CsA a des effets rénaux vasoconstricteurs aigus, nécessitant une validation expérimentale de sa protection dans l'IR rénale. Au cours de ce travail de thèse, nous avons mis au point un modèle murin d'IR rénale. Ensuite nous avons montré que le post-conditionnement à la CsA, ainsi que le post-conditionnement ischémique, permettent d'améliorer la fonction rénale avec un retard à l'ouverture du mPTP. Dans un deuxième travail, nous montrons que le pré conditionnement à la CsA est dose et temps dépendant, et médié en partie par l'augmentation d'expression d'une protéine chaperonne, l'Heat Shock Protéine 70 (HSP70). L'injection en bolus de CsA permet également d'améliorer la fonction rénale dans ce modèle d'IR avec un retard à l'ouverture du mPTP. Nos résultats ouvrent de nouvelles perspectives dans la protection rénale, notamment dans la réduction des épisodes d'insuffisance rénale aigue après chirurgie aortique ou en transplantation rénale

Pédiatrie obesity and its associated diseases hâve become a major public health challenge. However, thé return to daily physical and leisure activities, recommended by most international guidelines, can be difficult for obèse youths, due to low self-esteem, difficulties in integrating groups and poor physical fitness. Overweight combined with sedentarity progressively modify cardio-respiratory exercise tolérance, rendering difficult thé return to exercise and contributing to non-compliance with prescriptions for physical activity. To meet thé growing needs of professionals in thé field of physical activity responsible for thé management of thèse subjects, thé main objective of this doctoral thesis was to validate clinical tools exploring cardiorespiratory capacity in obèse adolescent.A 12 minute walk/run test, an adapted 20m shuttle walk test (starting speed 4 km.b.-1,incréments : 0.5 km.h-1.miir1) and a submaximal exercise test by cycle ergometer with 4 stageswere proposed to calculate indices of cardiorespiratory fitness (D12, Vmax, PMA).Time-varying spectral analysis of heart rate variability was studied to estimate intensitiessubmaximal exercise near ventilatory thresholds.-The "Childhood Obesity Perceived Exertion Scale" (COPE-10) was used to quantify thé intensity of exercise as perceived by thé subjects during exercise.Thèse non-invasive tools, inexpensive, useful in thé évaluation and follow-up of cardiorespiratory fitness in obèse adolescents, can easily be used to develop and personalise adapted re-training programmes in thèse overweight teenagers.; L'obésité pédiatrique et ses pathologies associées sont devenues un problème majeur de santé publique. La reprise des activités physiques quotidiennes et de loisirs, préconisée dans les recommandations internationales, est souvent complexe chez le jeune obèse en raison d'une image de soi dévalorisée, de difficultés d'intégration et d'une faible condition physique. L'excès pondéral, associé à la sédentarité, altère progressivement l'endurance cardiorespiratoire à l'exercice, freinant le retour à une pratique physique régulière et contribuant à la non-observance des prescriptions en activité physique. Pour répondre à un besoin croissant des professionnels de l'activité physique impliqués dans la prise en charge de ces jeunes, l'objectif de ce travail de thèse a été de valider des outils cliniques explorant l'endurance cardiorespiratoire chez l'adolescent obèse :Un test de marche/course de 12 minutes, un test de marche navette adapté sur 20 mètres (4km.h^ incrémenté de 0,5 km.HAmin-1) et un test sous-maximal sur ergocycle en 4 paliers ontpermis de déterminer des indices d'endurance cardiorespiratoire (D12, Vmax, PMA).L'analyse fréquentielle en temps variant de la variabilité de la fréquence cardiaque a permisd'estimer des intensités d'exercice sous-maximales proches des seuils ventilatoires.Le "Childhood Obesity Perceived Exertion Scale" (COPE-10) a permis de quantifier l'intensitéde l'exercice perçue au cours de l'effort.Ces outils non-invasifs et peu coûteux, utiles à l'évaluation initiale et au suivi de la condition physique du jeune obèse, peuvent être facilement utilisés pour concevoir et individualiser des programmes de réentraînement adaptés à ces jeunes.

Roles of cardiac fibroblasts (CF) in the regulation of myocardial structure and function have been emphasized in the last decade. Their implications in pathophysiological aspects of chronic heart diseases such as myocardial remodelling and fibrosis is now well established. However their contribution to the acute phase of ischemia reperfusion injury still remains elusive. We hypothesized that CF may contribute to cardiomyocytes (CM) protection against ischemia reperfusion (l/R) injuries. This study was designed to investigate this protection and identify some of its mechanisms. Experiments were performed both on isolated neonatal rat CF and CM in vitro and in vivo mice model of myocardial infarction. We demonstrated that the presence of CF increases CM viability in co-cultures and that CF protect CM against l/R injuries in a paracrine manner. lt was confirmed by a similar effect of hypoxic CF secretome alone on CM viability. These findings were corroborated by in vivo experiments in which an infarct size reduction was observed in CF secretome treated mice. Furthermore, experiments with Tissue lnhibitor of Metalloproteinases-1 (TlMP-1), abundantly detected in CF secretome, was able to both decrease CM cell death and infarct size. Experiments with pharmacological inhibitors provided more evidence that this paracrine protection is partly mediated by Pl3K/Akt and ERK signalling pathways. Our data demonstrated for the first time that CF participate in cardioprotection during the acute phase of ischemia reperfusion, via a paracrine pathway, involving TlMP-1. Besides this first work, other collaborative studies have been performed, to investigate a major target in cardioprotection research : the mitochondrial permeability transition pore and its regulation by chain respiratory complex l and Ca2+ transfers and finally its implication in multiple organ failure in cardiac arrest; Les cardiofibroblastes (CF) possèdent des rôles clés dans la régulation de la structure et du fonctionnement myocardique. Leurs implications physiopathologiques, notamment dans le remodelage et la fibrose, ont été largement décrites dans les maladies cardiovasculaires chroniques. Cependant, leurs rôles au cours de la phase aigüe d'ischémie-reperfusion (l/R) restent encore à élucider. Nous avons donc émis l'hypothèse que les CF pouvaient participer à la protection des cardiomyocytes (CM) face aux lésions d'l/R. Le but de ce travail a donc consisté en l'exploration et l'identification des mécanismes de cette protection. Un modèle cellulaire de CM et CF de rats nouveau-nés in vitro et un modèle d'l/R in vivo chez la souris ont été utilisés. Nos résultats montrent que la présence des CF, en co-culture avec les CM, augmente de façon paracrine leur viabilité, face aux lésions d'l/R. Cette action paracrine a été confirmée par l'utilisation du sécrétome de CF hypoxiques capable, à lui seul, d'augmenter la viabilité des CM. Ces résultats ont été corroborés par des expériences d'l/R in vivo, dans lesquelles les souris traitées avec le sécrétome de CF présentent une diminution de la taille d'infarctus. De plus, nous avons montré que TlMP-1, un facteur fortement détecté dans le sécrétome de CF, est capable de diminuer à la fois la mortalité cellulaire in vitro des CM et la taille de l'infarctus in vivo. L'utilisation d'inhibiteurs pharmacologiques nous a permis de mettre en évidence que cette protection paracrine était médiée en partie par l'activation des voies de signalisation Pl3K/Akt et ERK1/2. En conclusion cette étude démontre pour la première fois que les CF participent, de façon paracrine, à la protection des CM au cours la phase aigüe d'ischémie reperfusion. TlMP-1 semble être un des facteurs clé de cette cardioprotection par les CF. En parallèle de ce travail, plusieurs études collaboratives ont été réalisées, sur une cible majeure d'investigation dans la cardioprotection : le pore de transition de perméabilité mitochondriale et notamment sa régulation par le complexe l de la chaîne respiratoire et les échanges calciques, ainsi que son implication dans la défaillance multi-organe face à l'arrêt cardiaque

Introduction Cardiac surgery is frequently needed in patients with infective endocarditis (IE). Acute kidney injury (AKI) often complicates IE and is associated with poor outcomes. The purpose of the study was to determine the risk factors for post-operative AKI in patients operated on for IE. Methods A retrospective, non-interventional study of prospectively collected data (2000–2010) included patients with IE and cardiac surgery with cardio-pulmonary bypass. The primary outcome was post-operative AKI, defined as the development of AKI or progression of AKI based on the acute kidney injury network (AKIN) definition. We used ensemble machine learning (“Super Learning”) to develop a predictor of AKI based on potential risk factors, and evaluated its performance using V-fold cross validation. We identified clinically important predictors among a set of risk factors using Targeted Maximum Likelihood Estimation. Results 202 patients were included, of which 120 (59%) experienced a post-operative AKI. 65 (32.2%) patients presented an AKI before surgery while 91 (45%) presented a progression of AKI in the post-operative period. 20 patients (9.9%) required a renal replacement therapy during the post-operative ICU stay and 30 (14.8%) died during their hospital stay. The following variables were found to be significantly associated with renal function impairment, after adjustment for other risk factors: multiple surgery (OR: 4.16, 95% CI: 2.98-5.80, p

Cardiovascular diseases are a major problem of public health management. Ischemic and pharmacological pre and postconditioning should significantly improve the prognosis of patients suffering from myocardial ischemia/reperfusion. However, the morbi-mortality of these patients is still high and research must remain active. The first results of myocardial stem cell therapy show that we cannot regenerate myocardium but a recent meta-analysis reported positive effects that can be explained through a paracrine mechanism. Mesenchymal stem cells protect ischemic cardiomyocytes from reperfusion injury through a paracrine activation of the PI3kinase/Akt pathway in a similar way to ischemic postconditioning. The mediators of this protection could be growth factors such as VEGF or IGF-1 though we couldn’t demonstrate a direct effect of one or the other. Modulating the activity of the ATP synthase during ischemia is another promising therapeutic target. This enzyme reverses its activity and hydrolyses ATP when the supply in oxygen is impaired. This leads to the reduction of the cellular pool of ATP and accelerates cell death. We identified new small molecules with a similar effect to IF1 that can selectively inhibit the reverse activity of the ATP synthase, preserve ATP and thus increase cell survival in a preconditioning-like effect. These two different techniques could be part of the therapeutic arsenal against ischemia/reperfusion in the next decades., Les maladies cardiovasculaires constituent un problème de santé publique. Les pré et postconditionnement ischémiques mais aussi pharmacologiques constituent autant d‘avancées qui permettront l‘amélioration de la prise en charge des malades en situation d‘ischémie/reperfusion myocardique. Néanmoins, la morbi-mortalité des maladies cardiovasculaires reste importante et nécessite le développement de nouvelles techniques. Les premiers résultats de la thérapie cellulaire myocardique ont été décevants, et s‘il est désormais établi que l‘on ne peut régénérer le myocarde, les effets bénéfiques observés, notamment avec les cellules souches mésenchymateuses semblent en rapport avec un effet paracrine qui passe par l‘activation de la voie de signalisation PI3kinase/Akt sur un mécanisme comparable à celui du postconditionnement ischémique. Les médiateurs de cet effet sont vraisemblablement des facteurs de croissance comme le VEGF ou l‘IGF-1 même si un effet individuel direct de l‘une ou l‘autre de ces molécules n‘a pu être mis en évidence. La modulation de l‘activité de l‘ATP synthase mitochondriale est également une cible thérapeutique prometteuse. Cette enzyme inverse son activité et hydrolyse l‘ATP durant l‘ischémie, conduisant à dépléter le pool d‘ATP intracellulaire et accélérer la survenue de la mort cellulaire. De nouvelles molécules ayant un effet similaire à l‘IF1 permettent de bloquer cette inversion d‘activité de l‘ATP synthase, de préserver l‘ATP et donc d‘améliorer la survie cellulaire par un effet de type préconditionnement ischémique. Ces 2 techniques, très différentes mais non antinomiques, pourraient faire partie de l‘arsenal thérapeutique dans les années à venir

International audience; INTRODUCTION: Our aim was to describe inflammatory cytokines response in the peritoneum and plasma of patients with peritonitis. We also tested the hypothesis that scenarios associated with worse outcome would result in different cytokine release patterns. Therefore, we compared cytokine responses according to the occurrence of septic shock, mortality, type of peritonitis and peritoneal microbiology. METHODS: Peritoneal and plasma cytokines (IL-1, tumour necrosis factor alpha [TNFalpha], IL-6, IL-10, and IFN) were measured in 66 patients with secondary peritonitis. RESULTS: The concentration ratio between peritoneal fluid and plasma cytokines varied from 5 [2 - 21] (IFN) to 1310 [145 - 3888] (IL-1). There was no correlation between plasma and peritoneal fluid concentration of any cytokine. In the plasma, TNFalpha, IL-6, IFN, and IL-10 were higher in patients with shock versus no shock, and in nonsurvivors versus survivors (p[less than or equal to]0.03). There was no differential plasma release for any cytokine between community-acquired and postoperative peritonitis. Presence of anaerobes or Enterococcus specie in peritoneal fluid was associated with higher plasma TNFalpha: 50 [37-106] vs 38 [29-66] and 45 [36 - 87] vs 39 [27 - 67] pg/ml, respectively (p=0.02). In the peritoneal compartment, occurrence of shock did not result in any difference in peritoneal cytokines. Peritoneal IL-10 was higher in patients who survived (1505 [450 to 3130] vs 102 [9 to 710] pg/ml; p=0.04). Presence of anaerobes and Enterococcus specie was associated with higher peritoneal IFN: 2 [1-6] vs 10 [5-28] and 7 [2-39] vs 2 [1-6], p=0.01 and 0.05 respectively). CONCLUSIONS: Peritonitis triggers an acute systemic and peritoneal innate immune response with a simultaneous release of pro and anti-inflammatory cytokines. Greater levels of all cytokines were observed in the plasma of patients with the most severe conditions (shock, non survivors), but this difference was not reflected in their peritoneal fluid. There was always a large gradient in cytokine concentration between peritoneal and plasma compartments highlighting the importance of compartmentalization of innate immune response in peritonitis.

Background The aims of the present study were, firstly, to investigate in a cross-sectional analysis the age of peak Ironman performance within one calendar year in all qualifiers for Ironman Hawaii and Ironman Hawaii; secondly, to determine in a longitudinal analysis on a qualifier for Ironman Hawaii whether the age of peak Ironman performance and Ironman performance itself change across years; and thirdly, to determine the gender difference in performance. Methods In a cross-sectional analysis, the age of the top ten finishers for all qualifier races for Ironman Hawaii and Ironman Hawaii was determined in 2010. For a longitudinal analysis, the age and the performance of the annual top ten female and male finishers in a qualifier for Ironman Hawaii was determined in Ironman Switzerland between 1995 and 2010. Results In 19 of the 20 analyzed triathlons held in 2010, there was no difference in the age of peak Ironman performance between women and men (p > 0.05). The only difference in the age of peak Ironman performance between genders was in ‘Ironman Canada’ where men were older than women (p = 0.023). For all 20 races, the age of peak Ironman performance was 32.2 ± 1.5 years for men and 33.0 ± 1.6 years for women (p > 0.05). In Ironman Switzerland, there was no difference in the age of peak Ironman performance between genders for top ten women and men from 1995 to 2010 (F = 0.06, p = 0.8). The mean age of top ten women and men was 31.4 ± 1.7 and 31.5 ± 1.7 years (Cohen's d = 0.06), respectively. The gender difference in performance in the three disciplines and for overall race time decreased significantly across years. Men and women improved overall race times by approximately 1.2 and 4.2 min/year, respectively. Conclusions Women and men peak at a similar age of 32–33 years in an Ironman triathlon with no gender difference. In a qualifier for Ironman Hawaii, the age of peak Ironman performance remained unchanged across years. In contrast, gender differences in performance in Ironman Switzerland decreased during the studied period, suggesting that elite female Ironman triathletes might still narrow the gender gap in the future.

Epub 2012 Oct 30; Assessing implicit learning in the continuous pursuit-tracking task usually concerns a repeated segment of target displacements masked by two random segments, as referred to as Pew's paradigm. Evidence for segment learning in this paradigm is scanty and contrasts with robust sequence learning in discrete tracking tasks. The present study investigates this issue with two experiments in which participants (N = 56) performed a continuous tracking task. Contrary to Pew's paradigm, participants were presented with a training sequence that was continuously cycled during 14 blocks of practice, but Block 12 in which a transfer sequence was introduced. Results demonstrate sequence learning in several conditions except in the condition that was obviously the most similar to previous studies failing to induce segment learning. Specifically, it is shown here that a target moving too slowly combined with variable time at which target reversal occurs prevents sequence learning. In addition, data from a post-experimental recognition test indicate that sequence learning was associated with explicit perceptual knowledge about the repetitive structure. We propose that learning repetition in a continuous tracking task is conditional on its capacity to (1) allow participants to detect the repeated regularities and (2) restrict feedback-based tracking strategies.

International audience; The influences of sex and age upon endurance performance have previously been documented for both running and swimming. A number of recent studies have investigated how sex and age influence triathlon performance, a sport that combines three disciplines (swimming, cycling and running), with competitions commonly lasting between 2 (short distance: 1.5-km swim, 40-km cycle and 10-km run) and 8 h (Ironman distance: 3.8-km swim,180-km cycle and 42-km run) for elite triathletes. Age and sex influences upon performance have also been investigated for ultra-triathlons, with distances corresponding to several Ironman distances and lasting several days, and for off-road triathlons combining swimming, mountain biking and trail running. Triathlon represents an intriguing alternative model for analysing the effects of age and sex upon endurance and ultra-endurance ([6 h) performance because sex differences and age-related declines in performance can be analysed in the same individuals across the three separate disciplines. The relative participation of both females and masters athletes (age[40 years) in triathlon has increased consistently over the past 25 years. Sex differences in triathlon performance are also known to differ between the modes of locomotion adopted (swimming, cycling or running) for both elite and non-elite triathletes. Generally, time differences between sexes in swimming have been shown to be smaller on average than during cycling and running. Both physiological and morphological factors contribute to explaining these findings. Performance density (i.e. the time difference between the winner and tenth-placed competitor) has progressively improved (time differences have decreased) for international races over the past two decades for both males and females, with performance density now very similar for both sexes. For age-group triathletes, sex differences in total triathlon performance time increases with age. However,the possible difference in age-related changes in the physiological determinants of endurance and ultra-endurance performances between males and females needs further investigation. Non-physiological factors such as low rates of participation of older female triathletes may also contribute to the greater age-related decline in triathlon performance shown by females. Total triathlon performance has been shown to decrease in a curvilinear manner with advancing age. However, when triathlon performanceis broken down into its three disciplines, there is a smaller age-related decline in cycling performance than in running and swimming performances. Age-associated changes in triathlon performance are also related to the total duration of triathlon races. The magnitude of the declines in cycling and running performances with advancing age for short triathlons are less pronounced than for longer Ironman distance races. Triathlon distance is also important when considering how age affects the rate of the decline in performance. Off-road triathlon performances display greater decrements with age than road-based triathlons, suggesting that the type of discipline (road vs. mountain bike cycling and road vs. trail running) is an important factor in age-associated changes in triathlon performance.Finally, masters triathletes have shown relative improvements in their performances across the three triathlon disciplines and total triathlon event times during Ironman races over the past three decades. This raises an important issue as to whether older male and female triathletes have yet reached their performance limits during Ironman triathlons

International audience; Aging is one of the major risk factors of osteoarthritis. This pathology during which chondrocytes undergo modifications of their phenotype may result from alteration of transforming growth factor β (TGFβ) signaling. This study investigates the role of TGFβ response in the process of chondrocyte dedifferentiation/redifferentiation. Dedifferentiation was induced by successive passages of human articular chondrocytes, whereas their redifferentiation was performed by three-dimensional culture in alginate. Human mesenchymal stem cells were obtained from bone marrow and differentiated into chondrocyte-like phenotype by three-dimensional culture, embedded in the same scaffold. Protein and mRNA levels were analyzed by Western blot and real-time reverse transcription PCR. Regulatory mechanism was investigated using specific inhibitors (mithramycin), mRNA silencing or decoy oligonucleotides, and expression vectors. Chondrocyte dedifferentiation interfered with TGFβ signaling by decreasing TβRII mRNA and protein levels and subsequent TGFβ response. TβRII ectopic expression in passaged chondrocytes permitted to increase the expression of several matrix genes, such as aggrecan or type II collagen. Redifferentiation of passaged chondrocytes permitted to restore, at least in part, TβRII expression and was related to differentiation of human bone marrow mesenchymal stem cells toward chondrocytes, where both specific protein 1 (Sp1) and TβRII mRNA levels were increased. Moreover, Sp1 manipulation by silencing or ectopic expression and pharmacologic inhibition revealed a link between expression levels of this transcriptional factor, which is crucial for constitutive expression of TβRII in cartilage, and TGFβ response. Therefore, these data permit us to suggest an important role of TβRII expression in the maintenance of chondrocyte phenotype, which is altered with age, and bring new insights in our understanding of chondrogenesis process.

Introduction Guidelines dealing with severe sepsis and septic shock mostly rely on randomized controlled trials (RCTs) to ensure the best standards of care for patients. However, patients included in high-quality studies may differ from the routine population and alter external validity of recommendations. We aimed to determine to what extent non-inclusion criteria of RCTs dealing with severe sepsis and septic shock may affect application of their conclusions in routine care. Methods In a first step, the MEDLINE database was searched for RCTs treating severe sepsis and septic shock patients between 1992 and 2008, and non-inclusion criteria for these studies were abstracted. Two reviewers independently evaluated the articles, which were checked by a third reviewer. We extracted data on the study design, main intervention, primary endpoint, criteria for inclusion, and criteria for non-inclusion. In a second step, the distribution of the non-inclusion criteria was observed in a prospective multicenter cohort of severe sepsis and septic shock patients (Cub-Rea network, 1992 to 2008). Results We identified 96 articles out of 7,012 citations that met the screening criteria. Congestive heart failure (35%) and cancer (30%) were frequent exclusion criteria in selected studies, as well as other frequent disorders such as gastrointestinal and liver diseases and all causes of immune suppression. Of the 67,717 patients with severe sepsis and septic shock in the Cub-Rea database, 40,325 (60%) experienced at least one of the main exclusion criteria, including 11% of congestive heart failure patients and 11% of cancer patients. In addition, we observed a significant trend for increasing number of patients with these criteria along time. Conclusion Current exclusion criteria for RCTs dealing with severe sepsis and septic shock excluded most patients encountered in daily practice and limit external validity of the results of high-quality studies.

Background The present study examined the sex difference in swimming (7.8 km), cycling (360 km), running (84 km), and overall race times for Double Iron ultra-triathletes. Methods Sex differences in split times and overall race times of 1,591 men and 155 women finishing a Double Iron ultra-triathlon between 1985 and 2012 were analyzed. Results The annual number of finishes increased linearly for women and exponentially for men. Men achieved race times of 1,716 ± 243 min compared to 1,834 ± 261 min for women and were 118 ± 18 min (6.9%) faster (p < 0.01). Men finished swimming within 156 ± 63 min compared to women with 163 ± 31 min and were 8 ± 32 min (5.1 ± 5.0%) faster (p < 0.01). For cycling, men (852 ± 196 min) were 71 ± 70 min (8.3 ± 3.5%) faster than women (923 ± 126 min) (p < 0.01). Men completed the run split within 710 ± 145 min compared to 739 ± 150 min for women and were 30 ± 5 min (4.2 ± 3.4%) faster (p = 0.03). The annual three fastest men improved race time from 1,650 ± 114 min in 1985 to 1,339 ± 33 min in 2012 (p < 0.01). Overall race time for women remained unchanged at 1,593 ± 173 min with an unchanged sex difference of 27.1 ± 8.6%. In swimming, the split times for the annual three fastest women (148 ± 14 min) and men (127 ± 20 min) remained unchanged with an unchanged sex difference of 26.8 ± 13.5%. In cycling, the annual three fastest men improved the split time from 826 ± 60 min to 666 ± 18 min (p = 0.02). For women, the split time in cycling remained unchanged at 844 ± 54 min with an unchanged sex difference of 25.2 ± 7.3%. In running, the annual fastest three men improved split times from 649 ± 77 min to 532 ± 16 min (p < 0.01). For women, however, the split times remained unchanged at 657 ± 70 min with a stable sex difference of 32.4 ± 12.5%. Conclusions To summarize, the present findings showed that men were faster than women in Double Iron ultra-triathlon, men improved overall race times, cycling and running split times, and the sex difference remained unchanged across years for overall race time and split times. The sex differences for overall race times and split times were higher than reported for Ironman triathlon.

International audience; Purpose: The aim of this study was to evaluate concomitantly the changes in leg-spring behavior and the associated modifications in the lower limb muscular activity during a constant pace run to exhaustion at severe intensity. Methods: Twelve trained runners performed a running test at the velocity associated with _ VO 2max (5.1 70.3 m s −1 ; mean time to exhaustion: 3537 69 s). Running step spatiotemporal parameters and spring-mass stiffness were calculated from vertical and horizontal components of ground reaction force measured by a 6.60 m long force platform system. The myoelectrical activity was measured by wireless surface electrodes on eight lower limb muscles. Results: The leg stiffness decreased significantly (−8.9%; Po 0.05) while the vertical stiffness did not change along the exhaustive exercise. Peak vertical force (−3.5%; Po 0.001) and aerial time (−9.7%; P o0.001) decreased and contact time significantly increased (+4.6%; Po 0.05). The myoelectrical activity decreased significantly for triceps surae but neither vastus medialis nor vastus lateralis presented significant change. Both rectus and biceps femoris increased in the early phase of swing (+14.7%; P o0.05) and during the pre-activation phase (+16.2%; Po 0.05). Conclusion: The decrease in leg spring-stiffness associated with the decrease in peak vertical ground reaction force was consistent with the decline in plantarflexor activity. The biarticular rectus femoris and biceps femoris seem to play a major role in the mechanical and spatiotemporal adjustments of stride pattern with the occurrence of fatigue during such exhaustive run.

TO THE EDITOR: A recent study of Trappe et al. (3) showed that the aerobic power of octogenarian lifelong endurance athletes was approximately double that of untrained octogenarians (38 vs. 21 ml·kg 1 ·min 1 ). These remarkable aerobic capacities are the highest ever recorded in this age group. However, the impact of the identified physiological capacities on actual endurance performances has not been addressed, as no running performance indicators of the octogenarian athletes were provided in this study. We hereby suggest that, although trained octogenarian athletes can achieve levels of aerobic fitness well above their untrained counterpart, as a group they actually have not yet reached their limits of endurance performance. During the past decades, masters athletes (40 yr of age) have dramatically improved their performance in endurance events such as marathon running. An analysis of performances at the New York City Marathon during the 1980 –2010 period showed that running times of the best male masters runners between 65 and 79 years of age decreased significantly (2). However, due to the low rate of participation of athletes older than 80 years, the performances of octogenarian finishers were not analyzed. The current marathon world record for a male octogenarian athlete was set in 2011 at the Toronto marathon by a Canadian athlete (Ed Whitlock, age 80) who ra n3h1 5 min 54 s(http://

In cohort studies, variables are measured repeatedly and can be considered as trajectories. A classic way to work with trajectories is to cluster them in order to detect the existence of homogeneous patterns of evolution. Since cohort studies usually measure a large number of variables, it might be interesting to study the joint evolution of several variables (also called joint-variable trajectories). To date, the only way to cluster joint-trajectories is to cluster each trajectory independently, then to cross the partitions obtained. This approach is unsatisfactory because it does not take into account a possible co-evolution of variable-trajectories. KmL3D is an R package that implements a version of k-means dedicated to clustering joint-trajectories. It provides facilities for the management of missing values, offers several quality criteria and its graphic interface helps the user to select the best partition. KmL3D can work with any number of joint-variable trajectories. In the restricted case of two joint trajectories, it proposes 3D tools to visualize the partitioning and then export 3D dynamic rotating-graphs to PDF format.

Hypothalamus plays a major role in the regulation of energy homeostasis by the presence of neural circuits controlling food intake. These circuits are plastic and can be rewired during adulthood. We hypothesized that synaptic plasticity can occur during physiological conditions. We have shown that synaptic contact on hypothalamic anorexigen POMC neurons are rewired in mouse upon high fat diet (HFD). This synaptic process is mandatory to adjust energy intake and requires the glycan PSA (polysialic acid). PSA promotes synaptic plasticity in the brain by the weakening of cell-to-cell interaction by addition on NCAM (neural cell adhesion molecule). We hypothesized that a defect in brain synaptic plasticity capacity could be a risk factor in the etiology of metabolic diseases. We show that homeostatic feeding response to HFD ingestion was predictive to weight gain observed three months after HFD introduction. The feeding response to HFD was correlated with the hypothalamus PSA level. We show that chronic depletion of hypothalamic PSA accelerate the onset of diet induced obesity. These results indicate that a low hypothalamic PSA level prone to diet induced obesity. In parallel, we focus on the hypothalamic regulation of circulating cholesterol. Melanocortin system control level of circulating cholesterol. Using our model of diet induced synaptic plasticity; we show that there is a link between hypothalamic PSA and circulating cholesterol. A long term reduction of hypothalamic PSA level, lead to an accumulation of fat deposit in blood vessels. This whole work allows us to underscore the role of diet induced synaptic plasticity in the regulation of energy homeostasis.; L’hypothalamus joue un rôle clef dans la régulation de l’homéostasie énergétique grâce à la présence de circuits neuronaux contrôlant la prise alimentaire. Ces circuits peuvent être remodelés dans le cerveau. Nous avons émis l’hypothèse que la plasticité de ces circuits intervient en conditions physiologiques. Nous avons démontré que les synapses des neurones à pro-opiomélanocortine sont modifiées en fonction de l’alimentation. Ce processus de plasticité est indispensable pour ajuster la prise alimentaire et nécessite la présence d’un polymère glucidique appelé PSA (acide polysialique), se fixant sur les protéines d’adhésion cellulaire NCAM et limitant les contacts synaptiques. Nous avons évalué le lien entre la plasticité cérébrale et la vulnérabilité à développer une obésité chez des souris placées en régime gras pendant 3 mois. La réponse comportementale au régime gras était variable, et prédictive de la prise de poids à terme, et était liée aux taux de PSA hypothalamique. La déplétion chronique de PSA dans l’hypothalamus a accéléré la prise de poids et l’adiposité des animaux. Ces résultats suggèrent qu’une capacité réduite de plasticité synaptique est un facteur de risque de l’obésité. En parallèle, nous nous sommes intéressés à l’homéostasie du cholestérol circulant contrôlée par le système à mélanocortine. Il existe un mécanisme de régulation du cholestérol circulant dépendant de PSA dans l’hypothalamus. Une dérégulation de ce mécanisme a provoqué l’accumulation de dépôts graisseux dans les vaisseaux sanguins. L’ensemble de ces travaux a permis de mettre en évidence le rôle de la plasticité synaptique hypothalamique dans la régulation de l’homéostasie énergétique.

International audience; Aim: Examine the interest of progressive intermittent running test (15-15) entitled Spartacus to assess indirectly the global level of aerobic capacity of obese adolescents in comparison with the continuous Shuttle run test.Methods: Forty-three obese adolescents (33 girls and 10 boys) performed the two tests. Differences according to the “test”, “sex” and the interaction “test × sex” have been assessed for the maximum heart rate (HRmax), the final running speed, the total and net running durations and the perceived effort.Results and discussion: The results did not reveal any significant inter-test differences for FCmax and the perceived effort. As compared to the Shuttle run test, the Spartacus led to a 20% increased final running speed (11.5 vs. 9.4 km/h) and a 3.3 times longer total running duration (17.3 vs. 5.3 min) for a 1.7 times longer net exercise duration (8.7 vs. 5.3 min, P < 0.001). The results were neither significantly influenced by the “sex” nor by the “test × sex” interaction.Conclusion: The Spartacus intermittent test allowed obese adolescents to reach a similar psychophysiological state effort at the end of the run while producing an increased performance in both speed and duration.; Objectifs: Déterminer l’intérêt du test intermittent progressif de type 15-15 appelé Spartacus pour mesurer indirectement le niveau global de capacité aérobie d’adolescents obèses en le comparant au test continu Navette.Patients et méthodes: Quarante-trois adolescents obèses (33 filles et 10 garçons) ont réalisé les deux tests. L’influence du « type de test », du « sexe » et de leur interaction a été évaluée sur la fréquence cardiaque maximale (FCmax), la vitesse de fin de test, les durées totale de test et nette de course, et la difficulté perçue.Résultats: Les résultats ne montrent pas de différence significative inter-tests pour la FCmax et la difficulté perçue. Comparé au test Navette, le Spartacus permet d’obtenir une vitesse finale 20 % supérieure (11,5 vs. 9,4 km/h) et une durée totale de test 3,3 fois plus longue (17,3 vs. 5,3 min) pour une durée nette de course 1,7 fois supérieure (8,7 vs. 5,3 min) (p < 0,001). Il n’y a pas d’effets significatifs du « sexe » ni de l’interaction « type de test × sexe ».Conclusion: Le test Spartacus permet d’atteindre un même état psychophysiologique maximal en produisant une vitesse de course et une durée totale de test supérieures.

Background The aim of the present study was to compare the trends in participation, performance and age of finishers in ‘Badwater’ and ‘Spartathlon’ as two of the toughest ultramarathons in the world of more than 200 km of distance. Methods Running speed and age of male and female finishers in Badwater and Spartathlon were analyzed from 2000 to 2012. Age of peak performance and sex difference in running speed were investigated during the studied period. Results The number of female and male finishes increased in Badwater and Spartathlon. Women accounted on average for 21.5% ± 6.9% in Badwater and 10.8% ± 2.3% in Spartathlon. There was a significant increase in female participation in Badwater from 18.4% to 19.1% (p < 0.01) and in Spartathlon from 11.9% to 12.5% (p = 0.02). In men, the age of finishers was higher in Badwater (46.5 ± 9.3 years) compared to Spartathlon (44.8 ± 8.2 years) (p < 0.01). The age of female finishers of both races was similar with 43.0 ± 7.5 years in Badwater and 44.5 ± 7.8 years in Spartathlon (p > 0.05). Over the years, the age of the annual five fastest men decreased in Badwater from 42.4 ± 4.2 to 39.8 ± 5.7 years (p < 0.05). For women, the age remained unchanged at 42.3 ± 3.8 years in Badwater (p > 0.05). In Spartathlon, the age was unchanged at 39.7 ± 2.4 years for men and 44.6 ± 3.2 years for women (p > 0.05). In Badwater, women and men became faster over the years. The running speed increased from 7.9 ± 0.7 to 8.7 ± 0.6 km/h (p < 0.01) in men and from 5.4 ± 1.1 to 6.6 ± 0.5 km/h (p < 0.01) in women. The sex difference in running speed remained unchanged at 19.8% ± 4.8% (p > 0.05). In Spartathlon, the running speed was stable over time at 10.8 ± 0.7 km/h for men and 8.7 ± 0.5 km/h for women (p > 0.05). The sex difference remained unchanged at 19.6% ± 2.5% (p > 0.05). Conclusions These results suggest that for both Badwater and Spartathlon, (a) female participation increased, (b) the fastest finishers were approximately 40 to 45 years, and (c) the sex difference was at approximately 20%. Women will not outrun men in both Badwater and Spartathlon races. Master ultramarathoners can achieve a high level of performance in ultramarathons greater than 200 km under extreme conditions.

There has been a tremendous amount of information produced on peroxisome proliferator-activated receptors (PPARs). The interest in PPARs was originally driven largely by their role in hypolipidemia and hepatocarcinogenesis, but it soon became evident that they played important roles in the metabolic syndrome and overall health of organisms including regeneration of tissues, differentiation, insulin signaling, overall lipid metabolism, and immune response (reviewed in [1–7]). From a nutritional standpoint, the PPARs are of extreme importance because of their ability to bind and be activated by long-chain fatty acids and their metabolites. Therefore, the PPARs are recognized as ideal candidates for therapeutic use in order to improve metabolism and overall health through diet. At present, there is substantial interest in therapeutic applications tailored to regulate PPARs via synthetic drugs (e.g., [8]), but the exploitation of dietary approaches is not a reality yet. Most of our knowledge on PPARs has been produced by studies carried out in rodents and humans and little from other species, bovine and pig being the most studied among livestock species. The multitude of roles of PPARs and the possibility of regulating them through dietary approaches are also of interest in animal food production. Therefore, a comparative approach to bring together physiological and nutritional roles of PPARs across species appears critical. For this reason, this special issue was dedicated to PPARs interspecies comparisons with a larger emphasis on livestock species compared to animal models or humans. Among the 6 papers published, 3 focused specifically on ruminants and one on chicken. The review from Bionaz et al. assembled all the information pertaining to ruminant PPARs, with emphasis on functions, activation, and potential targets for nutrigenomics approaches to improve animal production and wellbeing. The review underscored that the information about PPARs in ruminants accumulated quickly in the last decade owing to the recognition of their potential importance in those mammalian species. The functional comparison among ruminant, mouse, and human highlighted a similar role of PPAR isotypes on lipid metabolism between species. However, the data highlighted differences in the response to long-chain fatty acids. Monogastrics are more sensitive to unsaturated while ruminants, particularly bovine, are more sensitive to saturated long-chain fatty acids. Based on PPARs data generated in nonruminants and ruminants, they proposed an integrative and dynamic model encompassing the activation (by long-chain fatty acids) of the three PPAR isotypes in order to optimize the adaptation to lactation. Among others, they also reviewed the data supporting a role of PPARγ in controlling milk fat synthesis in ruminants and demonstrated that this feature is not shared by mouse or, likely, other monogastrics. A pivotal role of PPARγ in controlling milk fat synthesis was confirmed by the paper of Shi et al. published in the present special issue. Those authors demonstrated, using a combination of PPARγ specific activator, gene expression, luciferase-PPRE assay, and siRNA techniques, that this nuclear receptor controls the expression of milk fat-related genes also in primary goat mammary epithelial cells. The activation of PPARγ using oral administration of 2,4-thiazolidinedione (TZD) in growing beef bulls was assessed by Arevalo-Turrubiarte et al. The authors aimed to test the effect of PPARγ activation on intramuscular fat (i.e., marbling). They observed a greater amount of TZD in liver of the treated animals, demonstrating an uptake of the drug via oral administration. The TZD treatment had no effect on carcass quality but had a strong effect on the expression of all three PPAR isotypes in liver (all decreased) and in muscle (increase only of PPARα). They observed also an overall increase in cell size and decrease of cellular synthesis in muscle and perirenal adipose tissue, but the opposite was observed in subcutaneous adipose. This effect was explained by higher insulin sensitivity due to the treatment. Activation of PPARγ with oral administration of a TZD in growing pigs also had no significant effect on marbling, but it did increase muscle fiber oxidative capacity regardless of fiber type [9]. As for bovine, the activation of PPARγ in swine may be useful to influence metabolism overall, but more studies are needed to examine this possibility. Takada and Kobayashi provided the first review of the three PPAR isotypes in poultry, particularly in chickens. Interestingly, they also provided a comparison with human PPARs both structurally and functionally. They uncovered several peculiar and unique functions in chicken PPARs and differences between chickens, and human PPARs. These data prompt for more chicken-specific studies in order to exploit the ability of PPARs to control lipid and glucose metabolism in this species. Mandard and Patsouris reviewed recent evidence establishing that PPARs are critical regulators of inflammation in mammals. In the last decade, PPARs have emerged as modulators of inflammatory responses. Therefore, the potential therapeutic usefulness of PPARα and PPARγ activation in the control of obesity and diabetes-induced chronic (low-grade) inflammation has extensively been studied over the last couple of years using rodents. The authors discussed different aspects of the interaction of PPARγ with adipose inflammation. In the light of the recent findings, it has become clear that, besides activating PPARγ in the adipocyte, pharmacological activation of this receptor extends to a much broader range of cell types, such as T regulatory cells, which is likely beneficial in the suppression of obesity-associated inflammation in white adipose tissue, as far as rodents are concerned. The impact of the pharmacological activation of mouse PPARα in the context of obesity-induced hepatic inflammation is also reviewed as well as the potential relevance of PPARβ/δ as a molecular drug target to fight liver inflammation in the case of nonalcoholic fatty liver disease. A growing body of evidence also indicates that PPARs are potent negative regulators of the acute-phase response in different species, ranging from mouse, rat, pig, cattle and humans. The review article by Mandard and Patsouris also expands on the potential beneficial use of PPAR (ant)agonists in the routine of livestock to prevent bacterial-induced excessive inflammatory reaction and associated diseases such as mastitis in dairy cows. PPARα is also known to be critical for energy homeostasis. In line with this, the review paper by Ringseis et al. thoroughly summarizes the implication of PPARα in carnitine homeostasis in no less than six different species including rat, mouse, pig, cattle, chicken, and human. The comparative analysis performed by the authors led them to conclude that PPARα displays a key regulator role in carnitine homeostasis in general. It is the process of cellular carnitine uptake, with the key role of the PPARα target carnitine transporter novel organic cation transporter 2, that is particularly well conserved across the above-mentioned species. All the papers in this special issue emphasized on one hand a similar function of PPARs among species, particularly related to lipid metabolism, but also, and more importantly, accentuated the differences and the species-specific functions and response to agonists. In summary, the analysis of PPARs across species highlighted the following: interspecies conserved functional roles of those nuclear receptors (e.g., regulation of lipid metabolism and inflammation); the potential for therapeutic intervention through nutritional modulation of PPARs in all species in order to prevent diseases and improve animal production; differences between species that prompt for more species-specific studies in order to fully exploit the abovementioned therapeutic roles through nutrition. Massimo Bionaz Gary J. Hausman Juan J. Loor Stephane Mandard

International audience; ABSTRACT: Human serum albumin (HSA) has been used for a long time as a resuscitation fluid in critically ill patients. It is known to exert several important physiological and pharmacological functions. Among them, the antioxidant properties seem to be of paramount importance as they may be implied in the potential beneficial effects that have been observed in the critical care and hepatological settings. The specific antioxidant functions of the protein are closely related to its structure. Indeed, they are due to its multiple ligand-binding capacities and free radical-trapping properties. The HSA molecule can undergo various structural changes modifying its conformation and hence its binding properties and redox state. Such chemical modifications can occur during bioprocesses and storage conditions of the commercial HSA solutions, resulting in heterogeneous solutions for infusion. In this review, we explore the mechanisms that are responsible for the specific antioxidant properties of HSA in its native form, chemically modified forms, and commercial formulations. To conclude, we discuss the implication of this recent literature for future clinical trials using albumin as a drug and for elucidating the effects of HSA infusion in critically ill patients.

Exercising in the heat and high relative humidity is a major challenge that athletes have to overcome, especially during the summer Olympic Games. For decades, scientists investigated innovative solutions amongst which the body cooling before competing (pre-cooling) or after competing (post-cooling) seemed to be a valuable mean of minimizing hyperthermia threats and increasing the recovery of the athletes. However, contradictory results have been reported concerning body cooling protocols (cold water immersion, cooling vests, water sprays, etc.), exposure time, exercise duration, environmental conditions and their efficiency. By preparing the 2008 Beijing Olympic Games, we managed to review the existing literature on those methods. We hypothesized that a cooling vest combined with a cooling headband would increase thermal comfort of elite cyclists and their performances on an anaerobic (Wingate Test) and endurance (20 minutes time-trial) exercises. The Wingate Test study showed no significant effect of pre-cooling on peak or mean power output despite a significant increase (P < 0.05) of fatigue indexes. During the endurance study, pre-cooling maneuvers induced significant improvement (P < 0.05) of the mean power output, of the thermal comfort and a significant decrease in rectal and skin temperatures. Another study concerning the influence of wearing different cycling shirt on perceived and physiological responses of cyclists showed that a large knitted shirt provided a better thermal comfort by decreasing significantly (P < 0.05) skin temperatures, but without affecting perceived exertion. Those positive results on elite athletes lead us to apply similar cooling strategies on a population experiencing disease-related thermoregulation troubles. We decided to initiate an exploratory clinical study aiming at investigating the effects of a cooling vest on motor and cognitive skills of patients with multiple sclerosis disease. This protocol obtained the clearance of the French National Ethics Committee – East Section II, and should start on the late of 2012.; La réalisation d’une performance sportive dans un environnement chaud est un challenge majeur que doivent surmonter les athlètes de haut niveau notamment à l’occasion des Jeux Olympiques d’été. Depuis plusieurs décennies, les scientifiques ont tenté de trouver des solutions innovantes. Parmi les réponses proposées, on distingue aujourd’hui le refroidissement corporel préalable ou consécutif à l’effort (le pré et le post-cooling, respectivement), qui permettrait de minimiser les risques d’hyperthermie et améliorerait la récupération de l’athlète. Cependant, les modalités d’utilisation de ces méthodes et leur efficacité font l’objet de conclusions pour le moins contradictoires en raison notamment des techniques de refroidissement mises en œuvre (refroidissement par immersion, vêtements thermorégulants, brumisation…), de la durée d’application, du type d’exercice réalisé et des conditions environnementales explorées. La préparation des Jeux Olympiques à Pékin, en Août 2008, a été une occasion unique de faire un état de l’art sur les méthodes existantes. Nous avons testé chez des cyclistes de haut niveau l’hypothèse selon laquelle une stratégie de refroidissement utilisant une veste garnie d’accumulateurs thermiques permettrait d’améliorer le confort thermique et la performance lors d’un exercice de type anaérobie (Wingate test) et lors d’une épreuve d’endurance de 20 minutes. L’étude menée sur le test de Wingate ne montre aucun effet significatif du pré-cooling sur le pic de puissance ni sur la puissance moyenne mais permet néanmoins d’améliorer significativement (P < 0,05) l’indice de fatigue des athlètes testés. Sur l’épreuve de 20 minutes, le pré-cooling permet une amélioration significative (P < 0,05) de la puissance moyenne développée, du confort thermique et une baisse significative des températures cutanées et rectales. Une autre étude portant sur l’influence de différents maillots sur les réponses physiologiques et perceptives de coureurs cyclistes a montré qu’un maillot constitué de larges mailles offrait un meilleur confort thermique en diminuant significativement (P < 0,05) la température cutanée, mais sans modifier la perception de l’effort. Les bénéfices observés chez les cyclistes de haut niveau nous ont orientés vers la mise en œuvre d’un protocole similaire appliqué à des personnes atteintes de pathologies affectant la thermorégulation. Ainsi, nous avons débuté un protocole de recherche clinique exploratoire visant à étudier les effets du port d’une veste thermorégulante sur les performances motrices et cognitives de patients atteints de sclérose en plaques. Ce protocole, qui a obtenu l’accord du Comité de Protection des Personnes du Grand Est –II, devrait commencer fin 2012.

Background In recent years, there was an increased interest in investigating the gender difference in performance and the age of peak performance in ultra-endurance performances such as ultra-triathlon, ultra-running, and ultra-swimming, but not in ultra-cycling. The aim of the present study was to analyze the gender difference in ultra-cycling performance and the age of peak ultra-cycling performance in the 720-km ‘Swiss Cycling Marathon’, the largest European qualifier for the ‘Race Across America’. Methods Changes in the cycling speed and age of 985 finishers including 38 women and 947 men competing in the Swiss Cycling Marathon from 2001 to 2012 covering a distance of 720 km with a change of altitude of 4,993 m were analyzed using linear regression. Results The gender difference in performance was 13.6% for the fastest cyclists ever, 13.9% ± 0.5% for the three fastest cyclists ever and 19.1% ± 3.7% for the ten fastest cyclists ever. The gender difference in performance for the annual top three women and men decreased from 35.0% ± 9.5% in 2001 to 20.4% ± 7.7% in 2012 (r 2 = 0.72, p = 0.01). The annual top three women improved cycling speed from 20.3 ± 3.1 km h−1 in 2003 to 24.8 ± 2.4 km h−1 in 2012 (r 2 = 0.79, p < 0.01). The cycling speed of the annual top three men remained unchanged at 30.2 ± 0.6 km h−1 (p > 0.05). The age of peak performance for the ten fastest finishers ever was 35.9 ± 9.6 years for men and 38.7 ± 7.8 years for women, respectively (p = 0.47). Conclusions The gender difference in ultra-cycling performance decreased over the 2001 to 2012 period in the 720-km Swiss Cycling Marathon for the annual top three cyclists and reached approximately 14%. Both women and men achieved peak performance at the age of approximately 36 to 39 years. Women might close the gender gap in ultra-endurance cycling in longer cycling distances. Future studies need to investigate the gender difference in performance in the Race Across America, the longest nonstop and non-drafting ultra-cycling race in the world.

International audience; INTRODUCTION: To provide up-to-date information on the prognostic factors associated with 28-day mortality in a cohort of septic shock patients in intensive care units (ICUs). METHODS: Prospective, multicenter, observational cohort study in ICUs from 14 French general (non-academic) and university teaching hospitals. All consecutive patients with septic shock admitted between November 2009 and March 2011 were eligible for inclusion. We prospectively recorded data regarding patient characteristics, infection, severity of illness, life support therapy and discharge. RESULTS: Among 10,941 patients admitted to participating ICUs between October 2009 and September 2011, 1495 (13.7%) patients presented inclusion criteria for septic shock and were included. Invasive mechanical ventilation was needed in 83.9% (n=1248), inotropes in 27.7% (n=412), continuous renal replacement therapy in 32.5% (n=484) and hemodialysis in 19.6% (n=291). Mortality at 28 days was 42% (n=625). Variables associated with time to mortality, right-censored at day 28: age (for each additional 10 yrs) (hazard ratio, HR=1.29; 95% confidence interval [CI]: 1.20-1.38), immunosuppression (HR=1.63; 95%CI: 1.37-1.96), Knaus class C/D score versus class A/B score (HR=1.36; 95%CI:1.14-1.62) and Sepsis-related Organ Failure Assessment (SOFA) score (HR=1.24 for each additional point; 95%CI: 1.21-1.27). Patients with septic shock and renal/urinary tract infection had a significantly longer time to mortality (HR=0.56; 95%CI: 0.42-0.75). CONCLUSION: Our observational data of consecutive patients from real-life practice confirm that septic shock is common and carries high mortality in general intensive care unit populations. Our results are in contrast with the clinical trial setting, and could be useful for healthcare planning and clinical study design.

Bartter's syndrome type III results from loss-of-function mutations in the CLCNKB gene that encodes the CLC-KB chloride channel. To date, few CLCNKB mutations have been fully functionally investigated. In this study, we have investigated the functional consequences of novel CLCNKB mutations (collected by the Department of Genetics of the European Georges Pompidou Hospital) in Xenopus laevis oocytes, HEK293T and MDCK cells, in terms of electrical activity and surface expression. We have demonstrated that all mutations decreased plasma membrane expression and conductance of CLC-KB in similar proportions, indicating that altered cell surface expression is the main functional defect caused by CLCNKB mutations. However, some mutations also alter external pH and calcium sensitivity. The physiological relevance of these regulations is open to question, but clearly, their alteration could have a pathological impact. In conclusion, this functional study highlights the essential role of CLC-KB in the preservation of sodium balance and provides new clues for finding specific therapeutic drugs that would be able to restore sufficient function of CLC-KB in patients with Bartter's syndrome type III. Moreover, functional analysis of mutations is an extremely powerful tool for structure-function studies. In association with the search of new partners, it should allow discovering the physiological regulations of this channel that are almost unknown., Le syndrome de Bartter de type III résulte de mutations du gène CLCNKB codant le canal chlorure CLC-KB. Un grand nombre de mutations a été répertorié, mais peu d'entre elles ont été caractérisées fonctionnellement. Devant ce manque de données, nous nous sommes fixés comme objectif de procéder à une analyse fonctionnelle des mutations de CLCNKB pour tenter d'approfondir davantage les mécanismes de régulation de CLC-KB. Ce travail a nécessité l'emploi de trois systèmes d'expression hétérologue, les ovocytes de Xenopus laevis et les lignées cellulaires rénales HEK293T et MDCK, afin de procéder à des analyses électrophysiologiques et des expériences de biologie cellulaire. Nous démontrons que toutes les mutations étudiées altèrent l'expression membranaire de la protéine et que la conductance résiduelle est proportionnée à cette expression. Ainsi, la réduction des courants provient d'une réduction du nombre de canaux et non d'une altération majeure de la conduction ou de la régulation. Nous rapportons également que certaines mutations modifient la sensibilité au pH et au calcium extracellulaires du CLC-KB. Cette altération peut avoir un impact pathologique majeur. En conclusion, cette étude fonctionnelle montre le rôle essentiel du CLC-KB dans le maintien de la balance sodée et laisse entrevoir un espoir thérapeutique à long terme de restauration des anomalies précisément identifiées. Enfin, l'analyse de mutations est un outil extrêmement puissant pour les études structure-fonction. Associée à la recherche de nouveaux partenaires, elle devrait permettre de découvrir les régulations physiologiques de ce canal, pour l'heure presqu'inconnues.

International audience; forthcoming

Purpose: To investigate changes in diffusion tensor imaging (DTI) measures in limbic system white matter of patients with temporal lobe epilepsy (TLE) using diffusion tensor tractography. Materials and Methods: DTI metrics including fractional anisotropy (FA), λ1, λ2, λ3, and trace (Tr) coefficients were obtained from tractography for bilateral fornix, superior and inferior cingulum fibers in 18 patients and 10 healthy controls. Hippocampal signal-to-noise ratio (SNR) quantitative analysis was performed in order to confirm the magnetic resonance imaging (MRI) hippocampal lesion presence or absence in TLE patients. Results: Nine patients presented unilateral hippocampal sclerosis (TLE+HS) and nine patients had no signal abnormalities on conventional MRI (TLE−HS). On the ipsilateral seizure side, all three investigated tracts showed significant DTI indices abnormalities in both patient groups when compared with controls, most marked on the inferior cingulum. Contralateral to the seizure side, the three tracts presented significant DTI parameters in only the TLE+HS group when compared with controls. Conclusion: The DTI abnormalities found in the TLE−HS group may suggest that in the inferior cingulum the structural integrity is more affected than in the fornix or superior cingulum white matter bundles. The eigenvalues taken separately add complementary information to the FA and Tr metrics and may be useful indices in better understanding the architectural reorganization of limbic system tracts in TLE patients without HS. J. Magn. Reson. Imaging 2012;36:561–568. © 2012 Wiley Periodicals, Inc.

BackgroundDespite the recommended guidelines, the neonatal management of pain and discomfort often remains inadequate. The purpose of the present study was to determine whether adding a pain and discomfort module to a computerized physician order entry (CPOE) system would improve pain and discomfort evaluation in premature newborns under invasive ventilation.MethodsAll newborns ResultsA total of 122 patients were included: 53 before and 69 after the incorporation of the module. The mean age was 30 (3) weeks GA. After the module was included, the percentage of patients who benefited from at least one pain and discomfort assessment per day increased from 64% to 88% (p p p p ConclusionsAdding a pain and discomfort tool to the CPOE system was a simple and effective way to improve the systematic evaluation of premature newborns who required ventilatory assistance.

International audience; Purpose : Age-related fMRI changes have not been extensively studied for language, whereas important adaptive mechanisms have been seen in other cognitive fields. This study examined age-related changes in fMRI activation during language tasks and, in particular, their dynamic course.Patients and methods fMRI was performed on 22 young and 21 old healthy right-handed subjects during a silent category word-generation task. Activation and dynamics of BOLD signals were studied separately during the first and second portions of each 30-s block.Results : Activation of the left frontal lobe was initially similar in young and old participants; however, it decreased after 30s in the old participants. On the other hand, additional areas were initially involved only in old subjects and especially in the default mode network.Conclusion :This study showed age-related differences in the dynamics of fMRI activation during a silent word-generation task, suggesting a different pattern of language function with aging.

International audience; In the last decades, the participation of elderly trained people in endurance events such as marathon running has dramatically increased. Previous studies suggested that the performance of master runners (>40 years) during marathon running has improved. The aims of the study were (1) to analyze the changes in participation and performance trends of master marathon runners between 1980 and 2009, and (2) to compare the gender differences in performance as a function of age across the years. Running times of the best male and female runners between 20 and 79 years of age who competed in the New York City Marathon were analyzed. Gender differences in performance times were analyzed for the top 10 male and female runners between 20 and 65 years of age. The participation of master runners increased during the 1980-2009 period, to a greater extent for females compared to males. During that period, running times of master runners significantly (P < 0.01) decreased for males older than 64 years and for females older than 44 years, respectively. Gender differences in running times decreased over the last three decades but remained relatively stable across the ages during the last decade. These data suggest that male (≥65 years) and female (≥45 years) master runners have probably not yet reached their limits in marathon performance. The relative stability of gender differences in marathon running times across the different age groups over the last decade also suggests that age-related declines in physiological function do not differ between male and female marathoners.

International audience

International audience; ABSTRACT: INTRODUCTION: Inadequate initial treatment and delayed hemodynamic stabilization (HDS) may be associated with increased risk of death in severe sepsis patients. METHODS: in order to compare the hemodynamic efficacy and safety of 6% HES 130/0.4 and NaCl 0.9% for HDS in patients with severe sepsis, we designed a prospective, multicenter, active-controlled, double-blind, randomized study in Intensive care units. RESULTS: 174 out of 196 patients reached HDS (88 and 86 patients for HES and NaCl, respectively). Significantly less HES was used to reach HDS versus NaCl (1,379 886 ml in the HES group and 1,709 1,164 ml in the NaCl group [Mean difference = -331 1,033, 95% CI -640 to -21, p=0.0185). Time to reach HDS was 11.8 10.1 hours versus 14.3 11.1 hours for HES and NaCl, respectively. Total quantity of study drug infused over four consecutive days, ICU and hospital LOS, and area under the curve of SOFA Score were comparable. Acute renal failure occurred in 24 (24.5%) and 19 (20%) patients for HES and NaCl, respectively (p=0.454). There was no difference between AKIN and RIFLE criteria among groups and no difference in mortality, coagulation, or pruritus up to 90 days after treatment initiation. CONCLUSION: Significantly less volume was required to achieve HDS for HES versus NaCl in the initial phase of fluid resuscitation in severe sepsis patients without any difference for adverse events in both groups.

Caveolin-1 and cavins proteins form membrane caveolae, invaginations of the plasma membrane that are particularly abundant adipocytes and endothelial cells within adipose tissue. Caveolin-1 deficiency leads to lipoatrophy in transgenic mice models suggesting a critical role in the control of lipid storage. Studies on Cav-1 deficient mice model (Cav1 (-/-) mice) also revealed important defects in the cardiovascular function, that are rescued by specific reexpression of Cav1 in endothelium (Cav1 RC mice).To address the contribution of endothelial caveolin-1 expression to the lipoatrophic phenotype, we compared metabolic phenotypes observed in Cav1 deficient with those of Cav1 RC and control mice and found a persistent lipoatrophic phenotype in Cav1 (-/-) mice. Considering the key role of caveolin-1 in the control of adipose tissue lipid storage capacity, we chose an overexpression approach of caveolin-1 and cavins 3T3-L1 adipocytes to investigate the underlying molecular mechanisms. All three cell lines contained a higher number of caveolae whereas only caveolin-1 overexpression led to lipid droplet expansion both in vitro and in vivo, suggesting that caveolin-1 control on lipid storage occurs outside of caveolae. In agreement, larger lipid droplets were found in cells expressing a caveolin-1-perilipin-GFP fusion construct, in which exogenous caveolin-1 strictly localized onto lipid droplets. Together our data demonstrate a specific role of lipid droplet caveolin-1 pool, independent of caveolae to modulate lipid droplet expansibility, Les cavéolines et les protéines cavines forment le manteau d'invaginations membranaires appelées cavéoles. Dans le tissu adipeux (TA), ces structures sont très abondantes dans les adipocytes et les cellules endothéliales. Une perte d'expression de cavéoline-1 a pour conséquence une lipoatrophie sévère chez les souris invalidées pour ce gène (Cav1(-/-)), ce qui a conduit à suggérer un rôle important de Cav1 pour le contrôle de la capacité de stockage du TA. Par ailleurs, les souris Cav1(-/-) présentent des défauts vasculaires, phénotype totalement corrigé par une réexpression spécifique de Cav1 au niveau de l'endothélium (souris Cav1 RC). Afin de déterminer les rôles respectifs de la cavéoline-1 adipocytaire et endothéliale dans l'établissement de la lipoatrophie observée chez les souris Cav1(-/-), nous avons comparé les phénotypes adipeux de souris contrôles, Cav1(-/-) et Cav1 RC et établi ainsi le rôle majeur de la cavéoline-1 adipocytaire dans l'apparition de ce phénotype. Pour caractériser les mécanismes impliqués, nous avons surexprimé Cav1 et les cavines dans la lignée adipocytaire 3T3-L1. Nous montrons que ces surexpressions augmentent le nombre de cavéoles à la membrane plasmique des adipocytes. En revanche, seule la surexpression de Cav1 induit la croissance des gouttelettes lipidiques (GL), suggérant que cet effet de Cav1 s'exerce en dehors des cavéoles. En accord, la surexpression de Cav1 exclusivement à la surface des GLs augmente la taille de ces organites dans les adipocytes. Ces résultats démontrent un rôle spécifique de la cavéoline-1 à la surface de la GL, indépendant des cavéoles, dans le contrôle de la capacité de stockage lipidique adipocytaire

International audience; UNLABELLED: ABSTRACT: BACKGROUND: Previous studies have shown a good agreement between central venous pressure (CVP) measurements from catheters placed in superior vena cava and catheters placed in the abdominal cava/common iliac vein. However, the influence of intra-abdominal pressure on such measurements remains unknown. METHODS: We conducted a prospective, observational study in a tertiary teaching hospital. We enrolled patients who had indwelling catheters in both superior vena cava (double lumen catheter) and femoroiliac veins (dialysis catheter) and into the bladder. Pressures were measured from all the sites, CVP, femoroiliac venous pressure (FIVP), and intra-abdominal pressure. RESULTS: A total of 30 patients were enrolled (age 62 ± 14 years; SAPS II 62 (52-76)). Fifty complete sets of measurements were performed. All of the studied patients were mechanically ventilated (PEP 3 cmH20 (2-5)). We observed that the concordance between CVP and FIVP decreased when intra-abdominal pressure increased. We identified 14 mmHg as the best intra-abdominal pressure cutoff, and we found that CVP and FIVP were significantly more in agreement below this threshold than above (94% versus 50%, P = 0.002). CONCLUSIONS: We reported that intra-abdominal pressure affected agreement between CVP measurements from catheter placed in superior vena cava and catheters placed in the femoroiliac vein. Agreement was excellent when intra-abdominal pressure was below 14 mmHg.

International audience; In the last decades, the participation of elderly trained people in endurance events such as marathon running has dramatically increased. Previous studies suggested that the performance of master runners (>40 years) during marathon running has improved. The aims of the study were (1) to analyze the changes in participation and performance trends of master marathon runners between 1980 and 2009, and (2) to compare the gender differences in performance as a function of age across the years. Running times of the best male and female runners between 20 and 79 years of age who competed in the New York City Marathon were analyzed. Gender differences in performance times were analyzed for the top 10 male and female runners between 20 and 65 years of age. The participation of master runners increased during the 1980-2009 period, to a greater extent for females compared to males. During that period, running times of master runners significantly (P < 0.01) decreased for males older than 64 years and for females older than 44 years, respectively. Gender differences in running times decreased over the last three decades but remained relatively stable across the ages during the last decade. These data suggest that male (≥65 years) and female (≥45 years) master runners have probably not yet reached their limits in marathon performance. The relative stability of gender differences in marathon running times across the different age groups over the last decade also suggests that age-related declines in physiological function do not differ between male and female marathoners.

International audience; BackgroundThe purpose of this study was to investigate participation and performance changes in the multistage ultramarathon 'Marathon des Sables' from 2003 to 2012.MethodsParticipation and performance trends in the four- or six-stage running event covering approximately 250 km were analyzed with special emphasis on the nationality and age of the athletes. The relations between gender, age, and nationality of finishers and performance were investigated using regression analyses and analysis of variance.ResultsBetween 2003 and 2012, a number of 7,275 athletes with 938 women (12.9%) and 6,337 men (87.1%) finished the Marathon des Sables. The finisher rate in both women (r 2 = 0.62) and men (r 2 = 0.60) increased across years (p < 0.01). Men were significantly (p < 0.01) faster than women for overall finishers (5.9 ± 1.6 km*h−1 versus 5.1 ± 1.3 km*h−1) and for the top three finishers (12.2 ± 0.4 km*h−1 versus 8.3 ± 0.6 km*h−1). The gender difference in running speed of the top three athletes decreased (r 2 = 0.72; p < 0.01) from 39.5% in 2003 to 24.1% in 2012 with a mean gender difference of 31.7 ± 2.0%. In men, Moroccans won nine of ten competitions, and one edition was won by a Jordanian athlete. In women, eight races were won by Europeans (France five, Luxembourg two, and Spain one, respectively), and two events were won by Moroccan runners.ConclusionsThe finisher rate in the Marathon des Sables increased this last decade. Men were significantly faster than women with a higher gender difference in performance compared to previous reports. Social or cultural inhibitions may determine the outcome in this event. Future studies need to investigate participation trends regarding nationalities and socioeconomic background, as well as the motivation to compete in ultramarathons.

International audience; IntroductionThe mortality benefit of whole-body computed tomography (CT) in early trauma management remains controversial and poorly understood. The objective of this study was to assess the impact of whole-body CT compared with selective CT on mortality and management of patients with severe blunt trauma.MethodsThe FIRST (French Intensive care Recorded in Severe Trauma) study is a multicenter cohort study on consecutive patients with severe blunt trauma requiring admission to intensive care units from university hospital trauma centers within the first 72 hours. Initial data were combined to construct a propensity score to receive whole-body CT and selective CT used in multivariable logistic regression models, and to calculate the probability of survival according to the Trauma and Injury Severity Score (TRISS) for 1,950 patients. The main endpoint was 30-day mortality.ResultsIn total, 1,696 patients out of 1,950 (87%) were given whole-body CT. The crude 30-day mortality rates were 16% among whole-body CT patients and 22% among selective CT patients (p = 0.02). A significant reduction in the mortality risk was observed among whole-body CT patients whatever the adjustment method (OR = 0.58, 95% CI: 0.34-0.99 after adjustment for baseline characteristics and post-CT treatment). Compared to the TRISS predicted survival, survival significantly improved for whole-body CT patients but not for selective CT patients. The pattern of early surgical and medical procedures significantly differed between the two groups.ConclusionsDiagnostic whole-body CT was associated with a significant reduction in 30-day mortality among patients with severe blunt trauma. Its use may be a global indicator of better management.

Background The fastest Ironman race times in ‘Ironman Hawaii’ were achieved in very recent years. This study investigated the change in sex difference in both race performance and the age of peak performance across years in the top ten athletes for split disciplines and overall race time in the ‘Ironman Hawaii’ between 1983 and 2012. Methods Changes in split times, overall race times, and age of athletes across years for the top ten overall and the fastest swimmers, cyclists, and runners were investigated using regression analyses and analyses of variance. Results Between 1983 and 2012, the overall top ten men and women finishers improved their swimming (only men), cycling, running, and overall race times. The sex difference in overall race time decreased significantly (p = 0.01) from 15.2% to 11.3% across time. For the split disciplines, the sex difference remained unchanged (p > 0.05) for swimming (12.5 ± 3.7%) and cycling (12.5 ± 2.7%) but decreased for running from 13.5 ± 8.1% to 7.3 ± 2.9% (p = 0.03). The time performance of the top ten swimmers remained stable (p > 0.05), while those of the top ten cyclists and top ten runners improved (p p > 0.05) in swimming (8.0 ± 2.4%), cycling (12.7 ± 1.8%), and running (15.2 ± 3.0%). Between 1983 and 2012, the age of the overall top ten finishers and the fastest swimmers, cyclists, and runners increased across years for both women and men (p Conclusions To summarize, for the overall top ten finishers, the sex difference decreased across years for overall race time and running, but not for swimming and cycling. For the top ten per discipline, the sex difference in performance remained unchanged. The athletes improved their performances across years although the age of peak performance increased.

International audience; Le but de cet article est de synthétiser les travaux portant sur les effets de l’attention volontaire sur l’apprentissage d’une habileté motrice. Les premiers modèles d’apprentissage considèrent que l’apprenant franchit plusieurs étapes au cours desquelles la sollicitation des processus attentionnels diminue (Fitts & Posner, 1967). Ainsi, la réalisation d’un mouvement nécessiterait d’engager de l’attention en début d’apprentissage alors qu’elle serait automatique en fin d’apprentissage. Cet article propose de vérifier cette affirmation au regard des recherches récentes qui révèlent que l’apprenant débutant module volontairement son attention a fin d’optimiser la réalisation de ses gestes.Cette focalisation attentionnelle est dite « interne » ou « externe » si elle porte respectivement sur le mouvement lui-même ou sur des éléments extérieurs au corps. La focalisation de l’attention a des répercutions importantes à la fois sur les performances et l’apprentissage. Ainsi, une focalisation externe entraîne de meilleurs résultats qu’une focalisation interne. L’explication de ce phénomène est controversée. Deux hypothèses seront présentées : celle de « l’action contrainte » formulée par Wulf (2007) et celle des « processus conscients » de Masters (Masters & Maxwell, 2004). En fin, cet article se terminera par la présentation des conséquences de ces travaux sur l’enseignement.

International audience; IntroductionThe benefits of transporting severely injured patients by helicopter remain controversial. This study aimed to analyze the impact on mortality of helicopter compared to ground transport directly from the scene to a University hospital trauma center.MethodsThe French Intensive Care Research for Severe Trauma cohort study enrolled 2,703 patients with severe blunt trauma requiring admission to University hospital intensive care units within 72 hours. Pre-hospital and hospital clinical data, including the mode of transport, (helicopter (HMICU) versus ground (GMICU), both with medical teams), were recorded. The analysis was restricted to patients admitted directly from the scene to a University hospital trauma center. The main endpoint was mortality until ICU discharge.ResultsOf the 1,958 patients analyzed, 74% were transported by GMICU, 26% by HMICU. Median injury severity score (ISS) was 26 (interquartile range (IQR) 19 to 34) for HMICU patients and 25 (IQR 18 to 34) for GMICU patients. Compared to GMICU, HMICU patients had a higher median time frame before hospital admission and were more intensively treated in the pre-hospital phase. Crude mortality until hospital discharge was the same regardless of pre-hospital mode of transport. After adjustment for initial status, the risk of death was significantly lower (odds ratio (OR): 0.68, 95% confidence interval (CI) 0.47 to 0.98, P = 0.035) for HMICU compared with GMICU. This result did not change after further adjustment for ISS and overall surgical procedures.ConclusionsThis study suggests a beneficial impact of helicopter transport on mortality in severe blunt trauma. Whether this association could be due to better management in the pre-hospital phase needs to be more thoroughly assessed.

International audience; BackgroundThe age-related decline in performance has been investigated in swimmers, runners and triathletes. No study has investigated the age-related performance decline in ultra-triathletes. The purpose of this study was to analyse the age-related declines in swimming, cycling, running and overall race time for both Triple Iron ultra-triathlon (11.4-km swimming, 540-km cycling and 126.6-km running) and Deca Iron ultra-triathlon (38-km swimming, 1,800-km cycling and 420-km running).MethodsThe age and performances of 423 male Triple Iron ultra-triathletes and 119 male Deca Iron ultra-triathletes were analysed from 1992 to 2010 using regression analyses and ANOVA.ResultsThe mean age of the finishers was significantly higher for Deca Iron ultra-triathletes (41.3 ± 3.1 years) compared to a Triple Iron ultra-triathletes (38.5 ± 3.3 years) (P ConclusionsThe magnitudes of age-related declines in performance in the three disciplines of ultra-triathlon differ slightly between Triple and Deca Iron ultra-triathlon. Although the ages of Triple Iron ultra-triathletes were on average younger compared to Deca Iron ultra-triathletes, the fastest race times were achieved between 25 and 44 years for both distances. Further studies should investigate the motivation and training of ultra-triathletes to gain better insights in ultra-triathlon performance.

International audience

International audience; à venir

International audience; The pro-inflammatory cytokine IL-1β has been shown to promote angiogenesis. It can have a neurotoxic or neuroprotective effect. Here, we have studied the expression of IL-1β in vivo and the effect of the IL-1 receptor antagonist on choroidal neovascularization (CNV) and retinal degeneration (RD). IL-1β expression significantly increased after laser injury (real time PCR) in C57BL/6 mice, in the C57BL/6 Cx3cr1(-/-) model of age-related macular degeneration (enzyme-linked immunoabsorbent assay), and in albino Wistar rats and albino BALB Cx3cr1(+/+) and Cx3cr1(-/-) mice (enzyme-linked immunoabsorbent assay) after light injury. IL-1β was localized to Ly6G-positive, Iba1-negative infiltrating neutrophils in laser-induced CNV as determined by IHC. IL-1 receptor antagonist treatment significantly inhibited CNV but did not affect Iba1-positive macrophage recruitment to the injury site. IL-1β significantly increased endothelial cell outgrowth in aortic ring assay independently of vascular endothelial growth factor, suggesting a direct effect of IL-1β on choroidal endothelial cell proliferation. Inhibition of IL-1β in light- and laser-induced RD models did not alter photoreceptor degeneration in Wistar rats, C57BL/6 mice, or RD-prone Cx3cr1(-/-) mice. Our results suggest that IL-1β inhibition might represent a valuable and safe alternative to inhibition of vascular endothelial growth factor in the control of CNV in the context of concomitant photoreceptor degeneration as observed in age-related macular degeneration.