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indexation en cours; Chemosensory anxiety signals effectively prime motor responses related to withdrawal behavior, such as the startle reflex, in adult humans. As the reproductive status strongly affects the response to social chemosignals, the current study examined whether chemosensory anxiety signals would augment the startle response in prepubertal children as it does in adults. Using cotton pads, axillary sweat was collected from 28 men while waiting for an important oral examination (anxiety condition), and during ergometer training (sport control condition). Using a constant-flow olfactometer, sweat samples and pure cotton samples (cotton control) were presented to 10 prepubertal girls aged 9-13years (M=11.25, SD=1.25) for 3000ms during inhalation. White noise bursts of 102dB(A) served as startle probes, and startle responses were recorded via electromyography of the orbicularis oculi muscle. The girls showed larger startle amplitudes to probes presented in the context of chemosensory anxiety signals as compared to a context of sport control sweat (p

Purpose:This study examined the effects of a five-week intervention combining vigorous interval training (VIT) with diet among twenty-four obese adolescents. Fourteen girls and ten boys (aged 14–15) schooled in a pediatric rehabilitation center participated. Methods:The VIT intensity was targeted and remained above 80% of maximal heart rate (HR) and over six kilocalories per minute. Pre- and postintervention measures were body composition (BMI, weight, body fat percentage), physical self-perceptions (PSP), physical fitness (6-min walking distance and work) and its associated physiological responses (HRpeak and blood lactate concentration). A series of two-way analyses of variance or covariance controlling for weight loss were used to examine the changes. Results:Significant improvements were found in body composition, physical fitness and PSP (endurance, activity level, sport competence, global physical self-concept and appearance). In addition, boys presented higher levels of perceived strength and global physical self-concept than girls. Finally, there was a significant increase in perceived endurance, sport competence, and global physical self-concept in girls only. Conclusion:This five-week VIT program combined with diet represents an effective means for improving body composition, physical fitness, and PSP in obese adolescents, the effects on PSP being larger among girls.

PPARγ-deficient mice die at E9.5 due to placental abnormalities. The mechanism by which this occurs is unknown. We demonstrated that the new endocrine factor EG-VEGF controls the same processes as those described for PPARγ, suggesting potential regulation of EG-VEGF by PPARγ. EG-VEGF exerts its functions via prokineticin receptor 1 (PROKR1) and 2 (PROKR2). This study sought to investigate whether EG-VEGF mediates part of PPARγ effects on placental development. Three approaches were used: 1) in vitro, using human primary isolated cytotrophoblasts and the extravillous trophoblast cell line (HTR-8/SVneo); 2) ex vivo, using human placental explants ( n = 46 placentas); and 3) in vivo, using gravid wild-type PPARγ+/− and PPARγ−/− mice. Major processes of placental development that are known to be controlled by PPARγ, such as trophoblast proliferation, migration, and invasion, were assessed in the absence or presence of PROKR1 and PROKR2 antagonists. In both human trophoblast cell and placental explants, we demonstrated that rosiglitazone, a PPARγ agonist, 1) increased EG-VEGF secretion, 2) increased EG-VEGF and its receptors mRNA and protein expression, 3) increased placental vascularization via PROKR1 and PROKR2, and 4) inhibited trophoblast migration and invasion via PROKR2. In the PPARγ−/− mouse placentas, EG-VEGF levels were significantly decreased, supporting an in vivo control of EG-VEGF/PROKRs system during pregnancy. The present data reveal EG-VEGF as a new mediator of PPARγ effects during pregnancy and bring new insights into the fine mechanism of trophoblast invasion.

Aim Neuromuscular electrical stimulation (NMES) causes early onset of neuromuscular fatigue. Peripheral electrophysiological explorations suggest that supra-spinal alterations are involved through sensitive afferent pathways. As sensory input is projected over the primary somatosensory cortex (S1), S1 area involvement in inhibiting the central motor drive can be hypothesized. This study assessed cortical activity under a fatiguing NMES protocol at low frequency. Methods Twenty healthy males performed five NMES sequences of 17 trains over the plantar flexors (30 Hz, 4 s on/6 s off). Before and after each sequence, neuromuscular tests composed of maximal voluntary contractions (MVCs) were carried out. Cortical activity was assessed during MVCs with functional near-infrared spectroscopy over S1 and primary motor (M1) areas, through oxy- [HbO] and deoxy-haemoglobin [HbR] variation. Electrophysiological data (H-reflex during MVC, EMG activity and level of voluntary activation) were also recorded. Results MVC torque significantly decreased after the first 17 NMES trains (P

The increase in blood pressure observed during physical activities is exaggerated in patients with hypertension, exposing them to a higher cardiovascular risk.Neural signals from the skeletal muscles appear to be overactive, resulting in this abnormal response in hypertensive patients.In the present study, we tested whether the attenuation of these neural signals in hypertensive patients could normalize their abnormal increase in blood pressure during physical activity.Attenuation of the neural signals from the leg muscles with intrathecal fentanyl injection reduced the blood pressure of hypertensive men during cycling exercise to a level comparable to that of normotensive men.Skeletal muscle afferent overactivity causes the abnormal cardiovascular response to exercise and was reverted in this experimental model, appearing as potential target for treatment.

International audience; The aim of this study was to compare cardiovascular hemodynamics and cerebral oxygenation/perfusion (COP) during and after maximal incremental exercise in obese individuals according to their aerobic fitness versus age-matched healthy controls (AMHC). Fifty-four middle-aged obese (OB) and 16 AMHC were recruited. Maximal cardiopulmonary function (gas exchange analysis), cardiac hemodynamics (impedance cardiography), and left frontal COP (near-infrared spectroscopy: NIRS) were measured continuously during a maximal incremental ergocycle test. During recovery, reoxygenation/perfusion rate (ROPR: oxyhemoglobin: Delta O(2)Hb, deoxyhemoglobin: Delta HHb and total hemoglobin: Delta tHb; with NIRS) was also measured. Obese participants (OB, n = 54) were divided into two groups according to the median VO2 peak: the low-fit obese (LF-OB, n = 27) and the high-fit obese (HF-OB, n = 27). During exercise, end tidal pressure of CO2 (PETCO2), and COP (Delta O(2)Hb, Delta HHb and Delta tHb) did not differ between groups (OB, LF-OB, HF-OB, AMHC). During recovery, PETCO2 and ROPR (Delta O(2)Hb, Delta HHb and DtHb) were similar between the groups (OB, LF-OB, HF-OB, AMHC). During exercise and recovery, cardiac index was lower (P < 0.05) in LF-OB versus the other two groups (HF-OB, AMHC). As well, systolic blood pressure was higher during exercise in the OB, LF-OB and HF-OB groups versus AMHC (P < 0.05). When compared to AMHC, obese individuals (OB, LF-OB, HF-OB) have a similar cerebral vasoreactivity by CO2 and cerebral hemodynamics during exercise and recovery, but a higher systolic blood pressure during exercise. Higher fitness in obese subjects (HF-OB) seems to preserve their cardiopulmonary and cardiac function during exercise and recovery.

International audience; Claudins are a family of proteins that forms paracellular barriers and pores determining tight junctions (TJ) permeability. Claudin-16 and-19 are pore forming TJ proteins allowing calcium and magnesium reabsorption in the thick ascending limb of Henle's loop (TAL). Loss-of-function mutations in the encoding genes, initially identified to cause Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis (FHHNC), were recently shown to be also involved in Amelogenesis Imperfecta (AI). In addition, both claudins were expressed in the murine tooth germ and Claudin-16 knockout (KO) mice displayed abnormal enamel formation. Claudin-3, an ubiquitous claudin expressed in epithelia including kidney, acts as a barrier-forming tight junction protein. We determined that, similarly to claudin-16 and claudin-19, claudin-3 was expressed in the tooth germ, more precisely in the TJ located at the apical end of secretory ameloblasts. The observation of Claudin-3 KO teeth revealed enamel defects associated to impaired TJ structure at the secretory ends of ameloblasts and accumulation of matrix proteins in the forming enamel. Thus, claudin-3 protein loss-of-function disturbs amelogenesis similarly to claudin-16 loss-of-function, highlighting the importance of claudin proteins for the TJ structure. These findings unravel that loss-of-function of either pore or barrier-forming TJ proteins leads to enamel defects. Hence, the major structural function of claudin proteins appears essential for amelogenesis.

IF 4.134; International audience; The sense of taste is responsible for the detection and ingestion of food to cover energetic requirements in health and disease. The change in taste perception might lead to malnutrition that is usually one of the frequent causes of morbidity and mortality in patients with cancer. In this review, we summarize the mechanisms of taste perception and how they are altered in cancer. We also address the question of the implication of inflammation, responsible for the alterations in taste modalities. We highlight the role of radio- and chemotherapy in the modulation of taste physiology. Other several factors like damage to taste progenitor cells and disruption of gut microbiota are also dealt with relation to taste perception in cancer. We further shed light on how to restore taste acuity, by using different preventive methods, dietary modifications and pharmacotherapy in subjects with advanced cancer state.

Background The alarming progression of pediatric obesity is associated with the development of sleep-disordered breathing (SDB), and both exhibit similar adverse cardiometabolic health outcomes. Physical activity level (PAL) may counteract sleep and metabolic disturbances. The present study investigates i) the association between the metabolic syndrome in childhood obesity and SDB, ii) the impact of SDB severity on cardiometabolic risk scores and PAL in children with obesity. Methods Maturation status (Tanner stages), anthropometric (height, weight, body mass index, waist circumference, body adiposity index) and cardiometabolic characteristics (systolic and diastolic blood pressure, lipid and glycemic profiles) were assessed in 83 obese children (mean ± SD, age: 10.7 ± 2.7 years). PAL and SDB were investigated with a step test and interviews, and an overnight sleep monitor, respectively. The presence or absence of metabolic syndrome (MS) was established and continuous cardiometabolic risk scores were calculated (MetScoreBMI and MetScoreWC). Results Obese children with (61.4%) and without (38.6%) MS present similar SDB. SDB severity is associated with increased insulin concentrations, MetScoreBMI and MetScoreWC (p Conclusions In a context where no consensus exists for SDB diagnosis in children, our results suggest the influence of SDB severity on cardiometabolic risk factors. Further studies are needed to explore the association between PAL and both metabolic and sleep alterations in obese children.

International audience; This study aims to examine the repeated effects of three sessions of vigorous interval training (VIT) in basketball, running-biking, and boxing on the physical self-perceptions (PSP) of obese adolescents participating in a dietary program. A sample of 24 obese adolescents performed the consecutive VIT sessions every week for 5 weeks. PSP were measured immediately after each training session. Analyses of covariance were used to examine changes in PSP. The results showed rapid and constant increases in PSP with significant differences according to sex, time, type of VIT, and an interaction of sex by time by type of VIT, mainly for basketball.

The aim of this investigation was to evaluate the effect of a 6-day food restriction period on the physiological responses and performance of 11 high-level weightlifters. After a period of weight maintenance (T2), they were assigned into two groups depending on whether they lost (Diet group, n = 6) or maintained their body weight (Control group, n = 5) during the course of those 6 days. An evaluation of performance and the measurement of salivary cortisol concentrations and salivary α-amylase (sAA) activity were performed during a simulated weightlifting competition which took place at T2, after a 6-day period of food restriction (T3). Dietary data were collected using a 6-day diet record. We noted a 41.8% decrease in mean energy intake during the dietary restriction period, leading to a 4.34% weight loss for the Diet group. Dietary restriction did not modify absolute performance levels, whilst a significant improvement was noted for the Control group. Furthermore, we noted a response of decreased...

International audience; High-intensity exercise may pose a risk to patients with postconcussion syndrome (PCS) when symptomatic during exertion. The case of a paralympic athlete with PCS who experienced a succession of convulsion-awakening periods and reported a marked increase in postconcussion symptoms after undergoing a graded symptom-limited aerobic exercise protocol is presented. Potential mechanisms of cerebrovascular function failure are then discussed.

IF 2.388; International audience; Pyrethroid insecticides are extensively used in agriculture and in household activities. During pregnancy, they might affect maternal metabolic status and there after fetal development. In this work, we studied metabolic and redox effects of low dose alpha-cypermethrin exposure in pregnant rats and their offspring. The diet containing alpha cypermethrin at 0.02 mg/kg/day was consumed during the entire gestation. Plasma biochemical parameters as well as liver lipid and oxidative stress markers were determined. Our results showed that alpha-cypermethrin induced an increase in body weight and in plasma glucose and lipid levels, as well as in plasma aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase activities in pregnant rats and their newborns. Pregnant rats showed cellular oxidative stress and altered oxidant antioxidant status when treated by the insecticide and these disturbances were also seen in their newborns. In conclusion, low dose alpha-cypermethrin exposure induced several metabolic and redox alterations leading to maternal physiological impairments and to fetal metabolic changes. Alpha-cypermethrin should be used with caution especially during pregnancy. (C) 2016 Elsevier Inc. All rights reserved.

En 2013, on estime que 40 à 50% des accidents corporels seraient dus à des défauts d'attention de la part du conducteur. Des études récentes ont mis en évidence la possibilité de détecter des états attentionnels dégradés afin de pouvoir mieux assister le conducteur ; ce thème de recherche représente donc un nouveau gisement de sécurité routière. Cette étude se concentre sur la détection de l'effort cognitif fournit par les conducteurs et cherche, par l'étude de la variation du rythme cardiaque, à identifier un indicateur d'effort sensible sur de courtes fenêtres temporelles.Chacun des 18 participants a passé 8 conditions expérimentales sur simulateur de conduite : la moitié où seule une tâche de comptage était demandée et l'autre moitié en réalisant une tâche supplémentaire de conduite sur simulateur. Il a été demandé aux participants soit d'effectuer la tâche cognitive soit de se relaxer et de ne pas prêter attention aux stimuli présentés (Effort Vs. Relaxation). Afin de réaliser la tâche de comptage, deux types de stimuli auditifs ont été présentés aux participants. Les participants ont effectué les conditions expérimentales dans des ordres partiellement contrebalancés. Le rythme cardiaque et la respiration ont été collectés.Les résultats de différents auteurs ont été répliqués y compris en conduite automobile. Dans les secondes qui suivent un effort cognitif, une légère décélération du rythme cardiaque puis une forte accélération ont été mises en évidence. A l'inverse, en condition de relaxation, une simple décélération cardiaque a été observée. Au terme de notre étude, il s'avère qu'il est possible de distinguer des patterns cardiaques d'effort et de relaxation sur de courtes fenêtre temporelle en observant la variation du rythme cardiaque moyenné sur un nombre conséquent d'épisodes. Toutefois, dans l'objectif de développer des systèmes capables de détecter en temps réel un effort cognitif important, ces dispositifs devront être capables de visualiser l'effort sur un unique évènement. Une piste intéressante consisterait à explorer la faisabilité de la suppression de l'influence de la respiration sur la variation du rythme cardiaque. Si cela s'avère efficace, des assistances pourraient ainsi permettre d'alerter le conducteur ou de pallier ses erreurs lorsque celui-ci ne peut plus assurer la tâche de conduite en raison d'un effort cognitif important.

ClC-K2 is present on the basolateral membrane of kidney epithelial cells, but little is known about its single channel properties. Pinelli et al. record unitary ClC-K2 currents from intercalated cells of mouse connecting tubules and investigate their regulation by voltage, pH, Cl−, and Ca2+., ClC-K2, a member of the ClC family of Cl− channels and transporters, forms the major basolateral Cl− conductance in distal nephron epithelial cells and therefore plays a central role in renal Cl− absorption. However, its regulation remains largely unknown because of the fact that recombinant ClC-K2 has not yet been studied at the single-channel level. In the present study, we investigate the effects of voltage, pH, Cl−, and Ca2+ on native ClC-K2 in the basolateral membrane of intercalated cells from the mouse connecting tubule. The ∼10-pS channel shows a steep voltage dependence such that channel activity increases with membrane depolarization. Intracellular pH (pHi) and extracellular pH (pHo) differentially modulate the voltage dependence curve: alkaline pHi flattens the curve by causing an increase in activity at negative voltages, whereas alkaline pHo shifts the curve toward negative voltages. In addition, pHi, pHo, and extracellular Ca2+ strongly increase activity, mainly because of an increase in the number of active channels with a comparatively minor effect on channel open probability. Furthermore, voltage alters both the number of active channels and their open probability, whereas intracellular Cl− has little influence. We propose that changes in the number of active channels correspond to them entering or leaving an inactivated state, whereas modulation of open probability corresponds to common gating by these channels. We suggest that pH, through the combined effects of pHi and pHo on ClC-K2, might be a key regulator of NaCl absorption and Cl−/HCO3− exchange in type B intercalated cells.

International audience; The aim of the study was to determine whether stretching durations influence acute changes of mechanical and neurophysiological properties of plantar flexor muscles. Plantar flexors of 10 active males were stretched in passive conditions on an isokinetic dynamometer. Different durations of static stretching were tested in 5 randomly ordered experimental trials (1, 2, 3, 4 and 10×30-s). Fascicle stiffness index, evoked contractile properties and spinal excitability (Hmax/Mmax) were examined before (PRE), immediately after (POST0) and 5 min after (POST5) stretching. No stretch duration effect was recorded for any variable. Moreover, whatever the stretching duration, stiffness index, peak twitch torque and rate of force development were significantly lower at POST0 and POST5 as compared to PRE (P

International audience; This study compared knee extensors' neuromuscular fatigue in response to two 30-minute stimulation patterns: constant frequency train (CFT) and doublet frequency train (DFT). Fifteen men underwent two separate sessions corresponding to each pattern. Measurements included torque evoked by each contraction and maximal voluntary contractions (MVC) measured before and immediately after the stimulation sessions. In addition, activation level and torque evoked during doublets (Pd) and tetanic contractions at 80-Hz (P80) and 20-Hz (P20) were determined in six subjects. Results indicated greater mean torque during the DFT stimulation session as compared with CFT. But, no difference was obtained between the two stimulation patterns for MVC and evoked torque decreases. Measurements conducted in the subgroup depicted a significant reduction of Pd, P20 and P80. Statistical analyses also revealed bigger P20 immediate reductions after CFT than after DFT. We concluded that DFT could be a useful stimulation pattern to produce and maintain greater force with quite similar fatigue than CFT.

Background: Psychological stress and recovery monitoring is a key issue for increasing athletes' health, well-being, and performance. This multi-study report examined changes and the dose–response relationships between recovery–stress psychological states, training load (TL), heart rate (HR), heart rate recovery (HRR), and heart rate variability (HRV) while providing evidence for the factorial validity of a short French version of the Recovery–Stress Questionnaire for Athletes (RESTQ-36-R-Sport). Methods: Four hundred and seventy-three university athletes (Study 1), 72 full expert swimmers (Study 2), and 11 national to international swimmers (Study 3) participated in the study. Data were analyzed through confirmatory factor analyses (Study 1), repeated ANOVAs and correlational analyses (Study 2), t tests and correlational analyses (Study 3). Results: Multiple-group confirmatory factor analyses showed that the RESTQ-36-R-Sport scores were partially invariant across gender, type of sport, and practice level (Study 1). A dose–response relationship was performed between TL and RESTQ-36-R-Sport scores during an ecological training program (Study 2). Finally, relationships were found between physiological (HRR) and psychological (RESTQ-36-R-Sport) states during an ecological tapering period leading to a national championship (Study 3). Conclusion: As a whole, these findings provided evidence for the usefulness of the short version of the RESTQ-36-R-Sport for regular monitoring to prevent potential maladaptation due to intensive competitive sport practice. Keywords: Adaptation, Confirmatory factor analysis, Heart rate variability, Monitoring, Recovery, Stress

Monocarboxylates have been implicated in the control of energy homeostasis. Among them, the putative role of ketone bodies produced notably during high-fat diet (HFD) has not been thoroughly explored. In this study, we aimed to determine the impact of a specific rise in cerebral ketone bodies on food intake and energy homeostasis regulation. A carotid infusion of ketone bodies was performed on mice to stimulate sensitive brain areas for 6 or 12 h. At each time point, food intake and different markers of energy homeostasis were analyzed to reveal the consequences of cerebral increase in ketone body level detection. First, an increase in food intake appeared over a 12-h period of brain ketone body perfusion. This stimulated food intake was associated with an increased expression of the hypothalamic neuropeptides NPY and AgRP as well as phosphorylated AMPK and is due to ketone bodies sensed by the brain, as blood ketone body levels did not change at that time. In parallel, gluconeogenesis and insulin sensitivity were transiently altered. Indeed, a dysregulation of glucose production and insulin secretion was observed after 6 h of ketone body perfusion, which reversed to normal at 12 h of perfusion. Altogether, these results suggest that an increase in brain ketone body concentration leads to hyperphagia and a transient perturbation of peripheral metabolic homeostasis.

International audience; The fluoranthene (Fluo) is one of the most abundant polycyclic aromatic hydrocarbons (PAHs) in human food and in marine compartments. However, the existing data on its genotoxicity is poor and controversial. The aim of this study was to assess in vitro the potential genotoxicity of Fluo in sole and its possible effect on CYP450 modulation. Freshly isolated hepatocytes were exposed for 24 h to a range of Fluo concentrations from 0.5 to 50 μM in both culture flasks and microplate wells. The ethoxyresorufin-O-deethylase (EROD) activity was measured as an indicator of the activity of the cytochrome P450 1A1 (CYP1A1). The genotoxic effects were evaluated by measuring both DNA strand breaks and DNA adducts by the alkaline comet assay and the postlabeling technique respectively. Calf thymus DNA was also exposed to Fluo in the presence of sole liver microsomes in order to check for Fluo DNA adduct formation. In sole hepatocytes, Fluo was shown to induce a decrease in the EROD activity in a concentration-dependent manner. A significant genotoxic effect was observed in terms of DNA strand breakage from an exposure concentration of 5 μM: despite a concentration-dependent effect was observed, it did not follow a linear dose-response. The response was similar whatever the way of exposure in flasks or in wells. One reproducible adduct was detected in the hepatocytes exposed to the highest concentrations of Fluo. The formation of Fluo adducts was confirmed by the detection of one reproducible adduct following in vitro exposure of calf thymus DNA to 100 and 200 μM of Fluo in the presence of sole microsomes. These results demonstrate the potential of sole hepatocytes to metabolize Fluo in 24 h into reactive species, able to induce genotoxicity by DNA strand breakage and DNA adduct formation. Moreover, a miniaturized cell exposure system was validated for further experiments using fewer amounts of hepatocytes and contaminants, and allowing exposure to PAH metabolites.

International audience; During the early period of running after cycling, EMG patterns of the leg are modified in only some highly trained triathletes. The majority of studies have analysed muscle EMG patterns at arbitrary, predetermined time points. The purpose of this study was to examine changes to EMG patterns of the lower limb at physiologically determined times during the cycle-run transition period to better investigate neuromuscular adaptations. Six highly trained triathletes completed a 10 min isolated run (IR), 30 min of rest, then a 20 min cycling procedure, before a 10 min transition run (C-R). Surface EMG activity of eight lower limb muscles was recorded, normalised and quantified at four time points. Oxygen uptake and heart rate values were also collected. Across all muscles, mean (+/- SD) EMG patterns, demonstrated significant levels of reproducibility for each participant at all four time points (alpha < 0.05; r = 0.52-0.97). Mean EMG patterns during C-R correlated highly with the IR patterns (alpha < 0.05). These results show that EMG patterns during subsequent running are not significantly affected by prior cycling. However, variability of muscle recruitment activity does appear to increase during C-R transition when compared to IR.

International audience; This study aimed to compare the response of salivary hormones of track and field athletes induced by preparation and pre-competitive training periods in an attempt to comment on the physiological effects consistent with the responses of each of the proteins measured. Salivary testosterone, cortisol, alpha-amylase, immunoglobulin A (IgA), chromogranin A, blood creatine kinase activity, and profile of mood state were assessed at rest in 24 world-class level athletes during preparation (3 times in 3 months) and pre-competitive (5 times in 5 weeks) training periods. Total mood disturbance and fatigue perception were reduced, while IgA (+61%) and creatine kinase activity (+43%) increased, and chromogranin A decreased (−27%) during pre-competitive compared to preparation period. A significant increase in salivary testosterone (+9 to +15%) and a decrease in testosterone/cortisol ratio were associated with a progressive reduction in training load during pre-competitive period (P < 0.05). None of the psycho-physiological parameters were significantly correlated to training load during the pre-competitive period. Results showed a lower adrenocortical response and autonomic activity, and an improvement of immunity status, in response to the reduction in training load and fatigue, without significant correlations of salivary hormones with training load. Our findings suggest that saliva composition is sensitive to training contents (season period) but could not be related to workload resulting from track and field athletics training.

International audience; Membrane conductance (Dm) and capillary lung volume (Vc) derived from NO and CO lung transfer measurements in humans depend on the blood conductance (θ) values of both gases. Many θ values have been proposed in the literature. In the present study, measurements of CO and NO transfer while breathing 15% or 21% O2 allowed the estimation of θNO and the calculation of the optimal equation relating 1/θCO to pulmonary capillary oxygen pressure (PcapO2). In 10 healthy subjects, the mean calculated θNO value was similar to the θNO value previously reported in the literature (4.5mmHgmin(-1)) provided that one among three θCO equations from the literature was chosen. Setting 1/θCO=a·PcapO2+b, optimal values of a and b could be chosen using two methods: 1) by minimizing the difference between Dm/Vc ratios for any PcapO2, 2) by establishing a linear equation relating a and b. Using these methods, we are proposing the equation 1/θCO=0.0062·PcapO2+1.16, which is similar to two equations previously reported in the literature. With this set of θ values, DmCO reached the morphometric range.

Import JabRef | WosArea Physiology; Sport Sciences; International audience; The use of electrical stimulation (ES) can contribute to our knowledge of how our neuromuscular system can adapt to physical stress or unloading. Although it has been recently challenged, the standard technique used to explore central modifications is the twitch interpolated method which consists in superimposing single twitches or high-frequency doublets on a maximal voluntary contraction (MVC) and to compare the superimposed response to the potentiated response obtained from the relaxed muscle. Alternative methods consist in (1) superimposing a train of stimuli (central activation ratio), (2) comparing the MVC response to the force evoked by a high-frequency tetanus or (3) examining the change in maximal EMG response during voluntary contractions, if this variable is normalized to the maximal M wave, i.e. EMG response to a single stimulus. ES is less used to examine supraspinal factors but it is useful for investigating changes at the spinal level, either by using H reflexes, F waves or cervicomedullary motor-evoked potentials. Peripheral changes can be examined with ES, usually by stimulating the muscle in the relaxed state. Neuromuscular propagation of action potentials on the sarcolemma (M wave, high-frequency fatigue), excitation-contraction coupling (e.g. low-frequency fatigue) and intrinsic force (high-frequency stimulation at supramaximal intensity) can all be used to non-invasively explore muscular function with ES. As for all indirect methods, there are limitations and these are discussed in this review. Finally, (1) ES as a method to measure respiratory muscle function and (2) the comparison between electrical and magnetic stimulation will also be considered.

International audience; Aim: Voluntary apnoea induces several physiological adaptations, including bradycardia, arterial hypertension and redistribution of regional blood flows. Elite breath-hold divers (BHDs) are able to maintain very long apnoea, inducing severe hypoxaemia without brain injury or black-out. It has thus been hypothesized that they develop protection mechanisms against hypoxia, as well as a decrease in overall oxygen uptake. Methods: To test this hypothesis, the apnoea response was studied in BHDs and non-divers (NDs) during static and dynamic apnoeas (SA, DA). Heart arterial oxygen saturation (SaO(2)), and popliteal artery blood flow were rate, recorded to investigate the oxygen-conserving effect of apnoea response, and the internal carotid artery blood flow was used to examine the mechanisms of cerebral protection. Results: The bradycardia and peripheral vasoconstriction were accentuated in BHDs compared with NDs (P < 0.01), in association with a smaller SaO(2) decrease (-2.7% vs. -4.9% during SA, P < 0.01 and -6% vs. -11.3% during DA, P < 0.01). Greater increase in carotid artery blood flow was also measured during apnoea in BHDs than in controls. Conclusion: These results confirm that elite divers present a potentiation of the well-known apnoea response in both SA and DA conditions. This response is associated with higher brain perfusion which may partly explain the high levels of world apnoea records.

International audience; BACKGROUND: Parecoxib, a selective cyclooxygenase-2 inhibitor, may reduce postoperative pain without increasing bleeding when administered before surgery. METHODS: We randomly assigned 62 patients scheduled for total hip arthroplasty to the following IV dosing schedule: 1) placebo at induction, at wound closure, and 12 h after induction (control); 2) parecoxib 40 mg at induction, placebo at wound closure, and parecoxib 40 mg 12 h after induction (pre); or, 3) placebo at induction, parecoxib 40 mg at wound closure, and parecoxib 40 mg 12 h after induction (post). Pain scores at rest and with movement were recorded every 4 h for 24 h using a visual analog scale. Treatment side effects were recorded every 4 h. Red cell loss for 5 days after surgery was calculated. RESULTS: Postoperative pain scores were less in the pre and post groups than in the control group. Postoperative bleeding was similar in the three groups. There were no significant differences between the pre and post groups, nor was their any trend suggesting a preemptive analgesic efficacy from preincision administration of parecoxib. Morphine use in the Postanesthesia Care Unit was reduced in the pre and post groups compared with the control group (14.2 +/- 2.0, and 15.7 +/- 2.0, vs 20.4 +/- 2.3 mg), although the trend was only significant (P < 0.05) in the pre group. The first pain score was also reduced in the pre and post groups compared to the control group (56.1 +/- 7.5 and 64.2 +/- 7.0 vs 78.3 +/- 5), but this was also only significant for the pre group (P = 0.001). The delay for first analgesic demand was increased for both the pre and post group compared to the control group (38 +/- 9 and 28.2 +/- 6.6 vs 18 +/- 6 min) but, again, this was only significant for the pre group (P = 0.05). Twenty-four hour consumption of morphine was similar in the pre (26 +/- 12 mg) and post groups (25 +/- 13 mg); both were significantly less than in the control group (47 +/- 27 mg, P < 0.001). CONCLUSIONS: Administration of parecoxib before hip arthroplasty did not provide preemptive analgesia. There was a trend towards improved analgesia immediately after surgery with preincision administration, consistent with the expected time course of nonsteroidal antiinflammatory drug's effect. Perioperative parecoxib administration, consisting of two injections spaced 12 h apart, improved postoperative analgesia over the first 24 h without increasing bleeding.

International audience; The purpose of this cross-sectional study was to investigate the change in 100-km running performance and in the age of peak performance for 100-km ultramarathoners. Age and running speed of the annual fastest women and men in all 100-km ultramarathons held worldwide between 1960 and 2012 were analyzed in 148,017 finishes with 18,998 women and 129,019 men using single, multivariate, and nonlinear regressions. Running speed of the annual fastest men increased from 8.67 to 15.65 km.h(-1) and from 8.06 to 13.22 km.h(-1) for the annual fastest women. For the annual 10 fastest men, running speed increased from 10.23 ± 1.22 to 15.05 ± 0.29 km.h(-1) (p < 0.0001) and for the annual 10 fastest women from 7.18 ± 1.54 to 13.03 ± 0.18 km.h(-1) (p < 0.0001). The sex difference decreased from 56.1 to 16.3% for the annual fastest finishers (p < 0.0001) and from 46.7 ± 8.7% to 14.0 ± 1.2% for the annual 10 fastest finishers (p < 0.0001). The age of the annual fastest men increased from 29 to 40 years (p = 0.025). For the annual fastest women, the age remained unchanged at 35.0 ± 9.7 years (p = 0.469). For the annual 10 fastest women and men, the age remained unchanged at 34.9 ± 3.2 (p = 0.902) and 34.5 ± 2.5 years (p = 0.064), respectively. To summarize, 100-km ultramarathoners became faster, the sex difference in performance decreased but the age of the fastest finishers remained unchanged at ∼ 35 years. For athletes and coaches to plan a career as 100-km ultramarathoner, the age of the fastest female and male 100-km ultramarathoners remained unchanged at ∼ 35 years between 1960 and 2012 although the runners improved their performance over time.

Epub 2015 Oct.; Previous studies have reported that reaction time in gait initiation was affected by emotion eliciting pictures. This study examined the effect of a change in the delay between image onset and the imperative “go” on reaction time. From a standing posture, 19 young adults had to walk (several steps) toward pleasant or unpleasant images in two conditions. In the short condition, the word “go” appeared 500 ms after image onset and participants were instructed to initiate gait as soon as possible after the word go appeared. In the long condition, the same procedure was used but the word “go” appeared 3000 ms after image onset. Results demonstrated that motor responses were faster for pleasant pictures than unpleasant ones in the short condition. In contrast, no significant difference was found between both categories of pictures in the long condition. Moreover, we found that self ratings of valence of unpleasant pictures were less unpleasant in the long condition than in the short one whereas there was no difference for pleasant pictures between both conditions. This result reflected a change in the affective significance of unpleasant pictures in the long condition. We also found in the long condition, that the body was inclined forward and to the stance limb during the standing posture and importantly with a similar extent for pleasant and unpleasant pictures. This change clearly reflected a facilitation of the gait initiation process. Overall, results suggested that this gait facilitation when confronted to unpleasant pictures resulted from emotional regulation processes enabling to reappraise these pictures and to override the initial avoidance tendency that they caused.

Newborn mice are attracted to mammary odor cues carried in murine milk and nipple secretions. However, murine milk odor is not equally attractive along lactation. The present study focuses on the differential response of 2day-old mouse pups of C57Bl/6 (C) and Balb/C (B) strains to the odor of milk (Experiment 1) and nipples (Experiment 2) that are matched/unmatched in terms of pup's age or strain. In Experiment 1, C and B pups were tested in a series of tests simultaneously opposing either murine milk and a blank (water), or two milks collected in early and late lactation (lactation days 2 and 15, respectively) from females belonging to their own or the other strain. Results showed that C and B pups were attracted to the odor of the different milks regardless of the lactation age and the strain of the donor female. Nevertheless, C and B pups preferred the odor conveyed by early- than late-lactation milk of either strain. Moreover, early-lactation milk from C females was more attractive than early-lactation milk from B females for pups of either strain. In Experiment 2, differential nipple grasping response of C and B pups was measured when they were exposed to nipples of females in early or late lactation. The proportion of C pups that grasped a nipple was greater when they were exposed to a nipple in early lactation regardless of the strain of the donor females, whereas the proportion of B pups that grasped a nipple was greater when they were exposed to a nipple in early lactation, but only from own strain. Thus, newborn mice prefer the odor of milk and nipples from females that are matched in lactation age. This result is discussed in terms of reciprocally adaptive mechanisms between lactating females and their newborn offspring.

International audience; The purpose of this study was to assess the prognostic value of a large panel of cytokines in aggressive non-Hodgkin's lymphoma (NHL) and to confront it to parameters of the International Prognostic Index (IPI). It investigated the concomitant determination of interleukin-2 (IL-2), soluble interleukin-2 receptor (sIL-2R), interleukin-4 (IL-4), interleukin-6 (IL-6) and interleukin-10 (IL-10) on a uniform population of 116 previously untreated patients. Commercially available enzyme-linked immunoassay kits were used for cytokines measurements. Results were correlated with complete remission (CR), overall survival (OS) and failure free survival (FFS). In univariate analysis, sIL-2R and IL-6 demonstrated prognostic significance for CR (p = 0.016 and p = 0.048), OS (p = 0.0011 and p = 0.0387) and FFS (p = 0.0001 and p = 0.0363), but multi-variate analysis failed to demonstrate an independent prognostic significance. In the intermediate group risk defined by IPI, patients presenting high level of sIL-2R or IL-6 demonstrated lower CR rate and survival than those with low level. In conclusion, sIL-2R and IL-6 serum levels are elevated in high grade NHL and are correlated to CR, OS and FFS, but this study did not support their independent prognostic value. However, sIL-2R and IL-6 measurements may improve risk assignment by IPI and allow a better prognostic evaluation of patients with intermediate prognosis NHL.

International audience; Torque time integral (TTI) is the combination of intensity and duration of a contraction. The aim of this study was to compare neuromuscular alterations following different isometric sub-maximal contractions of the knee extensor muscles but with similar TTI. Sixteen participants performed 3 sustained contractions at different intensities (25 %, 50 %, and 75 % of Maximal Voluntary Contraction (MVC) torque) with different durations (68.5 +/- 33.4 s, 35.1 +/- 16.8 s and 24.8 +/- 12.9 s, respectively) but similar TTI value. MVC torque, maximal voluntary activation level (VAL), M-wave characteristics and potentiated doublet amplitude were assessed before and immediately after the sustained contractions. EMG activity of the vastus lateralis (VL) and rectus femoris (RF) muscles was recorded during the sustained contractions. MVC torque reduction was similar in the 3 conditions after the exercise (-23.4 +/- 2.7 %). VAL decreased significantly in a similar extent (-3.1 +/- 1.3 %) after the 3 sustained contractions. Potentiated doublet amplitude was similarly reduced in the 3 conditions (-19.7 +/- 1.5 %), but VL and RF M-wave amplitudes remained unchanged. EMG activity of VL and RF muscles increased in the same extent during the 3 contractions (VL: 54.5 +/- 40.4 %; RF: 53.1 +/- 48.7 %). These results suggest that central and peripheral alterations accounting for muscle fatigue are similar following isometric contractions with similar TTI. TTI should be considered in the exploration of muscle fatigue during sustained isometric contractions.

The possible peripheral and/or central origin in the mechanisms responsible for day-time fluctuation in maximal torque of the triceps surae muscle were investigated with a special emphasis on antagonist muscle coactivation. Eleven healthy male subjects (physical education students) took part in this investigation. The electromechanical properties of the plantar flexor muscles were recorded at two different times of day: between 06:00 h and 08:00 h in the morning and between 17:00 h and 19:00 h in the evening. To investigate peripheral mechanisms, the posterior tibial nerve was stimulated at rest, using percutaneous electrical stimuli, to evoke single twitch, double twitch, and maximal tetanic contraction (100 Hz). Maximal voluntary contraction of the plantar flexors was also assessed by means of the relative electromyographic activity of respective agonist and antagonist muscles (soleus, gastrocnemius medialis, gastrocnemius lateralis, and tibialis anterior). A double twitch was delivered during maximal voluntary plantar flexion to record muscle activation (i.e., interpolated twitch technique). The coactivation level of the tibialis anterior muscle during plantar flexion was calculated. The results indicated a significant decrease in maximal voluntary muscle torque of triceps surae in the evening as compared with the morning (-7.0 %; p < 0.05). Concerning the central command, when extrapolated by the twitch interpolation technique, the decrease in mean activation level of -6.8 % was consistent with the fluctuation in torque (-7.0 %). Soleus muscle electromyographic activity (normalized to the M-wave) showed a significant decline (21.6 %; p < 0.001). Moreover, individual changes in MVC percentage were significantly related to those of normalized electromyographic activity of the soleus muscle (r = 0.688; p < 0.01). Thus, it indicated that the subject's capacity to activate the soleus muscle was affected by the time of day. The coactivation level in the tibialis anterior muscle during plantar flexion did not change significantly in the evening. Concerning peripheral mechanisms, we observed a decrease in maximal M-wave amplitude for soleus and gastrocnemii, associated with unchanged single twitch and tetanus torque. To conclude, impairment in soleus muscle central command seemed to be the mechanism in the origin of torque failure. Such information would be of importance in the investigation of day-time fluctuations in complex motor task performances implicating the triceps surae muscle.

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.

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

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

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.

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.

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://

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.

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.

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.