Repeated sprint training in hypoxia induces specific skeletal muscle adaptations through S100A protein signaling.

Athletes increasingly engage in repeated sprint training consisting in repeated short all-out efforts interspersed by short recoveries. When performed in hypoxia (RSH), it may lead to greater training effects than in normoxia (RSN); however, the underlying molecular mechanisms remain unclear. This study aimed at elucidating the effects of RSH on skeletal muscle metabolic adaptations as compared to RSN. Sixteen healthy young men performed nine repeated sprint training sessions in either normoxia (FIO2 = 0.209, RSN, n = 7) or normobaric hypoxia (FIO2 = 0.136, RSH, n = 9). Before and after the training period, exercise performance was assessed by using repeated sprint ability (RSA) and Wingate tests. Vastus lateralis muscle biopsies were performed to investigate muscle metabolic adaptations using proteomics combined with western blot analysis. Similar improvements were observed in RSA and Wingate tests in both RSN and RSH groups. At the muscle level, RSN and RSH reduced oxidative phosphorylation protein content but triggered an increase in mitochondrial biogenesis proteins. Proteomics showed an increase in several S100A family proteins in the RSH group, among which S100A13 most strongly. We confirmed a significant increase in S100A13 protein by western blot in RSH, which was associated with increased Akt phosphorylation and its downstream targets regulating protein synthesis. Altogether our data indicate that RSH may activate an S100A/Akt pathway to trigger specific adaptations as compared to RSN.

Cardiopulmonary haemodynamics in Tibetans and Han Chinese during rest and exercise.

During sea-level exercise, blood flow through intrapulmonary arteriovenous anastomoses (IPAVA) in humans without a patent foramen ovale (PFO) is negatively correlated with pulmonary pressure. Yet, it is unknown whether the superior exercise capacity of Tibetans well adapted to living at high altitude is the result of lower pulmonary pressure during exercise in hypoxia, and whether their cardiopulmonary characteristics are significantly different from lowland natives of comparable ancestry (e.g. Han Chinese). We found a 47% PFO prevalence in male Tibetans (n = 19) and Han Chinese (n = 19) participants. In participants without a PFO (n = 10 each group), we measured heart structure and function at rest and peak oxygen uptake ( V ̇ O 2 peak ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{peak}}}}$ ), peak power output ( W ̇ p e a k ${{\dot{W}}_{peak}}$ ), pulmonary artery systolic pressure (PASP), blood flow through IPAVA and cardiac output ( Q ̇ T ${{\dot{Q}}_{\mathrm{T}}} $ ) at rest and during recumbent cycle ergometer exercise at 760 Torr (SL) and at 410 Torr (ALT) barometric pressure in a pressure chamber. Tibetans achieved a higher W peak ${W}_{\textit{peak}}$ than Han, and a higher V ̇ O 2 peak ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{peak}}}}$ at ALT without differences in heart rate, stroke volume or Q ̇ T ${{\dot{Q}}_{\mathrm{T}}} $ . Blood flow through IPAVA was generally similar between groups. Increases in PASP and total pulmonary resistance at ALT were comparable between the groups. There were no differences in the slopes of PASP plotted as a function of Q ̇ T ${{\dot{Q}}_{\mathrm{T}}} $ during exercise. In those without PFO, our data indicate that the superior aerobic exercise capacity of Tibetans over Han Chinese is independent of cardiopulmonary features and more probably linked to differences in local muscular oxygen extraction. KEY POINTS: Patent foramen ovale (PFO) prevalence was 47% in Tibetans and Han Chinese living at 2 275 m. Subjects with PFO were excluded from exercise studies. Compared to Han Chinese, Tibetans had a higher peak workload with acute compression to sea level barometric pressure (SL) and acute decompression to 5000 m altitude (ALT). Comprehensive cardiac structure and function at rest were not significantly different between Han Chinese and Tibetans. Tibetans and Han had similar blood flow through intrapulmonary arteriovenous anastomoses (IPAVA) during exercise at SL. Peak pulmonary artery systolic pressure (PASP) and total pulmonary resistance were different between SL and ALT, with significantly increased PASP for Han compared to Tibetans at ALT. No differences were observed between groups at acute SL and ALT.

Blood shifts between body compartments during submaximal exercise with induced expiratory flow limitation in healthy humans.

External expiratory flow limitation (EFLe) can be applied in healthy subjects to mimic the effects of chronic obstructive pulmonary disease during exercise. At maximal exercise intensity, EFLe leads to exercise intolerance owing to respiratory pump dysfunction limiting venous return. We quantified blood shifts between body compartments to determine whether such effects can be observed during submaximal exercise, when the load on the respiratory system is milder. Ten healthy men (25.2 ± 3.2 years of age, 177.3 ± 5.4 cm in height and weighing 67.4 ± 5.8 kg) exercised at 100 W (∼40% of maximal oxygen uptake) while breathing spontaneously (CTRL) or with EFLe. We measured respiratory dynamics with optoelectronic plethysmography, oesophageal (Pes ) and gastric (Pga ) pressures with balloon catheters, and blood shifting between body compartments with double body plethysmography. During exercise, EFLe resulted in the following changes: (i) greater intrabreath blood shifts between the trunk and the extremities [518 ± 221 (EFLe) vs. 224 ± 60 ml (CTRL); P < 0.001] associated with lower Pes during inspiration (r = 0.53, P < 0.001) and higher Pga during expiration (r = 0.29, P < 0.024); and (ii) a progressive pooling of blood in the trunk over time (∼700 ml after 3 min of exercise; P < 0.05), explained by a predominant effect of lower inspiratory Pes (r = 0.54, P < 0.001) over that of increased Pga . It follows that during submaximal exercise, EFLe amplifies the respiratory pump mechanism, with a prevailing contribution from lower inspiratory Pes over increased expiratory Pga , drawing blood into the trunk. Whether these results can be replicated in chronic obstructive pulmonary disease patients remains to be determined. KEY POINTS: External expiratory flow limitation (EFLe) can be applied in healthy subjects to mimic the effects of chronic obstructive pulmonary disease and safely study the mechanisms of exercise intolerance associated with the disease. At maximal exercise intensity with EFLe, exercise intolerance results from high expiratory pressures altering the respiratory pump mechanism and limiting venous return. We used double body plethysmography to quantify blood shifting between the trunk and the extremities and to examine whether the same effects occur with EFLe at submaximal exercise intensity, where the increase in expiratory pressures is milder. Our data show that during submaximal exercise, EFLe amplifies the respiratory pump mechanism, each breath producing greater blood displacements between the trunk and the extremities, with a prevailing effect from lower inspiratory intrathoracic pressure progressively drawing blood into the trunk. These results help us to understand the haemodynamic effects of respiratory pressures during submaximal exercise with expiratory flow restriction.

Both Hypoxia and Hypobaria Impair Baroreflex Sensitivity but through Different Mechanisms.

Baroreflex sensitivity (BRS) is a measure of cardiovagal baroreflex and is lower in normobaric and hypobaric hypoxia compared to normobaric normoxia. The aim of this study was to assess the effects of hypobaria on BRS in normoxia and hypoxia. Continuous blood pressure and ventilation were recorded in eighteen seated participants in normobaric normoxia (NNx), hypobaric normoxia (HNx), normobaric hypoxia (NHx) and hypobaric hypoxia (HHx). Barometric pressure was matched between NNx vs. NHx (723±4 mmHg) and HNx vs. HHx (406±4 vs. 403±5 mmHg). Inspired oxygen pressure (PiO2) was matched between NNx vs. HNx (141.2±0.8 vs. 141.5±1.5 mmHg) and NHx vs. HHx (75.7±0.4 vs. 74.3±1.0 mmHg). BRS was assessed using the sequence method. BRS significantly decreased in HNx, NHx and HHx compared to NNx. Heart rate, mean systolic and diastolic blood pressures did not differ between conditions. There was the specific effect of hypobaria on BRS in normoxia (BRS was lower in HNx than in NNx). The hypoxic and hypobaric effects do not add to each other resulting in comparable BRS decreases in HNx, NHx and HHx. BRS decrease under low barometric pressure requires future studies independently controlling O2 and CO2 to identify central and peripheral chemoreceptors' roles.

Dealing with doping. A plea for better science, governance and education.

The creation of WADA contributed to harmonization of anti-doping and changed doping behavior and prevalence in the past 22 years. However, the system has developed important deficiencies and limitations that are causing harm to sports, athletes and society. These issues are related to the lack of evidence for most substances on the Prohibited List for performance or negative health effects, a lack of transparency and accountability of governance and decision-making by WADA and the extension of anti-doping policies outside the field of professional sports. This article tries to identify these deficiencies and limitations and presents a plea for more science, better governance and more education. This should lead to a discussion for reform among stakeholders, which should cover support of a new Prohibited List by actual research and evidence and introduce better governance with accountable control bodies and regulation. Finally, comprehensive education for all stakeholders will be the basis of all future positive improvements.

Intensity-dependent effects of exercise therapy on walking performance and aerobic fitness in symptomatic patients with lower-extremity peripheral artery disease: A systematic review and meta-analysis.

We investigated how nonpain-based exercise therapy intensity (light-to-moderate or vigorous) affects improvements in walking performance and cardiorespiratory fitness of patients with symptomatic lower-extremity peripheral artery disease (PAD). We searched the Embase, MEDLINE, Cochrane, Web of Science, and Google Scholar databases up to April 2021 and included randomized controlled trials reporting training therapies targeting exercise intensity (heart rate, oxygen consumption, or perceived exertion). The main outcomes were walking performance (pain-free [PFWD] and maximal [MWD] walking distance) and cardiorespiratory fitness (V̇O2peak). Secondary subanalyses examined the training modality (walking or other modalities) and the approach (high-intensity interval or moderate-intensity training). A total of 1132 patients were included. Light-to-moderate was superior to vigorous exercise intensity in improving MWD (223 m [95% CI 174 to 271], p < 0.00001; 153 m [95% CI 113 to 193], p < 0.00001; respectively) and PFWD (130 m [95% CI 87 to 173], p < 0.00001; 83 m [95% CI 61 to 104], p < 0.00001; respectively). When training modalities were considered, walking at a vigorous intensity (272 m [95% CI 207 to 337], p < 0.00001) showed the largest improvement in MWD compared to other exercise modalities. A larger increase in V̇O2peak was observed following vigorous (3.0 mL O2·kg-1·min-1 [95% CI 2.4 to 3.6], p < 0.00001) compared to light-to-moderate (1.1 mL O2·kg-1·min-1 [95% CI 0.4 to 1.7], p = 0.001) exercise intensity. These results indicate that vigorous was less effective than light-to-moderate intensity in improving walking performance, whereas it was more effective in improving V̇O2peak. When the training modalities were considered, walking at a vigorous intensity showed the greatest improvement in MWD. (PROSPERO Registration No.: CRD42020199469).

Priming the cardiodynamic phase of pulmonary oxygen uptake through voluntary modulations of the respiratory pump at the onset of exercise.

NEW FINDINGS: What is the central question of this study? The initial increase in oxygen uptake ( V̇O2 ) at exercise onset results from pulmonary perfusion changes secondary to an increased venous return. Breathing mechanics contribute to venous return through abdominal and intrathoracic pressures variation. Can voluntary breathing techniques (abdominal or rib cage breathing) increase venous return and improve V̇O2 at exercise onset? What is the main finding and its importance? Abdominal and rib cage breathing increase venous return and V̇O2 at exercise onset. This mechanism could be clinically relevant in patients with impaired cardiac function limiting oxygen transport. ABSTRACT: We examined how different breathing patterns can modulate venous return and alveolar gas transfer during exercise transients in humans. Ten healthy men transitioned from rest to moderate cycling while breathing spontaneously (SP) or with voluntary increases in abdominal (AB) or intrathoracic (RC) pressure swings. We used double body plethysmography to determine blood displacements between the trunk and the extremities (Vbs ). From continuous signals of airflow and O2 fraction, we calculated breath-by-breath oxygen uptake at the mouth and used optoelectronic plethysmography to correct for lung O2 store changes and calculate alveolar O2 transfer ( V̇O2A ). Oesophageal (Poes ) and gastric (Pga ) pressures were monitored using balloon-tipped catheters. Cardiac stroke volume was measured using impedance cardiography. During the cardiodynamic phase (Φ1) of V̇O2A -on kinetics (20 s following exercise onset), AB and RC increased total alveolar oxygen transfer compared to SP (227 ± 32, P = 0.019 vs. 235 ± 27, P = 0.001 vs. 206 ± 20 ml, mean ± SD). Pga and Poes swings increased with AB (by 24.4 ± 9.6 cmH2 O, P < 0.001) and RC (by 14.5 ± 5.7 cmH2 O, P < 0.001), respectively. AB yielded a greater increase in intra-breath Vbs swings compared with RC and SP (+0.30 ± 0.14 vs. +0.16 ± 0.11, P < 0.001 vs. +0.10 ± 0.05 ml, P = 0.006) and increased the sum of stroke volumes compared to SP (4.47 ± 1.28 vs. 3.89 ± 0.96 litres, P = 0.053), while RC produced significant central blood translocation from the extremities compared with SP (by 493 ± 311 ml, P < 0.001). Our findings indicate that combining exercise onset with AB or RC increases venous return, thus increasing mass oxygen transport above metabolic consumption during Φ1 and limiting the oxygen deficit incurred.

Respiratory alkalinization and posterior cerebral artery dilatation predict acute mountain sickness severity during 10 h normobaric hypoxia.

NEW FINDINGS: What is the central question of this study? The pathophysiology of acute mountain sickness (AMS), involving the respiratory, renal and cerebrovascular systems, remains poorly understood. How do the early adaptations in these systems during a simulated altitude of 5000 m relate to AMS risk? What is the main finding and its importance? The rate of blood alkalosis and cerebral artery dilatation predict AMS severity during the first 10 h of exposure to a simulated altitude of 5000 m. Slow metabolic compensation by the kidneys of respiratory alkalosis attributable to a brisk breathing response together with excessive brain blood vessel dilatation might be involved in early development of AMS. ABSTRACT: The complex pathophysiology of acute mountain sickness (AMS) remains poorly understood and is likely to involve maladaptive responses of the respiratory, renal and cerebrovascular systems to hypoxia. Using stepwise linear regression, we tested the hypothesis that exacerbated respiratory alkalosis, as a result of a brisk ventilatory response, sluggish renal compensation in acute hypoxia and dysregulation of cerebral perfusion predict AMS severity. We assessed the Lake Louise score (LLS, an index of AMS severity), fluid balance, ventilation, venous pH, bicarbonate, sodium and creatinine concentrations, body weight, urinary pH and cerebral blood flow [internal carotid artery (ICA) and vertebral artery (VA) blood flow and diameter], in 27 healthy individuals (13 women) throughout 10 h exposures to normobaric normoxia (fraction of inspired O2 = 0.21) and normobaric hypoxia (fraction of inspired O2 = 0.117, simulated 5000 m) in a randomized, single-blinded manner. In comparison to normoxia, hypoxia increased the LLS, ventilation, venous and urinary pH, and blood flow and diameter in the ICA and VA, while venous concentrations of both bicarbonate and creatinine were decreased (P < 0.001 for all). There were significant correlations between AMS severity and the rates of change in blood pH, sodium concentration and VA diameter and more positive fluid balance (P < 0.05). Stepwise regression found increased blood pH [beta coefficient (ß) = 0.589, P < 0.001] and VA diameter (ß = 0.418, P = 0.008) to be significant predictors of AMS severity in our cohort [F(2, 20) = 16.1, R2  = 0.617, P < 0.001, n = 24], accounting for 62% of the variance in peak LLS. Using classic regression variable selection, our data implicate the degree of respiratory alkalosis and cerebrovascular dilatation in the early stages of AMS development.

The Muscle-Brain Axis and Neurodegenerative Diseases: The Key Role of Mitochondria in Exercise-Induced Neuroprotection.

Regular exercise is associated with pronounced health benefits. The molecular processes involved in physiological adaptations to exercise are best understood in skeletal muscle. Enhanced mitochondrial functions in muscle are central to exercise-induced adaptations. However, regular exercise also benefits the brain and is a major protective factor against neurodegenerative diseases, such as the most common age-related form of dementia, Alzheimer's disease, or the most common neurodegenerative motor disorder, Parkinson's disease. While there is evidence that exercise induces signalling from skeletal muscle to the brain, the mechanistic understanding of the crosstalk along the muscle-brain axis is incompletely understood. Mitochondria in both organs, however, seem to be central players. Here, we provide an overview on the central role of mitochondria in exercise-induced communication routes from muscle to the brain. These routes include circulating factors, such as myokines, the release of which often depends on mitochondria, and possibly direct mitochondrial transfer. On this basis, we examine the reported effects of different modes of exercise on mitochondrial features and highlight their expected benefits with regard to neurodegeneration prevention or mitigation. In addition, knowledge gaps in our current understanding related to the muscle-brain axis in neurodegenerative diseases are outlined.

Toxic doses of caffeine are needed to increase skeletal muscle contractility.

Discrepant results have been reported regarding an intramuscular mechanism underlying the ergogenic effect of caffeine on neuromuscular function in humans. Here, we reevaluated the effect of caffeine on muscular force production in humans and combined this with measurements of the caffeine dose-response relationship on force and cytosolic free [Ca2+] ([Ca2+]i) in isolated mouse muscle fibers. Twenty-one healthy and physically active men (29 ± 9 yr, 178 ± 6 cm, 73 ± 10 kg, mean ± SD) took part in the present study. Nine participants were involved in two experimental sessions during which supramaximal single and paired electrical stimulations (at 10 and 100 Hz) were applied to the femoral nerve to record evoked forces. Evoked forces were recorded before and 1 h after ingestion of 1) 6 mg caffeine/kg body mass or 2) placebo. Caffeine plasma concentration was measured in 12 participants. In addition, submaximal tetanic force and [Ca2+]i were measured in single mouse flexor digitorum brevis (FDB) muscle fibers exposed to 100 nM up to 5 mM caffeine. Six milligrams of caffeine per kilogram body mass (plasma concentration ~40 µM) did not increase electrically evoked forces in humans. In superfused FDB single fibers, millimolar caffeine concentrations (i.e., 15- to 35-fold above usual concentrations observed in humans) were required to increase tetanic force and [Ca2+]i. Our results suggest that toxic doses of caffeine are required to increase muscle contractility, questioning the purported intramuscular ergogenic effect of caffeine in humans.

Neuromuscular adaptations to wide-pulse high-frequency neuromuscular electrical stimulation training.

PURPOSE: No studies have evaluated the potential benefits of wide-pulse high-frequency (WPHF) neuromuscular electrical stimulation (NMES) despite it being an interesting alternative to conventional NMES. Hence, this study evaluated neuromuscular adaptations induced by 3 weeks of WPHF NMES. METHODS: Ten young healthy individuals (training group) completed nine sessions of WPHF NMES training spread over 3 weeks, whereas seven individuals (control group) only performed the first and last sessions. Plantar flexor neuromuscular function (maximal voluntary contraction (MVC) force, voluntary activation level, H reflex, V wave, contractile properties) was evaluated before the first and last training sessions. Each training session consisted of ten 20-s WPHF NMES contractions (pulse duration: 1 ms, stimulation frequency: 100 Hz) interspaced by 40 s of recovery and delivered at an intensity set to initially evoke ~ 5% of MVC force. The averaged mean evoked forces produced during the ten WPHF NMES-evoked contractions of a given session as well as the sum of the ten contractions force time integral (total FTI) were computed. RESULTS: Total FTI (+ 118 ± 98%) and averaged mean evoked forces (+ 96 ± 91%) increased following the 3-week intervention (p < 0.05); no changes were observed in the control group. The intervention did not induce any change (p > 0.05) in parameters used to characterize plantar flexor neuromuscular function. CONCLUSION: Three weeks of WPHF NMES increased electrically evoked forces but induced no other changes in plantar flexor neuromuscular properties. Before introducing WPHF NMES clinically, optimal training program characteristics (such as frequency, duration and intensity) remain to be identified.

Three weeks of sprint interval training improved high-intensity cycling performance and limited ryanodine receptor modifications in recreationally active human subjects.

PURPOSE: Mechanisms underlying the efficacy of sprint interval training (SIT) remain to be understood. We previously reported that an acute bout of SIT disrupts the integrity of the sarcoplasmic reticulum (SR) Ca2+ release channel, the ryanodine receptor 1 (RyR1), in recreationally active human subjects. We here hypothesize that in addition to improving the exercise performance of recreationally active humans, a period of repeated SIT sessions would make the RyR1 protein less vulnerable and accelerate recovery of contractile function after a SIT session. METHODS: Eight recreationally active males participated in a 3-week SIT program consisting of nine sessions of four-six 30-s all-out cycling bouts with 4 min of rest between bouts. RESULTS: Total work performed during a SIT session and maximal power (Wmax) reached during an incremental cycling test were both increased by ~ 7.5% at the end of the training period (P < 0.05). Western blots performed on vastus lateralis muscle biopsies taken before, 1 h, 24 h and 72 h after SIT sessions in the untrained and trained state showed some protection against SIT-induced reduction of full-length RyR1 protein expression in the trained state. SIT-induced knee extensor force deficits were similar in the untrained and trained states, with a major reduction in voluntary and electrically evoked forces immediately and 1 h after SIT (P < 0.05), and recovery after 24 h. CONCLUSIONS: Three weeks of SIT improves exercise performance and provides some protection against RyR1 modification, whereas it does not accelerate recovery of contractile function.

Test-retest reliability of wide-pulse high-frequency neuromuscular electrical stimulation evoked force.

INTRODUCTION: We compare forces evoked by wide-pulse high-frequency (WPHF) neuromuscular electrical stimulation (NMES) delivered to a nerve trunk versus muscle belly and assess their test-retest intraindividual and interindividual reliability. METHODS: Forces evoked during 2 sessions with WPHF NMES delivered over the tibial nerve trunk and 2 sessions over the triceps surae muscle belly were compared. Ten individuals participated in 4 sessions involving ten 20-s WPHF NMES contractions interspaced by 40-s recovery. Mean evoked force and force time integral of each contraction were quantified. RESULTS: For both nerve trunk and muscle belly stimulation, intraindividual test-retest reliability was good (intraclass correlation coefficient > 0.9), and interindividual variability was large (coefficient of variation between 140% and 180%). Nerve trunk and muscle belly stimulation resulted in similar evoked forces. DISCUSSION: WPHF NMES locations might be chosen by individual preference because intraindividual reliability was relatively good for both locations. Muscle Nerve 57: E70-E77, 2018.

Objectively measured physical activity in population-representative parent-child pairs: parental modelling matters and is context-specific.

BACKGROUND: Evidence for the context-specific influence of parental modelling on physical activity (PA) in childhood remains inconclusive. This nationwide Swiss study assessed the cross-sectional association between objectively measured PA of parents and their children and whether it varied across different levels of sociodemographic and environmental factors. In a second step a structural equation-model (SEM) was used to assess, whether associations between children's PA and sociodemographic and environmental factors are mediated by the parental PA behaviour. METHODS: The population-based sample of the SOPHYA-study consisted of 889 children aged 6 to 16 years living in Switzerland and 1059 parents. PA was measured using accelerometers. Information on sociodemographics, sports behaviour, family characteristics, and perceived environment was obtained by telephone interview and parental questionnaire. Objective environmental data was allocated to each family's residential address using GIS (geographic information system). A structural equation model tested these factors for both independent associations with children's PA and associations mediated through the parental PA behaviour. RESULTS: Parental moderate to vigorous physical activity (MVPA) was associated with MVPA of their children in general (p < 0.001). Correlations between parents' and children's MVPA were stronger for children aged 10-12 years and for those living in the Italian speaking part of Switzerland. An increase of 1 min of mother's and of father's MVPA was associated with 0.24 and 0.21 min more MVPA in children, respectively. Father's PA was associated with that of their sons, but not with that of their daughters, whereas the association of mothers' and children's PA did not depend on the parent-offspring sex-match. The pathway analysis in our structural equation model showed direct effects on children's MVPA as well as indirect effects mediated by the parental PA behaviour. CONCLUSIONS: Parental modelling seems relevant for children's PA, but not to the same degree in all children. Interventions focusing on strengthening parental PA behaviour for the promotion of PA in the young must consider additional contextual factors related to the socio-cultural and structural environment.

Ryanodine receptor fragmentation and sarcoplasmic reticulum Ca2+ leak after one session of high-intensity interval exercise.

High-intensity interval training (HIIT) is a time-efficient way of improving physical performance in healthy subjects and in patients with common chronic diseases, but less so in elite endurance athletes. The mechanisms underlying the effectiveness of HIIT are uncertain. Here, recreationally active human subjects performed highly demanding HIIT consisting of 30-s bouts of all-out cycling with 4-min rest in between bouts (≤3 min total exercise time). Skeletal muscle biopsies taken 24 h after the HIIT exercise showed an extensive fragmentation of the sarcoplasmic reticulum (SR) Ca(2+) release channel, the ryanodine receptor type 1 (RyR1). The HIIT exercise also caused a prolonged force depression and triggered major changes in the expression of genes related to endurance exercise. Subsequent experiments on elite endurance athletes performing the same HIIT exercise showed no RyR1 fragmentation or prolonged changes in the expression of endurance-related genes. Finally, mechanistic experiments performed on isolated mouse muscles exposed to HIIT-mimicking stimulation showed reactive oxygen/nitrogen species (ROS)-dependent RyR1 fragmentation, calpain activation, increased SR Ca(2+) leak at rest, and depressed force production due to impaired SR Ca(2+) release upon stimulation. In conclusion, HIIT exercise induces a ROS-dependent RyR1 fragmentation in muscles of recreationally active subjects, and the resulting changes in muscle fiber Ca(2+)-handling trigger muscular adaptations. However, the same HIIT exercise does not cause RyR1 fragmentation in muscles of elite endurance athletes, which may explain why HIIT is less effective in this group.

Effects of increased participation on veteran running performance.

Contrary to elite performance that is approaching an asymptote, recent analyses suggested a trend for improvement in veterans. This might be attributable to a disproportionate increase in older age-group participation. We extracted 26 years (1987-2012) of men's results of a running event in Switzerland, "La Course de l'Escalade" (7.25 km). We investigated trends in performance by five-year age-groups, taking the 10, 20, 30, and 50 fastest in each group, and then the 1st, 5th, and 10th percentiles. Taking the 10, 20, 30 or 50 fastest runners there was a trend for improvement ranging from 0.07 to 0.22 min·year-1 (p < .0001; 95% CI -0.083 to -0.049 and p < .0001; 95% CI -0.250 to -0.196 respectively) in the elder age-groups. Taking the 1st, 5th, and 10th percentiles there were no trends for improvement, and actual deteriorations up to 0.13 (p < .0001; 95% CI +0.119 to +0.138) min·year-1. Mixed-effect models with repeated measures for runners, confirmed a global deteriorating trend with an estimate of +0.11 min·year-1 (p < .0001; 95% CI +0.107 to +0.116). The results suggest that increases in performance in older runners arise from modifications of sampling from a growing population.

Ethics of a relaxed antidoping rule accompanied by harm-reduction measures.

Harm-reduction approaches are used to reduce the burden of risky human behaviour without necessarily aiming to stop the behaviour. We discuss what an introduction of harm reduction for doping in sports would mean in parallel with a relaxation of the antidoping rule. We analyse what is ethically at stake in the following five levels: (1) What would it mean for the athlete (the self)? (2) How would it impact other athletes (the other)? (3) How would it affect the phenomenon of sport as a game and its fair play basis (the play)? (4) What would be the consequences for the spectator and the role of sports in society (the display)? and (5) What would it mean for what some consider as essential to being human (humanity)? For each level, we present arguments for and against doping and then discuss what a harm-reduction approach, within a dynamic regime of a partially relaxed antidoping rule, could imply. We find that a harm-reduction approach is morally defensible and potentially provides a viable escape out of the impasse resulting from the impossibility of attaining the eradication of doping. The following question remains to be answered: Would a more relaxed position, when combined with harm-reduction measures, indeed have less negative consequences for society than today's all-out antidoping efforts that aim for abstinence? We provide an outline of an alternative policy, allowing a cautious step-wise change to answer this question and then discuss the ethical aspects of such a policy change.

Does This Patient Have Acute Mountain Sickness?: The Rational Clinical Examination Systematic Review.

Importance: Acute mountain sickness (AMS) affects more than 25% of individuals ascending to 3500 m (11 500 ft) and more than 50% of those above 6000 m (19 700 ft). AMS may progress from nonspecific symptoms to life-threatening high-altitude cerebral edema in less than 1% of patients. It is not clear how to best diagnose AMS. Objective: To systematically review studies assessing the accuracy of AMS diagnostic instruments, including the visual analog scale (VAS) score, which quantifies the overall feeling of sickness at altitude (VAS[O]; various thresholds), Acute Mountain Sickness-Cerebral score (AMS-C; ≥0.7 indicates AMS), and the clinical functional score (CFS; ≥2 indicates AMS) compared with the Lake Louise Questionnaire Score (LLQS; score of ≥5). Data Extraction and Synthesis: Searches of MEDLINE and EMBASE from inception to May 2017 identified 1245 publications of which 91 were suitable for prevalence analysis (66 944 participants) and 14 compared at least 2 instruments (1858 participants) using a score of 5 or greater on the LLQS as a reference standard. To determine the prevalence of AMS for establishing the pretest probability of AMS, a random-effects meta-regression was performed based on the reported prevalence of AMS as a function of altitude. Main Outcomes and Measures: AMS prevalence, likelihood ratios (LRs), sensitivity, and specificity of screening instruments. Results: The final analysis included 91 articles (comprising 66 944 study participants). Altitude predicted AMS and accounted for 28% of heterogeneity between studies. For each 1000-m (3300-ft) increase in altitude above 2500 m (8200 ft), AMS prevalence increased 13% (95% CI, 9.5%-17%). Testing characteristics were similar for VAS(O), AMS-C, and CFS vs a score of 5 or greater on the LLQS (positive LRs: range, 3.2-8.2; P = .22 for comparisons; specificity range, 67%-92%; negative LRs: range, 0.30-0.36; P = .50 for comparisons; sensitivity range, 67%-82%). The CFS asks a single question: "overall if you had any symptoms, how did they affect your activity (ordinal scale 0-3)?" For CFS, moderate to severe reduction in daily activities had a positive LR of 3.2 (95% CI, 1.4-7.2) and specificity of 67% (95% CI, 37%-97%); no reduction to mild reduction in activities had a negative LR of 0.30 (95% CI, 0.22-0.39) and sensitivity of 82% (95% CI, 77%-87%). Conclusions and Relevance: The prevalence of acute mountain sickness increases with higher altitudes. The visual analog scale for the overall feeling of sickness at altitude, Acute Mountain Sickness-Cerebral, and clinical functional score perform similarly to the Lake Louise Questionnaire Score using a score of 5 or greater as a reference standard. In clinical and travel settings, the clinical functional score is the simplest instrument to use. Clinicians evaluating high-altitude travelers who report moderate to severe limitations in activities of daily living (clinical functional score ≥2) should use the Lake Louise Questionnaire Score to assess the severity of acute mountain sickness.

Optimal slopes and speeds in uphill ski mountaineering: a laboratory study.

PURPOSE: The purpose of this study was to estimate the energy cost of linear (EC) and vertical displacement (ECvert), mechanical efficiency and main stride parameters during simulated ski mountaineering at different speeds and gradients, to identify an optimal speed and gradient that maximizes performance. METHODS: 12 subjects roller skied on a treadmill at three different inclines (10, 17 and 24 %) at three different speeds (approximately 70, 80 and 85 % of estimated peak heart rate). Energy expenditure was calculated by indirect calorimetry, while biomechanical parameters were measured with an inertial sensor-based system. RESULTS: At 10 % there was no significant change with speed in EC, ECvert and mechanical efficiency. At 17 and 24 % the fastest speed was significantly more economical. There was a significant effect of gradient on EC, ECvert and mechanical efficiency. The most economical gradient was the steepest one. There was a significant increase of stride frequency with speed. At steep gradients only, relative thrust phase duration decreased significantly, while stride length increased significantly with speed. There was a significant effect of gradient on stride length (decrease with steepness) and relative thrust phase duration (increase with steepness). CONCLUSION: A combination of a decreased relative thrust phase duration with increased stride length and frequency decreases ECvert. To minimize the energy expenditure to reach the top of a mountain and to optimize performance, ski-mountaineers should choose a steep gradient (~24 %) and, provided they possess sufficient metabolic scope, combine it with a fast speed (~6 km h(-1)).

Optimal slopes and speeds in uphill ski mountaineering: a field study.

PURPOSE: The aim of this study is to describe the effects of speed and gradient during uphill ski mountaineering on energy expenditure, to relate any changes to changes in stride characteristics, and to determine an optimal gradient and speed allowing minimization of energy expenditure. METHODS: 11 subjects were tested on snowy trails using their mountaineering skis (fitted with skins), boots and poles, at three gradients (7, 11 and 33 %) at 80 % of maximum heart rate (HRmax), and at 11 % also at 90 and 100 % of HRmax. Energy expenditure was calculated by indirect calorimetry to derive energy cost of locomotion (EC), vertical energy cost (ECvert) and mechanical efficiency, while stride length, stride frequency, relative and absolute thrust phase duration, and slope gradient were measured with an inertial sensor-based system. RESULTS: At 11 % there was no change with speed in EC, ECvert and mechanical efficiency, while stride length and frequency increased and absolute thrust phase duration decreased. There was an effect of gradient on EC, ECvert and mechanical efficiency, while speed, stride length and stride frequency decreased and absolute and relative thrust phase duration increased. The most economical gradient (lowest ECvert) was the steepest one. CONCLUSION: During ski mountaineering uphill at shallow gradient (11 %), EC, ECvert and mechanical efficiency do not vary with speed, while at steeper gradient (33 %) economy is improved. It follows that to minimize energy expenditure and optimize performance to reach a place located at a higher altitude, an athlete should choose a steep gradient, if he/she is able to maintain a sufficient speed.