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Abstract Objective To assess the effectiveness of an exercise intervention, in addition to standard care, in preventing or delaying insulin prescription in women with gestational diabetes mellitus (GDM). Design Randomised controlled trial. Setting University hospital. Population Pregnant women at 25–35 weeks of gestation diagnosed with GDM. Methods Women in the intervention group participated in weekly, supervised, 30–45 min exercise sessions and were encouraged to accumulate more than 5000 steps per day, tracked by a pedometer, in addition to receiving usual care. The control group received standard care only. Main outcome measure Insulin prescription. Results From February 2008 through April 2013, 109 women were randomized into the intervention group (n = 57) or the usual care group (n = 52). Two women in the intervention group were excluded from the analysis (one was randomised in error and one was lost to follow-up). Six women never attended the exercise sessions, and two attended fewer than two sessions. However, two-third of women were considered as compliant to the intervention (attended more than 50% of sessions and/or averaged more than 5000 steps/day). The incidence of insulin prescription did not differ between the groups: 31 women (56%) in the intervention group versus 24 women (46%) in the control group (RR 1.22, 95% CI 0.84 to 1.78). The median time from randomization to insulin prescription was also similar between groups (14 days in the intervention group and 13 days in the control group). Conclusion This study did not demonstrate that an exercise program reduces or delays insulin prescription in women with GDM. Low adherence to the intervention, a small sample size, and the short duration of the program may explain the lack of observed benefit. Registered At clinicaltrials.gov, NCT03174340, 02/06/2017

Objective: The contribution of the mitochondrial electron transfer system to insulin secretion involves more than just energy provision. We identified a small RNA fragment (mt-tRF-LeuTAA) derived from the cleavage of a mitochondrially-encoded tRNA that is conserved between mice and humans. The role of mitochondrially-encoded tRNA-derived fragments remains unknown. This study aimed to characterize the impact of mt-tRF-LeuTAA, on mitochondrial metabolism and pancreatic islet functions. Methods: We used antisense oligonucleotides to reduce mt-tRF-LeuTAA levels in primary rat and human islet cells, as well as in insulin-secreting cell lines. We performed a joint transcriptome and proteome analysis upon mt-tRF-LeuTAA inhibition. Additionally, we employed pull-down assays followed by mass spectrometry to identify direct interactors of the fragment. Finally, we characterized the impact of mt-tRF-LeuTAA silencing on the coupling between mitochondrial metabolism and insulin secretion using high-resolution respirometry and insulin secretion assays. Results: Our study unveils a modulation of mt-tRF-LeuTAA levels in pancreatic islets in different Type 2 diabetes models and in response to changes in nutritional status. The level of the fragment is finely tuned by the mechanistic target of rapamycin complex 1. Located within mitochondria, mt-tRF-LeuTAA interacts with core subunits and assembly factors of respiratory complexes of the electron transfer system. Silencing of mt-tRF-LeuTAA in islet cells limits the inner mitochondrial membrane potential and impairs mitochondrial oxidative phosphorylation, predominantly by affecting the Succinate (via Complex II)-linked electron transfer pathway. Lowering mt-tRF-LeuTAA impairs insulin secretion of rat and human pancreatic β-cells. Conclusions: Our findings indicate that mt-tRF-LeuTAA interacts with electron transfer system complexes and is a pivotal regulator of mitochondrial oxidative phosphorylation and its coupling to insulin secretion.

Mitochondrial respiration extends beyond ATP generation, with the organelle participating in many cellular and physiological processes. Parallel changes in components of the mitochondrial electron transfer system with respiration render it an appropriate hub for coordinating cellular adaption to changes in oxygen levels. How changes in respiration under functional hypoxia (i.e., when intracellular O2 levels limit mitochondrial respiration) are relayed by the electron transfer system to impact mitochondrial adaption and remodeling after hypoxic exposure remains poorly defined. This is largely due to challenges integrating findings under controlled and defined O2 levels in studies connecting functions of isolated mitochondria to humans during physical exercise. Here we present experiments under conditions of hypoxia in isolated mitochondria, myotubes and exercising humans. Performing steady-state respirometry with isolated mitochondria we found that oxygen limitation of respiration reduced electron flow and oxidative phosphorylation, lowered the mitochondrial membrane potential difference, and decreased mitochondrial calcium influx. Similarly, in myotubes under functional hypoxia mitochondrial calcium uptake decreased in response to sarcoplasmic reticulum calcium release for contraction. In both myotubes and human skeletal muscle this blunted mitochondrial adaptive responses and remodeling upon contractions. Our results suggest that by regulating calcium uptake the mitochondrial electron transfer system is a hub for coordinating cellular adaption under functional hypoxia.

Abstract Background Decreased ryanodine receptor type 1 (RyR1) protein levels are a well‐described feature of recessive RYR1‐related myopathies. The aim of the present study was twofold: (1) to determine whether RyR1 content is also decreased in other myopathies and (2) to investigate the mechanisms by which decreased RyR1 protein triggers muscular disorders. Methods We used publicly available datasets, muscles from human inflammatory and mitochondrial myopathies, an inducible muscle‐specific RYR1 recessive mouse model and RyR1 knockdown in C2C12 muscle cells to measure RyR1 content and endoplasmic reticulum (ER) stress markers. Proteomics, lipidomics, molecular biology and transmission electron microscopy approaches were used to decipher the alterations associated with the reduction of RyR1 protein levels. Results RYR1 transcripts were reduced in muscle samples of patients suffering from necrotizing myopathy (P = 0.026), inclusion body myopathy (P = 0.003), polymyositis (P

Objectives: This study aims to quantify the cross-sectional and prospective associations between quality of life (QoL) and moderate-to-vigorous physical activity (MVPA).Methods: This study was based on the Swiss children’s Objectively measured PHYsical Activity cohort. The primary endpoint is the overall QoL score and its six dimensions. The main predictor is the average time spent in MVPA per day. Linear mixed effects and linear regression models respectively were used to investigate the cross-sectional and prospective associations between MVPA and QoL.Results: There were 352 participants in the study with complete data from baseline (2013–2015) and follow-up (2019). MVPA was positively associated with overall QoL and physical wellbeing (p = 0.023 and 0.002 respectively). The between-subject MVPA was positively associated with the overall QoL, physical wellbeing, and social wellbeing (p = 0.030, 0.017, and 0.028 respectively). Within-subject MVPA was positively associated with physical wellbeing and functioning at school (p = 0.039 and 0.013 respectively). Baseline MVPA was not associated with QoL 5 years later.Conclusion: Future longitudinal studies should employ shorter follow-up times and repeat measurements to assess the PA and QoL association.

Introduction Athletes increasingly engage in repeated sprint training that consists of repeated short all-out effort (< 10 s) interspersed by short recoveries (< 60 s). When performed in hypoxia (repeated sprints in hypoxia, RSH), it may lead to greater training effect than in normoxia (RSN). However, the mechanisms underlying this superior training effect of RSH are unclear. Specifically, the role of muscle metabolic response to RSH is still debated and results are heterogeneous. Clarifying the molecular pathways of skeletal muscle adaptations to RSH may thus provide new insights into the role of hypoxia-induced response to training. Methods Two groups of healthy young men (randomized) performed three training sessions/week for three weeks. Each training session consisted in six series of six sprints (6 s effort/24 s rest) in either normoxia (RSN, n = 7) or normobaric hypoxia (FiO2 = ~13%, RSH, n = 9). Before and after the training period, vastus lateralis muscle biopsies, a repeated sprint ability (RSA) test and a Wingate test were performed. Metabolic muscle adaptations were studied with proteomics and western blotting. Results RSN and RSH similarly improved power output (p < 0.05) during the RSA test (RSN: + 7.2 ± 7.7% vs. RSH: + 7.9 ± 6.6%) and the Wingate test (RSN: + 1.3 ± 3.6% vs. RSH: + 4.4 ± 5.0%). Proteomics revealed a decrease in several processes involved in oxidative phosphorylation, confirmed by Western Blot with a reduction (p < 0.05) in complexes I (- 19 ± 30%) and V (- 15 ± 24%) protein levels in response to both RSN and RSH. RSN and RSH increased (p < 0.05) protein levels of the hypoxia inducible factor 1α (HIF-1α, + 111 ± 50%) and vascular endothelial growth factor A (VEGFa, + 91 ± 60%). Protein levels of the glycolytic enzyme hexokinase II increased (+ 119 ± 183%, p < 0.05) after both training types. Only RSH induced increased glucose transporter 4 (GLUT4, + 31 ± 18%, p < 0.05) protein level, suggesting specific glycolytic adaptations in response to hypoxia, supported by proteomics data. This specific adaptation may be triggered through the signaling of S100A protein family as we observed an increased S100A13 protein level (+ 467 ± 353%, p < 0.05) and Akt phosphorylation (+ 21 ± 21%, time x group interaction, p < 0.05) as well as several other S100A proteins in proteomics only after RSH training. Discussion/Conclusion To conclude, RSH did not exhibit in greater performance improvement compared to RSN. However, it further improved the glycolytic phenotype compared to RSN, possibly through specific S100A13 proteins signaling. Thus, we suggest that the reported superiority of RSH to RSN in the literature may stem from superior glycolytic adaptations triggered through the activation of a specific pathway involving S100A13 protein. The potential role of S100A13 protein in skeletal muscle adaptative responses to exercise is novel and the present results open new research perspectives in this field.

IntroductionQuality of life (QoL) is an important health indicator among children and adolescents. Evidence on the effect of physical activity (PA)-related behaviors on QoL among youth remains inconsistent. Conventional accelerometer-derived PA metrics and guidelines with a focus on whole weeks may not adequately characterize QoL relevant PA behavior.ObjectiveThis study aims to a) identify clusters of accelerometer-derived PA profiles during weekend days among children and adolescents living in Switzerland, b) assess their cross-sectional and predictive association with overall QoL and its dimensions, and c) investigate whether the associations of QoL with the newly identified clusters persist upon adjustment for the commonly used PA metrics moderate-to-vigorous physical activity (MVPA) and time spent in sedentary behavior (SB).MethodsThe population-based Swiss children's Objectively measured PHYsical Activity (SOPHYA) cohort among children and adolescents aged 6 to 16 years was initiated at baseline in 2013. PA and QoL information was obtained twice over a five-year follow-up period. The primary endpoint is the overall QoL score and its six dimension scores obtained by KINDL® questionnaire. The primary predictor is the cluster membership of accelerometer-derived weekend PA profile. Clusters were obtained by applying the k-medoid algorithm to the distance matrix of profiles obtained by pairwise alignments of PA time series using the Dynamic Time Warping (DTW) algorithm. Secondary predictors are accelerometer-derived conventional PA metrics MVPA and SB from two combined weekend days. Linear regression models were applied to assess a) the cross-sectional association between PA cluster membership and QoL at baseline and b) the predictive association between PA cluster membership at baseline and QoL at follow-up, adjusting for baseline QoL.ResultsThe study sample for deriving PA profile clusters consisted of 51.4% girls and had an average age of 10.9 [SD 2.5] years). The elbow and silhouette methods indicated that weekend PA profiles are best classified in two or four clusters. The most differentiating characteristic for the two-clusters classification ("lower activity" and "high activity"), and the four-clusters classification ("inactive", "low activity", "medium activity", and "high activity"), respectively was the participant's mean counts per 15-seconds epoch. Participants assigned to high activity clusters were younger and more often male. Neither the clustered PA profiles nor MVPA or SB were cross-sectionally or predictively associated with overall QoL. The only association of a conventional PA metrics with QoL while adjusting for cluster membership was observed between MVPA during the weekend days and social well-being with a mean score difference of 2.4 (95%CI: 0.3 to 4.5; p = 0.025).ConclusionThe absence of strong associations of PA metrics for the weekend with QoL, except for the positive association between MVPA during the weekend days and social well-being, is in line with results from two randomized studies not showing efficacy of PA interventions on youth QoL. But because PA decreases with age, its promotion and relevance to QoL remain important research topics. Larger longitudinal study samples with more than two follow-up time points of children and adolescents are needed to derive new novel accelerometer-derived PA profiles and to associate them with QoL dimensions.

Introduction Neuromuscular electrical stimulation (NMES) is used in athletes to enhance muscle strength (Filipovic et al., 2012) or in patients to restore muscle strength (Nussbaum et al., 2017). The increased maximal voluntary contraction (MVC) torque of one limb (e.g. right leg) while transcutaneous NMES is concomitantly applied to the contralateral limb (e.g. left leg) has been termed contralateral facilitation. This effect has previously been reported for the knee extensors (Cattagni et al., 2018; Minetto et al., 2018) but the underlying mechanisms remain to be investigated. It is also not known whether or not other muscle groups may show contralateral facilitation. The aim of this study was to compare plantar flexor contralateral facilitation between a submaximal voluntary contraction (~10% MVC torque) and two evoked contractions with presumably distinct motor unit recruitment patterns (conventional and wide-pulse high-frequency [WPHF] NMES; Bergquist et al., 2011) of the ipsilateral plantar flexors, with respect to a resting condition. Methods Twenty-two healthy volunteers (4 women: mean ± SD, 26 ±4 yrs, 162 ±7 cm, 65 ±9 kg and 18 men: 26 ±6 yrs, 180 ±5 cm, 76 ±6 kg) took part to the experiments. Contralateral MVC torque and maximal voluntary activation level were measured in 4 different conditions: while the ipsilateral plantar flexors were at rest, voluntarily contracted at 10% of MVC torque or stimulated with conventional (0.1 ms, 30 Hz) and wide-pulse high frequency (1 ms, 100 Hz) NMES for 15 s at a pre-determined intensity to evoke 10% of MVC torque. Additional neurophysiological parameters (soleus H-reflex and V-wave amplitude and tibialis anterior coactivation level) were quantified in a subgroup of 12 participants (4 women and 8 men). Results Conventional and WPHF NMES of the ipsilateral plantar flexors did not induce any contralateral facilitation of MVC torque with respect to the resting condition (respectively: mean ± SD, 133 ±44, 133 ±43 and 135 ±39 Nm) as well as maximal voluntary activation level, while an ipsilateral voluntary contraction of the same intensity resulted in lower contralateral strength than conventional NMES. Moreover, no alteration in the neurophysiological parameters was observed in the different conditions. Discussion/Conclusion The absence of contralateral facilitation contrasts with the results obtained on the knee extensors and can be attributed to the absence of neural changes observed on the contralateral side. These findings should be considered by clinicians/researchers in lower limb rehabilitation settings, as it seems easier to induce contralateral facilitation in proximal vs. distal lower limbs. References Bergquist, A. J., Clair, J. M., Lagerquist, O., Mang, C. S., Okuma, Y., & Collins, D. F. (2011). Neuromuscular electrical stimulation: Implications of the electrically evoked sensory volley. European Journal of Applied Physiology, 111, 2409–2426. https://doi.org/10.1007/s00421-011-2087-9 Cattagni, T., Lepers, R., & Maffiuletti, N. A. (2018). Effects of neuromuscular electrical stimulation on contralateral quadriceps function. Journal of Electromyography and Kinesiology, 38, 111-118. https://doi.org/10.1016/j.jelekin.2017.11.013 Filipovic, A., Kleinöder, H., Dörmann, U., & Mester, J. (2012). Electromyostimulation: A systematic review of the effects of different electromyostimulation methods on selected strength parameters in trained and elite athletes. Journal of Strength and Conditioning Research, 26(9), 2600-2614. https://doi.org/10.1519/JSC.0b013e31823f2cd1 Minetto, M., Botter, A., Gamerro, G., Varvello, I., Massazza, G., Bellomo, R., Maffiuletti, N., & Saggini, R. (2018). Contralateral effect of short-duration unilateral neuromuscular electrical stimulation and focal vibration in healthy subjects. European Journal of Physical and Rehabilitation Medicine, 54(6), 911-920. Nussbaum, E., Houghton, P., Anthony, J., Rennie, S., Shay, B., & Hoens, A. (2017). Neuromuscular electrical stimulation for treatment of muscle impairment: Critical review and recommendations for clinical practice. Physiotherapy Canada, 69(5), 1-76. https://doi.org/10.3138/ptc.2015-88

Abstract Background Prehabilitation may improve postoperative clinical outcomes among patients undergoing major abdominal surgery. This study evaluated the potential effects of a high-intensity interval training (HIIT) program performed before major abdominal surgery on patients’ cardiorespiratory fitness and functional ability (secondary outcomes of pilot trial NCT02953119). Methods Patients were included before surgery to engage in a low-volume HIIT program with 3 sessions per week for 3 weeks. Cardiopulmonary exercise and 6-min walk (6MWT) testing were performed pre- and post-prehabilitation. Results Fourteen patients completed an average of 8.6 ± 2.2 (mean ± SD) sessions during a period of 27.9 ± 6.1 days. After the program, $$\dot{\mathrm{V}}$$ V ˙ O2 peak (+ 2.4 ml min−1 kg−1, 95% CI 0.8–3.9, p = 0.006), maximal aerobic power (+ 16.8 W, 95% CI 8.2–25.3, p = 0.001), $$\dot{\mathrm{V}}$$ V ˙ O2 at anaerobic threshold (+ 1.2 ml min−1 kg−1, 95%CI 0.4–2.1, p = 0.009) and power at anaerobic threshold (+ 12.4 W, 95%CI 4.8–20, p = 0.004) were improved. These changes were not accompanied by improved functional capacity (6MWT: + 2.6 m, 95% CI (− 19.6) to 24.8, p = 0.800). Conclusion A short low-volume HIIT program increases cardiorespiratory fitness but not walking capacity in patients scheduled for major abdominal surgery. These results need to be confirmed by larger studies.

Ryanodine receptor type 1 (RyR1) are involved in skeletal muscle contraction. Here, the authors show that a transient calcium leak in response to exercise-induced post translational modifications of RyR1 causes mitochondrial remodeling to improve respiration.

BACKGROUND: Objective mobility goals for elderly hospitalised medical patients remain debated. We therefore studied steps parameters of elderly patients hospitalised for an acute illness, to determine goals for future interventional trials and medical practice. METHODS: Observational study conducted from February to November 2018 in a medical ward of the Lausanne University Hospital, Switzerland. We measured the step parameters of consecutive medical patients aged ≥65 years admitted for an acute medical illness using a wrist accelerometer (Geneactiv). We also collected demographic, somatic and functional factors. RESULTS: Overall, 187 inpatients had their step parameters (daily step count, walking cadence and bout duration) measured with accelerometers worn for a mean of 3.6 days (standard deviation [SD] 3.2). Elderly inpatients (81.5 years, SD 8.5) walked a median of 603 steps daily (interquartile range [IQR] 456–809), at a median cadence of 100 steps/minute (IQR 99–101) with median walking bouts of 33 seconds (IQR 27–37) and with 70% of the walking bouts lasting less than 30 seconds. Patients walking ≥600 steps were younger (80.4 years, SD 8.9 vs 82.8 years,SD 7.9, p = 0.050) and had a longer length of stay (7.8 days, SD 5.1 vs 6.1 days, SD 4.1, p = 0.011) than those walking

Abstract The effectiveness of neuromuscular electrical stimulation (NMES) for rehabilitation is proportional to the evoked torque. The progressive increase in torque (extra torque) that may develop in response to low intensity wide-pulse high-frequency (WPHF) NMES holds great promise for rehabilitation as it overcomes the main limitation of NMES, namely discomfort. WPHF NMES extra torque is thought to result from reflexively recruited motor units at the spinal level. However, whether WPHF NMES evoked force can be modulated is unknown. Therefore, we examined the effect of two interventions known to change the state of spinal circuitry in opposite ways on evoked torque and motor unit recruitment by WPHF NMES. The interventions were high-frequency transcutaneous electrical nerve stimulation (TENS) and anodal transcutaneous spinal direct current stimulation (tsDCS). We show that TENS performed before a bout of WPHF NMES results in lower evoked torque (median change in torque time-integral: − 56%) indicating that WPHF NMES-evoked torque might be modulated. In contrast, the anodal tsDCS protocol used had no effect on any measured parameter. Our results demonstrate that WPHF NMES extra torque can be modulated and although the TENS intervention blunted extra torque production, the finding that central contribution to WPHF NMES-evoked torques can be modulated opens new avenues for designing interventions to enhance WPHF NMES.

Organized biannually in the Swiss Alps since 1984, the “Patrouille des Glaciers” (PDG) is one of the most challenging long-distance ski mountaineering (skimo) team competitions in the world. The race begins in Zermatt (1,616 m) and ends in Verbier (1,520 m), covering a total distance of 53 km with a cumulated 4,386 m of ascent and 4,482 m of descent. About 4,800 athletes take part in this competition, in teams of three. We hereby present the performance analysis of the uphill parts of this race of a member (#1) of the winning team in 2018, setting a new race record at 5 h and 35 min, in comparison with two amateur athletes. The athletes were equipped with the Global Navigation Satellite System (GNSS) antenna, a heart rate monitor, and a dedicated multisensor inertial measurement unit (IMU) attached to a ski, which recorded spatial-temporal gait parameters and transition events. The athletes' GNSS and heart rate data were synchronized with the IMU data. Athlete #1 had a baseline VO2 max of 80 ml/min/kg, a maximum heart rate of 205 bpm, weighed 69 kg, and had a body mass index (BMI) of 21.3 kg/m2. During the race, he carried 6 kg of gear and kept his heart rate constant around 85% of max. Spatiotemporal parameters analysis highlighted his ability to sustain higher power, higher pace, and, thus, higher vertical velocity than the other athletes. He made longer steps by gliding longer at each step and performed less kick turns in a shorter time. He spent only a cumulative 5 min and 30 s during skins on and off transitions. Skimo performance, thus, requires a high aerobic power of which a high fraction can be maintained for a prolonged time. Our results further confirm earlier observations that speed of ascent during endurance skimo competitions is a function of body weight and race gear and vertical energy cost of locomotion, with the latter function of climbing gradient. It is also the first study to provide some reference benchmarks for spatiotemporal parameters of elite and amateur skimo athletes during climbing using real-world data.

BACKGROUND: The COVID-19 pandemic and the resulting containment measures had and still have a profound impact on everyday life. Both the fear of infection and the imposed restrictions can have biopsychosocial consequences. The aim of the present study was to analyze whether there is a difference in the health-related quality of life (HRQoL) of primary school children in 2014/15 compared to in 2020, the first year of the COVID-19 pandemic. METHODS: The present study included 1,712 children aged 5 to 11 years who either participated in the baseline assessment of the SOPHYA cohort study in 2014/15 or were newly recruited during follow-up of the cohort in 2020. In both surveys, the children invited for participation were identified based on registry data. HRQoL was assessed with the validated KINDL-R questionnaire, which scores HRQoL along six different dimensions. RESULTS: The overall scores (82.4 [81.8; 83.0] vs. 79.6 [79,1; 80.2]), and in particular the emotional well-being scores (85.6 [84.6; 86.6] vs. 83.3 [82.4; 84.2]), were lower during the year of the pandemic (2020) compared to the survey year 2014/15. The highest decrease between 2014/15 and 2020 in the adjusted models was seen for the youngest age group (–3.9 points), followed by children from families with a high income (–3.2 points), girls (–3.1 points), Swiss citizens (–3.1 points) and children from the German-speaking part of Switzerland (–3.1 points). HRQoL was particularly low during periods with restrictions and at the height of the COVID-19 waves in 2020. CONCLUSION: The SOPHYA-study showed that HRQoL, and especially emotional well-being, was lower in 5 to 11-year-old children in Switzerland during the first year of the pandemic compared to the results from the survey conducted in 2014/15. In the year of the pandemic, the scores were lowest at the height of the COVID-19 waves and their associated restrictions. As it cannot be distinguished whether fear of the disease itself or the restrictions caused this decrease in HRQoL, containment policies should keep COVID-19 infections as low as possible, but still enable children to profit from protective factors such as leisure activities, physical activity and social contact.

Objective To assess the feasibility of a prehabilitation program and its effects on physical performance and outcomes after major abdominal surgery. Methods In this prospective pilot study, patients underwent prehabilitation involving three training sessions per week for 3 weeks preoperatively. The feasibility of delivering the intervention was assessed based on recruitment and adherence to the program. Its impacts on fitness (oxygen uptake (VO 2 )) and physical performance (Timed Up and Go Test, 6-Minute Walk Test) were evaluated. Results From May 2017 to January 2020, 980 patients were identified and 44 (4.5%) were invited to participate. The main obstacles to patient recruitment were insufficient time (

Contralateral facilitation, i.e., the increase in contralateral maximal voluntary strength that is observed when neuromuscular electrical stimulation (NMES) is applied to the ipsilateral homonymous muscle, has previously been reported for the knee extensors but the neurophysiological mechanisms remain to be investigated. The aim of this study was to compare plantar flexor contralateral facilitation between a submaximal voluntary contraction (~10% MVC torque) and two evoked contractions (conventional and wide-pulse high-frequency NMES) of the ipsilateral plantar flexors, with respect to a resting condition. Contralateral MVC torque and voluntary activation level were measured in 22 healthy participants while the ipsilateral plantar flexors were at rest, voluntarily contracted or stimulated for 15 s. Additional neurophysiological parameters (soleus H-reflex and V-wave amplitude and tibialis anterior coactivation level) were quantified in a subgroup of 12 participants. Conventional and wide-pulse high-frequency NMES of the ipsilateral plantar flexors did not induce any contralateral facilitation of maximal voluntary strength and activation with respect to the resting condition. Similarly, no alteration of neurophysiological parameters was observed in the different conditions. This absence of contralateral facilitation contrasts with some results previously obtained on the knee extensors but is consistent with the absence of neurophysiological changes on the contralateral soleus.

Objectives: We tested the hypotheses that respiratory muscle endurance training (RMET) improves endurance cycling performance differently in women and men and more so in hypoxia than in normoxia.Design: A prospective pre–post cross-over study with two testing conditions.Methods: Healthy and active women (seven, 24 ± 4 years, mean ± standard deviation [SD]) and men (seven, 27 ± 5 years) performed incremental cycling to determine maximum oxygen consumption (VO2peak) and power output (Wpeak) and on different days two 10-km cycling time trials (TTs) in normoxia and normobaric hypoxia (FiO2, 0.135, ~3,500 m equivalent), in a balanced randomized order. Next they performed supervised RMET in normoxia (4 weeks, 5 days/week, 30 min/day eucapnic hyperpnea at ~60% predicted maximum voluntary ventilation) followed by identical post-tests. During TTs, heart rate, ear oximetry reading, and Wpeak were recorded.Results: The VO2peak and Wpeak values were unchanged after RMET. The TT was improved by 7 ± 6% (p < 0.001) in normoxia and 16 ± 6% (p < 0.001) in hypoxia. The difference between normoxic and hypoxic TT was smaller after RMET as compared with that before RMET (14% vs. 21%, respectively, p < 0.001). All effects were greater in women (p < 0.001). The RMET did not change the heart rate or ear oximetry reading during TTs.Conclusion: We found a greater effect of RMET on cycling TT performance in women than in men, an effect more pronounced in hypoxia. These findings are congruent with the contention of a more pronounced performance-limiting role of the respiratory system during endurance exercise in hypoxia compared with normoxia and more so in women whose respiratory system is undersized compared with that of men.

The Wim Hof breathing method (WHBM) combines periods of hyperventilation (HV) followed by voluntary breath-holds (BH) at low lung volume. It has been increasingly adopted by coaches and their athletes to improve performance, but there was no published research on its effects. We determined the feasibility of implementing a single WHBM session before repeated sprinting performance and evaluated any acute ergogenic effects. Fifteen amateur runners performed a single WHBM session prior to a Repeated Ability Sprint Test (RAST) in comparison to voluntary HV or spontaneous breathing (SB) (control) in a randomized cross-over design. Gas exchange, heart rate, and finger pulse oxygen saturation (SpO2) were monitored. Despite large physiological effects in the SpO2 and expired carbon dioxide (VCO2) levels of both HV and WHBM, no significant positive or negative condition effects were found on RAST peak power, average power, or fatigue index. Finger SpO2 dropped to 60 ± 12% at the end of the BHs. Upon the last HV in the WHBM and HV conditions, end-tidal CO2 partial pressure (PETCO2) values were 19 ± 3 and 17 ± 3 mmHg, indicative of respiratory alkalosis with estimated arterial pH increases of +0.171 and of +0.181, respectively. Upon completion of RAST, 8 min cumulated expired carbon dioxide volumes in the WHBM and HV were greater than in SB, suggesting lingering carbon dioxide stores depletion. These findings indicate that despite large physiological effects, a single WHBM session does not improve anaerobic performance in repeated sprinting exercise.

Background: The outcome of surgery in deconditioned patients can be improved through prehabilitation. This study examined the effect of prehabilitation in patients diagnosed with lung cancer. Methods: Candidates for lung cancer resection were assigned to high-intensity interval training (n = 74) or usual care (n = 77). Cardiopulmonary exercise testing and 6-min walk test were performed before and after training. High-intensity interval training consisted of 2–3-weekly, 2 × 10-min series of cycling at peak power, measured with cardiopulmonary exercise testing prior to training, with a 15-s on-off duty cycle, preceded by a 5-min warm-up and followed by a 5-min cool-down. Work-rate, heart-rate, saturation, dyspnoea and leg effort were monitored. Results: Waiting time (median 25 days) allowed a median of 8 high-intensity interval training sessions to be performed. Adherence to mean high-intensity interval training was 87% (18% standard deviation; SD). High-intensity interval training power increased (23 watt, 95% confidence interval (95% CI): 20–26 watt), as did heart rate (14 bpm, 95% CI 11–16 bpm). Resting heart rate (–6 bpm, 95% CI –4 to –7 bpm) and heart rate 1 min post-cool-down decreased (–5 bpm, 95% CI –4 to –7 bpm). Aerobic capacity increased after high-intensity interval training (14%, 95% CI 3–26%), as did peak power output (median 7%, 95% CI 2–13%), but not after usual care. Six-min walk test score increased after high-intensity interval training (median 20%, 95% CI 14–26%), but not after usual care. Conclusion: Short-term high-intensity interval training is feasible in deconditioned patients and increases cardio-respiratory fitness and walking capacity.

The hematological module of the Athlete Biological Passport (ABP) is used in elite sport for antidoping purposes. Its aim is to better target athletes for testing and to indirectly detect blood doping. The ABP allows to monitor hematological variations in athletes using selected primary blood biomarkers [hemoglobin concentration (Hb) and reticulocyte percentage (Ret%)] with an adaptive Bayesian model to set individual upper and lower limits. If values fall outside the individual limits, an athlete may be further targeted and ultimately sanctioned. Since (Hb) varies with plasma volume (PV) fluctuations, possibly caused by training load changes, we investigated the putative influence of acute and chronic training load changes on the ABP variables. Monthly blood samples were collected over one year in 10 male elite cyclists (25.6 ± 3.4 years, 181 ± 4 cm, 71.3 ± 4.9 kg, 6.7 ± 0.8 W.kg−1 5-min maximal power output) to calculate individual ABP profiles and monitor hematological variables. Total hemoglobin mass (Hbmass) and PV were additionally measured by carbon monoxide rebreathing. Acute and chronic training loads–respectively 5 and 42 days before sampling–were calculated considering duration and intensity (training stress score, TSSTM). (Hb) averaged 14.2 ± 0.0 (mean ± SD) g.dL−1 (range: 13.3–15.5 g·dl−1) over the study with significant changes over time (P = 0.004). Hbmass was 1030 ± 87 g (range: 842–1116 g) with no significant variations over time (P = 0.118), whereas PV was 4309 ± 350 mL (range: 3,688–4,751 mL) with a time-effect observed over the study time (P = 0.014). Higher acute–but not chronic—training loads were associated with significantly decreased (Hb) (P

The Tibetans’ better aerobic exercise capacity at altitude remains ill-understood. We tested the hypothesis that Tibetans display better muscle and brain tissue oxygenation during exercise in hypoxia. Using near-infrared spectrometry (NIRS) to provide indices of tissue oxygenation, we measured oxy- and deoxy-hemoglobin ([O2Hb] and [HHb], respectively) responses of the vastus lateralis muscle and the right prefrontal cortex in ten Han Chinese and ten Tibetans during incremental cycling to exhaustion in a pressure-regulated chamber at simulated sea-level (air at 1 atm: normobaric normoxia) and 5,000 m (air at 0.5 atm: hypobaric hypoxia). Hypoxia reduced aerobic capacity by ∼22% in both groups (d = 0.8, p < 0.001 vs. normoxia), while Tibetans consistently outperformed their Han Chinese counterpart by ∼32% in normoxia and hypoxia (d = 1.0, p = 0.008). We found cerebral [O2Hb] was higher in Tibetans at normoxic maximal effort compared Han (p = 0.001), while muscle [O2Hb] was not different (p = 0.240). Hypoxic exercise lowered muscle [O2Hb] in Tibetans by a greater extent than in Han (interaction effect: p < 0.001 vs. normoxic exercise). Muscle [O2Hb] was lower in Tibetans when compared to Han during hypoxic exercise (d = 0.9, p = 0.003), but not during normoxic exercise (d = 0.4, p = 0.240). Muscle [HHb] was not different between the two groups during normoxic and hypoxic exercise (p = 0.778). Compared to Han, our findings revealed a higher brain tissue oxygenation in Tibetans during maximal exercise in normoxia, but lower muscle tissue oxygenation during exercise in hypoxia. This would suggest that the Tibetans privileged oxygenation of the brain at the expense of that of the muscle.

Despite a wealth of sport nutrition guidelines for adult athletes, there are currently no nutrition guidelines for youth winter sports athletes. Whilst it may be pragmatic to apply nutrition guidelines for adult athletes to youth winter sports athletes, it is inappropriate. Due to a paucity of research on youth athletes, it is impossible to provide evidence-based guidelines for this population, so careful extrapolation from the theoretical and practical considerations that apply to other athletic groups is necessary. Youth winter sport athletes undergo rapid biological growth and maturation which influences their nutritional requirements. A varied and balanced diet that ensures sufficient energy availability for optimal growth and maturation as well as sporting performance is the cornerstone of youth athlete nutrition and should also allow for youth athletes to meet their micronutrient requirements. In some cases, micronutrient status (e.g., vitamin D and iron) should be monitored and optimized if appropriate by a medical professional. Dietary supplement use is prevalent amongst youth athletes, however is often unnecessary. Education of youth athletes, their parents and coaches on best nutritional practices as well as the risks associated with dietary supplements is vital for their long-term athletic development. Further research in youth winter sports athletes across different stages of growth and maturation competing in a variety of sports is urgently required in order to inform nutritional guidelines for this population.

PurposeThe present study aimed to determine whether whole-body fat oxidation and muscle deoxygenation kinetics parameters during exercise were related in individuals with different aerobic fitness levels.MethodsEleven cyclists [peak oxygen uptake (V.O2⁢p⁢e⁢a⁢k): 64.9 ± 3.9 mL⋅kg–1⋅min–1] and 11 active individuals (V.O2⁢p⁢e⁢a⁢k: 49.1 ± 7.4 mL⋅kg–1⋅min–1) performed a maximal incremental cycling test to determine V.O2⁢p⁢e⁢a⁢k and a submaximal incremental cycling test to assess whole-body fat oxidation using indirect calorimetry and muscle deoxygenation kinetics of the vastus lateralis (VL) using near-infrared spectroscopy (NIRS). A sinusoidal (SIN) model was used to characterize fat oxidation kinetics and to determine the intensity (Fatmax) eliciting maximal fat oxidation (MFO). The muscle deoxygenation response was fitted with a double linear model. The slope of the first parts of the kinetics (a1) and the breakpoint ([HHb]BP) were determined.ResultsMFO (p = 0.01) and absolute fat oxidation rates between 20 and 65% V.O2⁢p⁢e⁢a⁢k were higher in cyclists than in active participants (p < 0.05), while Fatmax occurred at a higher absolute exercise intensity (p = 0.01). a1 was lower in cyclists (p = 0.02) and [HHb]BP occurred at a higher absolute intensity (p < 0.001) than in active individuals. V.O2⁢p⁢e⁢a⁢k was strongly correlated with MFO, Fatmax, and [HHb]BP (r = 0.65–0.88, p ≤ 0.001). MFO and Fatmax were both correlated with [HHb]BP (r = 0.66, p = 0.01 and r = 0.68, p < 0.001, respectively) and tended to be negatively correlated with a1 (r = -0.41, p = 0.06 for both).ConclusionThis study showed that whole-body fat oxidation and muscle deoxygenation kinetics were both related to aerobic fitness and that a relationship between the two kinetics exists. Individuals with greater aerobic fitness may have a delayed reliance on glycolytic metabolism at higher exercise intensities because of a longer maintained balance between O2 delivery and consumption supporting higher fat oxidation rates.

IntroductionBaroreflex sensitivity (BRS) is essential to ensure rapid adjustment to variations in blood pressure (BP). Spontaneous baroreflex function can be assessed using continuous recordings of blood pressure. The goal of this study was to compare four methods for BRS quantification [the sequence, Bernardi’s (BER), frequency and transfer function methods] to identify the most consistent method across an extreme range of conditions: rest and exercise, in normoxia, hypoxia, hypocapnia, and hypercapnia.MethodsUsing intra-radial artery BP in young healthy participants, BRS was calculated and compared using the four methods in normoxia, acute and chronic hypoxia (terrestrial altitude of 5,260 m) in hypocapnia (hyperventilation), hypercapnia (rebreathing) and during ramp exercise to exhaustion.ResultsThe sequence and BER methods for BRS estimation showed good agreement during the resting and exercise protocols, whilst the ultra- and very-low frequency bands of the frequency and transfer function methods were more discrepant. Removing respiratory frequency from the blood pressure traces affected primarily the sequence and BER methods and occasionally the frequency and transfer function methods.Discussion/ConclusionThe sequence and BER methods contained more respiratory related information than the frequency and transfer function methods, indicating that the former two methods predominantly rely on respiratory effects of BRS. BER method is recommended because it is the easiest to compute and even though it tends to overestimate BRS compared to the sequence method, it is consistent with the other methods, whilst its interquartile range is the smallest.

Abstract 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

Some children are inactive on weekends but active on weekdays. Correlates of such behavior remain to be clarified. We assessed school, out-of-school and family correlates of compliance with physical activity (PA) recommendations during weekdays among weekend non-compliant youth in Switzerland. Cross-sectional data collected in 2013–2015 from the SOPHYA study. PA was objectively measured during one week using waist-worn accelerometers. Compliance with PA recommendations (≥60min/day of moderate-to-vigorous PA) was assessed separately for weekend and weekdays. Data on school sport, transport to school, sports club participation, household income, parent's PA and education were collected by phone interview and questionnaires. Data from 540 youth (316 girls) aged 6–16years were available for analysis. Participants who were compliant to recommendations during weekdays were more frequently boys (50.3% vs. 31.4%, p

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.

Submaximal step tests are often used for estimation of maximum oxygen consumption (VO2max) in humans. The validity of the Actiheart step test for VO2max estimation was not fully studied yet. Therefore, purpose of the study was to estimate VO2max using the Actiheart step test and to compare the data with measured VO2max in endurance trained athletes (ATH) and healthy non-athletes (CON). 68 ATH (54% men, 28.0±5.4 yrs, 20.9±1.7 kg∙m-2) and 63 CON (46% men, 27.6±5.1 yrs, 22.1±1.7 kg∙m-2) performed the Actiheart step test and a spiroergometry for assessment of VO2max. In addition, resting metabolic rate (RMR; indirect calorimetry), maximum heart rate (HRmax; heart rate monitoring system during spiroergometry), and sleeping heart rate (SHR; Actiheart 6-day long term measurement) were determined. Validity of two different Actiheart software entry modes was assessed: (1) AHraw (estimated RMR [Schofield] and HRmax [Tanaka], SHR = 70 bpm) and (2) AHcomplete (measured RMR, HRmax, and SHR). Validity was investigated using linear regression (R2 and standard error of the estimate (SEE)) and repeated-measures ANOVA with a Bonferroni post-hoc correction. The level of significance was set to α=0.05. VO2max estimated by AHraw was significant related to measured VO2max in women CON (R2=0.22; p

Background: Tibetans experience lose less aerobic exercise capacity in hypoxia compared to lowland Han. We tested if inhalation of iloprost (to counter hypoxic pulmonary vasoconstriction) and furosemide (to decrease afferent vagal traffic from pulmonary receptors) improve performance in hypoxia in Han compared to Tibetans. Methods: 8 Tibetans and 8 Han, living at 2,260 m, did incremental uphill treadmill running to exhaustion at ambient pressure on day 1, followed by three runs at 5,000 m (hypobaric chamber) after inhalation of iloprost (ILO), furosemide (FUR) or placebo (PLA), on different days in a counter-balanced order. Results: In Han the performance decrement from 2,260 m to 5,000 m was greater than in Tibetans (p

Sprint interval training (SIT) has emerged as a time-efficient training regimen for young individuals. Here, we studied whether SIT is effective also in elderly individuals and whether the training response was affected by treatment with the antioxidants vitamin C and E. Recreationally active elderly (mean age 65) men received either vitamin C (1 g/day) and vitamin E (235 mg/day) or placebo. Training consisted of nine SIT sessions (three sessions/week for three weeks of 4-6 repetitions of 30-s all-out cycling sprints) interposed by 4 min rest. Vastus lateralis muscle biopsies were taken before, 1 h after, and 24 h after the first and last SIT sessions. At the end of the three weeks of training, SIT-induced changes in relative mRNA expression of reactive oxygen/nitrogen species (ROS)- and mitochondria-related proteins, inflammatory mediators, and the sarcoplasmic reticulum Ca2+ channel, the ryanodine receptor 1 (RyR1), were blunted in the vitamin treated group. Western blots frequently showed a major (>50%) decrease in the full-length expression of RyR1 24 h after SIT sessions; in the trained state, vitamin treatment seemed to provide protection against this severe RyR1 modification. Power at exhaustion during an incremental cycling test was increased by ~5% at the end of the training period, whereas maximal oxygen uptake remained unchanged; vitamin treatment did not affect these measures. In conclusion, treatment with the antioxidants vitamin C and E blunts SIT-induced cellular signaling in skeletal muscle of elderly individuals, while the present training regimen was too short or too intense for the changes in signaling to be translated into a clear-cut change in physical performance.

Background: Nitrate is a precursor of nitric oxide (NO), an important regulator of cerebral perfusion in normoxic and hypoxic conditions. Nitrate supplementation could be used to improve cerebral perfusion and oxygenation during exercise in hypoxia. The effects of dietary nitrate supplementation on cerebral haemodynamics during exercise in severe hypoxia (arterial O2 saturation < 70%) have not been explored.Methods: In twelve trained male cyclists, we measured blood pressure (BP), middle cerebral artery blood velocity (MCAv), cerebrovascular resistance (CVR) and prefrontal oxyhaemoglobin and deoxyhaemoglobin concentration (O2Hb and HHb, respectively) during 15 km cycling time trials (TT) in normoxia and severe hypoxia (11% inspired O2, peripheral O2 saturation ∼66%) following 3-day oral supplementation with placebo or sodium nitrate (0.1 mmol/kg/day) in a randomised, double-blinded manner. We tested the hypothesis that dietary nitrate supplementation increases MCAv and cerebral O2Hb during TT in severe hypoxia.Results: During TT in normoxia, nitrate supplementation lowered MCAv by ∼2.3 cm/s and increased cerebral O2Hb by ∼6.8 μM and HHb by ∼2.1 μM compared to normoxia placebo (p ≤ 0.01 for all), while BP tended to be lowered (p = 0.06). During TT in severe hypoxia, nitrate supplementation elevated MCAv (by ∼2.5 cm/s) and BP (by ∼5 mmHg) compared to hypoxia placebo (p < 0.01 for both), while it had no effect on cerebral O2Hb (p = 0.98), HHb (p = 0.07) or PETCO2 (p = 0.12). Dietary nitrate had no effect of CVR during TT in normoxia or hypoxia (p = 0.19).Conclusion: Our findings indicate that during normoxic TT, the modulatory effect of dietary nitrate on regional and global cerebral perfusion is heterogeneous. Meanwhile, the lack of major changes in cerebral perfusion with dietary nitrate during hypoxic TT alludes to an exhausted cerebrovascular reserve.

Introduction: Baroreflex sensitivity (BRS) is essential to ensure rapid adjustment to variations in blood pressure (BP). Little is known concerning the adaptive responses of BRS during acclimatization to high altitude at rest and during exercise.Methods: Twenty-one healthy sea-level residents were tested near sea level (SL, 130 m), the 1st (ALT1) and 16th day (ALT16) at 5,260 m using radial artery catheterization. BRS was calculated using the sequence method (direct interpretation of causal link between BP and heartrate). At rest, subjects breathed a hyperoxic mixture (250 mmHg O2, end tidal) to isolate the preponderance of CO2 chemoreceptors. End-tidal CO2 varied from 20 to 50 mmHg to assess peripheral chemoreflex. Rebreathing provoked incremental increase in CO2, increasing BP to assess baroreflex. During incremental cycling exercise to exhaustion, subjects breathed room air.Results: Resting BRS decreased in ALT1 which was exacerbated in ALT16. This decrease in ALT1 was reversible upon additional inspired CO2, but not in ALT16. BRS decrease during exercise was greater and occurred at lower workloads in ALT1 compared to SL. At ALT16, this decrease returned toward SL values.Discussion/Conclusion: This study is the first to report attenuated BRS in acute hypoxia, exacerbated in chronic hypoxia. In ALT1, hypocapnia triggered BRS reduction whilst in ALT16 resetting of chemoreceptor triggered BRS reduction. The exercise BRS resetting was impaired in ALT1 but normalized in ALT16. These BRS decreases indicate decreased control of BP and may explain deteriorations of cardiovascular status during exposure to high altitude.

Anti-gravity treadmills facilitate locomotion by lower-body positive pressure (LBPP). Effects on cardiorespiratory regulation are unknown. Healthy men (30 ± 8 y, 178.3 ± 5.7 cm, 70.3 ± 8.0 kg; mean ± SD) stood upright (n = 10) or ran (n = 9) at 9, 11, 13, and 15 km.h−1 (5 min stages) with LBPP (0, 15, 40 mmHg). Cardiac output (CO), stroke volume (SV), heart rate (HR), blood pressure (BP), peripheral resistance (PR), and oxygen uptake (VO2) were monitored continuously. During standing, LBPP increased SV [by +29 ± 13 (+41%) and +42 ± 15 (+60%) ml, at 15 and 40 mmHg, respectively (p < 0.05)] and decreased HR [by −15 ± 6 (−20%) and −22 ± 9 (−29%) bpm (p < 0.05)] resulting in a transitory increase in CO [by +1.6 ± 1.0 (+32%) and +2.0 ± 1.0 (+39%) l.min−1 (p < 0.05)] within the first seconds of LBPP. This was accompanied by a transitory decrease in end-tidal PO2 [by −5 ± 3 (−5%) and −10 ± 4 (−10%) mmHg (p < 0.05)] and increase in VO2 [by +66 ± 53 (+26%) and +116 ± 64 (+46%) ml.min−1 (p < 0.05)], suggesting increased venous return and pulmonary blood flow. The application of LBPP increased baroreflex sensitivity (BRS) [by +1.8 ± 1.6 (+18%) and +4.6 ± 3.7 (+47%) at 15 and 40 mmHg LBPP, respectively P < 0.05]. After reaching steady-state exercise CO vs. VO2 relationships remained linear with similar slope and intercept for each participant (mean R2 = 0.84 ± 0.13) while MAP remained unchanged. It follows that (1) LBPP affects cardiorespiratory integration at the onset of exercise; (2) at a given LBPP, once reaching steady-state exercise, the cardiorespiratory load is reduced proportionally to the lower metabolic demand resulting from the body weight support; (3) the balance between cardiovascular response, oxygen delivery to the exercising muscles and blood pressure regulation is maintained at exercise steady-state; and (4) changes in baroreflex sensitivity may be involved in the regulation of cardiovascular parameters during LBPP.

Electrically-evoked low-frequency (submaximal) force is increased immediately following high-frequency stimulation in human skeletal muscle. Although central mechanisms have been suggested to be the major cause of this low-frequency force potentiation, intramuscular factors might contribute. Thus, we hypothesized that two intramuscular Ca2+-dependent mechanisms can contribute to the low-frequency force potentiation: increased sarcoplasmic reticulum Ca2+ release and increased myofibrillar Ca2+ sensitivity. Experiments in humans were performed on the plantar flexor muscles at a shortened, intermediate, and long muscle length and electrically evoked contractile force and membrane excitability (i.e., M-wave amplitude) were recorded during a stimulation protocol. Low-frequency force potentiation was assessed by stimulating with a low-frequency tetanus (25 Hz, 2 s duration), followed by a high-frequency tetanus (100 Hz, 2 s duration), and finally followed by another low-frequency (25 Hz, 2 s duration) tetanus. Similar stimulation protocols were performed on intact mouse single fibers from flexor digitorum brevis muscle, whereby force and myoplasmic free [Ca2+] ([Ca2+]i) were assessed. Our data show a low-frequency force potentiation that was not muscle length-dependent in human muscle and it was not accompanied by any increase in M-wave amplitude. A length-independent low-frequency force potentiation could be replicated in mouse single fibers, supporting an intramuscular mechanism. We show that at physiological temperature (31°C) this low-frequency force potentiation in mouse fibers corresponded with an increase in sarcoplasmic reticulum (SR) Ca2+ release. When mimicking the slower contractile properties of human muscle by cooling mouse single fibers to 18°C, the low-frequency force potentiation was accompanied by minimally increased SR Ca2+ release and hence it could be explained by increased myofibrillar Ca2+ sensitivity. Finally, introducing a brief 200 ms pause between the high- and low-frequency tetanus in human and mouse muscle revealed that the low-frequency force potentiation is abolished, arguing that increased myofibrillar Ca2+ sensitivity is the main intramuscular mechanism underlying the low-frequency force potentiation in humans.

The maximum aerobic metabolic rate can be expressed in multiple metabolically equivalent tasks (MET), i.e., METmax. The purpose was to quantify the error when the conventional (3.5 mL∙kg−1∙min−1) compared to an individualized 1-MET-value is used for calculating METmax and estimating activity energy expenditure (AEE) in endurance-trained athletes (END) and active healthy controls (CON). The resting metabolic rate (RMR, indirect calorimetry) and aerobic metabolic capacity (spiroergometry) were assessed in 52 END (46% male, 27.9 ± 5.7 years) and 53 CON (45% male, 27.3 ± 4.6 years). METmax was calculated as the ratio of VO2max over VO2 during RMR (METmax_ind), and VO2max over the conventional 1-MET-value (METmax_fix). AEE was estimated by multiplying published MET values with the individual and conventional 1-MET-values. Dependent t-tests were used to compare the different modes for calculating METmax and AEE (α = 0.05). In women and men CON, men END METmax_fix was significantly higher than METmax_ind (p < 0.01), whereas, in women END, no difference was found (p > 0.05). The conventional 1-MET-value significantly underestimated AEE in men and women CON, and men END (p < 0.05), but not in women END (p > 0.05). The conventional 1-MET-value appears inappropriate for determining the aerobic metabolic capacity and AEE in active and endurance-trained persons.

The mechanisms underlying task failure from fatiguing physical efforts have been the focus of many studies without reaching consensus. An attractive but debated model explains effort termination with a critical peripheral fatigue threshold. Upon reaching this threshold, feedback from sensory afferents would trigger task disengagement from open-ended tasks or a reduction of exercise intensity of closed-ended tasks. Alternatively, the extant literature also appears compatible with a more global critical threshold of loss of maximal voluntary contraction force. Indeed, maximal voluntary contraction force loss from fatiguing exercise realized at a given intensity appears rather consistent between different studies. However, when looking at individual data, the similar maximal force losses observed between different tasks performed at similar intensities might just be an artifact of data aggregation. It would then seem possible that such a difference observed between individual and aggregated data also applies to other models previously proposed to explain task failure from fatiguing physical efforts. We therefore suggest that one should be cautious when trying to infer models that try to explain individual behavior from aggregated data.

Better understanding is needed regarding the effects of exercise alone, without any imposed dietary regimens, as a single tool for body-weight regulation. Thus, we evaluated the effects of an 8-week increase in activity energy expenditure (AEE) on ad libitum energy intake (EI), body mass and composition in healthy participants with baseline physical activity levels (PAL) in line with international recommendations. Forty-six male adults (BMI = 19·7–29·3 kg/m2) participated in an intervention group, and ten (BMI = 21·0–28·4 kg/m2) in a control group. Anthropometric measures, cardiorespiratory fitness, EI, AEE and exercise intensity were recorded at baseline and during the 1st, 5th and 8th intervention weeks, and movement was recorded throughout. Body composition was measured at the beginning and at the end of the study, and resting energy expenditure was measured after the study. The intervention group increased PAL from 1·74 (se 0·03) to 1·93 (se 0·03) (P

Micronutrient requirements do not scale linearly with physical activity-related energy expenditure (AEE). Inactive persons may have insufficient micronutrient intake because of low energy intake (EI). We extracted data from NHANES 2003–2006 on 4015 adults (53 ± 18 years (mean ± SD), 29 ± 6 kg/m2, 48% women) with valid physical activity (accelerometry) and food intake (2 × 24 h-dietary recall) measures. Total energy expenditure (TEE) was estimated by summing the basal metabolic rate (BMR, Harris-Benedict), AEE, and 10% of TEE for the thermic effect of food, to calculate the physical activity levels (PAL = TEE/BMR). Energy intake (EI) was scaled to match TEE assuming energy balance. Adjusted food intake was then analyzed for energy and micronutrient content and compared to estimated average requirements. The NHANES population was physically insufficiently active. There were 2440 inactive (PAL < 1.4), 1469 lightly to moderately active (PAL1.4 < 1.7), 94 sufficiently active (PAL1.7 < 2.0), and 12 very active participants (PAL ≥ 2.0). The inactive vs. active had significantly lower intake for all micronutrients apart from vitamin A, B12, C, K, and copper (p < 0.05). The inactive participants had insufficient intake for 6/19 micronutrients, while the active participants had insufficient intake for 5/19 (p < 0.05) micronutrients. Multiple linear regression indicated a lower risk for insufficient micronutrient intake for participants with higher PAL and BMI (p < 0.001). Symmetrical up-scaling of PAL and EI to recommended physical activity levels reduced the frequency of micronutrient insufficiencies. It follows that prevalence of insufficient micronutrient intake from food in NHANES might be partly determined by low energy turnover from insufficient PAL.

An understanding of human responses to hypoxia is important for the health of millions of people worldwide who visit, live, or work in the hypoxic environment encountered at high altitudes. In spite of dozens of studies over the last 100 years, the basic mechanisms controlling acclimatization to hypoxia remain largely unknown. The AltitudeOmics project aimed to bridge this gap. Our goals were 1) to describe a phenotype for successful acclimatization and assess its retention and 2) use these findings as a foundation for companion mechanistic studies. Our approach was to characterize acclimatization by measuring changes in arterial oxygenation and hemoglobin concentration [Hb], acute mountain sickness (AMS), cognitive function, and exercise performance in 21 subjects as they acclimatized to 5260 m over 16 days. We then focused on the retention of acclimatization by having subjects reascend to 5260 m after either 7 (n = 14) or 21 (n = 7) days at 1525 m. At 16 days at 5260 m we observed: 1) increases in arterial oxygenation and [Hb] (compared to acute hypoxia: PaO2 rose 9±4 mmHg to 45±4 while PaCO2 dropped a further 6±3 mmHg to 21±3, and [Hb] rose 1.8±0.7 g/dL to 16±2 g/dL; 2) no AMS; 3) improved cognitive function; and 4) improved exercise performance by 8±8% (all changes p

Hypoxia increases the ventilatory response to exercise, which leads to hyperventilation-induced hypocapnia and subsequent reduction in cerebral blood flow (CBF). We studied the effects of adding CO2 to a hypoxic inspired gas on CBF during heavy exercise in an altitude naïve population. We hypothesized that augmented inspired CO2 and hypoxia would exert synergistic effects on increasing CBF during exercise, which would improve exercise capacity compared to hypocapnic hypoxia. We also examined the responsiveness of CO2 and O2 chemoreception on the regulation ventilation ([Formula: see text]E) during incremental exercise. We measured middle cerebral artery velocity (MCAv; index of CBF), [Formula: see text]E, end-tidal PCO2, respiratory compensation threshold (RC) and ventilatory response to exercise ([Formula: see text]E slope) in ten healthy men during incremental cycling to exhaustion in normoxia and hypoxia (FIO2 = 0.10) with and without augmenting the fraction of inspired CO2 (FICO2). During exercise in normoxia, augmenting FICO2 elevated MCAv throughout exercise and lowered both RC onset and[Formula: see text]E slope below RC (P0.05). The [Formula: see text]E slope above RC was unchanged with either hypoxia or augmented FICO2 (P>0.05). We found augmenting FICO2 increased CBF during sub-maximal exercise in normoxia, but not in hypoxia, indicating that the 'normal' cerebrovascular response to hypercapnia is blunted during exercise in hypoxia, possibly due to an exhaustion of cerebral vasodilatory reserve. This finding may explain the lack of improvement of exercise capacity in hypoxia with augmented CO2. Our data further indicate that, during exercise below RC, chemoreception is responsive, while above RC the ventilatory response to CO2 is blunted.

INTRODUCTION: In affluent countries habitual physical activity (PA) levels are low while participation of middle-aged people in road running events is increasing. We compared PA determinants of runners aged 50+ to those of a general population sample of similar age in Switzerland. METHOD: Cross-sectional study comparing 580 road running event participants to 1,067 general population subjects. Binary logistic regression was used to predict group membership and multinomial logistic regression to describe relationships between regular PA levels, health and socio-economic status, adjusted for age, marital status and sex. RESULTS: There was better health status, higher socio-economic position, less obesity and less depression in the runners than in the general population. People in self-reported “poor / very poor” and “good” health categories were less likely than the “excellent/very good” category to engage in vigorous regular PA compared to moderate regular PA. CONCLUSIONS: Our findings confirm the association of PA with better health and higher socio-economic status in people aged 50+ but do not allow conclusions on causality. Further research and managerial effort should be expanded to develop programmes for the inactive population. New and existing prevention programmes should be undertaken to increase the awareness of target audiences. Popular road running events should be seen as having important public health potential and should be fostered.

“Metabolic Equivalent” (MET) represents a standard amount of oxygen consumed by the body under resting conditions, and is defined as 3.5 mL O2/kg × min or ~1 kcal/kg × h. It is used to express the energy cost of physical activity in multiples of MET. However, universal application of the 1-MET standard was questioned in previous studies, because it does not apply well to all individuals. Height, weight and resting metabolic rate (RMR, measured by indirect calorimetry) were measured in adolescent males (n = 50) and females (n = 50), women during pregnancy (gestation week 35–41, n = 46), women 24–53 weeks postpartum (n = 27), and active men (n = 30), and were compared to values predicted by the 1-MET standard. The RMR of adolescent males (1.28 kcal/kg × h) was significantly higher than that of adolescent females (1.11 kcal/kg × h), with or without the effects of puberty stage and physical activity levels. The RMR of the pregnant and post-pregnant subjects were not significantly different. The RMR of the active normal weight (0.92 kcal/kg × h) and overweight (0.89 kcal/kg × h) adult males were significantly lower than the 1-MET value. It follows that the 1-MET standard is inadequate for use not only in adult men and women, but also in adolescents and physically active men. It is therefore recommended that practitioners estimate RMR with equations taking into account individual characteristics, such as sex, age and Body Mass Index, and not rely on the 1-MET standard.

Background. Oropharyngeal receptors signal presence of carbohydrate to the brain. Mouth rinses with a carbohydrate solution facilitate corticomotor output and improve time-trial performance in well-trained subjects in a fasted state. We tested for this effect in nonathletic subjects in fasted and nonfasted state. Methods. 13 healthy non-athletic males performed 5 tests on a cycle ergometer. After measuring maximum power output (Wmax), the subjects cycled four times at 60% Wmax until exhaustion while rinsing their mouth every 5 minutes with either a 6.4% maltodextrin solution or water, one time after an overnight fast and another after a carbohydrate rich breakfast. Results. Mouth rinsing with maltodextrin improved time-to-exhaustion in pre- and postprandial states. This was accompanied by reductions in the average and maximal rates of perceived exertion but no change in average or maximal heart rate was observed. Conclusions. Carbohydrate mouth rinsing improves endurance capacity in both fed and fasted states in non-athletic subjects.