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.

Cross-Sectional but Not Prospective Association of Accelerometry-Derived Physical Activity With Quality of Life in Children and Adolescents.

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.

Functional hypoxia reduces mitochondrial calcium uptake.

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.

Ryanodine receptor type 1 content decrease-induced endoplasmic reticulum stress is a hallmark of myopathies.

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 < 0.001) and juvenile dermatomyositis (P < 0.001) and in muscle samples of myotonic dystrophy type 2 (P < 0.001), presymptomatic (P < 0.001) and symptomatic (P < 0.001) Duchenne muscular dystrophy, Becker muscular dystrophy (P = 0.004) and limb-girdle muscular dystrophy type 2A (P = 0.004). RyR1 protein content was also significantly decreased in inflammatory myopathy (-75%, P < 0.001) and mitochondrial myopathy (-71%, P < 0.001) muscles. Proteomics data showed that depletion of RyR1 protein in C2C12 myoblasts leads to myotubes recapitulating the common molecular alterations observed in myopathies. Mechanistically, RyR1 protein depletion reduces ER-mitochondria contact length (-26%, P < 0.001), Ca2+ transfer to mitochondria (-48%, P = 0.002) and the mitophagy gene Parkinson protein 2 transcripts (P = 0.037) and induces mitochondrial accumulation (+99%, P = 0.005) and dysfunction (P < 0.001). This was associated to the accumulation of deleterious sphingolipid species. Our data showed increased levels of the ER stress marker chaperone-binding protein/glucose regulated protein 78, GRP78-Bip, in RyR1 knockdown myotubes (+45%, P = 0.046), in mouse RyR1 recessive muscles (+58%, P = 0.001) and in human inflammatory (+96%, P = 0.006) and mitochondrial (+64%, P = 0.049) myopathy muscles. This was accompanied by increased protein levels of the pro-apoptotic protein CCAAT-enhancer-binding protein homologous protein, CHOP-DDIT3, in RyR1 knockdown myotubes (+27%, P < 0.001), mouse RyR1 recessive muscles (+63%, P = 0.009), human inflammatory (+50%, P = 0.038) and mitochondrial (+51%, P = 0.035) myopathy muscles. In publicly available datasets, the decrease in RYR1 content in myopathies was also associated to increased ER stress markers and RYR1 transcript levels are inversely correlated with ER stress markers in the control population. CONCLUSIONS: Decreased RyR1 is commonly observed in myopathies and associated to ER stress in vitro, in mouse muscle and in human myopathy muscles, suggesting a potent role of RyR1 depletion-induced ER stress in the pathogenesis of myopathies.

AltitudeOmics: effects of 16 days acclimatization to hypobaric hypoxia on muscle oxygen extraction during incremental exercise.

Acute altitude exposure lowers arterial oxygen content ([Formula: see text]) and cardiac output ([Formula: see text]) at peak exercise, whereas O2 extraction from blood to working muscles remains similar. Acclimatization normalizes [Formula: see text] but not peak [Formula: see text] nor peak oxygen consumption (V̇o2peak). To what extent acclimatization impacts muscle O2 extraction remains unresolved. Twenty-one sea-level residents performed an incremental cycling exercise to exhaustion near sea level (SL), in acute (ALT1) and chronic (ALT16) hypoxia (5,260 m). Arterial blood gases, gas exchange at the mouth and oxy- (O2Hb) and deoxyhemoglobin (HHb) of the vastus lateralis were recorded to assess arterial O2 content ([Formula: see text]), [Formula: see text], and V̇o2. The HHb-V̇o2 slope was taken as a surrogate for muscle O2 extraction. During moderate-intensity exercise, HHb-V̇o2 slope increased to a comparable extent at ALT1 (2.13 ± 0.94) and ALT16 (2.03 ± 0.88) compared with SL (1.27 ± 0.12), indicating increased O2 extraction. However, the HHb/[Formula: see text] ratio increased from SL to ALT1 and then tended to go back to SL values at ALT16. During high-intensity exercise, HHb-V̇o2 slope reached a break point beyond which it decreased at SL and ALT1, but not at ALT16. Increased muscle O2 extraction during submaximal exercise was associated with decreased [Formula: see text] in acute hypoxia. The significantly greater muscle O2 extraction during maximal exercise in chronic hypoxia is suggestive of an O2 reserve.NEW & NOTEWORTHY During incremental exercise muscle deoxyhemoglobin (HHb) and oxygen consumption (V̇o2) both increase linearly, and the slope of their relationship is an indirect index of local muscle O2 extraction. The latter was assessed at sea level, in acute and during chronic exposure to 5,260 m. The demonstrated presence of a muscle O2 extraction reserve during chronic exposure is coherent with previous studies indicating both limited muscle oxidative capacity and decrease in motor drive.

Appetite, Hypoxia, and Acute Mountain Sickness: A 10-Hour Normobaric Hypoxic Chamber Study.

Barclay, Holly, Saptarshi Mukerji, Bengt Kayser, and Jui-Lin Fan. Appetite, hypoxia and acute mountain sickness: A 10-hour normobaric hypoxic chamber study. High Alt Med Biol. 24:329-335, 2023. Background: The effects of hypoxia and acute mountain sickness (AMS) on appetite and food preferences are moot, especially during the early phase of hypoxic exposure. We examined the effects of a 10-hour hypoxic exposure on appetite and food preference. Methods: We assessed appetite (hunger, satisfaction, fullness, perceived appetite, and lost appetite), food preferences (sweet, salty, savory, and fatty), and AMS (Lake Louise score) with questionnaires in 27 healthy individuals (13 women) across 10-hour exposures to normobaric normoxia (fraction of inspired O2 [FiO2]: 0.21) and normobaric hypoxia (FiO2: 0.12, equivalent of 5,000 m) in a randomized, single-blinded manner. Results and Conclusions: Compared with normoxia, hypoxia decreased hunger and appetite (p = 0.040 and <0.001, respectively), which was mediated by a decreased desire for sweet, salty, and fatty foods (p < 0.05 for all). AMS was associated with a decreased desire for sweet (R = -0.438, p = 0.032) and salty foods (R = -0.460, p = 0.024) and greater loss of appetite (R = -0.619, p = 0.018). Our findings suggest that acute hypoxia rapidly suppresses appetite and that AMS development further amplifies anorexia. Clinical Trial Registration Number: ACTRN12618000548235.

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.

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.

Steps parameters of elderly patients hospitalised for an acute medical illness in a Swiss University Hospital: a monocentric observational pilot-study.

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 <600 steps. Patients at high risk of bed sores walked less (564 steps, IQR 394-814 vs 626, IQR 526-840) than those with a lower risk of sores. CONCLUSION: During a hospitalisation for an acute medical illness, patients aged ≥65 years walk a mere 603 steps daily and most of the time for periods of less than 30 seconds. This information should be used to build up future interventional trials or to set mobility goals for patients hospitalised in Swiss hospitals.

Acute Effects of Neuromuscular Electrical Stimulation on Contralateral Plantar Flexor Neuromuscular Function.

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.

Strengthening Altitude Knowledge: A Delphi Study to Define Minimum Knowledge of Altitude Illness for Laypersons Traveling to High Altitude.

Berendsen, Remco R., Peter Bärtsch, Buddha Basnyat, Marc Moritz Berger, Peter Hackett, Andrew M. Luks, Jean-Paul Richalet, Ken Zafren, Bengt Kayser, and the STAK Plenary Group. Strengthening altitude knowledge: a Delphi study to define minimum knowledge of altitude illness for laypersons traveling to high altitude. High Alt Med Biol. 23:330-337, 2022. Introduction: A lack of knowledge among laypersons about the hazards of high-altitude exposure contributes to morbidity and mortality from acute mountain sickness (AMS), high-altitude cerebral edema (HACE), and high-altitude pulmonary edema (HAPE) among high-altitude travelers. There are guidelines regarding the recognition, prevention, and treatment of acute-altitude illness for experts, but essential knowledge for laypersons traveling to high altitudes has not been defined. We sought expert consensus on the essential knowledge required for people planning to travel to high altitudes. Methods: The Delphi method was used. The panel consisted of two moderators, a core expert group and a plenary expert group. The moderators made a preliminary list of statements defining the desired minimum knowledge for laypersons traveling to high altitudes, based on the relevant literature. These preliminary statements were then reviewed, supplemented, and modified by a core expert group. A list of 33 statements was then presented to a plenary group of experts in successive rounds. Results: It took three rounds to reach a consensus. Of the 10 core experts invited, 7 completed all the rounds. Of the 76 plenary experts, 41 (54%) participated in Round 1, and of these 41 a total of 32 (78%) experts completed all three rounds. The final list contained 28 statements in 5 categories (altitude physiology, sleeping at altitude, AMS, HACE, and HAPE). This list represents an expert consensus on the desired minimum knowledge for laypersons planning high-altitude travel. Conclusion: Using the Delphi method, the STrengthening Altitude Knowledge initiative yielded a set of 28 statements representing essential learning objectives for laypersons who plan to travel to high altitudes. This list could be used to develop educational interventions.

Exceptional Performance in Competitive Ski Mountaineering: An Inertial Sensor Case Study.

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.

Short term high-intensity interval training in patients scheduled for major abdominal surgery increases aerobic fitness.

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, [Formula: see text]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), [Formula: see text]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.

Priming cardiac function with voluntary respiratory maneuvers and effect on early exercise oxygen uptake.

Oxygen uptake (V̇o2) at exercise onset is determined in part by acceleration of pulmonary blood flow ([Formula: see text]). Impairments in the [Formula: see text] response can decrease exercise tolerance. Prior research has shown that voluntary respiratory maneuvers can augment venous return, but the corollary impacts on cardiac function, [Formula: see text] and early-exercise V̇o2 remain uncertain. We examined 1) the cardiovascular effects of three distinct respiratory maneuvers (abdominal, AB; rib cage, RC; and deep breathing, DB) under resting conditions in healthy subjects (Protocol 1, n = 13), and 2) the impact of pre-exercise DB on pulmonary O2 transfer during initiation of moderate-intensity exercise (Protocol 2, n = 8). In Protocol 1, echocardiographic analysis showed increased right ventricular (RV) cardiac output and left ventricular (LV) cardiac output (RVCO and LVCO, respectively), following AB (by +23 ± 13 and +18 ± 15%, respectively, P < 0.05), RC (+23 ± 16; +14 ± 15%, P < 0.05), and DB (+27 ± 21; +23 ± 14%, P < 0.05). In Protocol 2, DB performed for 12 breaths produced a pre-exercise increase in V̇o2 (+801 ± 254 mL·min-1 over ∼6 s), presumably from increased [Formula: see text], followed by a reduction in pulmonary O2 transfer during early phase exercise (first 20 s) compared with the control condition (149 ± 51 vs. 233 ± 65 mL, P < 0.05). We conclude that 1) respiratory maneuvers enhance RVCO and LVCO in healthy subjects under resting conditions, 2) AB, RC, and DB have similar effects on RVCO and LVCO, and 3) DB can increase [Formula: see text] before exercise onset. These findings suggest that pre-exercise respiratory maneuvers may represent a promising strategy to prime V̇o2 kinetics and thereby to potentially improve exercise tolerance in patients with impaired cardiac function.NEW & NOTEWORTHY We demonstrate that different breathing maneuvers can augment both right and left-sided cardiac output in healthy subjects. These maneuvers, when performed immediately before exercise, result in a pre-exercise "cardiodynamic" increase in oxygen uptake (V̇o2) associated with a subsequent reduction in the "cardiodynamic" V̇o2 normally seen during early exercise. We conclude that pre-exercise breathing maneuvers are a plausible tool worthy of additional study to prime V̇o2 kinetics and improve exercise tolerance in patients with cardiovascular disease.

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.

Hematological variables in recreational breath-hold divers: a longitudinal study.

BACKGROUND: The influence of regular breath-hold training on hematological variables is not fully understood. We monitored hematological variables in breath-hold divers (BHDs) and active controls over a year expecting both breath-hold training and seasonal effects. METHODS: In 11 recreational BHDs (36±9 years, 177±8 cm, 72±9 kg) and 12 active controls (22±2 years, 174±8 cm, 70±13 kg) monthly blood samples were analyzed with the hematological module of WADA's athlete biological passport. Hemoglobin mass and plasma volume were measured indirectly by the CO-rebreathing method for the last eight months of the study. Breath-hold training sessions were recorded online. Days without breath-hold training, or the number of hours prior to blood sampling when training was realized within the last 24 hours, were recorded. RESULTS: Hematology did not differ significantly between BHDs and controls over the study time (P>0.05). However, hematological values varied significantly over time for both groups suggesting seasonal effects. Blood sampling 19 hours or more after a breath hold training did not indicate any acute effects of breath holding training. CONCLUSIONS: In comparison with a physically active lifestyle, regular breath-hold training does not induce significant variations over one year for the hematological module of the ABP.

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).

Acute RyR1 Ca2+ leak enhances NADH-linked mitochondrial respiratory capacity.

Sustained ryanodine receptor (RyR) Ca2+ leak is associated with pathological conditions such as heart failure or skeletal muscle weakness. We report that a single session of sprint interval training (SIT), but not of moderate intensity continuous training (MICT), triggers RyR1 protein oxidation and nitrosylation leading to calstabin1 dissociation in healthy human muscle and in in vitro SIT models (simulated SIT or S-SIT). This is accompanied by decreased sarcoplasmic reticulum Ca2+ content, increased levels of mitochondrial oxidative phosphorylation proteins, supercomplex formation and enhanced NADH-linked mitochondrial respiratory capacity. Mechanistically, (S-)SIT increases mitochondrial Ca2+ uptake in mouse myotubes and muscle fibres, and decreases pyruvate dehydrogenase phosphorylation in human muscle and mouse myotubes. Countering Ca2+ leak or preventing mitochondrial Ca2+ uptake blunts S-SIT-induced adaptations, a result supported by proteomic analyses. Here we show that triggering acute transient Ca2+ leak through RyR1 in healthy muscle may contribute to the multiple health promoting benefits of exercise.

Feasibility of a prehabilitation program before major abdominal surgery: a pilot prospective study.

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 (VO2)) 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 (<3 weeks) prior to scheduled surgery (n = 276, 28%) and screening failure (n = 312, 32%). Of the 44 patients, 24 (55%) declined to participate, and 20 (23%) were included. Of these, six (30%) were not adherent to the program. Among the remaining 14 patients, VO2 at ventilatory threshold significantly increased from 9.7 to 10.9 mL/min/kg. No significant difference in physical performance was observed before and after prehabilitation. CONCLUSION: Although prehabilitation seemed to have positive effects on exercise capacity, logistic and patient-related difficulties were encountered. The program is not feasible in its current form for all-comers.

COVID-19 pandemic and health related quality of life in primary school children in Switzerland: a repeated cross-sectional study.

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.