Matto Leeuwis, Ralf Rienks, Maarten A Frens, Johan J M Pel, Patrick A Forbes
{"title":"Energetic cost of weight shifting and asymmetric weight-bearing during standing in humans.","authors":"Matto Leeuwis, Ralf Rienks, Maarten A Frens, Johan J M Pel, Patrick A Forbes","doi":"10.1152/japplphysiol.00294.2026","DOIUrl":"10.1152/japplphysiol.00294.2026","url":null,"abstract":"<p><p>During prolonged standing, humans commonly shift their weight and spontaneously alternate between symmetric and highly asymmetric standing, bearing most of their body weight on one leg. Here, we tested the hypothesis that humans adopt asymmetric weight-bearing to reduce metabolic cost by exploiting the sublinear scaling of muscle activation maintenance costs predicted by metabolic models. We measured energy expenditure using indirect calorimetry while participants (<i>n</i> = 20) completed three randomized standing conditions: <i>1</i>) static symmetric standing, <i>2</i>) symmetric standing with periodic lateral weight shifts, and <i>3</i>) asymmetric standing with periodic switching of the supporting leg. Weight shifting every 30 s from an otherwise symmetric stance increased overall energy expenditure by 5.3% [95% CI: 2.4%, 8.3%] relative to static symmetric standing. Maintaining an asymmetric posture while shifting to the other leg every 30 s increased energy expenditure by a further 7.0% [3.5%, 10.4%], contrary to our hypothesis that asymmetry would reduce metabolic cost. We additionally measured postural variability and plantarflexor muscle activity to explore potential mechanisms underlying energetic differences. Asymmetric weight-bearing increased postural variability relative to symmetric standing, with the average mediolateral upper-body velocity increasing by 118% [90%, 147%], suggesting that an increased stabilization effort contributed to the cost. Muscle activity in the weight-bearing leg strongly increased for the medial gastrocnemius, whereas soleus activity increased less than predicted. These findings demonstrate that weight shifting and asymmetric weight-bearing, two common standing behaviors, may not reflect behavioral energetic optimization and instead originate from nonenergetic objectives such as alleviating discomfort or fatigue.<b>NEW & NOTEWORTHY</b> Natural human posture is often highly asymmetric, similar to the relaxed stance of Michelangelo's David, and is characterized by frequent weight shifts between limbs. We experimentally tested whether such postures reduce the energetic cost of standing. Contrary to our hypothesis, participants expended more energy when standing in asymmetric postures and when shifting their weight periodically during symmetric standing, suggesting that these common postural behaviors come at an energetic expense.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"994-1005"},"PeriodicalIF":3.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7619477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eloisa Herrera-Ospina, Ernesto Ramirez, Rachel Bailey, Samuel T Stiles, Qudus A Ojikutu, Shiva C Viswanath, Steven R Steinhubl, Shih-Chun Kao, Bruno T Roseguini, Igor A Fernandes
{"title":"Does a pharmacologically driven elevation in cerebral blood flow modulate cognition during combined hypoxic and thermal stress?","authors":"Eloisa Herrera-Ospina, Ernesto Ramirez, Rachel Bailey, Samuel T Stiles, Qudus A Ojikutu, Shiva C Viswanath, Steven R Steinhubl, Shih-Chun Kao, Bruno T Roseguini, Igor A Fernandes","doi":"10.1152/japplphysiol.00414.2026","DOIUrl":"10.1152/japplphysiol.00414.2026","url":null,"abstract":"<p><p>Cognitive performance during environmental stress is highly variable, and the mechanisms underlying this heterogeneity remain unclear. Cerebral blood flow (CBF) has been proposed as a key determinant of neural performance during hypoxia and heat stress. However, whether experimentally increasing CBF modifies executive function during combined hypoxic and thermal stress has not been directly tested. Thirteen healthy young adults completed a randomized, double-blind, placebo-controlled crossover study. Participants ingested 1,000 mg of acetazolamide (ACZ) or a placebo (PLA) 4 h before testing. CBF was quantified from bilateral internal carotid and vertebral artery blood flow. Executive function was assessed using a Go/No-Go Flanker task during normothermia, hypoxia ([Formula: see text] ≈ 0.10), hyperthermia (+1.5°C to 2.0°C in core temperature), and combined hypoxic-hyperthermic conditions. ACZ increased CBF by ≈200 mL/min (+20% to 32%) across conditions (<i>P</i> < 0.05). Compared with PLA, ACZ shortened reaction time during normoxic-normothermia (-11 ms, <i>P</i> = 0.026) and combined hypoxic-hyperthermic exposure (-9 ms, <i>P</i> = 0.021). ACZ also reduced response variability during combined hypoxic-hyperthermic exposure (σ: 0.140 vs. 0.151, <i>P</i> = 0.041). Hyperthermia was associated with faster responses (<i>P</i> < 0.001), whereas hypoxia reduced response accuracy by approximately 1.5 percentage points (<i>P</i> = 0.027). Pharmacological augmentation of CBF modulated processing speed and response variability without improving response accuracy during environmental stress. These effects did not extend to response accuracy and were not consistently observed across environmental stress conditions, suggesting that increasing CBF alone is insufficient to preserve executive function during environmental strain.<b>NEW & NOTEWORTHY</b> Acetazolamide increases cerebral blood flow (CBF), but whether this perfusion \"reserve\" protects executive function during combined hypoxic and thermal stress is unknown. We tested cognition during normothermia, hypoxia, hyperthermia, and combined stress after acetazolamide or placebo in a randomized, double-blind crossover design. Although acetazolamide increased CBF, cognitive benefits were limited to faster, more consistent responses during normoxic-normothermic and hypoxic-hyperthermic exposures, suggesting that increasing cerebral perfusion alone is insufficient to protect executive function during environmental stress.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"597-609"},"PeriodicalIF":3.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13463305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148578828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bryce N Balmain, Valentin Mons, Andrew R Tomlinson, James P MacNamara, Abidan Abulimiti, Michael G Leahy, Denis J Wakeham, Kevin Lutz, Linda S Hynan, Benjamin D Levine, Satyam Sarma, Tony G Babb
{"title":"Oxygen cost of breathing and its association with dyspnea in older patients with heart failure with preserved ejection fraction and obesity.","authors":"Bryce N Balmain, Valentin Mons, Andrew R Tomlinson, James P MacNamara, Abidan Abulimiti, Michael G Leahy, Denis J Wakeham, Kevin Lutz, Linda S Hynan, Benjamin D Levine, Satyam Sarma, Tony G Babb","doi":"10.1152/japplphysiol.00432.2026","DOIUrl":"10.1152/japplphysiol.00432.2026","url":null,"abstract":"<p><p>Obesity is associated with an increased oxygen (O<sub>2</sub>) cost of breathing, which could contribute to dyspnea on exertion (DOE) and exercise intolerance. Many patients with heart failure with preserved ejection fraction (HFpEF) also have obesity, but whether an elevated O<sub>2</sub> cost of breathing contributes to DOE and exercise intolerance in these patients is unclear. Therefore, the purpose of this study was to examine the O<sub>2</sub> cost of breathing and its association with DOE and exercise intolerance in patients with HFpEF and obesity. We evaluated 14 patients with HFpEF and obesity [HFpEF-Ob, body mass index (BMI): 40.4 ± 5.4 kg/m<sup>2</sup>], 11 older control adults with obesity (CTL-Ob, BMI: 36.1 ± 5.7 kg/m<sup>2</sup>), and 20 older control adults without obesity (CTL-nonOb, BMI: 25.5 ± 2.9 kg/m<sup>2</sup>). All participants performed an eucapnic voluntary hyperpnea task at 30-40 L/min (EVH<sub>LOW</sub>) and 50-60 L/min (EVH<sub>HIGH</sub>), a 6-min submaximal constant-load cycling test, and a maximal incremental cycling test. The O<sub>2</sub> cost of breathing was higher in HFpEF-Ob compared with CTL-nonOb (2.95 ± 0.66 vs. 2.11 ± 0.43 mL/L, <i>P</i> = 0.001) but was not different compared with CTL-Ob (2.48 ± 0.73 mL/L, <i>P</i> = 0.130 vs. HFpEF-Ob). The rating of perceived breathlessness (RPB) was ≥1-unit higher in HFpEF-Ob, which is considered clinically significant. The O<sub>2</sub> cost of breathing was associated with BMI (<i>r</i><sup>2</sup> = 0.457, <i>P</i> < 0.001), RPB (<i>r</i><sup>2</sup> = 0.280, <i>P</i> < 0.001), and peak oxygen consumption ([Formula: see text]) in mL/min/kg (<i>r</i><sup>2</sup> = 0.161, <i>P</i> = 0.006). These findings suggest that the magnitude of obesity could increase the O<sub>2</sub> cost of breathing, which could subsequently contribute to greater sensations of DOE and exercise intolerance in patients with HFpEF and obesity.<b>NEW & NOTEWORTHY</b> This study shows that the oxygen cost of breathing is higher in patients with heart failure with preserved ejection fraction and obesity compared with healthy older adults without obesity but is not different from that of healthy older adults with obesity. A higher oxygen cost of breathing is further associated with a greater magnitude of obesity, more pronounced exertional dyspnea, and reduced exercise tolerance.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"610-618"},"PeriodicalIF":3.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13474405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148536123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Laura Leuci, Jørgen Melau, Antonio Messina, Mike Tipton, Luca Carenzo
{"title":"Beyond hypothermia: mechanisms of death, rescue, and prevention in cold water immersion.","authors":"Laura Leuci, Jørgen Melau, Antonio Messina, Mike Tipton, Luca Carenzo","doi":"10.1152/japplphysiol.00578.2026","DOIUrl":"10.1152/japplphysiol.00578.2026","url":null,"abstract":"<p><p>Cold water immersion (CWI) is a significant cause of open-water drowning mortality. Epidemiological data challenge the prevailing assumption that hypothermia is the primary mechanism of death, pointing instead to acute responses that precede core cooling. The four-stage model (cold shock response, swimming failure, hypothermia, and circum-rescue collapse) provides a framework for understanding the sequential threats faced by an immersion victim. The cold shock response, triggered within seconds of immersion, can cause death through aspiration, hypocapnia-induced cerebral hypoperfusion, and cardiac arrhythmia before core temperature begins to fall; autonomic conflict and underlying channelopathies are candidate mechanisms for sudden arrhythmic death in susceptible individuals. Swimming failure follows as peripheral neuromuscular cooling impairs motor function at near-normal core temperatures. Hypothermia develops only after sustained exposure, and in most cold water drowning deaths it occurs after aspiration-induced hypoxic arrest rather than as the primary cause of death. Circum-rescue collapse, driven primarily by the abrupt loss of hydrostatic pressure on extraction, also carries significant mortality risk. Although fewer than 10% of drowning victims present in a shockable rhythm, when such a rhythm is encountered it should prompt investigation for a primary arrhythmic cause that may have precipitated submersion. This narrative review examines the four-stage model of CWI in light of these developments and addresses the modifying effects of alcohol and psychoactive substances, self-rescue strategies, and implications for prehospital management.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"760-769"},"PeriodicalIF":3.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148630196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Association between neural-drive variability and motor function in middle-aged and older adults.","authors":"Roger M Enoka, Jacques Duchateau","doi":"10.1152/japplphysiol.00442.2026","DOIUrl":"10.1152/japplphysiol.00442.2026","url":null,"abstract":"<p><p>The purpose of this review was to examine the extent to which variability in the cumulative set of action potentials sent from the spinal cord (neural drive) to limb muscles can explain the variance in performance of middle-aged and older adults on the NIH Toolbox measures of motor function. Neural-drive variability is attributable to two spinal mechanisms: low-frequency oscillations in the shared synaptic input onto alpha motor neurons and synaptic noise in the generation and transmission of action potentials by individual motor neurons. Evidence indicates that the coefficient of variation for force during submaximal contractions (a behavioral proxy for neural-drive variability) explains moderate amounts of the variance in performance scores on the tests for balance, dexterity, and endurance, whereas locomotion is associated with motor-unit discharge characteristics in calf muscles and handgrip strength seems to be related to the timing of motor-unit activity across forearm-hand muscles. These findings indicate that some of the variance in performance on a range of dynamic motor tasks can be explained by neural-drive variability during submaximal isometric contractions. Future work needs to expand the repertoire of tasks from which measures of neural-drive variability are derived, which may increase its explanatory power for the observed variance in performance scores of middle-aged and older adults on Toolbox measures of motor function.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"745-759"},"PeriodicalIF":3.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148630222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rachel N Logue Cook, Adina F Turcu, Carrie A Karvonen-Gutierrez, Sandra K Hunter
{"title":"Sex hormones and menopause hormone therapy predict muscle strength across the lifespan.","authors":"Rachel N Logue Cook, Adina F Turcu, Carrie A Karvonen-Gutierrez, Sandra K Hunter","doi":"10.1152/japplphysiol.00366.2026","DOIUrl":"10.1152/japplphysiol.00366.2026","url":null,"abstract":"<p><p>Aging is associated with declines in muscle strength, yet after menopause the relative rate of decline is greater in females than males. Whether sex hormones are predictive of strength across the lifespan and with aging is largely unknown. This study assessed the impact of sex hormone concentrations and menopause hormone therapy (MHT) on muscle strength in aging. Handgrip strength, sex hormone concentrations {total testosterone, bioavailable testosterone [free androgen index (FAI)], estradiol, bioavailable estradiol [free estradiol index (FEI)]}, and history of female MHT use were extracted or calculated from the National Health and Nutrition Examination Survey (NHANES) for 4,330 participants (2,194 females). Males were 36%-40% stronger than females throughout adulthood. One-year averages of total testosterone (<i>r</i> = 0.48, <i>P</i> < 0.01), FAI (<i>r</i> = 0.86, <i>P</i> < 0.001), and FEI (<i>r</i> = 0.71, <i>P</i> < 0.001) were associated with strength in males. All hormones were correlated with strength in females, with estradiol (<i>r</i> = 0.81, <i>P</i> < 0.001) and FEI correlations (<i>r</i> = 0.82, <i>P</i> < 0.001) the strongest. Multiple linear regressions demonstrated that the FAI was a predictor of strength, whereas total testosterone was not, in both males and females, and that estradiol and FEI were indicative of female strength in later adulthood. Handgrip strength in older females with a history of MHT use was 1.9 kg greater than those with no MHT history (<i>P</i> < 0.01), and this advantage widened with age (2.4% at 60 yr to 14.3% at ≥80 yr). This study strongly suggests <i>1</i>) age-related declines in endogenous sex hormones, particularly bioavailable hormones, contribute to strength reductions with aging; and <i>2</i>) MHT may have the potential to offset meaningful strength reductions with advanced aging.<b>NEW & NOTEWORTHY</b> We demonstrate that sex hormone concentrations are associated with age-related declines in muscle strength across the lifespan. Bioavailable testosterone was a predictor of handgrip strength, whereas total testosterone was not in both males and females, and estradiol was a strong predictor of strength in females during midlife and older age. Furthermore, menopause hormone therapy may have beneficial effects on strength maintenance in older females, particularly in sedentary females.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"731-744"},"PeriodicalIF":3.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13555377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148603324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chiettha Prajnadewie, Billy L Luu, Harrison T Finn, Anandit J Mathew, Simon C Gandevia, Anna L Hudson, Jane E Butler
{"title":"Spinal root magnetic stimulation: evaluating the limitations of a less invasive method to assess voluntary activation of the respiratory muscles.","authors":"Chiettha Prajnadewie, Billy L Luu, Harrison T Finn, Anandit J Mathew, Simon C Gandevia, Anna L Hudson, Jane E Butler","doi":"10.1152/japplphysiol.00960.2025","DOIUrl":"10.1152/japplphysiol.00960.2025","url":null,"abstract":"<p><p>Spinal root magnetic stimulation can be used to assess diaphragm voluntary activation (VA), but its validity during inspiratory efforts remains unclear. In addition, its use to evaluate abdominal muscle VA during expiratory efforts has not been explored. This study investigates spinal root magnetic stimulation as a method to assess VA of inspiratory and expiratory muscles. In 13 healthy participants (8 female, 18-40 yr), magnetic stimulation was delivered over the cervical spine (C6) and lower thoracic spine (T10) to activate the diaphragm (<i>n</i> = 11) during inspiratory efforts and the abdominal muscles (<i>n</i> = 11) during expiratory efforts, respectively. A nasogastric catheter recorded inspiratory transdiaphragmatic and expiratory gastric pressures. During voluntary 25/50/75/100% maximal inspiratory and expiratory efforts, stimuli were delivered at 100% stimulator output to produce a superimposed twitch and, ∼5 s later, a resting twitch, to calculate VA. Good utility of the technique was assessed per individual as <i>r</i><sup>2</sup> ≥ 0.7 and 95% prediction interval (95% PI) limits within 25% of the predicted VA. For inspiratory muscles, VA had poor correspondence and predictability (<i>r</i><sup>2</sup> = 0.26-0.85; 95% PI limits: 27.1%-74.5%) with contraction intensity in 8/11 participants and good correspondence and predictability (<i>r</i><sup>2</sup> = 0.83-0.90; 95% PI limits: 22.7%-23.8%) in 3/11 participants. For expiratory muscles, VA had good correspondence and predictability (<i>r</i><sup>2</sup> = 0.73-0.97; 95% PI limits: 10.4%-20.8%) with contraction intensity in 7/11 participants and poor correspondence and predictability (<i>r</i><sup>2</sup> = 0.13-0.72; 95% PI limits: 19.0%-40.0%) in 4/11 participants. Spinal root magnetic stimulation can be used with caveats to assess expiratory muscle VA only, requiring individualized testing across multiple contraction intensities and a comparison of estimated versus measured resting twitches.<b>NEW & NOTEWORTHY</b> Magnetic stimulation of the cervical spinal roots cannot be used to assess voluntary activation of the diaphragm reliably during inspiratory efforts. However, magnetic stimulation of the thoracic spinal roots could be used to assess abdominal muscle voluntary activation during expiratory efforts but, importantly, required estimation of the twitch response at rest. This novel, less invasive method may be used to assess expiratory muscle activation, but requires testing across a range of contraction intensities.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"702-715"},"PeriodicalIF":3.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J Pierre Zila-Velasque, Pamela Grados-Espinoza, Sebastian Abanto-Urbano, Mely Olarte-Durand, Martha I Vilca-Salas, Paula C Moran-Ballon, Carlos Quispe-Vicuña, Victor Velasquez-Rimachi, Joel Sequeiros, Kateriny Margot Regalado-Rodriguez, Patrick E Zila-Velasque, Sthefano E Zila-Velasque, Sheidy Clemente-Tueros, Fernando Terry, Carlos Alva-Diaz
{"title":"Cerebral hemodynamic changes at high altitude in adults: a systematic review and meta-analysis of transcranial Doppler and duplex ultrasound studies.","authors":"J Pierre Zila-Velasque, Pamela Grados-Espinoza, Sebastian Abanto-Urbano, Mely Olarte-Durand, Martha I Vilca-Salas, Paula C Moran-Ballon, Carlos Quispe-Vicuña, Victor Velasquez-Rimachi, Joel Sequeiros, Kateriny Margot Regalado-Rodriguez, Patrick E Zila-Velasque, Sthefano E Zila-Velasque, Sheidy Clemente-Tueros, Fernando Terry, Carlos Alva-Diaz","doi":"10.1152/japplphysiol.00176.2026","DOIUrl":"10.1152/japplphysiol.00176.2026","url":null,"abstract":"<p><p>Exposure to intermediate and high altitude induces hypobaric hypoxia, which may alter cerebral hemodynamics through complex interactions involving hypoxia-driven vasodilation, hypocapnia, hematologic changes, and vascular remodeling; however, cerebrovascular responses vary substantially between native high-altitude populations and lowlander individuals. We conducted a systematic review and meta-analysis to quantify altitude-related changes in cerebral blood flow (CBF) and related hemodynamic parameters and to explore sources of heterogeneity. Major databases were searched through inception to November 2025 for observational studies evaluating cerebral hemodynamics at ≥1,500 m above sea level. Outcomes included mean velocity (MV), volumetric blood flow, arterial diameter, cerebrovascular conductance, cerebral oxygen saturation, autoregulation index, and global CBF. Random-effects models (Paule-Mandel) were used to pool mean differences, with subgroup and metaregression analyses performed; certainty of evidence was assessed with GRADE. Fifty-five studies including 1,935 participants were analyzed. Altitude exposure was associated with a reduction in mean cerebral artery velocity [mean difference (MD) -5.79 cm/s; 95% confidence interval (CI) -9.37 to -2.21; <i>I</i><sup>2</sup> = 96%], reduced volumetric blood flow (MD -32.99 mL/min; 95% CI -45.24 to -20.73; <i>I</i><sup>2</sup> = 98%), decreased arterial diameter (MD -0.27 mm; 95% CI -0.45 to -0.08; <i>I</i><sup>2</sup> = 91%), lower cerebrovascular conductance (MD -0.43 mL/min/mmHg; 95% CI -0.65 to -0.21; <i>I</i><sup>2</sup> = 24%), reduced cerebral oxygen saturation (MD -4.45%; 95% CI -6.77 to -2.14; <i>I</i><sup>2</sup> = 74%), and lower global cerebral blood flow (MD -155.00 mL/min; 95% CI -350.11 to 40.11; <i>I</i><sup>2</sup> = 95%), although heterogeneity was substantial across outcomes. Subgroup analyses suggested that native high-altitude populations and lowlander individuals exhibit distinct cerebrovascular responses, with population status, age, and altitude level explaining part of the observed variability. Overall certainty of evidence was very low. These findings indicate that exposure to altitude is associated with heterogeneous but consistent alterations in cerebral hemodynamic parameters, with marked differences between native and nonnative populations, underscoring the importance of population-specific physiological adaptation when interpreting cerebrovascular responses to hypoxia.<b>NEW & NOTEWORTHY</b> In this first global meta-analysis of ultrasound-based cerebral hemodynamics at ≥1,500 m, we show that altitude exposure is associated with lower cerebral blood flow velocity, volumetric flow, arterial diameter, and oxygen saturation in healthy adults. Native status, age, and altitude level partly explain marked heterogeneity. These findings highlight distinct adaptive patterns between native and nonnative populations and underscore the need for standardized, longitudinal s","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"717-730"},"PeriodicalIF":3.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148561935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Reliability and validity of surface electromyography to identify contractile muscle fatigue during cycling in people with COPD.","authors":"Simone Pancera, Paulien Mellaerts, Daniel Langer, Mathieu Brancaleone, Mykyta Chunikhin, Luc Janssens, Bart Vanrumste, Wim Janssens, Stephanie Everaerts, Heleen Demeyer, Thierry Troosters","doi":"10.1152/japplphysiol.00541.2026","DOIUrl":"10.1152/japplphysiol.00541.2026","url":null,"abstract":"<p><p>Surface electromyography (sEMG) may provide reliable biomarkers of contractile muscle fatigue (CMF) during exercise in chronic obstructive pulmonary disease (COPD). This study aimed to: <i>1</i>) determine the test-retest reliability of amplitude- and frequency-based sEMG metrics recorded from the quadriceps muscle during a constant-work-rate cycling test (CWRT); <i>2</i>) assess their criterion validity for detecting CMF against potentiated twitch force (TWp); and <i>3</i>) explore associations between sEMG metrics and physiological outcomes. Adults with COPD referred for pulmonary rehabilitation performed two CWRTs to the limit of tolerance (<i>T</i><sub>lim</sub>) at 75%-80% of the individual peak workload, with physiological responses recorded. CMF was assessed by: <i>1</i>) amplitude- (root mean square, RMS) and frequency-based sEMG metrics recorded from the right quadriceps, analyzed per pedal stroke and expressed as <i>Z</i>-score changes at <i>T</i><sub>lim</sub> relative to a fatigue-free baseline; and <i>2</i>) the postexercise change in TWp of the right quadriceps. Relative and absolute test-retest reliability, and criterion validity of sEMG against TWp were assessed. Twenty-five participants completed the assessments. Among the sEMG metrics, only vastus lateralis RMS showed adequate relative reliability [intraclass correlation coefficient (95% CI) = 0.79 (0.74-0.85)] but a nonnegligible standard error of measurement of 0.58. Moreover, vastus lateralis RMS showed 86% sensitivity and specificity versus TWp in identifying CMF. An increase of ≥0.65 <i>Z</i>-scores identified the threshold for sEMG-based CMF. Changes in vastus lateralis RMS were moderately correlated with physiological responses at <i>T</i><sub>lim</sub> (<i>P</i> < 0.05). In conclusion, vastus lateralis RMS derived from sEMG can be used as a biomarker of CMF during cycling in individuals with COPD.<b>NEW & NOTEWORTHY</b> This study provides novel evidence that exercise-induced changes in the amplitude of the vastus lateralis surface electromyography signal during a standardized constant-work-rate cycling test can represent a reliable and valid biomarker of quadriceps contractile muscle fatigue in individuals with moderate-to-severe COPD.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"840-850"},"PeriodicalIF":3.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148724477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Virginia G Content, Alexandria R McKenna, Auni C Williams, Jody L Greaney, Anna E Stanhewicz, Lacy M Alexander
{"title":"Methods for analyzing acetylcholine-induced vasodilation in human skin.","authors":"Virginia G Content, Alexandria R McKenna, Auni C Williams, Jody L Greaney, Anna E Stanhewicz, Lacy M Alexander","doi":"10.1152/japplphysiol.00379.2026","DOIUrl":"10.1152/japplphysiol.00379.2026","url":null,"abstract":"<p><p>Intradermal microdialysis, combined with laser-Doppler flowmetry and local heating, is commonly used to investigate mechanisms of endothelial function and dysfunction in the cutaneous microcirculation. Local perfusion of acetylcholine (ACh), with and without <i>N</i><sup>G</sup>-nitro-l-arginine methyl ester [l-NAME; a nonselective nitric oxide (NO) synthase inhibitor], allows for direct assessment of pharmacologically induced endothelium- and NO-dependent vasodilation. However, variability in the analysis and reporting of cutaneous vascular conductance (CVC) responses to in vivo cholinergic stimulation limits reproducibility. The purpose of this investigation was to compare analytical approaches used to quantify in vivo cutaneous vasodilation by retrospectively analyzing ACh dose-response data and NO-dependent vasodilation using five methods. Curve-modeling approaches included nonlinear regression with: <i>1</i>) no constraints, <i>2</i>) Hill slope constraint, and <i>3</i>) top and bottom constraints. Point-by-point analysis and area under the dose-response curve (AUC) were also evaluated following graded ACh perfusion with and without l-NAME coperfusion. Nonlinear regression without constraints exhibited the highest rate of data exclusion due to poor model fit. Although all analysis methods detected the expected differences in CVC responses between ACh with and without l-NAME, each approach had distinct limitations. Nonlinear regression provides detailed pharmacodynamic parameters, including maximal and minimal vasodilator responses, logEC<sub>50</sub>, and Hill slope, whereas point-by-point analysis and AUC offer straightforward quantitative assessments of NO-dependent vasodilation. Based on this retrospective analysis, we recommend the unconstrained model (<i>methods 1A/1B</i>) for characterizing the ACh dose-response relation, as the curves best reflect the visualized data. Point-by-point analysis, AUC, and l-NAME-sensitive component calculations may be more appropriate for quantifying NO-dependent vasodilation.<b>NEW & NOTEWORTHY</b> Although dose-response curves are commonly used to characterize in vivo cutaneous cholinergic vasodilator responses, modeling parameters and analytical approaches vary widely across studies. Here, we compare five methods applied to graded acetylcholine perfusion with and without <i>N</i><sup>G</sup>-nitro-l-arginine methyl ester [l-NAME; a nonselective nitric oxide (NO) synthase inhibitor] coperfusion to quantify NO-dependent vasodilation. We highlight key advantages and limitations of each method and provide practical recommendations for their implementation.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"933-944"},"PeriodicalIF":3.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13629242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148813141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}