Journal of applied physiology最新文献

{"title":"Motor unit discharge behavior in human muscles throughout force gradation: a systematic review and meta-analysis with meta-regression.","authors":"J Greig Inglis, Hélio V Cabral, Caterina Cosentino, Alberto Bonardi, Francesco Negro","doi":"10.1152/japplphysiol.00863.2024","DOIUrl":"10.1152/japplphysiol.00863.2024","url":null,"abstract":"<p><p>The analysis of motor unit (MU) discharge behavior provides an effective way of assembling information about the generation and control of movement. In this systematic review and meta-analysis, we identified and summarized the literature investigating MU discharge rate and discharge rate variability (CoV-ISI) during voluntary isometric contractions at various force levels. Databases were searched up to January 7, 2025, and a total of 262 studies were included. The meta-means of MU discharge rate and CoV-ISI were estimated and compared across human muscles. The influence of contraction intensity on MU discharge behavior was assessed through linear meta-regressions. At low-to-moderate forces [<60% maximal voluntary contraction (MVC)], the first dorsal interosseous, biceps brachii (BB), and forearm extensors (FEs) had the highest discharge rate, whereas the soleus had the lowest. At high force levels (>60% MVC), the tibialis anterior (TA) had the highest mean discharge rate compared with all other muscles, with the soleus maintaining the lowest. Regarding CoV-ISI results at low forces (<30% MVC), the TA had the lowest CoV-ISI values, except in comparison with the vastii. In addition, the vastii had lower CoV-ISI values than the FE, gastrocnemius medialis, and soleus. Contraction intensity was positively associated with the mean discharge rates in all muscles investigated, although some muscles showed steeper slopes than others. Similar results were observed for CoV-ISI meta-regressions, with muscle-specific differences in slope. These findings suggest potential variations in neural control strategies across muscles during force gradation, such as differences in the relative contribution of rate coding to facilitate increasing force demands.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1050-1065"},"PeriodicalIF":3.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648606","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":"Eight weeks of eccentric training at long-muscle length increases fascicle length independently of adaptations in passive mechanical properties.","authors":"Baptiste Bizet, Antoine Nordez, Tristan Tallio, Lilian Lacourpaille, Thomas Cattagni, Julian Colard, Yohan Betus, Sylvain Dorel, Aurélie Sarcher, Olivier Seynnes, Ricardo J Andrade","doi":"10.1152/japplphysiol.00859.2024","DOIUrl":"10.1152/japplphysiol.00859.2024","url":null,"abstract":"<p><p>Eccentric exercise training is believed to induce an increase in muscle fascicle length. However, the mechanisms underlying this adaptation are not fully understood. This study aimed to determine if an increase in gastrocnemius medialis fascicle length following an 8-wk eccentric training is linked to changes in muscle tissue and joint mechanical properties. Thirty-three physically active young adults were assigned to one of the two training protocols targeting the plantar flexors: eccentric exercise at <i>1</i>) long-muscle length or <i>2</i>) short-muscle length. Fascicle length and muscle shear modulus of the gastrocnemius medialis were assessed using ultrasound imaging during passive ankle rotations, alongside measurements of passive ankle torque. A total of 27 participants successfully completed the training program and data processing stage (long-muscle length, <i>n</i> = 15; short-muscle length, <i>n</i> = 12). Maximal voluntary isometric torque increased significantly following the training programs (9.5%), with no differences between training groups. An increase in fascicle length (mean 8.5%) was observed in the long-muscle length group, from 39.5 ± 0.7° to 36.8 ± 0.8° in plantar flexion, but not in the short-muscle length group. Notably, this macrostructural adaptation was detected only at muscle lengths shorter than the slack length (i.e., absence of any muscle passive tension). The eccentric training did not alter the muscle shear modulus or slack length. Collectively, these findings suggest that fascicle length adaptations in response to eccentric training were unrelated to changes in passive muscle-tendon mechanical properties. Consequently, the increase in fascicle length may be attributed to an increase in sarcomere length and/or an addition of sarcomeres in series.<b>NEW & NOTEWORTHY</b> We demonstrate that an 8-wk eccentric training program significantly increases gastrocnemius medialis fascicle length in humans, independent of any adaptions in passive muscle-tendon mechanical properties. Fascicle length adaptions were specific to the group that trained at long-muscle lengths, highlighting the importance of the muscle-tendon length range during eccentric exercise programs. This factor may be crucial for fine-tuning structural adaptations at the fascicle level, likely through the addition of sarcomeres in series.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"939-949"},"PeriodicalIF":3.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573036","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":"Redefining muscular action: human \"adductor\" magnus is designed to act primarily for hip \"extension\" rather than adduction in living young individuals.","authors":"Katsuki Takahashi, Hironoshin Tozawa, Raki Kawama, Taku Wakahara","doi":"10.1152/japplphysiol.00600.2024","DOIUrl":"10.1152/japplphysiol.00600.2024","url":null,"abstract":"<p><p>Human leg muscles are uniquely enlarged for upright bipedalism, and the adductor magnus is one of the largest muscles. Although this muscle is recognized as a hip adductor, hip adduction torque is not greatly required during human locomotion, such as walking and running. The functional role of this giant muscle remains unclear. Here, we tested the hypothesis that the human adductor magnus acts primarily for hip extension rather than adduction in living young individuals. Utilizing diffusion tensor imaging, we reconstructed fascicles over the entire muscle in 15 young adults at the hip neutral position. We divided the muscle into three portions based on fascicle insertion and examined their three-dimensional architectures. The posterior and anterior-distal portions comprised over 80% of the whole muscle volume and physiological cross-sectional area. These portions demonstrated a longer moment arm for hip extension than adduction. Consequently, the potential torque (maximal torque-generating capacity) of the whole muscle was over twofold greater for hip extension than adduction. The hip extension potential torque was correlated with the maximal hip extension torque measured with a dynamometer. These results highlight the architectural design of the adductor magnus, favoring hip extension over adduction, providing novel insights into its functional role beyond the frontal plane in human locomotor mechanics.<b>NEW & NOTEWORTHY</b> The human adductor magnus, one of the largest leg muscles, is traditionally considered a hip \"adductor.\" However, its functional role is unclear. We found that the torque-generating capacity of this muscle for hip extension was substantially greater than that for hip adduction and explained the exerted torque for hip extension. Our findings highlight the important role of the adductor magnus as a major hip \"extensor,\" having implications for mechanisms of human locomotion and musculoskeletal simulations.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1088-1099"},"PeriodicalIF":3.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730169","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":"Cerebrovascular responses to muscle metaboreflex activation in patients living with heart failure with reduced ejection fraction.","authors":"Thomas J Jurrissen, Adam M S Luchkanych, Natasha G Boyes, Rory A Marshall, M Rafique Khan, Alexander Zhai, Haissam Haddad, Darcy D Marciniuk, Corey R Tomczak, T Dylan Olver","doi":"10.1152/japplphysiol.00834.2024","DOIUrl":"10.1152/japplphysiol.00834.2024","url":null,"abstract":"<p><p>Impaired cerebrovascular control in patients with heart failure with reduced ejection fraction (HFrEF) has been attributed to cardiac impairment and exaggerated sympathetic-mediated cerebral vasoconstriction. The goal of this study was to examine the effect of muscle metaboreflex activation (MMA) on cerebrovascular hemodynamics in patients with HFrEF under conditions of preserved cardiac output. It was hypothesized that reductions in the index of cerebral blood flow and cerebrovascular conductance (CVCi) during MMA would be exaggerated in HFrEF and independent of reduced cardiac output. Middle cerebral blood velocity (MCA_Vmean; transcranial Doppler), blood pressure, cardiac output (Finometer), and end-tidal CO₂ were examined at rest, during isometric handgrip, and during muscle MMA (postexercise circulatory occlusion) in 18 patients with HFrEF and 21 healthy, sex-, and age-matched controls. To minimize differences in β-adrenergic control, patients with HFrEF withdrew from β-blockade medications before the study. Cardiac index and blood pressure were not significantly different between groups under any condition. The MCA_Vmean was lower at rest and during exercise in HFrEF. The CVCi (MCA_Vmean/mean arterial pressure) and MCA_Vmean decreased during MMA in the control group. In contrast, the CVCi remained unchanged and MCA_Vmean increased during MMA in the HFrEF group. Despite similar systemic hemodynamics, patients with HFrEF display lower MCA_Vmean at rest and an increase in MCA_Vmean during MMA. These novel findings implicate aspects other than reduced cardiac output or exaggerated sympathetic constriction as underlying causes of altered cerebrovascular regulation in HFrEF.<b>NEW & NOTEWORTHY</b> Compared with controls, patients with heart failure with reduced ejection fraction (HFrEF) displayed reduced indices of cerebral perfusion at rest and increases in perfusion in response to postexercise circulatory occlusion (PECO, method to isolate muscle metaboreflex activation). This occurred despite similar cardiac output and blood pressure values between groups. Thus, lower resting indices of cerebral perfusion and increased perfusion during sympathoexcitation in HFrEF may occur independently from differences in systemic hemodynamics.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"891-898"},"PeriodicalIF":3.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542044","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":"Heart rate variability during exercise can quantify cardiorespiratory deconditioning in 55- to 65-yr-old men and women exposed to head-down bed rest.","authors":"Jeremy Rabineau, Eric T Hedge, Roxanne Fournier, Carmelo J Mastrandrea, Richard L Hughson","doi":"10.1152/japplphysiol.00017.2025","DOIUrl":"10.1152/japplphysiol.00017.2025","url":null,"abstract":"<p><p>The heart rate variability (HRV) features HRV_0.75 and HRV_0.5, obtained by detrended fluctuation analysis during incremental cycle ergometer tests, have been shown to correlate with indices of cardiorespiratory fitness. Here, we evaluate the ability of these features to track individual changes in cardiorespiratory fitness induced by head-down bed rest (HDBR) among late middle-aged adults. Twenty-two healthy participants (55-65 yr old, 11 women) were exposed to 14-day HDBR. Eleven participants were assigned to a group performing daily aerobic and resistive exercises during HDBR, whereas the others were assigned to a control group with no countermeasure intervention. We measured gas exchange and electrocardiography during incremental cycle ergometer tests pre- and post-HDBR. The countermeasure preserved oxygen uptake (V̇o₂) at the two ventilatory thresholds (VT1 and VT2), HRV_0.75 and HRV_0.5. However, these four features decreased in the control group after HDBR. A large and proportional bias was evidenced between V̇o₂ at VT1 and HRV_0.75, which was less the case for V̇o₂ at VT2 versus HRV_0.5. However, the intraindividual changes in the control group were correlated (<i>r</i>_rm = 0.66 for VT1 vs. HRV_0.75 and <i>r</i>_rm = 0.82 for V̇o₂ at VT2 vs. HRV_0.5, both <i>P</i> < 0.001). Overall, this study indicated that HRV_0.75 and HRV_0.5 can be used to longitudinally monitor changes in cardiorespiratory fitness in late middle-aged adults with physical deconditioning. Future research can apply these methods to other study populations.<b>NEW & NOTEWORTHY</b> We report the applicability of two heart rate variability features (HRV_0.75, HRV_0.5) computed during exercise to assess changes in cardiorespiratory fitness. Although previous cross-sectional studies suggested that these features were highly correlated to the ventilatory thresholds, we highlight the fact that they should not be considered as equivalent. More easily obtained than ventilatory thresholds, HRV_0.75 and HRV_0.5 could be used as fitness markers along a continuum of the physiological response between rest and maximal exercise.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1002-1010"},"PeriodicalIF":3.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657381","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":"Sexually dimorphic mechanisms of H₂O₂-mediated dilation in porcine coronary arterioles with ischemia and endurance exercise training.","authors":"Kalen Johnson, Jeff F Bray, Cristine L Heaps","doi":"10.1152/japplphysiol.00761.2024","DOIUrl":"10.1152/japplphysiol.00761.2024","url":null,"abstract":"<p><p>We determined the impact of sex on H₂O₂-mediated dilation in coronary arterioles and the contribution of K⁺ channels after exercise training in ischemic heart disease. We hypothesized that arterioles from male and female swine would similarly display impaired H₂O₂-induced dilation after chronic occlusion that would be corrected by exercise training. Yucatan miniswine were surgically instrumented with an ameroid constrictor around the proximal left circumflex artery, gradually inducing occlusion and a collateral-dependent myocardium. Arterioles from the left anterior descending artery myocardial region served as nonoccluded controls. Eight weeks postoperatively, swine of each sex were separated into sedentary and exercise-trained (progressive treadmill regimen; 5 days/wk for 14 wk) groups. Collateral-dependent arterioles of sedentary female pigs displayed impaired sensitivity to H₂O₂ that was reversed with exercise training. In contrast, male pigs exhibited enhanced sensitivity to H₂O₂ in collateral-dependent versus nonoccluded arterioles in both sedentary and exercise-trained groups. Large-conductance, calcium-dependent K⁺ (BKCa) and 4-aminopyridine (AP)-sensitive voltage-gated K⁺ (Kv) channels contributed to H₂O₂-mediated dilation in nonoccluded and collateral-dependent arterioles of exercise-trained females, but not in arterioles of sedentary female or sedentary or exercise-trained male swine. BKCa channel, protein kinase A (PKA), and protein kinase G (PKG) protein levels were not significantly different between groups, nor were kinase enzymatic activities. Taken together, our studies suggest that in female swine, exercise training stimulates the coupling of H₂O₂ signaling with BKCa and 4-AP-sensitive Kv channels, compensating for impaired dilation in collateral-dependent arterioles. Interestingly, coronary arterioles from neither sedentary female or male swine, regardless of training status, depended upon BKCa or 4-AP-sensitive Kv channels for H₂O₂-mediated dilation.<b>NEW & NOTEWORTHY</b> The current studies reveal sexually dimorphic adaptations to H₂O₂-mediated dilation, and unique contributions of K⁺ channels, in coronary arterioles from swine subjected to chronic ischemia and exercise training; findings important for development of therapeutic strategies. In female swine, chronic ischemia attenuates dilation, which is reversed by exercise training via BKCa and Kv channel stimulation. In male swine, ischemia enhances dilation to H₂O₂, which is further augmented by exercise training and independent of BKCa and Kv channels.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"950-963"},"PeriodicalIF":3.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584862","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":"Short bouts of hypoxia improve insulin sensitivity in adults with type 2 diabetes.","authors":"Jiahui Zhao, Sahar D Massoudian, Sten Stray-Gundersen, Frank Wojan, Sophie Lalande","doi":"10.1152/japplphysiol.00932.2024","DOIUrl":"10.1152/japplphysiol.00932.2024","url":null,"abstract":"<p><p>Hypoxia stimulates glucose uptake independently from the action of insulin. The purpose of this study was to determine the effect of intermittent hypoxia, consisting of alternating short bouts of breathing hypoxic and room air, on glucose concentration, insulin concentration, and insulin sensitivity during an oral glucose tolerance test in adults with type 2 diabetes and adults with normal glycemic control. Nine adults with type 2 diabetes (2 women, HbA1c: 7.3 ± 1.5%, age: 52 ± 13 yr) and nine adults with normal glycemic control (4 women, HbA1c: 5.4 ± 0.1%, age: 24 ± 4 yr) performed a 2-h oral glucose tolerance test on two separate visits to the laboratory. Following ingestion of the glucose drink, participants were exposed to either an intermittent hypoxia protocol, consisting of eight 4-min hypoxic cycles at a targeted oxygen saturation of 80% interspersed with breathing room air to resaturation, or a sham protocol consisting of eight 4-min normoxic cycles interspersed with breathing room air. Intermittent hypoxia did not attenuate the increase in glucose concentration but attenuated the increase in insulin concentration in response to an oral glucose tolerance test in comparison with the sham protocol in adults with type 2 diabetes. Insulin sensitivity was greater during intermittent hypoxia in comparison with the sham protocol in adults with type 2 diabetes (0.043 ± 0.036 vs. 0.032 ± 0.046 μmol/kg/min/pmol, <i>P</i> = 0.01), but did not change in the control group (0.122 ± 0.015 vs. 0.128 ± 0.008 μmol/kg/min/pmol, <i>P</i> = 0.12). In conclusion, intermittent hypoxia improved insulin sensitivity in adults with type 2 diabetes.<b>NEW & NOTEWORTHY</b> The aim of this study was to determine the effect of short bouts of hypoxia, which stimulates glucose uptake, on glucose concentration, insulin concentration, and insulin sensitivity during an oral glucose tolerance test in adults with type 2 diabetes and adults with normal glycemic control. Intermittent hypoxia acutely improved insulin sensitivity in adults with type 2 diabetes.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"873-880"},"PeriodicalIF":3.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515809","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":"Directional sensitivity analysis of the cerebral pressure-flow relationship during normothermia and moderate hyperthermia.","authors":"Mahmoudreza Taghizadeh, R Matthew Brothers, Lawrence Labrecque, Marc-Antoine Roy, Daniel Gagnon, Jonathan D Smirl, Craig G Crandall, Patrice Brassard","doi":"10.1152/japplphysiol.00712.2024","DOIUrl":"10.1152/japplphysiol.00712.2024","url":null,"abstract":"<p><p>Dynamic cerebral autoregulation (dCA) reacts differently when mean arterial pressure (MAP) increases versus decreases (i.e., directional sensitivity). Although heat stress alters dCA, its influence on directional sensitivity remains unclear. This analysis investigated the impact of moderate hyperthermia on the directional sensitivity in the cerebral pressure-flow relationship. Ten healthy participants (7 males; age: 37 ± 12 yr; body mass: 75 ± 9 kg) underwent 6 min of oscillatory lower body negative pressure (OLBNP) to induce large MAP fluctuations at 0.03 and 0.10 Hz under normothermic and moderately hyperthermic conditions (+1.0°C increase in core temperature) induced via a water-perfused suit. We calculated changes in middle cerebral artery mean blood velocity (MCAv) per alterations to MAP to compute absolute and relative ratios adjusted for time intervals during each OLBNP-induced MAP increase (ΔMCAv_T/[Formula: see text]; %MCAv_T/[Formula: see text]) and decrease (ΔMCAv_T/[Formula: see text]; %MCAv_T/[Formula: see text]). Thereafter, we compared average absolute and relative ratios. There was no main effect of MAP direction on ΔMCAv_T/ΔMAP_T or %MCAv_T/%MAP_T during either 0.03 Hz (<i>P</i> = 0.291, <i>P</i> = 0.281) or 0.10 Hz (<i>P</i> = 0.295, <i>P</i> = 0.178) OLBNP. Regardless of MAP direction, ΔMCAv_T/[Formula: see text] (0.65 ± 0.17 vs. 0.84 ± 0.22 cm·s^-1·mmHg^-1), ΔMCAv_T/[Formula: see text] (0.70 ± 0.15 vs. 0.85 ± 0.18 cm·s^-1·mmHg^-1) (thermal state: <i>P</i> = 0.009), %MCAv_T/[Formula: see text] (0.92 ± 0.22 vs. 1.33 ± 0.60), and %MCAv_T/[Formula: see text] (1.01 ± 0.27 vs. 1.30 ± 0.51) (thermal state: <i>P</i> = 0.001) were lower in hyperthermia at 0.03-Hz OLBNP. Regardless of thermal states, these findings suggest an absence of dCA directional sensitivity. Reduced directional sensitivity metrics during hyperthermia may indicate more efficient dCA at very low frequency.<b>NEW & NOTEWORTHY</b> Recent evidence highlights the importance of considering directional sensitivity in dynamic cerebral autoregulation. The current analysis found no directional sensitivity in the cerebral pressure-flow relationship during 0.03- and 0.10-Hz oscillatory lower body negative pressure in normothermia or moderate hyperthermia in healthy participants. However, reduced directional sensitivity metrics during moderate hyperthermia suggest that dynamic cerebral autoregulation may become more efficient under moderate heat stress.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1079-1087"},"PeriodicalIF":3.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12128508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730165","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}

{"title":"Whole genome transcriptomic profiling reveals distinct sex-specific responses to heat stroke.","authors":"Abderrezak Bouchama, Maria Gomez, Mashan L Abdullah, Saeed Al Mahri, Shuja Shafi Malik, Saber Yezli, Sameer Mohammad, Cynthia Lehe, Bisher Abuyassin, Robert Hoehndorf","doi":"10.1152/japplphysiol.00001.2025","DOIUrl":"10.1152/japplphysiol.00001.2025","url":null,"abstract":"<p><p>Heat-related mortality remains health challenges exacerbated by climate change, with sex-based differences in outcomes, yet underlying mechanisms remain poorly understood. This study examined transcriptomic responses to heat exposure in peripheral blood mononuclear cells from 19 patients with heat stroke (HS; 8 males, mean age 64.8 ± 6.6 yr; 11 females, mean age 49.7 ± 11 yr) and 19 controls (11 males, mean age 48.9 ± 9.6 yr; 8 females, mean age 44.9 ± 11.8 yr). At admission, gene expression revealed upregulation of heat shock protein genes, and pathway analysis demonstrated activation of heat shock and unfolded protein responses across both sexes consistent with proteotoxic stress. However, distinct metabolic, oxidative stress, cell cycle control, and immune responses were observed within each sex. Females displayed inhibition of protein synthesis, oxidative phosphorylation, and metabolic pathways, including glucose metabolism, indicative of a hypometabolic state. Males maintained metabolic activity precooling and enhanced adenosine triphosphate production postcooling. Females activated nuclear factor erythroid 2-related factor 2 (NRF2)-mediated oxidative stress responses and inhibited DNA replication and mitosis, potentially mitigating genomic instability, whereas these pathways showed limited regulation in males. Females promoted innate immunity via interleukin (IL)-6, inflammasome, and triggering receptor expressed on myeloid cells 1 (TREM1) signaling, whereas males showed suppression of both innate and adaptive immunity, including IL-12, Th1, and T-cell receptor pathways. Upstream analysis identified over 100 transcription factors in both sexes. Males primarily relied on transcriptional mechanisms, whereas females also exhibited translational regulation via La ribonucleoprotein 1 (LARP1), fragile X messenger ribonucleoprotein 1 (FMR1), insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1), and eukaryotic translation initiation factor 6 (EIF6). These findings suggest distinct, sex-specific molecular adaptations to heat stroke, underscoring the need for targeted therapeutic strategies to mitigate heat-induced morbidity and mortality.<b>NEW & NOTEWORTHY</b> Heat-related mortality continues to rise with climate change. Our transcriptomic analysis reveals distinct sex-specific metabolic strategies to heat stroke: females enter a hypometabolic state, an evolutionary adaptation that conserves energy, whereas males sustain metabolic activity. Transcription factors and a subset of translation regulators in females modulate proteostasis and bioenergetics, driving these sex-specific pathways. These novel findings highlight the critical need to consider sex-specific differences in heat-related illnesses and inform carefully targeted interventions to improve patient outcomes.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"964-978"},"PeriodicalIF":3.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604951","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":"Pharyngeal electrical stimulation favorably modifies healthy human pharyngoesophageal function: a randomized trial using high-resolution manometry impedance.","authors":"Marthe Everaert, Shaheen Hamdy, Ann Goeleven, Jan Tack, Tim Vanuytsel, Nathalie Rommel","doi":"10.1152/japplphysiol.00516.2024","DOIUrl":"10.1152/japplphysiol.00516.2024","url":null,"abstract":"<p><p>Despite positive clinical evidence for the effects of pharyngeal electrical stimulation (PES) on swallowing performance in disease, it remains unknown which specific swallow characteristics improve. Using high-resolution manometry impedance (HRMI) with pressure flow analysis (PFA), we aimed to assess the effects of PES on normal swallow function and to evaluate the impact of pharyngeal length variability on electrode placement. As part of a prospective randomized controlled trial (RCT), 20 asymptomatic volunteers were randomly assigned to 3 days of PES or SHAM treatment. HRMI assessments were conducted at baseline (during which pharyngeal length measurements were acquired) and repeated at 1-2 h, and at 24-72 h following PES or SHAM treatment. Twenty healthy adults [10 males, median age: 28.0 (interquartile range, IQR 23.8-45.0) yr, age range: 20-65 yr] participated in this RCT. We developed an objective, standardized method of catheter placement based on pharyngeal length measurements. Over 3 days, the median stimulation intensity of PES was 11 mA. When compared with the SHAM group, the PES group scored better on multiple pharyngeal and esophageal metrics resulting in improved global swallow function values 1-2 h after treatment (<i>P</i> = 0.029). One day later, most of these beneficial effects were no longer present. This study suggests that PES can temporarily alter swallow function in healthy individuals. Functional reserve in healthy individuals may be further enhanced by PES. In the majority of volunteers, electrode position needed to be adjusted 1-3 cm to account for variations in pharyngeal length.<b>NEW & NOTEWORTHY</b> Pharyngeal electrical stimulation (PES) positively influences clinical swallow-outcomes in patients with neurogenic dysphagia. Its effect on the underlying swallowing physiology remains unknown. Our study evaluated this effect of PES in healthy individuals using high-resolution manometry impedance. PES showed short-term improved pharyngeal contractility, upper esophageal sphincter relaxation, proximal esophageal contractility and bolus flow, resulting in improved swallowing. One day later, most of these beneficial effects were no longer present as expected in already intact swallow systems.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"988-1001"},"PeriodicalIF":3.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458023","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}