{"title":"Are biologically meaningful effect sizes a factor in study design? A systematic review of translational chronic variable stress studies.","authors":"Crispin Jordan, Nicola Romanò, John Menzies","doi":"10.1113/EP092884","DOIUrl":"https://doi.org/10.1113/EP092884","url":null,"abstract":"<p><p>The design of in vivo studies using laboratory animals is normally guided by the 3Rs: Replacement, Reduction and Refinement. The concept of Reduction is particularly important in the context of estimating sample size; the selected sample size should allow the detection of a predetermined effect size using appropriate statistical tests, but not at the expense of using too many animals. To explore this, we conducted a systematic review of animal studies using chronic variable stress to ask whether the authors used a biologically meaningful effect size to determine the sample size. Only one article in our sample of 385 reported doing this, and most articles did not report a justification for the sample size used. Determining a biologically meaningful effect size is not always straightforward, but all appropriately powered studies based on a biologically meaningful effect size are useful, including studies where the data do not support the hypothesis. Accordingly, we believe the use of biologically meaningful effect sizes is central to decisions about study design and interpretation, and we discuss reasons and ways to promote its use.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Milan Mohammad, Abdullahi A Mohamed, Jari Dahmen, Jonathan J Bjerre-Bastos, Andreas Pihl
{"title":"The art of sharing: From research to outreach in the social media era.","authors":"Milan Mohammad, Abdullahi A Mohamed, Jari Dahmen, Jonathan J Bjerre-Bastos, Andreas Pihl","doi":"10.1113/EP092887","DOIUrl":"https://doi.org/10.1113/EP092887","url":null,"abstract":"","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hyperthermia-induced cytotoxicity and modulation of PD-L1 and MHC-I expression in human non-small cell lung cancer cell lines.","authors":"Yun-Chieh Tu, Wei-Chen Yeh, Yi-Wei Fang, Ko-Hsuan Lo, Lei-Ni Liang, Xu-Chen Liu, Chia-Chi Tsai, Chih-Cheng Cheng, Meng-Chieh Lin, Hsin-Hsien Yu, Bor-Chyuan Su","doi":"10.1113/EP092791","DOIUrl":"https://doi.org/10.1113/EP092791","url":null,"abstract":"<p><p>Hyperthermia has recently been applied to treat human non-small cell lung cancer (NSCLC). However, the mechanisms underlying cytotoxic sensitivity of NSCLC cells to hyperthermia are not fully understood. In this study, five NSCLC cell lines with different epidermal growth factor receptor (EGFR), Kirsten rat sarcoma and tumor protein p53 mutation profiles (A549, H292, H1299, PC9 and H1975) were used to evaluate effects of hyperthermia. All tested cell lines except H1975 were sensitive to hyperthermia-induced cytotoxicity. Annexin V-propidium iodide double staining, Poly(ADP-ribose) polymerase (PARP) cleavage and scanning electron microscopy revealed that apoptosis and necrosis were induced by hyperthermia in different lines. Tetramethylrhodamine, ethyl ester analysis further revealed that hyperthermia affected mitochondrial function in the four hyperthermia-sensitive lines. Transmission electron microscopic analysis revealed degeneration of cristae and ruptured mitochondria upon exposure to hyperthermia. Hyperthermia also caused elevation of reactive oxygen species in sensitive cells. In addition to these effects, hyperthermia impacted cell survival-related signalling proteins (EGFR, FAK and Akt). In particular, hyperthermia increased phosphorylated EGFR but suppressed total EGFR, phosphorylated Akt and total Akt in sensitive cells. Moreover, hyperthermia could modulate immunomodulatory molecules. Major histocompatibility complex-I (MHC-I) and surface programmed death ligand-1 (PD-L1) were both elevated by hyperthermia in all tested NSCLC cell lines except PC9. Taken together, our findings provide insights into the potential influence of different somatic mutations in NSCLC cells on hyperthermia-induced cytotoxicity and regulation of key immunomodulatory molecules.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rachel M Cottle, Kat G Fisher, Olivia K Leach, David E Conroy, Lacy M Alexander, W Larry Kenney
{"title":"Intermittent hand and forearm immersion in 20°C water attenuates thermal, cardiovascular, and perceptual strain in older adults during heat stress.","authors":"Rachel M Cottle, Kat G Fisher, Olivia K Leach, David E Conroy, Lacy M Alexander, W Larry Kenney","doi":"10.1113/EP092789","DOIUrl":"https://doi.org/10.1113/EP092789","url":null,"abstract":"<p><p>Adults >65 years of age experience deleterious health effects during extreme heat events at a greater rate than any other age cohort. The purpose of this study was to identify the effectiveness of acute intermittent hand and forearm (H+F) water immersion and/or chronic (7 week) folic acid supplementation on reducing thermal and cardiovascular strain in older adults during heat stress. Twelve older adults (six female; 65-89 years of age) were exposed to 2 h of heat stress at 34°C and 77% relative humidity during seated rest, with and without H+F immersion, following folic acid or placebo supplementation. During immersion trials, participants immersed both H+F in cool tap water (∼20°C) for 10 min at min 60 and 90. Core temperature, skin temperature and heart rate were monitored continuously, and blood pressure and the rate-pressure product were recorded every 10 min. Data were analysed as absolute changes and as a delta from min 50 (i.e., immediately before cooling). There was no effect of folic acid on any variable (all p > 0.05). Absolute and delta core temperature, skin temperature and heart rate increased over time (p ≤ 0.041); however, H+F water immersion attenuated this increase (p ≤ 0.046) after the first cooling bout. Likewise, absolute and delta RPP increased over time (p ≤ 0.047), but absolute RPP was attenuated with H+F water immersion (p = 0.003). These data suggest that intermittent H+F water immersion effectively attenuates thermal and cardiovascular strain for older adults at rest during heat stress.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Unlimited adaptations of muscle fibres to exercise; are you kidding me?","authors":"Hans Degens, Paul Hendrickse","doi":"10.1113/EP092983","DOIUrl":"https://doi.org/10.1113/EP092983","url":null,"abstract":"","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"An eye on long-duration spaceflight: Controversies, countermeasures and challenges.","authors":"Vincent Wing Sum Ng, Susan Patricia Mollan","doi":"10.1113/EP091561","DOIUrl":"https://doi.org/10.1113/EP091561","url":null,"abstract":"<p><p>Space flight-associated neuroocular syndrome (SANS) is a consequence of long-duration space flight and is detected in two-thirds of astronauts. In-flight, this can cause a change in the refraction of the eyes, requiring graded hypermetropic 'superfocus adjustable' glasses, optic nerve head oedema and choroidal folds. While the optic disc oedema resolves on returning to gravitational force, the choroidal folds and axial length shortening remain. Controversy remains over the role of intracranial pressure in the development of these changes. A recent case report has re-energised the debate as to whether nutraceuticals and an individual's genetic expression of the 1-carbon metabolic pathway are a major component for the development of this condition. The strict 6° head down tilt bed rest platform remains the cornerstone for evaluating analogous pathological changes and trialling potential targeted therapies. The translational application of a glucagon-like peptide 1 receptor agonist for the treatment of raised intracranial pressure in idiopathic intracranial hypertension may be of significance as a potential countermeasure for SANS. The aim of this narrative review is to explore the controversies in the integration of the presumed pathophysiological factors and to debate suitable countermeasures.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Phillip J Wallace, Steve Lidstone, Josh G Nowlan, Johnathan Ljubanovich, Brandon J McKinlay, Stephen A Klassen, Stephen S Cheung
{"title":"Individuals with persisting post-concussion symptoms with physiological subtype demonstrate altered cardiovascular and autonomic responses to face cooling.","authors":"Phillip J Wallace, Steve Lidstone, Josh G Nowlan, Johnathan Ljubanovich, Brandon J McKinlay, Stephen A Klassen, Stephen S Cheung","doi":"10.1113/EP092583","DOIUrl":"https://doi.org/10.1113/EP092583","url":null,"abstract":"<p><p>Individuals with persisting post-concussion symptoms with physiological subtype (PPCS-P) demonstrate exercise intolerance due to exacerbation of concussion-like symptoms during incremental exercise. We tested the hypothesis that individuals with PPCS-P (n = 12) would have a blunted cardiac autonomic response to face cooling compared to healthy controls (CTRL, n = 12). Participants were supine and performed a 5 min baseline, then experienced a 3 min face cold pressor test followed by 5 min of recovery. A three-lead electrocardiogram was used to measure heart rate and root mean square of successive differences in R-R intervals (RMSSD), finger photoplethysmography was used to measure mean arterial pressure (MAP), and laser-Doppler flowmetry was used to measure finger skin blood flux. The PPCS-P group had a lower exercise tolerance (9.9 ± 3.2 min, P < 0.001) and lower peak heart rate (170.0 ± 14.0 beats·min<sup>-1</sup>, P < 0.001) compared to CTRL (19.6 ± 2.5 min; 193.0 ± 5.0 beats·min<sup>-1</sup>). PPCS-P demonstrated a blunted mean heart rate (CTRL: ∆-4.0 ± 5.0 beats·min<sup>-1</sup>, PPCS-P: ∆2.0 ± 4.0 beats·min<sup>-1</sup>; group effect: P < 0.001) and mean RMSSD (CTRL: ∆26.6 ± 34.7 ms, PPCS-P: ∆-1.8 ± 33.9 ms; group effect: P = 0.026) responses at 2 min of face cooling compared to CTRL. Both groups had a significant increase in MAP during face cooling, where at 2 min, MAP was higher in PPCS-P (∆+13.2 ± 5.5 mmHg) compared to CTRL (∆+8.7 ± 6.9 mmHg, group effect: P < 0.001). Furthermore, PPCS-P had a sustained lower finger skin blood flux (group effect: P < 0.001) during face cooling (PPCS-P: ∆-48.2 ± 27.1%, CTRL: ∆-12.8 ± 24.7% at 2 min). These data suggest that individuals with PPCS-P demonstrate altered cardiac and peripheral autonomic function during face cooling compared to healthy controls.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anna Simon, Richard A Lofthouse, Philip Miti, Robert W Banks, Guy S Bewick
{"title":"Calcium regulation of muscle spindle mechanosensory afferent function.","authors":"Anna Simon, Richard A Lofthouse, Philip Miti, Robert W Banks, Guy S Bewick","doi":"10.1113/EP092558","DOIUrl":"https://doi.org/10.1113/EP092558","url":null,"abstract":"<p><p>Extracellular calcium is crucial for the normal function of muscle spindle sensory afferents. They express multiple calcium buffering proteins. Extracellular calcium is essential for recycling of synaptic-like vesicles (SLVs) in the terminals and for the stretch-evoked inward calcium current of the receptor potential. Conversely, removal of calcium from the extracellular medium abolishes stretch-evoked action potentials (APs). However, the calcium channel(s) involved and mechanism(s) of action are unknown. This study begins identifying the channels involved and their actions. Specific calcium channel toxins, agonists and antagonists were examined for effects on stretch-evoked muscle spindle afferent discharge, and live spindle sensory terminal labelling with FM1-43 was used to monitor SLV recycling in adult rat lumbrical muscle. Voltage-gated calcium channels, particularly P/Q-type (Ca<sub>v</sub>2.1) and L-type (Ca<sub>v</sub>1.1-1.4), strongly regulated the firing frequency of APs in response to a standard stretch, probably by regulating the opening of 'big', 'intermediate' and 'small' calcium-activated potassium channels (K<sub>Ca</sub>), with direct evidence for BK (K<sub>Ca</sub>1.1), SK (most likely K<sub>Ca</sub>2.2) and IK (K<sub>Ca</sub>3.1) involvement. Moreover, calcium from two different sources regulated separate aspects of SLV recycling. Thus, L-type channel blockers inhibited FM1-43 release, while TRPV4 (transient receptor potential, vanilloid, type 4) channel blockers entirely inhibited FM1-43 uptake. No role in SLV recycling was found for P/Q type channels, and no role at all was found for N-type (Ca<sub>v</sub>2.3) channels. Overall, these studies pinpoint multiple different aspects of calcium signalling, through different channel families, and produce the first evidence of a role for a mechanosensory TRPV4 channel in muscle spindle sensory terminal function.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Spaceborne and spaceborn: Physiological aspects of pregnancy and birth during interplanetary flight.","authors":"Arun V Holden","doi":"10.1113/EP092290","DOIUrl":"https://doi.org/10.1113/EP092290","url":null,"abstract":"<p><p>Crewed interplanetary return missions that are on the planning horizon will take years, more than enough time for initiation and completion of a pregnancy. Pregnancy is viewed as a sequence of processes - fertilization, blastocyst formation, implantation, gastrulation, placentation, organogenesis, gross morphogenesis, birth and neonatal development - each of which needs to be completed successfully, and each of which has a probability of success. The effects of the environment of interplanetary flight - microgravity and galactic cosmic rays (GCR) - on these probabilities are inferred from Earth and low Earth orbit experiments and observations and current models of morphogenesis. The principal hazards for intrauterine development are due to interactions with GCRs, where a variable flux of high energy particles would be interacting with a growing embryonic and fetal target volume, and produce linear tracks of ionization-associated damage. Short term damage would be predominantly mediated via reactive oxygen species, and long-term damage via DNA. Exposure to GCRs is expected to increase the probabilities of implantation failure and of premature labour. A live healthy birth would be possible, but its likelihood reduced. The long time scale of growth and development of the neonatal brain makes delayed manifestation of neurological or behavioural disorders likely.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lawrence Labrecque, Marc-Antoine Roy, Shahrzad Soleimani Dehnavi, Mahmoudreza Taghizadeh, Joel S Burma, Jonathan D Smirl, Patrice Brassard
{"title":"Quantification of the cerebral pressure-flow relationship directional sensitivity: Reliability of shorter repeated squat-stand durations.","authors":"Lawrence Labrecque, Marc-Antoine Roy, Shahrzad Soleimani Dehnavi, Mahmoudreza Taghizadeh, Joel S Burma, Jonathan D Smirl, Patrice Brassard","doi":"10.1113/EP092357","DOIUrl":"https://doi.org/10.1113/EP092357","url":null,"abstract":"<p><p>The magnitude of changes in middle cerebral artery mean blood velocity (MCAv) is attenuated when mean arterial pressure (MAP) increases compared with when MAP decreases. This directional sensitivity has been characterized using a time-corrected ratio calculated on MCAv and MAP changes induced by repeated squat-stands (RSS) at 0.05 and 0.10 Hz for 300 s (∆MCAv<sub>T</sub>/∆MAP<sub>T</sub>). Herein, we examined the reliability of the metric within reduced RSS durations. Ninety-nine (25 females) healthy human participants (26 ± 5 years) performed 300 s RSS at 0.05 Hz (20 s cycles) and 0.10 Hz (10 s cycles) while MCAv and MAP were measured continuously. The ∆MCAv<sub>T</sub>/∆MAP<sub>T</sub> was calculated for each transition [increase (INC); decrease (DEC)] of MAP for 60, 120, 180, 240 and 300 s. A two-way ANOVA was completed, and the absolute (Bland-Altman plot) and relative (coefficient of variation and intraclass correlation coefficient) reliability were calculated to compare shorter-duration recordings with 300 s (reference standard). At 0.05 Hz, ∆MCAv<sub>T</sub>/∆MAP<sub>T</sub> was similar between INC and DEC and comparable to the 300 s reference from 120 s onwards. At 0.10 Hz, ∆MCAv<sub>T</sub>/∆MAP<sub>T</sub> was lower during INC (p < 0.0001). Bland-Altman plots indicated that differences trended towards zero (greater agreement) with increasing duration. Averaged coefficients of variation were <10% from 120 s (0.05 Hz) and 60 s (0.10 Hz) onwards. All intraclass correlation coefficients were >0.90 for recordings of ≥180 s in both frequencies. Although the 300 s reference is optimal, RSS duration could be shortened to 180 s, if needed, to identify this hysteresis-like pattern reliably using ∆MCAv<sub>T</sub>/∆MAP<sub>T</sub>.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}