Adaptations to heat and hypoxia are typically studied in isolation but are often encountered in combination. Whether the adaptive response to multiple stressors affords the same response as when examined in isolation is unclear. We examined 1) the influence of overnight moderate normobaric hypoxia on the time course and magnitude of adaptation to daily heat exposure and 2) whether heat acclimation (HA) was ergogenic and whether this was influenced by an additional hypoxic stimulus. Eight males [V̇o_2max = 58.5 (8.3) ml·kg⁻¹·min⁻¹] undertook two 11-day HA programs (balanced-crossover design), once with overnight normobaric hypoxia (HA_Hyp): 8 (1) h per night for 10 nights [[ ] = 0.156; S_pO₂ = 91 (2)%] and once without (HA_Con). Days 1, 6, and 11 were exercise-heat stress tests [HST (40°C, 50% relative humidity, RH)]; days 2–5 and 7–10 were isothermal strain [target rectal temperature (T_re) ~38.5°C], exercise-heat sessions. A graded exercise test and 30-min cycle trial were undertaken pre-, post-, and 14 days after HA in temperate normoxia (22°C, 55% RH; F_IO₂ = 0.209). HA was evident on day 6 (e.g., reduced T_re, mean skin temperature (T̄_sk), heart rate, and sweat [Na⁺], P < 0.05) with additional adaptations on day 11 (further reduced T̄_sk and heart rate). HA increased plasma volume [+5.9 (7.3)%] and erythropoietin concentration [+1.8 (2.4) mIU/ml]; total hemoglobin mass was unchanged. Peak power output [+12 (20) W], lactate threshold [+15 (18) W] and work done [+12 (20) kJ] increased following HA. The additional hypoxic stressor did not affect these adaptations. In conclusion, a separate moderate overnight normobaric hypoxic stimulus does not affect the time course or magnitude of HA. Performance may be improved in temperate normoxia following HA, but this is unaffected by an additional hypoxic stressor.

A survey of inbred mouse strains showed that strain C3H/he was the most comparable to man in respect of its susceptibility to Leishmania major and the subsequent healing of lesions produced by this organism. L. arabica proved to have a lower virulence than L. major and prior inoculation with the former resulted in a decrease of the lesion sizes following subsequent L. major challenge. Moreover, L. major lesions that did develop in mice previously inoculated with L. arabica generally healed faster.

High altitude residents have a lower incidence of type 2 diabetes mellitus (T2DM). Therefore, we examined the effect of repeated overnight normobaric hypoxic exposure on glycaemic control, appetite, gut microbiota and inflammation in adults with T2DM. Thirteen adults with T2DM [glycated haemoglobin (HbA1_c): 61.1 ± 14.1 mmol mol⁻¹; aged 64.2 ± 9.4 years; four female] completed a single‐blind, randomised, sham‐controlled, cross‐over study for 10 nights, sleeping when exposed to hypoxia (fractional inspired O₂ [] = 0.155; ∼2500 m simulated altitude) or normoxic conditions ( = 0.209) in a randomised order. Outcome measures included: fasted plasma [glucose]; [hypoxia inducible factor‐1α]; [interleukin‐6]; [tumour necrosis factor‐α]; [interleukin‐10]; [heat shock protein 70]; [butyric acid]; peak plasma [glucose] and insulin sensitivity following a 2 h oral glucose tolerance test; body composition; appetite indices ([leptin], [acyl ghrelin], [peptide YY], [glucagon‐like peptide‐1]); and gut microbiota diversity and abundance [16S rRNA amplicon sequencing]. During intervention periods, accelerometers measured physical activity, sleep duration and efficiency, whereas continuous glucose monitors were used to assess estimated HbA1_c and glucose management indicator and time in target range. Overnight hypoxia was not associated with changes in any outcome measure (P > 0.05 with small effect sizes) except fasting insulin sensitivity and gut microbiota alpha diversity, which exhibited trends (P = 0.10; P = 0.08 respectively) for a medium beneficial effect (d = 0.49; d = 0.59 respectively). Ten nights of overnight moderate hypoxic exposure did not significantly affect glycaemic control, gut microbiome, appetite, or inflammation in adults with T2DM. However, the intervention was well tolerated and a medium effect‐size for improved insulin sensitivity and reduced alpha diversity warrants further investigation. image Key points: Living at altitude lowers the incidence of type 2 diabetes mellitus (T2DM). Animal studies suggest that exposure to hypoxia may lead to weight loss and suppressed appetite. In a single‐blind, randomised sham‐controlled, cross‐over trial, we assessed the effects of 10 nights of hypoxia (fractional inspired O₂ ∼0.155) on glucose homeostasis, appetite, gut microbiota, inflammatory stress ([interleukin‐6]; [tumour necrosis factor‐α]; [interleukin‐10]) and hypoxic stress ([hypoxia inducible factor 1α]; heat shock protein 70]) in 13 adults with T2DM. Appetite and inflammatory markers were unchanged following hypoxic exposure, but an increased insulin sensitivity and reduced gut microbiota alpha diversity were associated with a medium effect‐size and statistical trends, which warrant further investigation using a definitive large randomised controlled trial. Hypoxic exposure may represent a viable therapeutic intervention in people with T2DM and particularly those unable or unwilling to exercise because barriers to uptake and adherence may be lower than for other lifestyle interventions (e.g. diet and exercise).

Background and Aims: The evaluation of breathing function is crucial in the clinical examination of the respiratory system. The Total Faulty Breathing Scale (TFBS) could be used in clinical settings to quantify the measurement of breathing dysfunction. Reliability data for the TFBS are available for males, but there is a requirement to determine reliability for females and to develop reference values. The aim of this study, therefore, was to determine the reliability in females and to establish the preliminary reference values for the TFBS.Methods: Twenty‐three healthy female participants for reliability and 44 (7 male and 37 female) participants for preliminary reference values participated in this cross‐sectional study. For both aspects of the study, participants were instructed to breathe at their own pace with no specific instruction. Then each participant was observed carrying out normal breathing for a period of 10 breaths and deep breathing for a period of 10 breaths while being assessed with the TFBS.Results: Intrarater and interrater reliability of the TFBS showed a kappa value of 0.769 and 0.751, respectively, indicating substantial agreement for female participants. The preliminary reference categories for TFBS were reported to be normal for 20 (45.5%) participants and mild faulty breathing for the remaining 24 (54.4%) participants.Conclusions: The findings of this study suggested that TFBS was reliable to measure breathing function among female participants, and the reference categories may be helpful in the identification of normal and faulty breathing.

Background: Oestradiol has been implicated as a factor in substrate utilisation in male and mouse studies but the effect of acute changes during the menstrual cycle is yet to be fully understood. Objective: To determine the role of oestradiol in respiratory exchange ratio (RER) during exercise at various intensities. Methods: This systematic review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. From inception to November 2023, four online databases (Cochrane, SPORTDiscus, MEDline and Web of Science) were searched for relevant articles. Studies that reported a resting oestradiol measurement in naturally menstruating women with exercise at a percentage of maximal aerobic capacity (%V˙O_2max) were included. Mean and standard deviation for oestradiol, RER and exercise intensity were extracted and study quality assessed using a modified Downs and Black checklist. Risk of bias was assessed using I₂ measure of heterogeneity and Egger’s regression test, assessment of bias from methodological quality was identified by sensitivity analysis. Eligible datasets were extracted for pairwise comparisons within a meta-analysis and correlation between change in oestradiol and change in RER. Data were also pooled to produce a mean and standard deviation for RER for menstrual stage and for low and high oestradiol groups. Results: Twenty-four articles were identified, over 50% were identified as high quality. Sixteen articles included datasets eligible for meta-analysis. Eleven articles utilised a submaximal constant-load exercise intensity, finding a standardised mean difference of − 0.09 ([CI: −0.35–0.17], p = 0.5) suggesting no effect of menstrual phase on constant-load exercise RER. In six articles using incremental exercise tests to exhaustion, a standardised mean difference of 0.60 ([CI 0.00–1.19], p = 0.05) was identified towards a higher maximal RER attained in follicular compared to luteal phase. There was no correlation (R = −0.26, p = 0.2) between change in oestradiol and change in RER between phases. All 24 articles, totalling 650 participants, were included in pooled analysis. When grouped by menstrual cycle phase or when grouped by oestradiol levels, RER was higher in the follicular phase than the luteal phase at low and high constant load exercise intensities. Discussion: Findings from the pooled-analysis and meta-analysis suggest that there may be menstrual cycle phase differences in RER that are intensity dependent. These differences may be related to sex hormone levels, but this was not supported by evidence of correlation between differences in RER and differences in oestradiol. At present, it remains best practice to assess performance in the same menstrual cycle phase if seeking to assess change from baseline.

Background: Fibromyalgia is a chronic pain condition characterised by altered pain processing, widespread pain, and symptoms including sleep disturbance, fatigue, and psychological distress. Emerging evidence suggests that modifiable multimodal lifestyle factors may influence inflammation and pain mechanisms; however, the relationships between multimodal lifestyle factors, systemic inflammatory biomarkers, and pain processing remain poorly understood. In this study we aimed to investigate the associations between lifestyle factors, inflammatory biomarkers, and experimental and clinical pain outcomes in women with fibromyalgia. Methods: Women with fibromyalgia were invited to participate in this exploratory cross-sectional study. Lifestyle factors included diet, perceived stress, sleep, physical activity, heart rate variability, and BMI. Plasma IL-6, IL-10, and TNF-α were measured. Pain outcomes included quantitative sensory testing and patient-reported outcome measures. Spearman’s rank correlations and multiple linear regression analyses adjusted for age and disease duration were performed. Bootstrap 95% confidence intervals were calculated for all estimates, and False Discovery Rate (FDR) corrections using the Benjamini–Hochberg procedure were applied as a sensitivity analysis. Results: Twenty patients were included. Correlation analyses demonstrated that higher perceived stress was strongly associated with greater fibromyalgia impact (r = 0.68, p < 0.001, n = 20), central sensitization (r = 0.67, p < 0.001, n = 20), and current pain intensity (r = 0.64, p = 0.002, n = 20). A more pro-inflammatory diet was positively associated with IL-6 (r = 0.46, p = 0.04, n = 20) and IL-10 (r = 0.47, p = 0.10, n = 13), while higher TNF-α concentrations were associated with lower pressure pain thresholds (overall; r = −0.55, p = 0.021, n = 19; tibialis: r = −0.57, p = 0.010, n = 19). Following adjustment for age and disease duration, associations between stress and fibromyalgia impact, central sensitization, and current and worst pain intensity, together with associations between pro-inflammatory diet and IL-6 and IL-10, and between BMI and IL-10 showed similar directions and effect estimates. However, following FDR adjustment as a sensitivity analysis, no associations retained statistical significance. Conclusions: This study suggests that different modifiable lifestyle factors may be associated with distinct aspects of pain and inflammatory processes in women with fibromyalgia. Perceived stress showed the most consistent associations with pain-related outcomes, while dietary inflammatory potential showed preliminary associations with inflammatory biomarkers that need further investigation.