Intermittent apnoeas may induce hypoalgesia; however, the effects of low-lung-volume static apnoea have not been investigated. Eighty healthy participants were randomized to an apnoea group (AG) or a control group (CG). The AG performed a 6-min protocol of intermittent static apnoea at low lung volume (passive exhalation), whereas the CG breathed normally in the supine position. Pressure pain thresholds (PPTs) were assessed at the thumb, tibialis anterior and C7, together with heart rate (HR), oxygen saturation ( S p O 2 ), and systolic and diastolic blood pressure (SBP and DBP). Open-ended questions explored sensations, emotions and adverse effects. ANCOVA (baseline pressure pain threshold) revealed no significant between-group differences in PPT at thumb (mean difference [MD] = -0.209 kg/cm2; 95% CI: -0.584, 0.158; P = 0.268), tibialis (MD = 0.014 kg/cm2; 95% CI: -0.341, 0.354; P = 0.939), or C7 (MD = -0.276 kg/cm2; 95% CI: -0.669, 0.102; P = 0.169). Intrasession analyses showed higher values in the AG for S p O 2 (MD = 0.598%, P = 0.009), percentage maximum heart rate (MD = 4.344%, P < 0.0001), SBP (MD = 15.344 mmHg, P < 0.0001) and DBP (MD = 14.273 mmHg, P < 0.0001). The AG reported more distress-related sensations and emotions, whereas the CG described more comfort-related experiences. Adverse effects were mild. A 6-min intermittent low-lung-volume static apnoea did not induce hypoalgesia despite autonomic and cardiovascular activation and was well tolerated. These findings suggest respiratory-induced autonomic stress may be insufficient to modulate nociceptive processing, highlighting the importance of physiological conditions under which breath-hold interventions may influence pain. Trial registration: This study was prospectively registered on 27 November 2023, at ClinicalTrials.gov (Identifier: NCT06158256).
Exertional dyspnoea is a debilitating symptom in chronic obstructive pulmonary disease (COPD) and often persists after the cessation of exercise. The underlying mechanisms are not fully understood, and a potential contributing factor that has not previously been investigated is alveolar-capillary membrane breaching with extravasation of fluid into the lungs. Sixteen individuals with COPD and 16 age- and sex-matched healthy controls were included. Alveolar-capillary membrane permeability was quantified using the pulmonary clearance index (PCI), calculated from scintigraphically determined alveolar clearance of 99mTc-labelled diethylenetriaminepentaacetic acid at rest and following an acute exercise bout performed at maximal exertion, as determined by a prior cardiopulmonary exercise test. In addition, lung tissue mass (LTM) was assessed using low-dose computed tomography, with rest-to-post-exercise changes interpreted as reflecting alterations in interstitial fluid accumulation. The mean change in PCI from rest-to-post-exercise was -0.01 [95% CI: -0.09, 0.06]%/min in the COPD group and -0.05 [95% CI: -0.12, 0.02]%/min in the healthy control group (Group × Time interaction, P = 0.446). The mean change in LTM from rest-to-post-exercise was 16.5 [95% CI: -7.0, 40.0]g/1.73 m2 in the COPD group and 35.2 [95% CI: 11.7, 58.7]g/1.73 m2 in the healthy control group (Group × Time interaction, P = 0.258). In conclusion, the present study found no evidence of alveolar-capillary membrane breaching following maximal exercise, neither in individuals with COPD nor in healthy matched controls.
Older adults are at heightened susceptibility to heat-related cardiovascular complications when exposed to indoor overheating. While ceiling fans are recommended as an accessible cooling intervention, their effects on cardiac autonomic regulation remain unclear. In this randomized crossover study, 20 healthy older adults (median age 71 years, 12 female) completed two 8-h exposures to simulated indoor overheating (31°C, 45% relative humidity) while bed-resting with either no fan (control) or ceiling fan use (∼1.5 m/s airflow). Core temperature and heart rate were monitored. Before exposure and between hours 6 and 7, participants underwent cardiac autonomic response testing including measures of heart rate variability (SDNN, RMSSD - indices of overall and parasympathetic/vagal cardiac autonomic modulation, respectively) and supine-to-standing tests (30:15 ratio, systolic blood pressure response) as well as self-reported symptoms of orthostatic intolerance. Ceiling fan use reduced peak core temperature (0.2°C [95% CI: 0.1-0.3]; P < 0.001), heart rate (-5 beats/min [-10 to 0]; P = 0.03), and attenuated heat-induced reductions in RMSSD (4.7 ms [0.2-9.2]; P = 0.04) compared to control. However, fan use did not influence SDNN, blood pressure during postural changes, cardiac response to standing, or symptoms of orthostatic intolerance. While ceiling fans provided modest reductions in core temperature and heart rate and partially preserved RMSSD, they offered limited overall cardiovascular and autonomic protection in older adults during prolonged heat exposure. These findings indicate that, despite some beneficial effects, ceiling fans provide limited cardiovascular autonomic protection, underscoring the need for comprehensive cooling strategies to safeguard older adults during indoor overheating.
Hot flushes of menopause are associated with elevated blood pressure (BP) and diminished macrovascular endothelial function, an initiating factor in the onset of atherosclerosis. Whether microvascular endothelial function is impaired in females with hot flushes, however, remains unknown. We hypothesised that postmenopausal females with hot flushes would have reduced microvascular endothelial function and elevated BP in comparison to age-matched females without hot flushes. Participants were healthy postmenopausal females, aged 45-70 years; participants experiencing at least three hot flushes per day were placed in the hot flush (HF) group (n = 16), whereas participants with no history of hot flushes were placed in the non-HF group (n = 18). Heart rate (ECG) and BP (finger plethysmography) were measured during a 10 min rest period, and endothelial function was measured with pulse amplitude tonometry (EndoPAT 2000), quantified by the reactive hyperaemia index (RHI) and the natural logarithm of the RHI (LnRHI). Groups were similar in age, age at menopause and body mass index, in addition to systolic BP, diastolic BP and heart rate between groups (P > 0.05). The RHI was lower in the HF group (1.87 ± 0.47 a.u.) compared with the non-HF group (2.31 ± 0.67 a.u., P = 0.047), and the difference between LnRHI in the HF group (0.63 ± 0.21 a.u.) and the non-HF group was nearly significant (0.80 ± 0.27 a.u., P = 0.052). New findings from this study demonstrate a lower microvascular endothelial function in females with hot flushes in comparison to females without hot flushes, although BP and heart rate were not different between the groups. The reduced microvascular endothelial function demonstrated in females with hot flushes is likely to contribute to greater cardiovascular disease development.
Cerebral blood flow (CBF) often becomes compromised in patients suffering from cardiovascular diseases, increasing the risk of neurodegenerative disease and vascular dementia. There is an urgent need for treatments to address cardiovascular risk without compromising brain perfusion, yet the impact of many existing treatments on CBF are not well understood. An exclusive focus on arterial blood pressure (BP) control against a background of cerebral vascular damage may miss an opportunity to restore cerebral haemodynamic regulation and mitigate risk to cognitive function. This Symposium Review focuses on the possibility and promise of assessing and optimising CBF during treatment for cardiovascular diseases. This is especially relevant given the new interest in pathways that protect brain health via cerebrospinal fluid exchange, such as the glymphatic system. Insights into the fundamental mechanisms connecting vascular motility and brain health can be gleaned from conscious, high-fidelity measurements of CBF. We believe that CBF monitoring is crucial in the development of novel compounds, or re-evaluation of current drugs.
The vascular sympathetic baroreflex is critical for stabilising blood pressure. A notable feature of this reflex is hysteresis, a directional asymmetry in responsiveness during rising versus falling pressure that is evident in young adults but attenuated in older age. Whether age-related reduction reflects altered mechanical transduction at baroreceptors or changes in neural processing remains unclear. We compared the mechanical and neural components of the sympathetic baroreflex, with specific focus on hysteresis, in healthy young (21-30 years old, n = 20) and middle-aged (50-63 years, n = 14) males. Continuous recordings of arterial pressure (photoplethysmography), muscle sympathetic nerve activity (MSNA; microneurography) and common carotid artery diameter (ultrasound) were obtained during 6 min of supine rest. Spontaneous baroreflex gain was quantified for mechanical (diastolic pressure into carotid diameter) and neural (carotid diameter into MSNA) components, and overall (diastolic pressure into MSNA), with rising and falling pressure sequences analysed separately. Young men exhibited clear hysteresis in the overall baroreflex loop, whereas this was absent in middle-aged men. Mechanical hysteresis was not observed in either age group. In contrast, young men displayed pronounced neural hysteresis (Falling: -0.302 ± 0.157 vs. Rising: -0.128 ± 0.88% bursts µm-1, P < 0.001; g = 1.37), whereas neural hysteresis was absent in middle-aged men (Falling: -0.345 ± 0.400 vs. Rising: -0.396 ± 0.368% burst µm-1, P = 0.348, g = 0.13). These findings suggest that age-related loss of spontaneous sympathetic baroreflex hysteresis is more apparent within the neural rather than the mechanical component.
Circulatory shock remains difficult to manage because fluid resuscitation and catecholamines may exacerbate vascular dysfunction and tissue hypoperfusion. This prospective physiological analysis, embedded within a multicentre phase IV study, examined whether selectively targeting the venous circulation with centhaquine improves circulatory dynamics in spontaneously breathing patients with mixed hypovolaemic-vasodilatory shock (MHVS). Fifteen spontaneously breathing adults with MHVS received centhaquine (0.01 mg kg-1) in addition to standard care. Over 300 min, mean circulatory filling pressure analogue increased from 6.03 ± 0.22 to 7.28 ± 0.21 mmHg and driving pressure for venous return from 5.88 ± 0.22 to 7.16 ± 0.21 mmHg (adjusted P < 0.001 for both), while estimated central venous pressure remained near atmospheric pressure and resistance to venous return remained unchanged. Cardiac output increased from 5.62 ± 0.22 to 6.80 ± 0.24 L min-1 and mean arterial pressure from 56.8 ± 1.5 to 69.8 ± 2.0 mmHg (adjusted P < 0.001 for both). Effective arterial elastance and systemic vascular resistance did not significantly change over time. Patients received 677 ± 79 mL of crystalloids during the study period, and no drug-related adverse events were observed. The findings of this preliminary physiological study suggest that selective venoconstriction may augment venous return and systemic haemodynamics in spontaneously breathing patients with MHVS without evidence of major adverse haemodynamic effects.
Renal ischaemia-reperfusion (I/R) injury leads to acute tubular necrosis and renal failure, triggering pathological mechanisms including inflammation, reactive oxygen species generation, apoptosis and mitochondrial dysfunction. The mitochondrial peptide humanin (HN), known to possess anti-apoptotic and anti-inflammatory properties, has been shown to counteract oxidative stress and restore mitochondrial function. This study aimed to investigate the effects of S14G-humanin (humanin G, HNG) on renal I/R injury. Sprague-Dawley male rats were divided into four groups (n = 48): (1) Sham, (2) I/R, (3) HNG-Sham, and (4) HNG-I/R. In I/R groups, renal artery ligation was performed for 45 min followed by 24-h reperfusion. HNG (2 mg/kg, i.v.) was administered 10 min before reperfusion. Urine was collected during reperfusion, and the experiment was terminated by collecting blood and tissue samples. Blood urea nitrogen and serum creatinine levels were elevated in the I/R group and were not affected by HNG treatment. Glutathione level and superoxide dismutase activity, which were diminished in the I/R group, were significantly restored following HNG administration. Myeloperoxidase activity and malondialdehyde levels were significantly decreased in HNG-I/R group compared to the I/R group. ATP levels and mitochondrial complex I activity were significantly increased in the HNG-I/R group compared to I/R. The percentage of apoptotic cells, markedly increased in I/R, was significantly reduced in HNG-I/R. Signal transducer and activator of transcription 3 (STAT3) and extracellular signal-regulated kinases 1 and 2 (ERK1/2) phosphorylation also increased in HNG-I/R rats compared to I/R animals. HNG mitigates renal I/R injury by attenuating oxidative stress, inflammation and apoptosis while enhancing antioxidant capacity and mitochondrial function, through STAT3 and/or ERK1/2 activation.
Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels are important regulators of cardiac pacemaking and neuronal excitability, yet their temperature dependence has not been compared systematically across mammalian isoforms and species in standardized experimental conditions. Here, we performed a standardized electrophysiological characterization of mouse, rat and human HCN isoforms using stable CHO cell lines and automated patch-clamp recordings across multiple temperatures and pharmacological conditions. Among the four isoforms, HCN3 did not generate detectable currents when expressed as a homomeric channel in the conditions tested, suggesting that additional factors might be required for functional activity. Comparative analysis of the remaining isoforms revealed a conserved kinetic hierarchy, with HCN1 exhibiting the fastest activation kinetics, HCN2 intermediate kinetics and HCN4 the slowest, and temperature accelerated channel gating across isoforms. Canonical modulation by cAMP and ZD7288 further showed that key regulatory features of HCN channels could be quantified reproducibly in identical experimental conditions. Together, these results provide a standardized comparative framework for interpreting HCN channel behaviour across physiological temperatures and species and establish a public reference dataset for future experimental and computational studies.
Groups of motor units receive common synaptic inputs from specialized networks of premotor neurons to produce movement. Here, we test whether common inputs received by motor units in the first dorsal interosseous are fixed or task-dependent during submaximal isometric contractions. Discharge times of motor units were identified and tracked across a set of conditions. Factor analysis identified a single motor unit mode that captured most of the covariation in the discharge rates of motor units, presumably reflecting common synaptic inputs. This was supported by the high correlation values between motor unit pairs from the same participant. Next, displacement analysis on the discharge rates of motor units was computed to capture the magnitude of departures from a monotonic control structure expected from fixed common inputs. For the same force profile, activity of motor units was limited to a set of discharge rate-time trajectories across trials, suggesting a constrained pattern of premotor inputs to motor units. Importantly, changes in force profile and muscle length modulated synaptic inputs to motor units, as observed in the divergent rate-time trajectories of motor units and high displacement values. These findings highlight that common input is a key feature in the neural control of motor units and is subject to substantial modulation. The composition of inputs to motor units depends on the force profile and muscle length, and the system relies on reusing a common input structure when performing the same task.
The rising prevalence of overweight and obesity, together with associated cardiometabolic disorders, underscores the need for additional strategies alongside established interventions. The growing popularity of contrast therapy - alternating exposure to heat and cold, a practice common in traditional Finnish sauna bathing - has prompted interest in its potential cardiovascular and metabolic health benefits. This systematic review outlines the acute and chronic effects of contrast therapy on cardiometabolic outcomes. The review followed PRISMA guidelines and searched three databases (PubMed, Scopus, Web of Science) until 17 June 2025. Interventional studies reporting cardiovascular and/or metabolic outcomes were included; 21 studies were identified, of which 19 contributed to data synthesis. Continuous outcomes were converted to standardised mean differences to enable comparison. Little evidence for effects of contrast therapy was found on resting heart rate, blood pressure or vascular health, all indicators of cardiovascular risk, and metabolic outcomes, including glucose and lipid metabolism. Some evidence of heat adaptation was observed, indicated by attenuated acute heart rate and core temperature responses, and decreased resting core temperature upon contrasting thermal exposure. However, the evidence base is limited, restricting the ability to draw firm conclusions or provide clear recommendations. Well-designed, controlled studies, with systematic assessment of vascular and metabolic outcomes, are needed to further clarify the acute and long-term effects of contrast therapy on cardiometabolic health.
Cold-water immersion (CWI) is among the most widely used post-exercise recovery modalities in elite sport and clinical rehabilitation, yet a fundamental paradox now emerges from the evidence: the same protocols that accelerate parasympathetic reactivation and reduce perceived muscle soreness also suppress the molecular and cellular machinery of skeletal-muscle hypertrophy when applied repeatedly across resistance-training mesocycles. This narrative review synthesises the multi-axis acute physiological response to CWI, the meta-analytic evidence supporting its acute recovery benefits, and the molecular, cellular and longitudinal evidence documenting its chronic attenuation of resistance-training adaptations. Acute CWI (10-15°C, 10-15 min) consistently augments parasympathetic reactivation, reduces soreness within 24-72 h (network meta-analytic SUCRA 88%) and modulates inflammatory time-courses. In parallel, equivalent protocols attenuate post-resistance-exercise mechanistic target of rapamycin complex 1 signalling, ribosomal biogenesis and satellite-cell-mediated myonuclear addition, translating into reduced type II fibre cross-sectional area and modest impairments of strength gain (effect size -0.23). Endurance-related microvascular and mitochondrial adaptations appear less affected and may be selectively enhanced. A protocol-by-goal decision framework links CWI parameters - water temperature, duration, body coverage and temporal placement - to expected adaptive outcomes across hypertrophy, strength, endurance and concurrent training contexts. CWI is neither uniformly beneficial nor uniformly harmful; its effects are predictable and depend on the training goal. CWI should be used when fast recovery between sessions matters most, and withheld after resistance training when muscle growth is the main goal of the training block.
The physiological adaptations of long-term high-altitude residents without high-altitude genetic ancestry remain poorly characterized. This study investigated whether permanent residence at low altitude (1200 m) influences performance at higher altitude (2500 m). We compared exercise responses at 2500 m in endurance-trained athletes living for several years at 1200 m versus those residing at sea level. Twenty-five male endurance athletes [13 altitude residents (AR) and 12 sea-level residents (SLR)] performed maximal incremental cycle ergometer tests in their habitual environment (BASE: 1200 m or sea level) and in simulated moderate altitude (2500 m, inspired P O 2 = 109 mmHg). Gas-exchange, heart rate, oxygen saturation, ventilatory and performance outcomes were measured continuously. At BASE, no between-group differences were observed in anthropometrics, spirometry or aerobic capacity, while ventilatory reserve was more reduced in the AR group (P = 0.004). Both groups exhibited significant reductions in aerobic capacity, maximal oxygen saturation and peak power output at 2500 m compared with BASE. However, AR athletes exhibited a lower percentage drop in maximal oxygen saturation (P < 0.001) and aerobic capacity (P = 0.027). Maximal heart rate decreased significantly in SLR but remained unchanged in AR. At rest, the 2500 m condition significantly reduced oxygen saturation in SLR (P < 0.001) but not in AR. In conclusion, long-term residence and training at 1200 m attenuate hypoxia-induced performance decrements at 2500 m, mainly through better preservation of arterial oxygen saturation. Chronic exposure to low altitude might therefore induce functional pulmonary adaptations, with practical implications for endurance athletes training or competing at moderate altitude.
The two-kidney, one-clip (2K1C) model produces renovascular hypertension. The effects on the clipped kidney (CK) are well described, while the non-clipped kidney (NCK) is used as a model to evaluate the effects of high blood pressure. Although most of these effects have been described at later stages of 2K1C hypertension, it remains unclear whether immune antigen-presenting cells (APCs) expand early in the NCK during the first stages of 2K1C hypertension. Our objective was to determine whether the 2K1C model increases the presence and/or distribution of APCs in the NCK during the early phase of renovascular hypertension. Male C57BL/6J mice underwent sham surgery or 2K1C surgery (n = 6). Blood pressure was assessed, and NCKs were collected on day 7. Global expression of major histocompatibility complex (MHC)-II (APC marker) and F4/80 (monocyte/macrophage lineage) was quantified by immunoblotting, while spatial distribution was evaluated by immunohistochemistry (IHC) and morphological analysis. 2K1C produced a significant increase in blood pressure in the NCK without albuminuria. Immunoblot experiments showed no significant differences in global MHC-II or F4/80 levels between sham and 2K1C groups in the NCK. However, IHC revealed a focal increase in F4/80+ signal and a significant rise in F4/80+ area fraction, consistent with localized monocytic/macrophage enrichment not captured by whole-tissue homogenates from NCK. By contrast, F4/80 immunostaining was observed in conspicuous resident cells. After 7 days of 2K1C hypertension, contralateral renal APC expansion is not evident at the global protein level, yet focal F4/80+ enrichment suggests early regional and focal immune remodelling that may precede later overt inflammation.
Prolonged glucocorticoid exposure induces skeletal muscle atrophy through suppression of protein synthesis and activation of catabolic signalling pathways. Although exercise attenuates glucocorticoid-induced muscle loss, whether exercise-induced increases in body temperature contribute remains unclear. In this study, we examined whether exercise in different thermal conditions modulates skeletal muscle atrophy and intracellular signalling during glucocorticoid exposure. Female Sprague-Dawley rats (n = 48) were assigned to six groups: control (CON), dexamethasone-treated (DEX), cold exercise (∼5°C; CE), cold exercise with dexamethasone (CED), warm exercise (25°C; WE) and warm exercise with dexamethasone. Exercise protocols were matched, and dexamethasone was administered for 5 days. Dexamethasone reduced plantaris muscle mass (by 17%, P < 0.0001) and fibre cross-sectional area (27%, P < 0.0001). During dexamethasone treatment, exercise in a cold environment provided partial protection, with muscle mass higher than DEX (P = 0.0476), but both muscle mass and fibre CSA remained lower than CON (P = 0.0096 and P = 0.0215, respectively). In contrast, exercise in a warm environment preserved muscle mass and fibre CSA (no difference vs. CON) and resulted in higher muscle mass (P = 0.0070) and fibre CSA (P < 0.0001) than DEX. Exercise-induced increases in rectal temperature were associated with higher Hsp72 and Hsp25 expression, partial preservation of Akt-FoxO3a signalling and reduced MuRF1 expression, whereas exercise in a cold environment showed minimal heat shock protein response and limited suppression of catabolic signalling. These findings indicate that exercise-induced elevation of body temperature enhances protection against glucocorticoid-induced skeletal muscle atrophy and support a role for heat-associated cellular stress responses in modulating muscle protein turnover during glucocorticoid exposure.
Infantile epileptic spasms syndrome (IESS) is characterized by epileptic spasms (ES) in infants and hypsarrhythmia on EEG. High-frequency oscillations (HFOs), defined as oscillatory events at >80 Hz, reflect rapid spatiotemporal dynamics of cortical activity and might serve as novel biomarkers for epilepsy. In this study, we investigated the association among hypsarrhythmia, ES and scalp HFOs in IESS, focusing on their spatiotemporal and morphological characteristics. We analysed scalp EEG recordings from 22 paediatric patients with IESS (12 males; age range, 0-12 years), classified into four groups: hypsarrhythmia with ES; hypsarrhythmia without ES; multifocal interictal epileptiform discharges (IED); and non-multifocal IED. The proportions of EEG recordings with at least one detected scalp HFO differed significantly among the groups, being 100.0% in hypsarrhythmia with ES, 90.9% in hypsarrhythmia without ES, 36.0% in multifocal IED and 29.4% in non-multifocal IED (P < 0.001). Age-adjusted odds ratios [95% confidence intervals] for high HFO detection rates were significantly greater in the hypsarrhythmia groups than in the IED groups (with ES, 24.66 [4.86-125.10], P < 0.001; and without ES, 8.38 [1.94-36.20], P = 0.004). Receiver operating characteristic analysis showed that scalp HFO detection rates discriminated ES activity with an area under the curve of 0.92, 100% sensitivity and 77.4% specificity. Compared with the IED groups, the hypsarrhythmia groups exhibited lower-frequency HFOs, with the lowest HFO frequencies being observed in the hypsarrhythmia with ES group. These findings suggest that the spatiotemporal and morphological characteristics of scalp HFOs might provide complementary multidimensional biomarkers for hypsarrhythmia and assessing ictal states in IESS.
The striatum is a brain region within the basal ganglia that plays a crucial role in generating behaviour and mediating perception. The tail striatum (TS) is a poorly understood striatal domain with predominantly sensory functions. Recent evidence supports that abnormal TS dopamine transmission in dopaminergic disease contributes to sensory symptoms by dysregulating TS medium spiny neurons (MSNs). Importantly, the ventral TS is segregated into medial, intermediate and lateral divisions in which TS-MSNs express D1 and D2 dopamine receptors unevenly, but the functional significance of this is unclear. We aimed to gain insight into the functional significance of this organisation and to investigate how TS-MSNs are modulated by dopamine. We used whole-cell patch clamping in rat (P45-55, both sexes) brain slices to conduct the first in-depth electrophysiological characterisation of TS-MSNs and compared them across divisions. The adjacent dorsolateral striatum (DLS) was included for comparison. We also investigated how bath-applied dopamine and selective dopamine agonists SKF38393 and quinpirole modulate MSNs in each region. We found that TS-MSNs are electrophysiologically distinct from DLS-MSNs, reflecting the established functional differences between these domains. TS-MSNs were more depolarised than DLS-MSNs at rest and had lower rheobase. We also identified functional heterogeneity across the TS divisions. The intermediate division had higher rheobase than the medial or lateral divisions. At rheobase, lateral division TS-MSNs showed higher firing frequencies than medial or intermediate division TS-MSNs. Finally, TS-MSNs showed weaker modulation by dopamine, SKF38393 and quinpirole than DLS-MSNs, which was also uneven across divisions. These data provide a novel electrophysiological characterisation of TS-MSNs, showing they are functionally distinct from DLS-MSNs and heterogeneous across divisions, which could have implications for dopaminergic diseases.
Ramadan is a sacred religious practice observed by Muslims that involves abstaining from food and water from sunrise to sunset for 1 month. Prior work has reported that peak oxygen uptake ( V ̇ O 2 peak ) can decline during Ramadan in parallel with reduced physical activity. We investigated whether dietary nitrate supplementation could attenuate the decrease in V ̇ O 2 peak during 10 days of Ramadan fasting. In a randomized design, 21 healthy participants (13 females) were assigned to ingest 70 mL of beetroot juice (∼6.45 mmol nitrate; n = 10), twice a day for 10 days consecutively, or a non-supplement control (n = 11). The V ̇ O 2 peak was assessed by indirect calorimetry during a maximal cycle ergometer ramp test. After 10 days of Ramadan fasting, the change in body mass was not different between groups [change (∆), -0.91 ± 1.3 vs. -0.27 ± 1.2 kg (control vs. nitrate), P = 0.25], nor were the changes in resting systolic (P = 0.21) or diastolic (P = 0.53) blood pressure or urine specific gravity (P = 0.17). Subjective sleep quality declined over time in both groups (P < 0.01). Participants self-reported a decline (n = 17) or no change (n = 4) in regular physical activity, and the number of exercise bouts during the 10 days of Ramadan did not differ between groups (2.5 ± 2.0 vs. 3.3 ± 2.4, P = 0.44). Absolute V ̇ O 2 peak decreased in the control group compared with the dietary nitrate supplementation group (∆, -155 ± 168 vs. +67 ± 162 mL min-1, P < 0.01), as did V ̇ O 2 peak relative to body mass (∆, -2.4 ± 2.5 vs. +0.3 ± 1.9 mL kg-1 min-1, P = 0.02) and peak power output (∆, -12 ± 16 vs. ∆+2 ± 10 W, P = 0.04). Dietary nitrate supplementation might represent a practical nutritional strategy to preserve aerobic capacity during Ramadan fasting.
Acute mountain sickness (AMS) is common after ascent to altitude, yet individual susceptibility remains difficult to predict and diagnosis relies on subjective report. Sleep disturbances and nocturnal hypoxaemia at altitude may provide insight, but their relationship to AMS is incompletely understood. In a sub-study of a randomized, placebo-controlled trial, 112 healthy, lowland-dwelling volunteers rapidly ascended to 3810 m. AMS was assessed using the 2018 Lake Louise Scoring System (LLSS); sleep scores were recorded separately. Overnight monitoring used the WatchPAT300 device to measure oxygen saturation, oxygen desaturation index, respiratory disturbance index, apnoea-hypopnoea index and inferred sleep stage. Thirty-eight participants (34%) developed AMS by the 2018 LLSS criteria. Compared with unaffected individuals, those with AMS had lower mean nocturnal S p O 2 , greater cumulative time with S p O 2 < 70%, and higher oxygen desaturation index and respiratory disturbance index on nights 2 and 3. Respiratory disturbance indices improved only in participants without AMS, while AMS-positive subjects demonstrated persistent reductions in estimated deep sleep, and higher self-reported sleep disturbance scores. A sensitivity analysis applying 1993 LLSS criteria identified 64 subjects (58%) with AMS, and strengthened between-group differences in nocturnal S p O 2 , but not respiratory indices. In exploratory multivariable analysis, cumulative time with S p O 2 < 70% and first-night sleep disturbance score at altitude remained independently associated with AMS. In summary, nocturnal hypoxaemia was associated with AMS status under both 2018 and 1993 criteria, while failure of respiratory index normalization and impaired sleep architecture are associated with AMS persistence, suggesting a longitudinal signal of failed acclimatization. These findings support further examination of sleep-related metrics in relation to AMS assessment.
