Physiological Reports最新文献

Estimating minute ventilation (V̇_E) is essential for assessing the health impacts of environmental exposures during exercise field-studies. Predictive equations using heart rate (HR) are commonly used, but overlook exercise intensity domains, and reduced accuracy is shown, particularly for females. Thus, we developed predictive equations for females' V̇_E based on HR responses at different exercise intensity domains using a Bayesian approach. Nineteen physically active females performed an incremental running test with breath-by-breath measurements of V̇_E, metabolic rate, and HR. The first and second ventilatory thresholds were identified by measurement of the ventilatory equivalent for oxygen and carbon dioxide, respectively. The Bayesian framework showed that the model fit for estimating V̇_E by HR was improved when the incremental running test and its intensity domains were considered. An exponential model provided the best fit (V̇_E = 2.86 × exp.(0.019 × HR)) for the full incremental running test (R² = 0.957), whereas linear models yielded superior fits when analyzing individual moderate (V̇_E = -32.92 + (HR × 0.19)), heavy (V̇_E = -101.94 + (HR × 0.99)) and severe (V̇_E = -268.81 + (HR × 1.98)) exercise intensity domains (R² = 0.977). Accurate estimates of V̇_E from HR measurements must consider the exercise intensity domain and the linear regression model for better biomonitoring of human exposures.

HIV infection and combination antiretroviral therapy (cART) can cause metabolic and cardiovascular changes in adolescents, who often have low physical activity (PA), harming their health. To investigate the relationship between PA levels and phase angle (PhA), we analyze potential moderating and mediating effects. Cross-sectional study with 47 adolescents (10-18 years) with vertically transmitted HIV. PA was assessed using PAQ-C; PhA was measured by tetrapolar bioelectrical impedance. Aerobic capacity was assessed by a submaximal bench step test, muscular strength by handgrip test, and body composition by anthropometric measures (arm muscle area [AMA] and body fat percentage [%BF]). Correlation, regression, and mediation and moderation analyses were performed. 61.7% showed inadequate PhA (<5.0°), mostly girls. A significant correlation existed between PA and PhA (r = 0.39; p = 0.01), maintained in adjusted regressions (β = 1.087; p = 0.001). General mediation and moderation effects were not confirmed; however, conditional analyses revealed high muscular strength significantly moderated the PA-PhA link (β = 1.0537; p = 0.0024). VO_{2 peak}, %BF, and AMA showed significant conditional effects at different levels. PA and PhA are directly associated, independent of confounders, and muscular strength, aerobic capacity, and body composition partially moderate this relation in adolescents with HIV.

Perceptual decision-making processes, particularly in the context of eye movements and reaction times (RT), have been studied to better understand how the brain integrates and responds to sensory information. Recent models have decomposed the process into multiple intermediate steps, including detection, instruction processing, decision, and motor response. To investigate the impact of the observer's expectations on each of these steps, we conducted two experiments on 24 participants (including both female and male participants), manipulating respectively the stimuli's location expectation (left or right) and the eye movement expectation (saccade or antisaccade). The results revealed limited evidence for the influence of location expectation on saccadic RT and moderate evidence for antisaccadic RT. Conversely, there was strong evidence of the influence of movement expectations on both movements' RT. This suggests an asymmetric impact of expectations on the different steps of perceptual decision-making, with strong impact on motor response and instruction processing. These findings challenge the common attribution of expectation effects solely to the decision-making module from previous works, emphasizing the importance of considering multi-module integration in perceptual decision models.

This study examined how sex influences blood flow during exercise at altitude and relative contributions of adrenergic mechanisms. Thirteen participants (8 M/5F) were tested at low and high altitude (days 3-11). Participants performed rhythmic handgrip for 3 min at 25% maximal voluntary contraction during local infusions of saline, propranolol (β-adrenergic blockade), and phentolamine with propranolol (α-β-adrenergic blockade). Doppler ultrasound was used to examine brachial artery blood flow (FBF) and calculate forearm vascular conductance (FVC). Resting FBF and FVC were higher in males compared to females across all conditions (p = 0.024; p = 0.025, respectively). Blockade condition significantly altered FBF and FVC (p < 0.001 for both) but there was no effect of altitude (p = 0.330; p = 0.718, respectively). During exercise, ΔFBF was influenced by condition (p < 0.001), but not by sex (p = 0.696) or altitude (p = 0.813). Similarly, ΔFVC was different across conditions (control: 9.4 ± 2.3 mL/min/mmHg/FAV; β-blockade: 11.4 ± 12.8 mL/min/mmHg/FAV; α-β-blockade: 3.9 ± 1.1 mL/min/mmHg/FAV; p < 0.001), with no effect of sex (p = 0.646) or altitude (p = 0.889). These results suggest males and females do not respond differently to exercise at altitude, and light-intensity exercise hyperemia may be preserved during early acclimatization. α-adrenergic receptors appear important for exercising blood flow, but β-adrenergic receptors may not be critical in this response.

The lipid mediator 20-HETE is produced by ω-hydroxylation of arachidonic acid mediated by cytochrome P450 (CYP) enzymes including CYP4A, which has four distinct isoforms in rodents. Several laboratories demonstrated that 20-HETE synthesis inhibition reduces infarct volume following middle cerebral artery occlusion (MCAO) in male animals. Here, we investigated whether neuroprotection with the 20-HETE synthesis inhibitor HET0016 administered after transient MCAO in rats differs by sex and whether ischemia differentially induces Cyp4a genes in a sex-dependent manner. HET0016 significantly improved sensorimotor performance and reduced infarct volume compared to vehicle treatment in males. However, these improvements were less consistent in females. Cyp4a2 and Cyp4a3 genes were detected at similar levels in brain tissue from male and female rats undergoing sham surgery or MCAO/reperfusion. Interestingly, the Cyp4a8 gene was detectable in intact and castrated males and increased 3-4-fold after MCAO. In contrast, Cyp4a8 was undetectable in brains of intact or ovariectomized female rats. Oxygen-glucose deprivation in cultured murine neurons revealed male-selective induction of the homolog gene Cyp4a12a, the knockdown of which blocked the increase in 20-HETE. These results indicate that innate male-selective Cyp4a gene induction and 20-HETE signaling are significant factors that can contribute to sex differences in the outcomes from ischemic stroke.

The airway epithelium serves as the first line of defense against inhaled insults present in the external environment by acting as a physical barrier and through host defense mechanisms. Proper maintenance of these host defense mechanisms relies on the regulation of airway surface liquid (ASL) composition and properties, a process that is tightly controlled by various ion transporters, including the cystic fibrosis transmembrane conductance regulator (CFTR) protein. With evidence suggesting dysfunctional CFTR-mediated bicarbonate secretion leads to airway acidification, resulting in impaired host defenses, there is increased interest in improving ASL pH. The aim of our study was to determine whether pharmacological interventions, via cAMP and CFTR modulators, lead to an increase in pH. Human airway epithelial (Calu-3) cells were exposed to various combinations of cAMP and CFTR modulating agents to assess their effectiveness at elevating apical base secretions (apical fluid) pH. Our results show that pharmacological interventions with cAMP elevating agents and CFTR modulator VX-770 led to significant increases in pH, with combinations leading to greater increases compared to single drug interventions. Our study suggests that cAMP and CFTR modulation has potential as a therapeutic strategy for elevating ASL pH and may be beneficial for respiratory diseases with ASL abnormalities.

Periods of low energy availability (LEA) are common in elite athletes and typically arise from reduced energy intake, often involving some degree of carbohydrate (CHO) restriction. Whether the metabolic profile created by energy restriction per se is distinct compared to that driven by CHO restriction is unknown. Using untargeted metabolomics, we examined metabolic perturbations linked to CHO restriction and energy restriction in plasma from elite male endurance athletes. In a semi-randomized controlled trial, athletes (n = 20) completed one of three 5-day dietary interventions: high energy-high CHO (HCHO); LEA (energy-restricted, CHO-reduced); or low-CHO, high-fat (LCHF; energy-matched, CHO-restricted). Plasma samples were taken at multiple timepoints pre- and post a standardized 25 km race walk protocol. Metabolomic analysis was performed using liquid chromatography-mass spectrometry (LC-MS), with multivariate analysis conducted using RM-ASCA+ and hierarchical clustering. A total of 5391 metabolic features were detected and 138 metabolites annotated. LCHF induced substantial metabolic perturbations, especially after prolonged exercise, including elevations in fatty acyls, hydroxy acids, dicarboxylic acids and acylcarnitine intermediates, responses not seen under LEA. We conclude that CHO restriction concomitant with a high-fat load induces a greater metabolic perturbation in selected lipid-based metabolites than short-term LEA exposure in elite athletes undergoing prolonged endurance exercise.

Heart rate variability (HRV) is a sensitive marker of autonomic regulation. This study examined adolescents in the long-term postoperative period after early surgical correction of aortic coarctation (CoA) compared with age-matched healthy peers. Seventy adolescents (35 CoA, 35 controls; 12-17 years) underwent 5-min resting ECG and respiratory monitoring. HRV was analyzed using time domain, frequency domain, and nonlinear methods; respiratory rate was included as a covariate in ANCOVA models. Adolescents with repaired CoA showed lower time domain indices (SDNN, RMSSD, pNN50; all p < 0.01), reduced total spectral power (p = 0.002), and higher VLF (p < 0.001). Group differences in SDNN, RMSSD, and the LF/HF remained significant after adjustment for respiratory rate, indicating that autonomic alterations were not explained by breathing patterns. Nonlinear analysis revealed reduced Poincaré plot parameters (SD1, SD2; p < 0.01) and higher fractal scaling (DFA Alpha2; p < 0.001) in the CoA group, whereas entropy measures and DFA Alpha1 did not differ. These findings demonstrate persistent and selective alterations in autonomic regulation during adolescence despite anatomically successful repair. The coexistence of altered and preserved HRV features suggests domain specific reorganization rather than uniform loss of complexity. Nonlinear HRV indices may improve long term monitoring and help guide individualized rehabilitation.

Dynamic ultrasound indices assess preload-dependent changes in stroke volume via the Frank-Starling mechanism and guide fluid therapy. This study aimed to determine optimal cutoff values for ultrasound-derived peak aortic (ΔVAo) and carotid (ΔVCa) velocity variations to predict fluid responsiveness in critically ill pediatric oncology patients. In this prospective cohort, 83 children underwent 88 fluid challenges with 10 mL/kg saline. Fluid responsiveness was defined as a >15% increase in cardiac index, measured by left ventricular outflow tract Doppler after volume expansion. Fluid responsiveness occurred in 54.5% of assessments. ΔVAo demonstrated the highest predictive accuracy, with a 16.3% cutoff (sensitivity 91.6%, specificity 80%, AUC 0.89). ΔVCa showed moderate performance (cutoff 14.2%; sensitivity 79.1%, specificity 65%, AUC 0.75), while ΔIVC was not predictive (AUC 0.56). In mechanically ventilated patients (n = 60), ΔVAo remained accurate (cutoff 16.3%; AUC 0.90), whereas ΔVCa was modest (cutoff 16.5%; AUC 0.74). In spontaneously breathing patients (n = 28), ΔVAo cutoff was 15.5% (sensitivity 95%, specificity 87.5%, AUC 0.89), and ΔVCa was 13.2% (sensitivity 100%, specificity 50%, AUC 0.69). ΔVAo is a reliable predictor of fluid responsiveness in critically ill pediatric oncology patients. ΔVCa may serve as an alternative, though with lower accuracy.

Arterionephrosclerosis is characterized by focal global glomerulosclerosis (FGGS), which is a constant feature of aging and hypertension. FGGS begins as normal-appearing glomeruli that undergo tuft contraction (TC) and progress to global glomerulosclerosis (GGS). Kidney tissue from 26 hypertensive and 25 age-matched non-hypertensive patients was analyzed for glomerular volume and for podocyte number using a WT1 antibody. Immunohistochemistry (IHC) was employed to detect the senescence-related biomarkers p16, p21, β-galactosidase (GLB1), and 5-nucleotidase (CD73). Antibodies against annexin 3 (ANXA3), cytokeratin 7, and CD44 were used to evaluate parietal epithelial cell (PEC) activation. The relationships between biomarkers, hypertension, TC, and GGS were quantitatively analyzed. With TC, podocyte numbers decreased in association with increased glomerular p16, p21, GLB1, and CD73 expression. With TC, WT1, CK7, and CD44-expressing PEC increased. TC and GGS expressed senescent markers in hypertensive and non-hypertensive kidneys; however, the frequency of TC (p < 0.01) and GGS (p < 0.001) was greater in hypertensive kidneys, and glomerular expression of senescence markers was correspondingly higher. Additionally, greater p16 and p21 expression was observed in the tubular atrophy of hypertension. As FGGS developed, podocyte depletion, cellular senescence markers, and PEC activation were associated with TC and increased with hypertension.