Frontiers in Physiology

Sarcopenia is a geriatric condition characterized by the loss of muscle strength, muscle mass, and physical performance, yet its neural mechanisms remain insufficiently understood. This study aimed to identify cortical indicators of motor and cognitive functioning in individuals with sarcopenia using functional near-infrared spectroscopy (fNIRS), along with electromyography (EMG) and hand dynamometer measurements. 30 sarcopenia patients (age 67.33 {+/-} 7.48, F/M: 22/8) and 38 healthy controls (age 65.37 {+/-} 4.18, F/M: 29/9) participated in three experimental sessions designed to probe different neural systems: a Hand Grip task to assess motor function, an N-Back task to evaluate working memory, and an Oddball task to measure attention and inhibitory control. fNIRS measurements were carried out during all experimental sessions, while EMG and force output were extracted from the Hand Grip task. Group differences and neural-behavioral relationships were examined using t-tests, correlations, and repeated measures analyses. Participants with sarcopenia demonstrated significantly reduced EMG activity and force production. Although motor cortex responses during the Hand Grip task were similar between groups, the N-Back task revealed lower activation in the precentral, middle frontal, and superior frontal regions in the sarcopenia group. In contrast, the Oddball task showed increased right-hemisphere activation in sarcopenic individuals, suggesting compensatory recruitment. Significant correlations between cortical activity, grip strength, and Chair Stand Test performance indicated shared neural pathways linking motor and cognitive function. These findings highlight altered neural processing in sarcopenia and emphasize the importance of integrating neuroimaging with clinical measures to advance early detection and targeted intervention strategies. HighlightsO_LIfNIRS assessed motor and cognitive cortical activity in sarcopenia. C_LIO_LISarcopenia showed lower EMG amplitude and grip force output. C_LIO_LINo group difference in motor cortex activation during hand grip. C_LIO_LIN-back revealed lower frontal and precentral activation in sarcopenia. C_LIO_LIOddball showed higher right-hemisphere activation in sarcopenia. C_LI

Hypermobile Ehlers-Danlos Syndrome (hEDS) is a genetic connective tissue disorder characterized by hypermobile joints, chronic pain, fatigue, brain fog, orthostatic intolerance, and GI symptoms and dysmotility. Its heterogeneous presentation contributes to poor quality of life, inappropriate interventions, and prolonged diagnostic delays, often up to 10 years. This study primarily aimed to determine if physiological signals captured by a medical-grade wrist wearable could characterize autonomic patterns in hEDS and relate them to symptoms. Individuals with hEDS (n=30) and healthy controls (n=28) wore a medical grade smartwatch for 30 days, collecting continuous heart rate variability, activity, oxygen saturation, and blood pressure, alongside initial baseline symptom and quality-of-life surveys. Individuals with hEDS showed greater instability and variability in both systolic and diastolic blood pressure as well as the HRV metric LF/HF ratio, in comparison to healthy controls (p-values: 0.04, 0.02, 0.02). During sleep, metrics of parasympathetic activity (HRV measures: HF power, pNN50, RMSSD) trended lower in hEDS than healthy in comparison. As expected, survey domains assessing physiologic symptoms and quality-of-life were significantly worse in the hEDS cohort (p-values < 0.05). Notably, autonomic metrics correlated with GI symptoms in the hEDS cohort (Spearman's {rho} range: 0.38-0.60), and psychological symptoms in the healthy cohort (Spearman's {rho} range: -0.47-0.41). Principal component analysis (PCA) of physiologic and symptom features clearly separated groups, supporting distinct physiologic profiles. Combination of GI symptom index and wearable monitoring show promise as a hybrid screening approach that could substantially shorten the time to diagnosis in this population.

ObjectiveWhile there are numerous reports on heart rate and its variabilities, a detailed analysis of the component intervals for healthy adults in well controlled condition is lacking. This study analyzes the effect of age, sex, and Body Mass Index (BMI) on nine resting electrocardiogram (ECG) intervals and their intra-individual variabilities in healthy adults under the same testing environment. MethodsUsing the "Autonomic Aging" dataset, ECG recordings from 1,121 healthy volunteers (ages 18-92) were processed. The study employed a specialized segmentation algorithm to identify key ECG markers. We analyze statistically how age, BMI, and sex impact the durations and variabilities of nine ECG intervals. ResultsFifty years of age serves as a critical transition age for cardiac aging for all subjects as a whole. Above this age, the active interval, which is the combined atrial and ventricular conduction time, increases three times faster than at a younger age, primarily driven by lengthening of depolarization times. Compared to the opposite sex, older low-BMI males have a longer atrial conduction time, and older low-BMI females have a larger variability in the ventricular conduction time. High BMI increases the heart rate by reducing the length of the idle interval, i.e., the isoelectric segment at the end of a cardiac cycle. The rate increase is more pronounced among older subjects than younger ones. High BMI males start to exhibit an elevated heart rate and larger variability in the atrial conduction time in their 30s. High BMI females start to show a larger variability in the ventricular repolarization time around 50 years old. ConclusionAge, BMI, and sex all have major impacts on the ECG intervals and their variability. A resting heart behaves largely like a pulse width modulation system, with a stable active interval and an adjustable idle interval to meet the varying needs for cardiac output. The durations and variabilities of the active interval, more than those of the RR interval, are indicators of a hearts health condition. A young and healthy heart tends to have a shorter duration and smaller variability in the active interval.

Experimental assessment and computational modeling were used to analyze substrate transport, tricarboxylic acid cycle kinetics, and oxidative phosphorylation in suspensions of purified cardiac mitochondria. The kinetics of ATP synthesis and carbohydrate oxidation, including during hypoxia and reoxygenation, were investigated using various substrate combinations and conditions. Model simulations fit to transient respiration and NAD(P)H measurements reveal novel insights into pyruvate dehydrogenase regulation, regulation of mitochondrial leak, and the clearance of oxaloacetate during respiration on succinate. High concentrations of succinate induced increased mitochondrial leak respiration driven in part by ROS-activated uncoupling. Oxidative phosphorylation under succinate-fueled respiration was inhibited by rapid buildup of oxaloacetate, inhibiting succinate dehydrogenase. Malic enzyme and oxaloacetate decarboxylase activities represent potenital pathways for removal of oxaloacetate, with glutamate further enhancing clearance. The developed model captures the observed transient behaviors as well as steady-state relationships between ATP synthesis rate and phosphate metabolite levels, lending a new systems-level understanding of mitochondrial energy metabolism. In sum, these findings offer a framework for simulating and interpreting mitochondrial function in vitro and in vivo. Key PointsThis study uses experiments and computer simulations to probe the interactions between substrate transport processes, TCA cycle kinetics, redox state, and oxidative ATP synthesis in cardiac mitochondria. The developed kinetic model simulates mitochondrial metabolism in vitro and represents a framework for integrative modeling of cardiac energy metabolism. Model-based analysis identifies a kinetic model of pyruvate dehydrogenase (PDH) deactivation during leak-state respiration and activation during oxidative phosphorylation. High levels of cation leak during respiration on succinate are explained by a ROS-dependent activation of uncoupling.

Background: For decades, cardiovascular physiology has been built on the assumption that arterial baroreceptors adjust heart rate (HR) to maintain a defined blood pressure set point. We challenge this paradigm fundamentally. Blood pressure and heart rate both change substantially in response to physiological stress and neither returns reliably to a fixed baseline value. This raises the question of whether a higher-order variable, one that remains stable while blood pressure and heart rate reset freely might better represent a truly defended, set-point quantity. Hypothesis: We hypothesized that the coefficient of variation of the instantaneous baroreceptor gain (IBS CV), expressed as the change in R-R interval per unit change in systolic blood pressure (SBP), is invariant across different physiological challenges. If IBS CV is fixed, then HR and SBP must vary proportionally, maintaining a stable gain relationship even as each changes in magnitude. Methods: To test this hypothesis, we had healthy adult volunteers undergo either the cold pressor test or passive orthostatic challenge. HR, SBP, IBS, and the coefficients of variation (CV, i.e. standard deviation / mean value) of each were measured at baseline and during each stress perturbation. Results: During orthostatic challenge, HR rose significantly while SBP fell significantly. Classically, this HR rise is attributed to baroreflex compensation for falling pressure. However, the critical observation is that SBP was not restored to baseline. Instead, it remained substantially reduced while HR stayed persistently elevated and HR CV increased significantly. A system primarily defending a blood pressure set point should augment baroreflex gain and suppress pressure variability; instead mean IBS showed no significant change, SBP CV amplified more than threefold, and IBS CV was unchanged. During the cold pressor test, both HR and SBP rose simultaneously, which is inconsistent with a pressure-defending system that would have suppressed HR in response to the large rise in SBP. IBS CV was also stable across this perturbation while SBP CV amplified dramatically. Conclusion: These findings challenge the classical baroreceptor set-point model and suggest that IBS CV, not blood pressure, is the primary regulated cardiovascular variable. Furthermore, IBS CV is likely to prove to be a more sensitive marker than blood pressure or heart rate variability for risk stratification in patients with hypertension, heart failure, or autonomic insufficiency.

Hypoxemia occurs in intermittent forms, such as obstructive sleep apnea, and in continuous forms, such as at high altitude, and is increasingly recognized as a modulator of cardiometabolic risk. Although hypoxemia alters postprandial glucose and lipid metabolism, its effects on ketone bodies remain unclear. Using a randomized crossover design, we examined whether six hours of normoxemia or intermittent hypoxemia (15 hypoxemic cycles/hour targeting [~]85% peripheral oxyhemoglobin saturation with 100% medical-grade nitrogen) alters plasma {beta}-hydroxybutyrate (BHB) concentrations in 12 young adult females (mean [SD]: 21 [3] years) following a high-fat meal (33% of estimated daily energy requirements; 59% of calories from fat). In a follow-up session, a subset (n = 8) completed six hours of continuous hypoxemia (fraction of inspired oxygen [~]12.0% in a normobaric chamber). Postprandial data were analyzed using baseline-adjusted linear mixed-effects models, with Bonferroni post hoc tests. A time x condition interaction (P = 0.010) indicated that BHB concentrations at 360 minutes were higher during continuous hypoxemia (0.247 mmol/L; 95% CI: 0.218-0.275) than normoxemia (0.176 mmol/L; 95% CI: 0.153-0.200; PBonferroni = 0.029) and intermittent hypoxemia (0.163 mmol/L; 95% CI: 0.139-0.186; PBonferroni = 0.002), representing increases of 13.0% and 14.2% in estimated marginal means, respectively. This response was accompanied by higher postprandial plasma glucose and triglyceride concentrations during continuous hypoxemia than during normoxemia and intermittent hypoxemia (PBonferroni [&le;] 0.002), despite similar plasma insulin and non-esterified fatty acid responses across conditions (P [&ge;] 0.081). These findings indicate that continuous hypoxemia increases late postprandial plasma BHB concentrations in young adult females. New FindingsO_ST_ABSWhat is the central question of this study?C_ST_ABSWhat are the effects of normoxemia, intermittent hypoxemia, and continuous hypoxemia on plasma {beta}-hydroxybutyrate (BHB) concentrations in young adult females after a high-fat meal? What is the main finding and its importance?Compared to normoxemia, young adult females showed higher postprandial plasma BHB concentrations during continuous hypoxemia, but not during intermittent hypoxemia, despite similar changes in plasma concentrations of two main regulators of BHB production (non-esterified fatty acids and insulin) across experimental conditions. These findings suggest that continuous hypoxemia modifies postprandial BHB concentrations through mechanisms not fully explained by circulating non-esterified fatty acids or insulin concentrations alone.

Circulating stem and progenitor cells (SPCs), including mesenchymal stromal cells (MSCs) and hematopoietic stem/progenitor cells (HSPCs), are mobilised after tissue injury but their temporal behaviour after hemorrhagic shock (HS) and relationship to cytokine milieus and outcome remain unclear. In a prospective observational cohort at JPN Apex Trauma Centre, AIIMS, New Delhi we studied 100 participants: 50 trauma patients with hemorrhagic shock and traumatic brain injury (HS index group), 25 trauma patients without HS, and 25 minor-injury controls. Peripheral blood was collected at admission (day 0) for all groups and additionally at days 3, 7 and 14 for the HS group. PBMCs were phenotyped by flow cytometry (HSPC markers: CD45, CD123, CD38, CD34; MSC markers: CD105, CD73, CD90) and serum SDF-1, VEGF-A, EGF, GRO- and GRO-{beta}, GM-CSF and G-CSF were measured by ELISA; group and time effects were evaluated with mixed-effects models and correlations by Spearman tests (two-tailed p<0.05). At admission, trauma patients without HS had significantly higher MSC and HSPC-like populations versus controls (p<0.0001). In the HS cohort SPC percentages rose modestly at day 0-3 then declined sharply by days 7-14 (time effect p<0.0001); non-survivors exhibited significantly higher early SPC and cytokine levels that persisted until death while survivors showed an early rise followed by decline (outcome and time interaction p<0.0001). All cytokines were up-regulated in trauma groups, peaked at day 0-3 in HS patients, and correlated positively with SPC counts (notably SDF-1, VEGF-A, G-CSF, Gro- and GM-CSF; Spearman p<0.05); higher early SPC and cytokine signatures associated with greater organ dysfunction (higher SOFA) and with timing of sepsis. These findings indicate that trauma provokes an early SPC and cytokine response that in HS is followed by later decline, and that persistent early elevation predicts worse outcomes, suggesting serial SPC and cytokine profiling may have prognostic value and identify an early therapeutic window for regenerative or immunomodulatory interventions.

Cerebral blood flow (CBF) control is essential for normal brain function and is disrupted in pathological conditions. Arterial diameters are tightly regulated to provide on demand increases in blood flow in regions of neuronal activity. Pericytes (PCs) exhibit robust myogenic tone and may also respond to neuronal activity to fine-tune local resistance and blood flow. Thus, mural control of microcirculatory resistance may extend beyond arteries and arterioles. Yet, PCs electrophysiology and contractility have not been thoroughly characterized, and this prohibits an integrated view of brain blood flow control. In this study, we develop a detailed mathematical model of mural cell electrophysiology, Ca2+ dynamics and biomechanics. The model is informed by electrophysiological data in smooth muscle cells (SMCs) or PCs and predictions are compared against pressure-induced responses in isolated arterioles and capillaries, respectively. Simulations recapitulate myogenic constrictions and examine differences in contractile dynamics as we move from arterioles to proximal and distal capillaries. In arteriole-to-capillary transitional (ACT) zone PCs, increased mechanosensitivity, more Ca2+ influx through non-selective cation (NSC) channels and/or a higher sensitivity of the contractile apparatus to Ca2+ can compensate for reduced L-type voltage-operated (VOCC) Ca2+ influx and allow for robust constrictions at the lower operating pressures of capillaries relative to the arterioles. A significant Ca2+ influx through NSC relative to VOCC, however, can decouple the PCs contractile apparatus from electrical signaling. Vasoactivity to chemomechanical stimuli along the arteriole to capillary axis is progressively driven by VOCC-independent Ca2+ influx and Ca2+ sensitization with slow kinetics. The proposed cell model can form the basis for detailed multiscale and multicellular models that will examine physiological function at a single vessel or vascular network levels and investigate CBF control in health and in disease. Key pointsO_LIA mural cell model of electrophysiology, calcium (Ca2+) dynamics and biomechanics is informed by data and adapted for modeling cerebral arteriole smooth muscle cells and capillary pericytes. C_LIO_LIIon channel activities are characterized by patch-clamp electrophysiology in isolated cerebral smooth muscle cell and pericytes, and capillary and arteriole electromechanical responses to transmural pressure changes are assessed using novel ex vivo preparations. C_LIO_LIMyogenic constrictions in arterioles can be reproduced by pressure-induced non-selective cation channel (NSC) activation that depolarizes the cell, opens L-type Ca2+ channels (VOCCs) and increases Ca2+ influx. C_LIO_LIRobust myogenic constrictions in arteriole-to-capillary transition (ACT) zone pericytes may reflect significant Ca2+ influx through NSC, increased mechanosensitivity, or higher sensitivity of the contractile apparatus to Ca2+, potentially compensating for reduced VOCC density relative to arteriolar smooth muscle. C_LIO_LIA significant contribution of NSC relative to VOCC in Ca2+ influx, can decouple the contractile apparatus from electrical signaling. C_LIO_LIThe model shows how gradients in ionic activities, mechanosensitivity and/or Ca2+ sensitivity can alter contractile phenotype and electromechanical coupling along the arteriole to capillary continuum. C_LIO_LIThe proposed model can form the basis for detailed multiscale and multicellular models that will investigate cerebral blood flow control in health and in disease. C_LI

Background and AimsHeart failure with preserved ejection fraction (HFpEF) exhibits profound phenotypic heterogeneity, which likely contributes to variable therapeutic response. We developed a physiology-informed digital twin-AI framework to predict individual hemodynamic and myocardial energetic responses to accelerated atrial pacing and tested whether simulated physiologic response corresponds to responders in the myPACE randomized clinical trial. MethodsPatient-specific digital twins were constructed for 146 HFpEF patients and used to train a variational autoencoder that generated a virtual HFpEF population (n = 25,000). The model simulated pacing-induced changes in left atrial pressure (LAP), systolic blood pressure (SBP), cardiac output (CO), and cardiac efficiency (CE; derived from myocardial oxygen-demand estimates). These simulations served as labels to train classifiers based on clinical variables available in myPACE, allowing us to examine associations with clinical end points and test a hypothesized relationship between CE and treatment response. ResultsSimulations revealed heterogeneous physiological responses, with 95.6% of virtual patients showing reduced LAP, 47.0% an SBP reduction greater than 8.5 mmHg, 93.8% increased CO, and 36.1% improved CE. Classifiers reproduced these patterns with high fidelity. In the myPACE trial, patients classified as having CE improvement or a larger SBP reduction experienced significantly greater 1-month improvements in quality-of-life scores and larger NT-proBNP reductions. ConclusionsA physiology-informed digital twin-AI framework can predict hemodynamic and energetic responses corresponding to clinical benefit in HFpEF patients receiving accelerated atrial pacing. CE improvement functioned as a mechanistic indicator, while SBP reduction served as an accessible clinical correlate, offering mechanistically grounded guidance for patient-specific pacing and motivating prospective validation. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=122 SRC="FIGDIR/small/26347199v1_ufig1.gif" ALT="Figure 1"> View larger version (63K): org.highwire.dtl.DTLVardef@4a550eorg.highwire.dtl.DTLVardef@163b85org.highwire.dtl.DTLVardef@19db16dorg.highwire.dtl.DTLVardef@1eb6cf5_HPS_FORMAT_FIGEXP M_FIG C_FIG

Uncontrolled hemorrhage remains a leading cause of traumatic death, driven by rapid physiological deterioration that is often difficult to detect during the compensated phase. While large-animal models provide critical insights into these dynamics, they are resource-intensive, motivating the need for efficient computational frameworks that can mechanistically interpret cardiovascular responses. We developed and calibrated a closed-loop zero-dimensional (0D) lumped-parameter model (LPM) using hemodynamic data from 43 anesthetized swine subjected to controlled hemorrhage (10%, 20%, or 30% of total blood volume). The computational framework, incorporates a dynamic heart model with a custom time-varying elastance function, a multi-compartment aorta, and distal Windkessel models representing vascular beds. The model was calibrated at discrete time snapshots throughout the 30-minute hemorrhage protocol to reproduce group-averaged experimental waveforms for aortic flow, regional organ flows, and systemic pressures. The calibrated model successfully reproduced experimental hemodynamic targets and waveform morphology across all hemorrhage severities. Analysis of the calibrated parameters revealed distinct physiological mechanisms driving hemodynamic adaptation during hemorrhage: a preferential increase in renal resistance compared to carotid resistance, indicating flow redistribution to vital organs, and a progressive mobilization of venous unstressed volume to sustain cardiac filling. Furthermore, the model captured the distinct shift toward preload limitation state for 30% hemorrhage group. This study establishes a physiologically interpretable in-silico framework capable of predicting both global and regional hemodynamic responses to acute blood loss, providing a validated foundation for future applications in trauma care and resuscitation modeling.

Kidneys play an essential role in balancing fluid and electrolyte levels. Two mouse strains, C57Bl/6 and 129S2/SV, are routinely used to study renal physiology in laboratory settings, and prior observations suggest that significant differences in salt and water handling exist between them. This study aims to further establish the sources of these observed differences at both expressional and functional levels, in male and female mice. At baseline, male 129S2/SV mice displayed decreased Na+ and increased K+ plasma concentrations compared to C57Bl/6 males, while no statistical differences were observed between female mice. Interestingly, 129S2/SV male mice had lower glomerular density than C57Bl/6 males. Immunoblotting shows that 129S2/SV mice of both sexes had increased expression of NHE3 and NKCC2 compared to their C57Bl/6 counterparts. Both total and phosphorylated NCC were more abundant in female mice as compared to males, indicating sexual dimorphism. Furthermore, 129S2/SV females had higher expression of total and phosphorylated NCC compared to C57Bl/6 females. In contrast, the expression of SGLT2, ENaC subunits, and Na+/K+-ATPase were comparable between C57Bl/6 and 129S2/SV mice of both sexes. When challenged with diuretics intended to block NKCC2, NCC or ENaC, 129S2/SV male mice responded with a smaller diuresis and natriuresis than their C57Bl/6 counterparts. Taken together, our data suggest that differential expression of key Na+ transporters along the nephron contributes to differences in Na+/K+ homeostasis between these two mouse strains. NEW & NOTEWORTHYWe assessed the influence of genetic background on the expression of key Na+ transporters along the nephron in two commonly used inbred mouse strains, C57Bl/6 and 129S2/SV. We found that the kidney expression of NHE3, NKCC2, and NCC are strain dependent. Additionally, murine strain significantly contributes to the diuretic responses induced by hydrochlorothiazide, amiloride, and furosemide.

BackgroundMenopausal obesity is a type of obesity in women during menopause where the decline of ovarian function and the decrease of estrogen levels lead to an imbalance between energy intake and consumption in the body, resulting in fat accumulation and weight gain. Moxibustion, as a green therapy of non-interventional external treatment that prevents and treats diseases through thermal stimulation of relevant acupoints, has been widely used in clinical practice because of its simplicity, convenience, effectiveness, low price and high compliance. PurposeTo clarify the pathogenesis of menopausal obesity and the biological mechanism of moxibustion treatment for menopausal obesity. MethodsWe selected 9 plasma samples from menopausal obese patients before and after moxibustion treatment, as well as 9 plasma samples from the healthy control group. After sample mixing and replication, DIA quantitative proteomics analysis was used to screen out differentially expressed proteins, and bioinformatics analysis was conducted. ResultsThe plasma proteomic analysis revealed a significant increase in the protein expression levels of APOC2 and PZP in menopausal obesity patients. These differential proteins primarily participate in biological regulation, cell metabolism, and reproductive development processes. Their biological processes and molecular functions are mainly associated with enzyme inhibitor activity, calcium-dependent protein binding, lipid localization, and plasma lipoprotein particle assembly. The pathogenesis of menopause obesity is linked to the accumulation of visceral fat resulting from changes in sex hormone levels and reduced energy consumption following the decline of female ovarian function. Following moxibustion treatment, there was a notable down-regulation in the plasma levels of sialoglycoprotein receptor 2 (ASGR2), membranin A1 (ANXA1), and human heterogeneous nuclear ribonucleoprotein C (HNRNPC) among menopausal obesity patients. Their biological processes and molecular functions were primarily concentrated on intracellular hagy, nucleic acid binding, tissue regeneration, and neutrophil clearance. ConclusionThe mechanism underlying moxibustions effectiveness in treating menopausal obesity may involve down-regulating HNRNPC expression, activating the PI3K/Akt/mTOR autophagy signaling pathway, regulating hormone levels to delay ovarian aging thereby improving lipid metabolism.

We present a deep learning model that predicts left atrial (LA) volume from standard 12-lead ECG recordings and basic patient data. This approach offers a low-cost, scalable alternative to MRI-based LA volume measurement, which remains the clinical gold standard but is often inaccessible. Our model performs regression directly on LA volume targets and leverages Shapley values to provide interpretable feature importance. Results highlight the predictive value of ECG signals and demonstrate that patient features such as weight and height contribute meaningfully to the estimation.

The aim of this study was to investigate the effects of cognitive dual-tasking on low-frequency oscillations during quiet standing in older adults. Thirty-two older adults (age 71{+/-}8 yrs) were categorized into high- and low-risk fall groups. Both groups performed three trials each of the following tasks: 1) quiet standing with eyes open - on a force plate; 2) quiet standing with eyes open and verbal memory encoding task - on a force plate; and 3) quiet sitting with eyes open and verbal memory encoding task - not on a force plate. We found that: A) older adults at high fall risk exhibit greater postural sway when compared with older adults at low fall risk, B) most of the absolute and normalized wavelet power from 0-4 Hz is concentrated within the 0-1 Hz frequency band across all directions, and C) the absolute change in wavelet power in the 0-1 Hz band from single to dual-task is associated with increased total COP sway displacement irrespective of fall risk group. Based on these findings, it is concluded that nonlinear postural sway measures provide valuable insights into age-associated changes in fall risk and dual-task performance. Focusing on low-frequency oscillations, particularly in the 0-1 Hz band, could enable the earlier identification of individuals at high risk of falls and a better understanding of how the dual-tasking paradigm challenges the aging population.

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia worldwide and is strongly associated with increased risks of stroke, heart failure, and mortality. Traditional methods to predict AF and prognostic its associated risks often fail to capture the full complexity of AF patterns, limiting their predictive accuracy. In spite of the improvements achieved by machine learning (ML) techniques, state-of-the-art AF-focused predictors do not generally incorporate longitudinal data, reducing their capacity to model the dynamic and evolving nature of individual behaviors and physiological indicators over time. The absence of a longitudinal perspective restricts understanding of how AF risk develops and changes across prognostic windows. This study addresses these limitations by developing superior ML models tailored to predict adverse events within a longitudinal Portuguese cohort of individuals with AF. The work targets six clinical endpoints: stroke, all-cause death, cardiovascular death, heart failure hospitalizations, inpatient visits, and acute coronary syndrome. The predictors yielded an AUC of 0.65 for 1-year stroke prediction, outperforming CHA2DS_2-VASc (0.59). For all-cause mortality prediction, the models achieved an AUC of 0.78 against the 0.72 reference of GARFIELD-AF. In addition to predictive advances, the study identifies determinants of AF-related risks and introduces a prototype decision-support tool for clinical use.

Whole-cell patch-clamp studies often fail to observe the expected effect of melatonin on the IK1 current in cardiomyocytes, which may be due to cytoplasmic dialysis and the loss of key components of the intracellular signaling system. The aim of this study was to develop a simple theoretical model to estimate the expected effect on the IK1 inward-rectifying potassium current in an experiment with intact melatonin signaling. The modeling was performed using a well-established model of rat cardiomyocyte electrophysiology (Pandit et al., 2001). The maximum conductance of IK1 (gK1) channels was chosen as the target for modulation, consistent with the established mechanism of direct receptor-mediated increase in potassium conductance under the action of melatonin.Realistic modulation values were used for the modeling. The -50% value for the antagonist effect of 1 M luzindole was obtained by direct calculation from our experimental data. The +20% value for the agonist effect (melatonin) was determined by generalizing literature data and reflects the typical expected strength of signaling pathway modulation, rather than being strictly tied to a specific concentration.It was shown that modulation of gK1 in the specified ranges leads to significant changes in IK1 amplitude in the physiologically important range of resting potentials. The developed model serves as a "computational benchmark" for validating experimental protocols, allowing one to distinguish methodological artifacts from a true lack of effect.

The growth of bivalve shells is neither homogeneous nor continuous in time, resulting in the formation of growth patterns that correspond to the alternation of growth lines and increments deposited at regular intervals of time. The control of periodic increment formation is poorly understood and several hypotheses have been proposed. It has been proposed that environmental factors directly impact shell growth patterns, although it occasionally fails to adequately explain the observed shell growth patterns. The present study investigates the alternative hypothesis that the process of shell biomineralisation is controlled by biological clocks. This study demonstrates the existence of a functional circadian clock in M. galloprovincialis, as evidenced by molecular and behavioural results. Core circadian clock genes and biomineralisation genes have been observed to be expressed in the same cells of the mantle as revealed by in situ hybridisation experiments. However, the expression of core circadian clock genes and biomineralisation genes tested in situ and in aquaria exhibited different rhythmic profiles. This finding suggests that the clock does not directly activate the expression of the targeted biomineralisation genes in the mantle. Nevertheless, a significant rhythm of expression of biomineralisation-related genes was observed in mussels reared under free-running conditions, revealing the endogenous nature of the rhythm. The present study suggests that biological clocks play a role in controlling shell biomineralisation in M. galloprovincialis, although the precise underlying mechanism remains to be elucidated.

PurposeWhile bowel sound auscultation represents a key component of abdominal examination, its utility is limited because bowel sounds (BS) are intermittent, variable, and influenced by factors such as diet and digestive state. This renders it challenging to use them for a quantitative assessment of gastrointestinal health. MethodsBS signals were recorded from 84 subjects (39 patients and 45 healthy controls) using an acoustic SonicGuard sensor and categorized into four patterns. Metadata on physiological parameters were collected to examine their influence on BS characteristics and the differences between healthy and patient BS patterns. ResultsBowel sound patterns are significantly influenced by meal timing, caffeine consumption, and medication intake. Significant differences between healthy and patient groups were also observed in sound count, duration, energy, and waveform shape. These differences were mirrored in the performance of machine learning models finetuned for BS patterns classification, with performance depending on the group used for training and evaluation. ConclusionBS patterns present a promising quantitative indicators of gas-trointestinal health when analyzed alongside relevant physiological parameters.

The left ventricle (LV) exhibits torsional deformation during systole, and mechanical relaxation begins during the isovolumic phase. Recent advances in imaging techniques, such as MRI, have revealed that myocardial tissue deformation and sarcomere length changes occur during the isovolumic relaxation phase, even when the chamber volume remains constant. Although such ventricular deformation during the isovolumic phase is considered important for blood ejection and filling efficiency, its mechanistic contribution to contraction and relaxation remains unresolved. In this study, we hypothesized that sarcomere length dynamics during the isovolumic phase affect the isovolumic contraction and relaxation time (IVCT and IVRT) by regulating the contraction force via the force-velocity relationship of ventricular myocytes. To investigate this hypothesis, we focused on experimentally reported differences in the relationship between sarcomere length and LV volume across the endocardial and epicardial layers, as described by Rodriguez et al. We constructed and compared two types of hemodynamic models within the same integrated framework consisting of a circulation model, a LV model, and a myocardial cell contraction model by Negroni-Lascano et al., which differ only in how sarcomere length is determined: a volume-based length model (VL model), in which sarcomere length is uniquely determined by LV volume, and a volume-force-coupled length model (VFL model), in which sarcomere length is determined by the balance between LV volume and contraction force. Simulation results showed that in the VFL model, compared to the VL model, sarcomere length changed during the isovolumic phase, leading to a decrease in contractile force and shortening of IVRT, which may contribute to improved hemodynamic efficiency. These results indicate that sarcomere length dynamics can mechanically regulate force decay during isovolumic relaxation, even under constant left ventricular volume. This study provides a theoretical framework for understanding the contributions of different layers within the LV wall to diastolic function during the isovolumic relaxation phase.

BackgroundChronic gastroduodenal symptoms are challenging to diagnose and treat. Body surface gastric mapping provides non-invasive biomarkers of gastric function, but the requirement of a standard meal for postprandial assessment can be difficult for severely symptomatic patients. AimsTo assess the impact of reduced meal sizes and fasting on body surface gastric mapping metrics to determine clinical interpretability under non-standard nutritional loads. MethodsHealthy controls (n=60) underwent a 4.5-hour Gastric Alimetry test. Three age, sex, and BMI-matched groups (n=20 each) were compared: Standard Meal (482 kCal), Nutrient bar + Water (250 kcal), and Fasted (no meal). Principal Gastric Frequency, Gastric Alimetry Rhythm Index, BMI-Adjusted Amplitude, and fed:fasted Amplitude Ratio were analyzed against normative intervals. ResultsMeal status significantly affected amplitude-based metrics; the Standard Meal group exhibited higher BMI-Adjusted Amplitude (p<0.001) and fed:fasted Amplitude Ratio (p=0.001) than Fasted and Bar + Water groups. Frequency and rhythm-based metrics were resilient; Principal Gastric Frequency (p=0.245) and Gastric Alimetry Rhythm Index (p=0.336) showed no significant differences across conditions. While amplitude deviations were common in the Fasted group (20% fell below the normative range), Gastric Alimetry Rhythm Index and Principal Gastric Frequency remained within normal reference ranges for 95% of participants across all conditions. ConclusionsWhile consuming <50% of the standard meal significantly reduces gastric amplitude, gastric rhythm remains stable. Principal Gastric Frequency and Gastric Alimetry Rhythm Index function as reliable biomarkers of gastric myoelectrical function regardless of nutritional state.