Open Access Publications - Department of Kinesiology & Applied Physiology

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Open access publications by faculty, postdocs, and graduate students in the Department of Kinesiology & Applied Physiology.

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Motors and Dampers: The Energetic Tradeoffs in the Shod Foot With Increasing Walking Velocity
(Journal of Foot and Ankle Research, 2025-11-11) Henderson, Adrienne; Bruening, Dustin; Arch, Elisa
Background The dual influences of velocity and footwear on ankle-foot energetics are particularly relevant for clinical populations who rely on footwear during ambulation. Although walking velocity influences energetic demands of foot structures, footwear may modify these relationships by restricting joint motion. This study aimed to characterize ankle-foot energetics while participants walked at a wide range of velocities while wearing supportive shoes. Methods Eighteen healthy participants walked at four height-normalized velocities (0.4–1.0 statures/second) in supportive footwear while kinematic and kinetic data were collected. Ankle, midtarsal, and metatarsophalangeal (MTP) work was quantified and compared using repeated-measures ANOVAs with Holm pairwise tests. Results MTP positive and negative work increased with shod walking velocity, though negative work increased substantially more than positive work. Midtarsal positive work also increased while maintaining minimal negative work across all velocities. Ankle positive work significantly increased with velocity accompanied by small but significant increases in negative work. Conclusions At all velocities, the MTP joint functioned as a mechanical damper and its damping characteristics became more pronounced as velocity increased. The midtarsal joint functioned as a strut, with a small motor role which became more prominent as velocity increased. The ankle had mixed roles, primarily between strut and spring, with a small damper/motor role that traded off with velocity (less damper more motor as velocity increased). The presence of supportive footwear attenuated positive and negative work across velocities when compared to previous barefoot studies, with the largest difference in the midtarsal's negative work, suggesting footwear substantially modifies natural foot mechanics through increasing velocities.
Motor segmentation: a key neuromuscular impairment in people with parkinson’s disease
(Experimental Brain Research, 2025-11-02) Daniels, Rebecca J.; Knight, Christopher A.
Healthy adults (OA) achieve rapid isometric force production with a brief, high amplitude burst of neural excitation. In some people with Parkinson’s disease (PwPD), transient reductions in neural excitation (motor segmentation) reduce rates of force development (RFD) and prolong contractions. Segmentation has strong relationships with time and rate-based measures of slowing in rapid contractions and is reliably measured from the second derivative of force (F”(t)). We sought more information about how segmentation affects neuromuscular control in PwPD. Aim 1 was to determine the prevalence of PwPD with segmentation (PDSeg). Aim 2 was to determine how force performance differs in PDSeg, PwPD without segmentation (PDNoSeg), and OA. Aim 3 was to quantify force segment durations. Fifty-seven PwPD ON medication and 22 OA performed rapid isometric finger abduction contractions to 20–60% of maximal voluntary contraction force. The median number of force segments to 90% of peak force were measured from F”(t) zero crossings. Additional outcomes included median times to peak force (tPF) and peak RFD (tRFD), and peak RFD (RFDpk). 68% of PwPD had segmentation (median segments ≥ 2, 95% CI [0.55 0.80]). PDSeg had slower tPF, tRFD and RFDpk than PDNoSeg and OA (all p ≤ 0.012, 0.38 ≤ r ≤ 0.85). PDNoSeg and OA did not have statistically different tPF, tRFD, or RFDpk (p > 0.05). PDSeg had consistent segment durations (coefficient of variation ≤ 25.5%) and shorter first segment durations compared to PDNoSeg and OA (p < 0.001, r ≥ 0.68), indicating PDSeg had reduced neuromuscular excitation prior to peak force. Segmentation identifies specific pathophysiology in neuromuscular control that exacerbates slowing in isometric force production.
Sodium intake and biological sex inﬂuence urinary endothelin-1 in salt-resistantadults: a pilot study
(American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2025-08-19) Nasci, Victoria L.; Benjamin, Jazmine I.; Stock, Jseph M.; Romberger, Nathan T.; Watso, Joseph C.; Babcock, Matthew C.; Wenner, Megan M.; Robinson, Austin T.; Gohar, Eman Y.
Hypertension is more prevalent in males than age-matched premenopausal females. Average sodium intake in the United States ishigher than recommended and is a risk factor for developing hypertension. Sex differences in renal sodium homeostasis may underliesex differences in hypertension prevalence. For example, renal endothelin-1 (ET-1) plays a key role in the maintenance of blood pres-sure and sodium homeostasis. Previous rodent studies demonstrate that females excrete higher urinary ET-1 compared with males,and increasing dietary sodium promotes urinary ET-1 excretion only in male rats. However, the impact of sex on sodium and renal ET-1 signaling in humans is unclear. Therefore, we aimed to determine whether the renal ET-1 system responds differently to salt loadingin male and female human research participants. To test our hypothesis, normotensive salt-resistant male and female participantswere administered a low (1 g/day), recommended (2.3 g/day), and high (7 g/day) sodium diet for 10 days each in random order. The24-h urine samples were collected and assessed for sodium and ET-1. Following increased dietary sodium, both males and femalesincreased urinary sodium excretion (diet: P < 0.001). Following increased dietary sodium, participants exhibited an increased urinaryET-1 excretion (diet: P ¼ 0.038). Interestingly, post hoc testing revealed that only females displayed an increase in ET-1 excretion (rec-ommended vs. high sodium, P ¼ 0.009). Overall, the current human study provides novel insights into potential sex-speciﬁc modula-tion of ET-1 and renal responses to dietary sodium. Further investigations are warranted to understand the underlying molecularmechanisms driving sex-related differences in renal ET-1 signaling and sodium handling.
Normative Data for Single- and Dual-Task Tandem Gait Performance in Collegiate Athletes
(Sports Medicine, 2025-10-03) Shumski, Eric J.; Lempke, Landon B.; Howell, David; Buckley, Thomas; Oldham, Jessie; Meehan, William; Lynall, Robert C.
Background Normative dual-task (concurrent cognitive and motor task) tandem gait has not been developed. Currently, only individual baseline data are used for tandem gait assessment post concussion. Objective The object was to (1) determine factors associated with single-task and dual-task tandem gait time among collegiate athletes across multiple institutions, and (2) provide robust normative data for single-task and dual-task tandem gait time based on clinically relevant factors. Methods Data were analyzed from 2,137 unique collegiate athletes (19.0 ± 1.1 years, 48.9% female, 23.7% with concussion history) from 2015 to 2022 during pre-injury baseline concussion testing from three universities. Tandem gait was performed under single- and dual-task conditions (serial subtraction by sixes/sevens, spelling five-letter words backward, reciting the months backward). The criteria for being a clinically relevant independent variable was (a) p value < 0.05, and (b) effect estimate of ≥ 1 s. Normative data based on established percentile thresholds were derived and stratified by clinically relevant factors. Results None of the single-task tandem gait times were clinically relevant, while sex and contact level were for dual task. Mean (95% confidence interval) for overall single- and dual-task tandem gait times were 12.07 s (11.95, 12.19) and 16.51 s (16.29, 16.73), respectively. Conclusion Our results provide robust normative data for single- and dual-task tandem gait stratified by relevant patient factors that can be immediately used by clinicians and future researchers. Future research should compare the use of individual baseline versus normative data for acute concussion tracking.
Inhibition of lipolysis in visceral adipose tissue from obese mice and humans prevents impairment of endothelial Kir2.1 channels
(Channels, 2025-09-25) Hudgins, Emma C.; Johnson, Erica J.; Rokkaa, Sabita; Kashyapa, Bhaswati; Mahugua, Arielle; Nguyenb, Thanh; Tasconec, Anthony R.; McCarthy, Elizabeth; Halbert, Caitlin; Fancher, Ibra S.
Accumulation of abdominal visceral adipose tissue (VAT) is a major risk factor for cardiovascular disease. Obesity-induced endothelial dysfunction is a precursor to severe disease, and we and others have shown that arteries embedded in VAT, but not subcutaneous adipose tissue, exhibit robust endothelial dysfunction. Using a mouse model of diet-induced obesity, we recently linked VAT from obese mice to the impairment of endothelial Kir2.1, a critical regulator of endothelial function. However, the mechanism by which VAT impairs Kir2.1 is unclear. As Kir2.1 impairment is dependent on endothelial CD36, we hypothesized that lipolytic VAT induces Kir2.1 impairment through fatty acids (FA). To test this, we first treated endothelial cells with palmitic acid (PA) to determine whether the addition of exogenous FAs recapitulated our original finding of Kir2.1 dysfunction when challenged with VAT. PA inhibited Kir2.1 assessed via whole-cell patch-clamp electrophysiology, an effect that was dependent on endothelialCD36. To determine whether inhibiting VAT lipolysis prevents Kir2.1 dysfunction in the presence of VAT in obese mice and humans, VAT was pretreated with small molecule inhibitors of adipose triglyceride lipase prior to incubating endothelial cells with adipose tissue. This approach also prevented VAT-induced impairment of endothelial Kir2.1suggesting that VAT-derived FAs may play a role. Furthermore, inhibition of lipolysis in the VAT of obese mice and humans significantly reduced endothelial FA uptake, similar to that observed when CD36 was downregulated. These findings advance our under-standing of the relationship between VAT and endothelial Kir2.1 impairment and place VAT-derived FAs as potential paracrine mediators.
A pilot study for self-guided, active robotic training of proprioception of the upper limb in chronic stroke
(Journal of NeuroEngineering and Rehabilitation, 2025-06-07) Tulimieri, Duncan T.; Kim, GilHwan; Hoh, Joanna E.; Sergi, Fabrizio; Semrau, Jennifer A
Background Proprioceptive impairments of the upper limb are common after stroke. These impairments are not typically addressed during assessment or rehabilitation. Currently, most robotic paradigms for training of the upper limb have focused solely on improving motor function or have targeted proprioception in individuals with combined use of visual feedback. Our goal was to design a training paradigm that directly targets proprioception of the upper limb, while minimizing reliance on other sensory information to improve sensorimotor function after stroke. Methods In this pilot study, 5 individuals with stroke and 5 age-matched controls were tested on a single-day proprioceptive training paradigm. Here, participants used a joystick with their less-affected arm to send commands to a KINARM exoskeleton that would passively move their more-affected arm. To complete the passive reaching task, participants relied only on proprioceptive feedback from the more-affected arm and were only given knowledge of results information after each trial. Sensorimotor function of the upper limb was measured pre- and post-training via robotic measures of motor function [Visually Guided Reaching (VGR)] and position sense [Arm Position Matching (APM)]. Sensorimotor function was quantified as a Task Score, which incorporated multiple task-relevant parameters for both VGR and APM. Changes in sensorimotor performance due to training were calculated as the pre- to post-training difference for VGR and APM within the control and stroke groups. Results We found significant improvements from pre-training to post-training for VGR in individuals with stroke (p < 0.001, CLES = 100) that were not observed in control participants (p = 0.87, CLES = 80). We observed significant changes from pre- to post-training in both VGR (Posture Speed, Reaction Time, Initial Direction Angle, Min–Max Speed Difference, and Movement Time) and APM (Contraction/Expansion Ratiox and Shifty) parameters. Conclusions Our novel proprioceptive training paradigm is one of the first to implement a self-guided sensory training protocol. We observed improvements in motor function and proprioception for individuals with stroke. This pilot study demonstrates the feasibility of self-guided proprioceptive training to improve motor and sensory function in individuals with stroke. Future studies aim to examine multi-day training to examine longer-term impacts on upper limb sensorimotor function.
Unrecognized and Unreported Concussions Among Community Rugby Players
(Sports, 2025-08-20) Wittmer, Rachael; Buckley, Thomas A.; Swanik, Charles Buz; Costantini, Katelyn M.; Ryan, Lisa; Daly, Ed; King, Regan E.; Daniels, Arryana J.; Hunzinger, Katherine J.
This study examined the prevalence of intentionally unreported and potentially unrecognized concussions in community rugby players and whether nondisclosure reasons vary by sex, position, or playing history. An online survey was completed by 1037 players (41.0% female; mean age 31.6 ± 11.3 years; 10.1 ± 8.1 years playing) who reported diagnosed, unreported, and unrecognized concussions. Poisson regression models estimated prevalence ratios (PRs), and Fisher’s exact tests compared reasons for nondisclosure. The diagnosed, unreported, and unrecognized concussion rates were 66.5%, 32.4%, and 42.2%, respectively. Players with diagnosed concussions had a 7.2-fold higher prevalence of nondisclosure and a 2.3-fold higher prevalence of nonrecognition. A longer playing history was linked to greater nondisclosure (PR: 1.2), and males had a higher prevalence of nonrecognition (PR: 1.4). Position and sex were not associated with nondisclosure; position and playing history did not affect recognition. While nondisclosure reasons were mostly consistent across demographics, players with a history of concussion were more likely to report avoiding removal from games or practices (38.5% vs. 13.6%, p = 0.021). Concussions are common in community rugby, with high rates of underreporting and unawareness, influenced by experience and prior concussions. These findings underscore the need for better education and reporting systems to improve player safety.
The Role of Sensory Impairments on Recovery and Rehabilitation After Stroke
(Current Neurology and Neuroscience Reports, 2025-03-06) Hoh, Joanna E.; Semrau, Jennifer A.
Purpose of Review The current review aims to address critical gaps in the field of stroke rehabilitation related to sensory impairment. Here, we examine the role and importance of sensation throughout recovery of neural injury, potential clinical and experimental approaches for improving sensory function, and mechanism-based theories that may facilitate the design of sensory-based approaches for the rehabilitation of somatosensation. Recent Findings Recently, the field of neurorehabilitation has shifted to using more quantitative and sensitive measures to more accurately capture sensory function in stroke and other neurological populations. These approaches have laid the groundwork for understanding how sensory impairments impact overall function after stroke. However, there is less consensus on which interventions are effective for remediating sensory function, with approaches that vary from clinical re-training, robotics, and sensory stimulation interventions. Summary Current evidence has found that sensory and motor systems are interdependent, but commonly have independent recovery trajectories after stroke. Therefore, it is imperative to assess somatosensory function in order to guide rehabilitation outcomes and trajectory. Overall, considerable work in the field still remains, as there is limited evidence for purported mechanisms of sensory recovery, promising early-stage work that focuses on sensory training, and a considerable evidencepractice gap related to clinical sensory rehabilitation.
Evidence of racial differences in peripheral blood pressure, central haemodynamics and arterial stiffness between young Black and White women
(Experimental Physiology, 2025-07-26) D'Agata, Michele N.; Hoopes, Elissa K.; Matias, Alexs A.; Rattigan, Mackenzie L.; Patterson, Freda; Witman, Melissa A.
Hypertension diagnosed via peripheral (brachial) blood pressure (pBP) is a strong independent predictor of overt cardiovascular disease (CVD). However, central (aortic) blood pressure (cBP), which is influenced by arterial stiffness, may be more strongly associated with CVD risk. Young Black women (BLW) demonstrate higher pBP than White women (WHW), but investigations of racial differences in central haemodynamics and arterial stiffness in young women are lacking. We assessed pBP, central haemodynamics and arterial stiffness in young, non-hypertensive BLW and WHW. We hypothesized that pBP, central haemodynamics (cBP, augmentation pressure (AP), augmentation index normalized to a heart rate of 75 beats per minute (AIx75), arterial wave reflections), and arterial stiffness (carotid–femoral pulse wave velocity (cf-PWV)) would be higher in BLW. Under standardized resting conditions, supine brachial pBP was measured, and central haemodynamics were estimated via pulse wave analysis using partial cuff inflation. cf-PWV was assessed via simultaneous carotid artery applanation tonometry and partial cuff inflation over the femoral artery. Participants were young, apparently healthy women who self-identified their race as Black (BLW: n = 44) or White (WHW: n = 40). Systolic pBP (P = 0.04) and diastolic pBP (P < 0.01) were higher among BLW. Systolic cBP (P < 0.01), diastolic cBP (P < 0.01), heart rate (P < 0.001), AP (P = 0.02), AIx75 (P < 0.001), arterial wave reflection magnitude (P = 0.40) and cf-PWV (P = 0.04) were all higher among BLW. Findings demonstrate elevations in pBP, central haemodynamics and arterial stiffness in young BLW versus WHW. Central haemodynamics and arterial stiffness may be promising targets in the early assessment of CVD risk in young BLW.
Absolute substrate oxidation rates are lower in older adults with amnestic mild cognitive impairment
(Physiological Reports, 2025-04-13) Rizzi, Nicholas A.; Kramer, Mary K.; DeConne, Theodore M.; Ellison, James M.; Lanzi, Alyssa M.; Overstreet, Matthew L.; Edwards, David G.; Cohen, Matthew L.; Johnson, Curtis L.; Martens, Christopher R.
Previous studies in individuals with mild cognitive impairment suggest that they may have altered systemic metabolic function at rest; however, metabolic function during aerobic exercise is not fully understood in this population. This study sought to determine whether individuals with amnestic mild cognitive impairment (aMCI) have lower rates of baseline and peak fat oxidation (FatOx) during a graded exercise test (GXT) compared with cognitively unimpaired control participants (CU). Twenty-two (22) older adults with aMCI and 21 age- and sex-matched adults completed a GXT to assess rates of substrate oxidation and peak oxygen consumption (VO2 peak). Rates of FatOx and carbohydrate oxidation (CHOOx) were assessed using VO2 and VCO2. Resting absolute (0.10 ± 0.03 vs. 0.09 ± 0.02 g/min, p = 0.126) and relative (1.5 ± 0.43 vs. 1.4 ± 0.44 mg/kg/min, p = 0.492) rates of FatOx, as well as resting absolute (0.51 ± 0.11 vs. 0.59 ± 0.15 g/min, p = 0.093) and relative (8.0 ± 2.3 vs. 7.5 ± 2.7 mg/kg/min, p = 0.126) rates of CHOOx were similar between groups. However, peak absolute rates of FatOx (0.33 ± 0.13 vs. 0.39 ± 0.10 g/min, p = 0.033) and CHOOx (1.9 ± 0.41 vs. 2.2 ± 0.49 g/min, p = 0.046) were significantly lower in the aMCI group. Time to fatigue (7.2 ± 2.0 vs. 8.7 ± 2.3 min, p = 0.033) and absolute VO2 peak (1.3 ± 0.34 vs. 1.6 ± 0.47 L/min, p = 0.024) were also significantly lower in the aMCI group. These findings suggest that absolute peak rates of whole-body FatOx and CHOOx are reduced during aerobic exercise in older adults with aMCI.
Collision Sports and Neurodegenerative Disease: Inclusion of Moderating Risk Factors
(Exercise and Sport Sciences Reviews, 2025-05-01) Buckley, Thomas A.; Caccese, Jaclyn B.; Jela, John J.
Collision sport participation with repetitive head impacts has been associated with increased risk of neurodegenerative diseases, but also have lower mortality rates for many individual conditions. The role of modifiable risk factors in later life development of neurodegenerative diseases in athletes is a clear knowledge gap and a potential opportunity for interventions to improve health related quality of life.
Associations of Collegiate Football Career and Incident Concussion with Players' Health: A Longitudinal Study from the CARE Consortium
(Sports Medicine, 2025-05-01) Hunzinger, Katherine J.; Caccese, Jaclyn B.; Law, Connor A.; Wittmer, Rachael M.; Buckley, Thomas A.; Broglio, Steven P.; McAllister, Thomas W.; McCrea, Michael A.; Pasquina, Paul F.; Schneider, Andrea L. C.; the CARE Consortium Investigators; Benjamin, Holly J.; D’Lauro, Christopher; Eckner, James T.; Giza, Christopher C.; Guskiewicz, Kevin M.; Kaminski, Thomas W.; Lintner, Laura J.; Master, Christina L; McDevitt, Jane; Mihalik, Jason P.; Miles, Chris; Ortega, Justus; Port, Nicholas L.; Putukian, Margot; Susmarski, Adam
Background The influence of repetitive head impacts on collegiate football players remains unclear as prior research is often limited to small samples or short-term studies focused on single seasons. Objective Our objective was to determine the associations between collegiate football career or incident concussion and changes in neurocognitive function, postural stability, and physical and psychological health. Methods In total, 574 football players enrolled in the Grand Alliance Concussion Assessment, Research and Education (CARE) Consortium (median age 18.0 years [interquartile range 18.0–19.0], 52% white race, 26% with incident concussion) completed baseline and exit evaluations (i.e., beginning and end of collegiate career) consisting of neurocognitive, postural stability, and physical/psychological health assessments, specifically, Immediate Post-Concussion Assessment and Cognitive Testing, Standardized Assessment of Concussion, Balance Error Scoring System, Sport Concussion Assessment Tool-5 (SCAT-5) Symptom checklist, and the Brief Symptom Inventory-18. Adjusted linear regression models incorporating inverse probability of attrition weighting were used to compare changes in scores between baseline and exit evaluations overall and by incident concussion status. Results Overall, athletes had small improvements in neurocognitive functioning and postural stability over time but had small increases in symptom severity. Both the incident concussion and no incident concussion groups improved similarly on neurocognitive and postural stability measures (all p > 0.05 for difference in change over time between incident concussion groups). Individuals with incident concussion reported fewer symptoms and lower symptom severity over time than did those without incident concussion (SCAT symptom count difference − 1.22; 95% confidence interval [CI] − 1.89 to − 0.54; SCAT symptom severity difference: − 2.46; 95% CI − 4.06 to − 0.86; Brief Symptom Inventory-18 somatization difference: − 0.55; 95% CI − 0.93 to − 0.17). Conclusions Overall, collegiate football players demonstrated small, non-clinically meaningful improvements in neurocognitive function and postural stability. Moreover, athletes who experienced a concussion reported slight improvements in physical/psychological health symptoms over their collegiate careers.
A Machine Learning Model for Post-Concussion Musculoskeletal Injury Risk in Collegiate Athletes
(Sports Medicine, 2025-03-27) Claros, Claudio C.; Anderson, Melissa N.; Qian, Wei; Brockmeier, Austin J.; Buckley, Thomas A.
Background Emerging evidence indicates an elevated risk of post-concussion musculoskeletal injuries in collegiate athletes; however, identifying athletes at highest risk remains to be elucidated. Objective The purpose of this study was to model post-concussion musculoskeletal injury risk in collegiate athletes by integrating a comprehensive set of variables by machine learning. Methods A risk model was developed and tested on a dataset of 194 athletes (155 in the training set and 39 in the test set) with 135 variables entered into the analysis, which included participant’s heath and athletic history, concussion injury and recovery-specific criteria, and outcomes from a diverse array of concussion assessments. The machine learning approach involved transforming variables by the weight of evidence method, variable selection using L1-penalized logistic regression, model selection via the Akaike Information Criterion, and a final L2-regularized logistic regression fit. Results A model with 48 predictive variables yielded significant predictive performance of subsequent musculoskeletal injury with an area under the curve of 0.82. Top predictors included cognitive, balance, and reaction at baseline and acute timepoints. At a specified false-positive rate of 6.67%, the model achieves a true-positive rate (sensitivity) of 79% and a precision (positive predictive value) of 95% for identifying at-risk athletes via a well-calibrated composite risk score. Conclusions These results support the development of a sensitive and specific injury risk model using standard data combined with a novel methodological approach that may allow clinicians to target high injury risk student athletes. The development and refinement of predictive models, incorporating machine learning and utilizing comprehensive datasets, could lead to improved identification of high-risk athletes and allow for the implementation of targeted injury risk reduction strategies by identifying student athletes most at risk for post-concussion musculoskeletal injury. Key Points - There is a well-established elevated risk of post-concussion subsequent musculoskeletal injury; however, prior efforts have failed to identify risk factors. - This study developed a composite risk score model with an area under the curve of 0.82 from common concussion clinical measures and participant demographics. - By identifying athletes at elevated risk, clinicians may be able to reduce injury risk through targeted injury risk reduction programs.
The impact of dietary sodium and fructose on renal sodium handling and blood pressure in healthy adults
(Physiological Reports, 2025-03-25) McMillan, Ronald K.; Stock, Joseph M.; Romberger, Nathan T.; Wenner, Megan M.; Chai, Sheau C.; Farquhar, William B.
Increased dietary sodium is linked to hypertension, but most young adults display “sodium-resistant” blood pressure (BP), meaning BP is not elevated with sodium loading. In sodium-resistant rodents, fructose induces salt-sensitive BP via increased renal sodium reabsorption. Therefore, we tested the impact of fructose and sodium on renal sodium handling and BP in healthy adults, hypothesizing that their combination would impair sodium excretion and increase BP. Thirty-six participants enrolled in a randomized, double-blind, crossover trial involving three diets varying in fructose and sodium. On day 7, participants wore ambulatory BP monitors and collected 24-h urine. Although high sodium increased urinary sodium excretion, excretion was 15% lower with high fructose plus high salt versus high salt alone (235.1 ± 85.0 vs. 277.9 ± 121.2 mmol/24 h, p = 0.05). Compared to the recommended diet, high salt alone did not significantly change 24 h. MAP; however, high fructose plus high salt modestly raised 24 h MAP (81 ± 6 vs. 84 ± 7 mmHg, p = 0.03). High fructose and high salt increased serum interleukin-6 concentrations compared to the recommended diet (0.31 ± 0.2 vs. 0.24 ± 0.19 pg/mL, p = 0.04). These findings suggest that increased sodium and fructose alter renal sodium handling and BP in young adults.
Short-term estradiol administration does not restore endothelin‐B receptor‐mediated vasodilation in postmenopausal women
(American Journal of Physiology - Heart and Circulatory Physiology, 2025-02-01) Nuckols, Virginia R.; Shoemaker, Leena N.; Kuczmarski, Andrew V.; Haigh, Katherine M.; McGinty, Shane J.; Del Vecchio, Angelica R.; Schwab, Allyson I.; Edwards, David G.; Taylor, Hugh S.; Wenner, Megan M.
The endothelin-B receptor (ETBR) mediates vasodilation in young women, an effect that is absent in postmenopausal women. We have previously demonstrated that ETBR-mediated vasodilation is regulated by estradiol (E2) in young women; however, the impact of E2 on ETBR function in postmenopausal women remains unknown. Accordingly, the objective of this study was to test the hypothesis that E2 exposure restores ETBR-mediated dilation in postmenopausal women. Ten healthy postmenopausal women (55 ± 2 yr of age, 5 ± 3 years since menopause) completed the study. E2 was administered by transdermal patch for 7 days (0.1 mg/day, Vivelle-Dot patch). Vasodilation in the cutaneous microcirculation (microvascular endothelial function) was measured via local heating (42°C) using laser Doppler flowmetry combined with intradermal microdialysis perfusions of lactated Ringer’s (control) and ETBR antagonist (BQ-788, 300 nM) at baseline and after E2 administration. There was no effect of E2 on ETBR function [hormone × site, F(1,9) = 0.77, P = 0.40]. These data demonstrate that in contrast to findings in premenopausal women, E2 administration does not restore ETBR function in postmenopausal women. NEW & NOTEWORTHY The vascular endothelial endothelin-B receptor (ETBR) mediates vasodilation in premenopausal women, an effect modulated by estradiol. ETBR-mediated vasodilation is lost in postmenopausal women, but the effect of exogenous estradiol administration on ETBR function in postmenopausal women is not known. During estradiol administration, ETBR blockade did not affect cutaneous microvascular vasodilatory response to local heating. We demonstrate that exogenous estradiol administration does not restore ETBR-mediated vasodilation in postmenopausal women.
Physical Activity in Pre-Ambulatory Children with Cerebral Palsy: An Exploratory Validation Study to Distinguish Active vs. Sedentary Time Using Wearable Sensors
(Sensors, 2025-02-19) Orlando, Julie M.; Smith, Beth A.; Hafer, Jocelyn F.; Paremski, Athylia; Amodeo, Matthew; Lobo, Michele A.; Prosser, Laura A.
Wearable inertial sensor technology affords opportunities to record the physical activity of young children in their natural environments. The interpretation of these data, however, requires validation. The purpose of this study was to develop and establish the criterion validity of a method of quantifying active and sedentary physical activity using an inertial sensor for pre-ambulatory children with cerebral palsy. Ten participants were video recorded during 30 min physical therapy sessions that encouraged gross motor play activities, and the video recording was behaviorally coded to identify active and sedentary time. A receiver operating characteristic curve identified the optimal threshold to maximize true positive and minimize false positive active time for eight participants in the development dataset. The threshold was 0.417 m/s2 and was then validated with the remaining two participants; the percent of true positives and true negatives was 92.2 and 89.7%, respectively. We conclude that there is potential for raw sensor data to be used to quantify active and sedentary time in pre-ambulatory children with physical disability, and raw acceleration data may be more generalizable than the sensor-specific activity counts commonly reported in the literature.
Endothelial dysfunction in middle-aged and older men with low testosterone is associated with elevated circulating endothelin-1
(American Journal of Physiology - Regulatory, Integrative and Comparative Physiology, 2025-03-01) Babcock, Matthew C.; DuBose, Lyndsey E.; Hildreth, Kerry L.; Stauffer, Brian L.; Kohrt, Wendy M.; Wenner, Megan M.; Moreau, Kerrie L.
Low testosterone in middle-aged/older men contributes to accelerated vascular aging, including endothelial dysfunction. However, the mechanisms by which low testosterone affects endothelial dysfunction are not well understood. We sought to determine whether higher endothelin-1 (ET-1) levels are associated with reduced brachial artery flow-mediated dilation (FMD) in middle-aged/older men with low testosterone. Plasma ET-1 was quantified in 60 men categorized as young (n = 20, age = 30 ± 4 yr, testosterone = 510 ± 63 ng/dL), middle-aged/older with normal testosterone (n = 20, age = 59 ± 6 yr, testosterone = 512 ± 115 ng/dL), or middle-aged/older with low testosterone (n = 20, age = 60 ± 8 yr, testosterone = 265 ± 47 ng/dL). Endothelial function was determined via brachial artery FMD. Venous and arterial endothelial cells were harvested via endovascular biopsy in a subset of participants and stained for ET-1 expression. Middle-aged/older men with normal testosterone exhibited lower brachial artery FMD (5.7 ± 2.2%) compared with young men (7.3 ± 1.3%, P = 0.020), which was exaggerated in middle-aged/older men with low testosterone (4.0 ± 1.8%, P = 0.010 vs. middle-aged/older men with normal testosterone). Plasma ET-1 was not different between young (5.6 ± 0.9 ng/dL) and middle-aged/older men with normal testosterone (6.0 ± 1.4 ng/dL, P = 0.681) but was higher in middle-aged/older men with low testosterone (7.7 ± 2.8 ng/dL) compared with both groups (P < 0.001 vs. young men; P = 0.013 vs. middle-aged/older men with normal testosterone). There was no difference in venous (P = 0.616) or arterial (P = 0.222) endothelial cell ET-1 expression between groups. There was a significant inverse association between plasma ET-1 and FMD (r =-0.371, P = 0.004). These data suggest that the accelerated age-associated reduction in endothelial dysfunction in middle-aged/older men with low testosterone is related to higher circulating ET-1. NEW & NOTEWORTHY Middle-aged/older men with low testosterone have reduced vascular endothelial function compared with young and age-matched men with normal testosterone. In this manuscript, we demonstrate that men with low testosterone have higher plasma endothelin-1, which is associated with worse brachial artery flow-mediated dilation. The source of higher plasma endothelin-1 remains unknown; however, higher circulating endothelin-1 appears to be a mechanism contributing to reduced vascular endothelial function in men with low testosterone.
Mechanical Properties of the Cortex in Older Adults and Relationships With Personality Traits
(Human Brain Mapping, 2025-02-06) Twohy, Kyra E.; Kramer, Mary K.; Diano, Alexa M.; Bailey, Olivia M.; Delgorio, Peyton L.; McIlvain, Grace; McGarry, Matthew D. J.; Martens, Christopher R.; Schwarb, Hillary; Hiscox, Lucy V.; Johnson, Curtis L.
Aging and neurodegeneration impact structural brain integrity and can result in changes to behavior and cognition. Personality, a relatively stable trait in adults as compared to behavior, in part relies on normative individual differences in cellular organization of the cerebral cortex, but links between brain structure and personality expression have been mixed. One key finding is that personality has been shown to be a risk factor in the development of Alzheimer's disease, highlighting a structure–trait relationship. Magnetic resonance elastography (MRE) has been used to noninvasively study age-related changes in tissue mechanical properties because of its high sensitivity to both the microstructural health and the structure–function relationship of the tissue. Recent advancements in MRE methodology have allowed for reliable property recovery of cortical subregions, which had previously presented challenges due to the complex geometry and overall thin structure. This study aimed to quantify age-related changes in cortical mechanical properties and the relationship of these properties to measures of personality in an older adult population (N = 57; age 60–85 years) for the first time. Mechanical properties including shear stiffness and damping ratio were calculated for 30 bilateral regions of the cortex across all four lobes, and the NEO Personality Inventory (NEO-PI) was used to measure neuroticism and conscientiousness in all participants. Shear stiffness and damping ratio were found to vary widely across regions of the cortex, upward of 1 kPa in stiffness and by 0.3 in damping ratio. Shear stiffness changed regionally with age, with some regions experiencing accelerated degradation compared to neighboring regions. Greater neuroticism (i.e., the tendency to experience negative emotions and vulnerability to stress) was associated with high damping ratio, indicative of poorer tissue integrity, in the rostral middle frontal cortex and the precentral gyrus. This study provides evidence of structure–trait correlates between physical mechanical properties and measures of personality in older adults and adds to the supporting literature that neurotic traits may impact brain health in cognitively normal aging.
Actin Polymerization Status Regulates Tenocyte Homeostasis Through Myocardin-Related Transcription Factor-A
(Cytoskeleton, 2024-11-27) West, Valerie C.; Owen, Kaelyn E.; Inguito, Kameron L.; Ebron, Karl Matthew M.; Reiner, Tori N.; Mirack, Chloe E.; Le, Christian H.; Marqueti, Rita de Cassia; Snipes, Steven; Mousavizadeh, Rouhollah; King, Rylee E.; Elliott, Dawn M.; Parreno, Justin
The actin cytoskeleton is a potent regulator of tenocyte homeostasis. However, the mechanisms by which actin regulates tendon homeostasis are not entirely known. This study examined the regulation of tenocyte molecule expression by actin polymerization via the globular (G-) actin-binding transcription factor, myocardin-related transcription factor-a (MRTF). We determined that decreasing the proportion of G-actin in tenocytes by treatment with TGFβ1 increases nuclear MRTF. These alterations in actin polymerization and MRTF localization coincided with favorable alterations to tenocyte gene expression. In contrast, latrunculin A increases the proportion of G-actin in tenocytes and reduces nuclear MRTF, causing cells to acquire a tendinosis-like phenotype. To parse out the effects of F-actin depolymerization from regulation by MRTF, we treated tenocytes with cytochalasin D. Exposure of cells to cytochalasin D increases the proportion of G-actin in tenocytes. However, as compared to latrunculin A, cytochalasin D has a differential effect on MRTF localization by increasing nuclear MRTF. This led to an opposing effect on the regulation of a subset of genes. The differential regulation of genes by latrunculin A and cytochalasin D suggests that actin signals through MRTF to regulate a specific subset of genes. By targeting the deactivation of MRTF through the inhibitor CCG1423, we verify that MRTF regulates Type I Collagen, Tenascin C, Scleraxis, and α-smooth muscle actin in tenocytes. Actin polymerization status is a potent regulator of tenocyte homeostasis through the modulation of several downstream pathways, including MRTF. Understanding the regulation of tenocyte homeostasis by actin may lead to new therapeutic interventions against tendinopathies, such as tendinosis.
Cerebral vasomotor reactivity to carbon dioxide using the rebreathe technique: assessment of within-day and between-day repeatability
(American Journal of Physiology - Regulatory, Integrative and Comparative Physiology, 2024-12-01) Nandadeva, Damsara; Skow, Rachel J.; Martin, Zachary T.; Patik, Jordan C.; Taherzadeh, Ziba; Ortiz, Alison; Kao, Yungfei; Fadel, Paul J.; Brothers, R. Matthew
The cerebral vasodilator response to increased arterial carbon dioxide (CO2) concentration, termed cerebral vasomotor reactivity (CVMR), is used to assess cerebral vascular function. We sought to assess the within-day and between-day repeatability of CVMR to rebreathing-induced hypercapnia. Twelve healthy adults performed a within-day short interval protocol (17 ± 2 min between trials), ten performed a within-day long interval protocol (145 ± 16 min between trials), and seventeen performed a between-day protocol (5 ± 2 days between visits). Repeatability of the slope of the percent change in middle cerebral artery mean blood velocity (%MCAvmean) and cerebral vascular conductance index (%CVCi), to the change in partial pressure of end-tidal CO2 (P⁢ETCO2) between the two trials/days was assessed. Within-day short interval, %MCAvmean slope demonstrated fair to excellent repeatability (intraclass correlation, ICC = 0.92 [95% confidence interval 0.72–0.98]; P < 0.001) while %CVCi slope showed more variability (ICC = 0.84 [0.47–0.95]; P = 0.002]). Within-day long interval, %MCAvmean (ICC = 0.95 [0.80–0.99]) and %CVCi (ICC = 0.94 [0.71–0.99]) slopes showed good to excellent and fair to excellent repeatability respectively (P < 0.001 for both). For between-day trials, better repeatability was observed for %CVCi (ICC = 0.85 [0.57–0.95]; P < 0.001) compared with %MCAvmean (ICC = 0.76 [0.33–0.91]; P = 0.004) slope. These findings indicate repeatable within- and between-day CVMR responses to rebreathe-induced hypercapnia. However, a longer interval may be better for within-day repeat trials, particularly for CVCi measures.

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