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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Item 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.Item 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.Item 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, AdamBackground 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.Item 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.Item 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.Item 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.Item 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.Item 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.Item 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.Item 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, JustinThe 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.Item 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. MatthewThe 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 (PETCO2) 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.Item Six-year follow-up of a world record-breaking master marathon runner(Journal of Applied Physiology, 2024-11-01) Romberger, Nathan T.; Stock, Joseph M.; McMillan, Ronald K.; Overstreet, Matthew L.; Lepers, Romuald; Joyner, Michael J.; Farquhar, William B.Endurance performance declines with advancing age. Of the three main physiological factors that determine endurance running performance [maximal oxygen consumption (V̇o2max), lactate threshold, and running economy (RE)], V̇o2max appears to be most affected by age. Although endurance performance declines with age, recently, endurance performance has rapidly improved in master athletes as the number of master athletes competing in endurance events has increased. Master athletes represent an intriguing model to study healthy aging. In this case study, we reassessed the physiological profile of a 76-yr-old distance runner who broke the marathon world record for men over 70 yr of age in 2018. This runner was tested a few months before breaking the world record and retested in 2024. Between 2018 and 2024, his marathon running velocity decreased significantly. Therefore, the purpose of this case study was to determine the physiological changes that explain his performance decline. RE remained similar to 2018, and while there was not a clear breakpoint in blood lactate, he still likely runs marathons at a high percentage (∼90%) of his V̇o2max. However, V̇o2max declined by 15.1%. HRmax declined by 3.2% and maximal O2 pulse declined by 12.4%, suggesting that maximal stroke volume and/or arteriovenous O2 difference decreased. Altogether, although this marathoner continues to compete at an elite level, his performance has declined since his record-breaking marathon due to a reduction in V̇o2max. This is likely caused by reductions in maximal stroke volume and/or arteriovenous O2 difference. We speculate that these changes reflect primarily age-related processes. NEW & NOTEWORTHY We performed 6-yr follow-up testing on a world record-breaking master marathon runner. We determined that his performance declined since his record-breaking marathon in 2018 primarily due to a reduction in V̇o2max. His max heart rate (HR) changed minimally, but his peak O2 pulse decreased, suggesting that his maximal stroke volume and/or arteriovenous O2 difference decreased. These changes likely reflect primarily age-related effects in the absence of an overt pathological disease process.Item Characterizing vascular and hormonal changes in women across the life span: a cross-sectional analysis(American Journal of Physiology - Heart and Circulatory Physiology, 2024-11-01) Wenner, Megan M.; Shenouda, Ninette; Shoemaker, Leena; Kuczmarski, Andrew; Haigh, Katherine; Del Vecchio, Angelica; Schwab, Allyson; McGinty, Shane J.; Edwards, David G.; Pohlig, Ryan T.; Nuckols, Virginia R.; DuBose, Lyndsey; Moreau, Kerrie L.Vascular dysfunction, marked by lower endothelial function and increased aortic stiffness, is a nontraditional risk factor that precedes the development of cardiovascular disease (CVD). However, the age at which these changes in vascular function occur in women and the degree to which reproductive hormones mediate these changes has not been characterized. Women free from major disease were enrolled across the adult life span (aged 18–70 yr, n = 140). Endothelial function was assessed as flow-mediated dilation (FMD) of the brachial artery during reactive hyperemia using duplex ultrasound and expressed as percent dilation. Aortic stiffness was measured by carotid-femoral pulse wave velocity (cfPWV). Blood samples were obtained to quantify reproductive hormone concentration. Regression models determined age-related breakpoints and mediating factors between age and vascular outcomes. FMD declined with age with a breakpoint and steeper decline occurring at 47 yr of age. Thereafter, age was independently associated with lower FMD (B = −0.13, P < 0.001). cfPWV was relatively stable until a breakpoint at age 48, and age was independently associated with higher cfPWV thereafter (B = 0.10, P < 0.001). Path analysis revealed that the association between age and FMD was partially mediated by follicle-stimulating hormone (abind = 0.051, P = 0.01) and progesterone (abind = 0.513, P < 0.001) but not estradiol (abind = −0.004, P = 0.08). No mediation was present for cfPWV. Age was associated with endothelial dysfunction and aortic stiffness in women beginning at 47 and 48 yr old, respectively, 3 to 4 yr before the average age of menopause. The association between age and endothelial dysfunction was explained in part by elevations in follicle-stimulating hormone and progesterone, but not declining estradiol. NEW & NOTEWORTHY We demonstrate that the age at which endothelial function declines and aortic stiffness increases in healthy women is 47 and 48, respectively. The inflection point in flow-mediated dilation (FMD) is 6 yr earlier than previously reported, and the association between age and FMD was mediated by follicle-stimulating hormone (FSH) and progesterone (P4) but not estradiol (E2). Graphical abstract available at: https://doi.org/10.1152/ajpheart.00373.2024Item Youth Soccer Heading Exposure and Its Effects on Clinical Outcome Measures(Sports, 2024-12-10) Wahlquist, Victoria E.; Buckley, Thomas A.; Caccese, Jaclyn B.; Glutting, Joseph J.; Royer, Todd D.; Kaminski, Thomas W.Purposeful heading, in which players may use their heads to advance the ball in play, is a unique part of soccer. Clinical outcome measures used to aid in the diagnosis of a concussion have long been a cornerstone of the contemporary measurements associated with the short- and long-term effects of monitoring repetitive head impacts (RHI) and soccer heading exposure. The effects of RHI in the youth population are still unknown, therefore, the purpose of this study was to examine if heading exposure is predictive of changes in self-reported symptoms, neurocognitive functioning, gait, and balance in female youth soccer players over the course of one soccer season. Small improvements in neurocognitive functioning and gait and slight deficits in balance were observed from pre- to post-season. All changes were not clinically relevant and likely due to a practice effect. The low heading exposure in our cohort of youth soccer players was likely not enough to elicit any changes in clinical measures. In general, our clinical outcomes did not change after a season of soccer play and change scores were not predicted by heading exposure.Item A long-term high-fat diet induces differential gene expression changes in spatially distinct adipose tissue of male mice(Physiological Genomics, 2024-11-11) Alradi, Malak; Askari, Hassan; Shaw, Mark; Bhavsar, Jaysheel D.; Kingham, Brewster F.; Polson, Shawn W.; Fancher, Ibra S.The accumulation of visceral adipose tissue (VAT) is strongly associated with cardiovascular disease and diabetes. In contrast, individuals with increased subcutaneous adipose tissue (SAT) without corresponding increases in VAT are associated with a metabolic healthy obese phenotype. These observations implicate dysfunctional VAT as a driver of disease processes, warranting investigation into obesity-induced alterations of distinct adipose depots. To determine the effects of obesity on adipose gene expression, male mice (n = 4) were fed a high-fat diet to induce obesity or a normal laboratory diet (lean controls) for 12–14 mo. Mesenteric VAT and inguinal SAT were isolated for bulk RNA sequencing. AT from lean controls served as a reference to obesity-induced changes. The long-term high-fat diet induced the expression of 169 and 814 unique genes in SAT and VAT, respectively. SAT from obese mice exhibited 308 differentially expressed genes (164 upregulated and 144 downregulated). VAT from obese mice exhibited 690 differentially expressed genes (262 genes upregulated and 428 downregulated). KEGG pathway and GO analyses revealed that metabolic pathways were upregulated in SAT versus downregulated in VAT while inflammatory signaling was upregulated in VAT. We next determined common genes that were differentially regulated between SAT and VAT in response to obesity and identified four genes that exhibited this profile: elovl6 and kcnj15 were upregulated in SAT/downregulated in VAT while trdn and hspb7 were downregulated in SAT/upregulated in VAT. We propose that these genes in particular should be further pursued to determine their roles in SAT versus VAT with respect to obesity. NEW & NOTEWORTHY A long-term high-fat diet induced the expression of more than 980 unique genes across subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT). The high-fat diet also induced the differential expression of nearly 1,000 AT genes. We identified four genes that were oppositely expressed in SAT versus VAT in response to the high-fat diet and propose that these genes in particular may serve as promising targets aimed at resolving VAT dysfunction in obesity.Item Roles and interplay of reinforcement-based and error-based processes during reaching and gait in neurotypical adults and individuals with Parkinson’s disease(PLoS Computational Biology, 2024-10-14) Roth, Adam M.; Buggeln, John H.; Hoh, Joanna E.; Wood, Jonathan M.; Sullivan, Seth R.; Ngo, Truc T.; Calalo, Jan A.; Lokesh, Rakshith; Morton, Susanne M.; Grill, Stephen; Jeka, John J.; Carter, Michael J.; Cashaback, Joshua G. A.From a game of darts to neurorehabilitation, the ability to explore and fine tune our movements is critical for success. Past work has shown that exploratory motor behaviour in response to reinforcement (reward) feedback is closely linked with the basal ganglia, while movement corrections in response to error feedback is commonly attributed to the cerebellum. While our past work has shown these processes are dissociable during adaptation, it is unknown how they uniquely impact exploratory behaviour. Moreover, converging neuroanatomical evidence shows direct and indirect connections between the basal ganglia and cerebellum, suggesting that there is an interaction between reinforcement-based and error-based neural processes. Here we examine the unique roles and interaction between reinforcement-based and error-based processes on sensorimotor exploration in a neurotypical population. We also recruited individuals with Parkinson’s disease to gain mechanistic insight into the role of the basal ganglia and associated reinforcement pathways in sensorimotor exploration. Across three reaching experiments, participants were given either reinforcement feedback, error feedback, or simultaneously both reinforcement & error feedback during a sensorimotor task that encouraged exploration. Our reaching results, a re-analysis of a previous gait experiment, and our model suggests that in isolation, reinforcement-based and error-based processes respectively boost and suppress exploration. When acting in concert, we found that reinforcement-based and error-based processes interact by mutually opposing one another. Finally, we found that those with Parkinson’s disease had decreased exploration when receiving reinforcement feedback, supporting the notion that compromised reinforcement-based processes reduces the ability to explore new motor actions. Understanding the unique and interacting roles of reinforcement-based and error-based processes may help to inform neurorehabilitation paradigms where it is important to discover new and successful motor actions. Author summary Reinforcement-based and error-based processes play a pivotal role in regulating our movements. Converging neuroanatomical evidence show interconnected reinforcement-based and error-based neural circuits. Yet is unclear how reinforcement-based and error-based processes interact to influence sensorimotor behavior. In our past work we showed that reinforcement-based and error-based processes are dissociable. Building on this work, here we show that these process can also interact to influence trial-by-trial sensorimotor behaviour.Item Comparing single- and multi-post labeling delays for the measurements of resting cerebral and hippocampal blood flow for cerebrovascular testing in midlife adults(Frontiers in Physiology, 2024-10-01) Decker, Kevin P.; Sanjana, Faria; Rizzi, Nick; Kramer, Mary K.; Cerjanic, Alexander M.; Johnson, Curtis L.; Martens, Christopher R.Objectives: To assess the reliability and validity of measuring resting cerebral blood flow (CBF) and hippocampal CBF using a single-post-labeling delay (PLD) and a multi-PLD pseudo-continuous arterial spin labeling (pCASL) protocol for cerebrovascular reactivity (CVR) testing. Methods: 25 healthy, midlife adults (57 ± 4 years old) were imaged in a Siemens Prisma 3T magnetic resonance imaging (MRI) scanner. Resting CBF and hippocampal CBF were assessed using two pCASL protocols, our modified single-PLD protocol (pCASL-MOD) to accommodate the needs for CVR testing and the multi-PLD Human Connectome Project (HCP) Lifespan protocol to serve as the reference control (pCASL-HCP). During pCASL-MOD, CVR was calculated as the change in CBF from rest to hypercapnia (+9 mmHg increase in end-tidal partial pressure of carbon dioxide [PETCO2]) and then normalized for PETCO2. The reliability and validity in resting gray matter (GM) CBF, white matter (WM) CBF, and hippocampal CBF between pCASL-MOD and pCASL-HCP protocols were examined using correlation analyses, paired t-tests, and Bland Altman plots. Results: The pCASL-MOD and pCASL-HCP protocols were significantly correlated for resting GM CBF [r = 0.72; F (1, 23) = 25.24, p < 0.0001], WM CBF [r = 0.57; F (1, 23) = 10.83, p = 0.003], and hippocampal CBF [r = 0.77; F (1, 23) = 32.65, p < 0.0001]. However, pCASL-MOD underestimated resting GM CBF (pCASL-MOD: 53.7 ± 11.1 v. pCASL-HCP: 69.1 ± 13.1 mL/100 g/min; p < 0.0001), WM CBF (pCASL-MOD: 32.4 ± 4.8 v. pCASL-HCP: 35.5 ± 6.9 mL/100 g/min; p = 0.01), and hippocampal CBF (pCASL-MOD: 50.5 ± 9.0 v. pCASL-HCP: 68.1 ± 12.5 mL/100 g/min; p < 0.0001). PETCO2 increased by 8.0 ± 0.7 mmHg to induce CVR (GM CBF: 4.8% ± 2.6%; WM CBF 2.9% ± 2.5%; and hippocampal CBF: 3.4% ± 3.8%). Conclusion: Our single-PLD pCASL-MOD protocol reliably measured CBF and hippocampal CBF at rest given the significant correlation with the multi-PLD pCASL-HCP protocol. Despite the lower magnitude relative to pCASL-HCP, we recommend using our pCASL-MOD protocol for CVR testing in which an exact estimate of CBF is not required such as the assessment of relative change in CBF to hypercapnia.Item The effectiveness of a neck strengthening program using the NecksLevel ® device in a population of youth female soccer players(International Journal of Physical Education, Sports and Health, 2024-06-28) O’Reilly, Erin; Delaney, Amanda; Schneider, Jeffrey; Ruggiero, LaurieResearch has shown that neck strengthening exercises can improve neck strength with a direct translation to a reduction in head acceleration during headers. The purpose of this research was to evaluate the use of a novel neck strengthening program on neck strength and girth in a population of youth female soccer players. Using a contemporary neck strengthening device we examined outcomes in isometric neck strength and neck girth in a cohort of 16 female youth (aged 12) soccer players. Paired samples T-tests were conducted to determine differences between pre-and post-training measures. Right Lateral Bending neck strength improved significantly pre- (16.4±5.0 lb.) to post- (17.1±4.4 lb.) training. Flexion, Extension, and Left Lateral Bending neck strength were also improved. These findings underscore the effectiveness of targeted neck-strengthening exercises in enhancing neck strength among female youth soccer athletes and highlight the importance of comprehensive strategies in concussion prevention.Item Emerging Natural and Synthetic Compounds in the Management of Diabetic Neuropathy: Targeting Oxidative Stress and Inflammation(Annals of Multidisciplinary Research, Innovation and Technology, 2024-06-30) Suman Kumar, Samanta; Deka, Dhritismita; Kandimalla, Raghuram; Ghosh, Aparajita; Barge, Sagar Ramrao; Kashyap, Bhaswati; Bharadwaj, Simanta; Talukdar, Narayan ChandraDiabetic neuropathy (DN) is a prevalent and threatening complication of diabetes, characterized by nerve damage resulting from chronic hyperglycemic conditions. Key factor in the pathogenesis of DN includes oxidative stress and inflammation, contributes to cellular damage (CD). Oxidative stress, chromatized by imbalance between pro-oxidants and antioxidants, leads to CD, while inflammation driven by pro-inflammatory cytokines, exacerbates the damage. Various factors, such as hyperglycemia-induced DNA damage, activation of transcription factors like NF-kB and Nrf2, and dysregulation of cytokine production contribute to the progression of DN. In this context, natural products and/or synthesized small molecules have garnered attention for their potential in mitigating oxidative stress and inflammation in DN. Natural products and synthesized small molecules have garnered attention for their potential in mitigrating oxidative stress and inflammation in DN. Compounds like sulforaphane, mangiferin, calpain, quercetin, curcumin, and resveratrol exhibit antioxidant and anti-inflammatory properties, thus showing promise in alleviating DN symptoms. Furthermore, various small molecules and herbal extracts have demonstrated efficacy in reducing oxidative stress, modulating cytokine levels, and improving nerve function in experimental models of DN. Combination therapies targeting multiple pathways involved in DN pathogenesis, such as the PARP inhibitor nicotinamide and the antioxidant melatonin, have shown promising results in ameliorating functional deficits and biochemical alterations associated with DN. This review aims to understanding the interplay between oxidative stress and inflammation and further exploration of natural products and synthesized small molecules as potential therapeutic agents for DN management.Item Device-estimated sleep metrics do not mediate the relation between race and blood pressure dipping in young black and white women(Journal of Clinical Hypertension, 2024-07-09) D'agata, Michele N.; Hoopes, Elissa K.; Keiser. Thomas; Patterson, Freda; Szymanski, Krista M.; Matias, Alexs A.; Brewer, Benjamin C.; Witman, Melissa A.Short, disturbed, and irregular sleep may contribute to blunted nocturnal blood pressure (BP) dipping, a predictor of cardiovascular disease. Black women (BLW) demonstrate less BP dipping and poorer sleep health than White women (WHW). However, it remains unclear whether device-estimated sleep health metrics mediate the relation between race and BP dipping in young women. We hypothesized that the relation between race and BP dipping would be partly mediated by sleep health metrics of sleep duration, sleep efficiency, and sleep regularity. Participants (20 BLW, 17 WHW) were 18–29 years old, normotensive, nonobese, and without evidence of sleep disorders. Systolic and diastolic BP dipping were derived from 24-h ambulatory BP monitoring. Habitual sleep duration and sleep efficiency were estimated via 14 days of wrist actigraphy. Sleep duration regularity was calculated as the standard deviation (SD) of nightly sleep duration (SDSD). Sleep timing regularity metrics were calculated as the SD of sleep onset and sleep midpoint (SMSD). Mediation analysis tested the mediating effect of each sleep metric on the relation between race and BP dipping. BLW experienced less systolic (P = .02) and diastolic (P = .01) BP dipping. Sleep duration (P = .14) was not different between groups. BLW had lower sleep efficiency (P < .01) and higher SDSD (P = .02), sleep onset SD (P < .01) and SMSD (P = .01). No sleep metrics mediated the relation between race and BP dipping (all indirect effects P > .38). In conclusion, mediation pathways of sleep health metrics do not explain racial differences in nocturnal BP dipping between young BLW and WHW.