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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 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.Item Lower vascular conductance responses to handgrip exercise are improved following acute antioxidant supplementation in young individuals with post-traumatic stress disorder(Experimental Physiology, 2024-05-06) Weggen, Jennifer B.; Darling, Ashley M.; Autler, Aaron S.; Hogwood, Austin C.; Decker, Kevin P.; Richardson, Jacob; Tuzzolo, Gina; Garten, Ryan S.Young individuals with post-traumatic stress disorder (PTSD) display peripheral vascular and autonomic nervous system dysfunction, two factors potentially stemming from a redox imbalance. It is currently unclear if these aforementioned factors, observed at rest, alter peripheral haemodynamic responses to exercise in this population. This study examined haemodynamic responses to handgrip exercise in young individuals with PTSD following acute antioxidant (AO) supplementation. Thirteen young individuals with PTSD (age 23 ± 3 years), and 13 age- and sex-matched controls (CTRL) participated in the study. Exercise-induced changes to arm blood flow (BF), mean arterial pressure (MAP) and vascular conductance (VC) were evaluated across two workloads of rhythmic handgrip exercise (3 and 6 kg). The PTSD group participated in two visits, consuming either a placebo (PL) or AO prior to their visits. The PTSD group demonstrated significantly lower VC (P = 0.04) across all exercise workloads (vs. CTRL), which was significantly improved following AO supplementation. In the PTSD group, AO supplementation improved VC in participants possessing the lowest VC responses to handgrip exercise, with AO supplementation significantly improving VC responses (3 and 6 kg: P < 0.01) by blunting elevated exercise-induced MAP responses (3 kg: P = 0.01; 6 kg: P < 0.01). Lower VC responses during handgrip exercise were improved following AO supplementation in young individuals with PTSD. AO supplementation was associated with a blunting of exercise-induced MAP responses in individuals with PTSD displaying elevated MAP responses. This study revealed that young individuals with PTSD exhibit abnormal, peripherally mediated exercise responses that may be linked to a redox imbalance. Highlights - What is the central question of this study? Do young individuals with post-traumatic stress disorder (PTSD) display abnormal peripheral haemodynamic responses during exercise? - What is the main finding and its importance? Young individuals with PTSD displayed lower vascular conductance (VC) during handgrip exercise compared to healthy counterparts. Antioxidant supplementation notably improved VC responses, especially in the subset of PTSD participants with the highest pressor responses during exercise. This study underscores abnormal peripherally mediated exercise responses in young individuals with PTSD, suggesting a potential link to a redox imbalance.Item Collegiate Athletes With Diabetes: Baseline Medical Comorbidities and Preseason Concussion Testing Performance(Journal of Athletic Training, 2024-03-26) Anderson, Melissa N.; Gallo, Caitlin A.; Passalugo, Scott W.; Nimeh, Jake M.; Edgar, Richard; Yengo-Kahn, Aaron M.; Neitz, Kristen; Terry, Douglas P.; Zuckerman, Scott L.; Broglio, Steven P.; McCrea, Michael; McAllister, Thomas; Pasquina, Paul; Buckley, Thomas A.; CARE Consortium InvestigatorsContext People with diabetes mellitus (DM) are at increased risk for adverse health events and complications throughout their lifetime. Whether DM significantly affects collegiate athletes’ concussion baseline testing performance remains unclear. Objectives To (1) describe the prevalence of DM and associated comorbidities and (2) compare concussion baseline testing performance between student-athletes with DM and student-athletes without DM (NoDM). Design Retrospective, cross-sectional study. Setting University. Patients or Other Participants Using the Concussion, Assessment, Research and Education (CARE) Consortium research database, we matched athletes with self-reported DM (N = 229) by institution, sex, age, sport, position, testing year, and concussion history to athletes with NoDM (N = 229; total sample mean age = 19.6 ± 1.4 years, women = 42%). Main Outcome Measure(s) Descriptive statistics and χ2 tests of independence with subsequent odds ratios were calculated. Independent-samples t tests compared baseline symptoms, neurocognitive testing, and balance performance between athletes with DM and athletes with NoDM. Effect sizes were determined for significant group differences. Results At baseline, athletes with DM had higher rates of self-reported pre-existing balance disorders, sleep disorders, seizure disorders, motion sickness, learning disorders, vision and hearing problems, psychiatric disorders, depression, bipolar disorder, nonmigraine headaches, and meningitis than athletes with NoDM (P values < .05). We found balance differences between groups (P = .032, Cohen d = 0.17) such that, on average, athletes with DM had 1 additional error on the Balance Error Scoring System (DM = 13.4 ± 6.5; NoDM = 12.1 ± 5.9). No other comparisons yielded significant results. Conclusions Although athletes with DM had high rates of self-reported balance disorders, sleep disorders, seizures, and meningitis, their baseline neurocognitive testing results were largely identical to those of athletes with NoDM. Our findings suggested that nonclinically meaningful differences were present in concussion baseline balance testing but no significant differences were noted in cognitive testing; however, the effect of DM on concussion recovery remains unknown. Key Points - We observed no clinically meaningful differences in neurocognitive testing and balance performance between groups; athletes with diabetes performed similarly to athletes without diabetes. - Athletes with diabetes had a disproportionally high rate of self-reported neurologic and mental health comorbidities compared with their nondiabetic counterparts.Item Integrative data analysis to identify persistent post-concussion deficits and subsequent musculoskeletal injury risk: project structure and methods(BMJ Open Sport & Exercise Medicine, 2024-01-19) Anderson, Melissa; Claros, Claudio Cesar; Qian, Wei; Brockmeier, Austin; Buckley, Thomas AConcussions are a serious public health problem, with significant healthcare costs and risks. One of the most serious complications of concussions is an increased risk of subsequent musculoskeletal injuries (MSKI). However, there is currently no reliable way to identify which individuals are at highest risk for post-concussion MSKIs. This study proposes a novel data analysis strategy for developing a clinically feasible risk score for post-concussion MSKIs in student-athletes. The data set consists of one-time tests (eg, mental health questionnaires), relevant information on demographics, health history (including details regarding the concussion such as day of the year and time lost) and athletic participation (current sport and contact level) that were collected at a single time point as well as multiple time points (baseline and follow-up time points after the concussion) of the clinical assessments (ie, cognitive, postural stability, reaction time and vestibular and ocular motor testing). The follow-up time point measurements were treated as individual variables and as differences from the baseline. Our approach used a weight-of-evidence (WoE) transformation to handle missing data and variable heterogeneity and machine learning methods for variable selection and model fitting. We applied a training-testing sample splitting scheme and performed variable preprocessing with the WoE transformation. Then, machine learning methods were applied to predict the MSKI indicator prediction, thereby constructing a composite risk score for the training-testing sample. This methodology demonstrates the potential of using machine learning methods to improve the accuracy and interpretability of risk scores for MSKI.Item Sleep Variability, Eating Timing Variability, and Carotid Intima‐Media Thickness in Early Adulthood(Journal of the American Heart Association Cardiovascular and Cerebrovascular Disease, 2023-10-03) Hoopes, Elissa K.; Witman, Melissa A.; D'Agata, Michele N.; Brewer, Benjamin; Edwards, David G.; Robson, Shannon M.; Malone, Susan K.; Keiser, Thomas; Patterson, FredaBackground Day‐to‐day variability in sleep patterns and eating timing may disrupt circadian rhythms and has been linked with various adverse cardiometabolic outcomes. However, the extent to which variability in sleep patterns and eating timing relate to atherosclerotic development in subclinical stages remains unclear. Methods and Results Generally healthy adults (N=62, 29.3±7.3 years, 66% female) completed 14 days of sleep and dietary assessments via wrist accelerometry and photo‐assisted diet records, respectively. Variability in sleep duration, sleep onset, eating onset (time of first caloric consumption), eating offset (time of last caloric consumption), and caloric midpoint (time at which 50% of total daily calories are consumed) were operationalized as the SD across 14 days for each variable. Separate regression models evaluated the cross‐sectional associations between sleep and eating variability metrics with end‐diastolic carotid intima‐media thickness (CIMT) measured via ultrasonography. Models adjusted for age, sex, systolic blood pressure, sleep duration, and total energy intake. Each 60‐minute increase in sleep duration SD and sleep onset SD were associated with a 0.049±0.016 mm (P=0.003) and 0.048±0.017 mm (P=0.007) greater CIMT, respectively. Variability in eating onset and offset were not associated with CIMT; however, each 60‐minute increase in caloric midpoint SD was associated with a 0.033±0.015 mm greater CIMT (P=0.029). Exploratory post hoc analyses suggested that sleep duration SD and sleep onset SD were stronger correlates of CIMT than caloric midpoint SD. Conclusions Variability in sleep patterns and eating timing are positively associated with clinically relevant increases in CIMT, a biomarker of subclinical atherosclerosis, in early adulthood.Item Melatonin supplementation does not alter vascular function or oxidative stress in healthy normotensive adults on a high sodium diet(Physiological Reports, 2023-12-18) Ramos Gonzalez, Macarena; Axler, Michael R.; Kaseman, Kathryn E.; Lobene, Andrea J.; Farquhar, William B.; Witman, Melissa A.; Kirkman, Danielle L.; Lennon, Shannon L.High sodium diets (HSD) can cause vascular dysfunction, in part due to increases in reactive oxygen species (ROS). Melatonin reduces ROS in healthy and clinical populations and may improve vascular function. The purpose was to determine the effect of melatonin supplementation on vascular function and ROS during 10 days of a HSD. We hypothesized that melatonin supplementation during a HSD would improve vascular function and decrease ROS levels compared to HSD alone. Twenty-seven participants (13 M/14 W, 26.7 ± 2.9 years, BMI: 23.6 ± 2.0 kg/m2, BP: 110 ± 9/67 ± 7 mmHg) were randomized to a 10-day HSD (6900 mg sodium/d) supplemented with either 10 mg of melatonin (HSD + MEL) or a placebo (HSD + PL) daily. Brachial artery flow-mediated dilation, a measure of macrovascular function, (HSD + PL: 7.1 ± 3.8%; HSD + MEL: 6.7 ± 3.4%; p = 0.59) and tissue oxygenation index (TSI) reperfusion rate, a measure of microvascular reactivity, (HSD + PL: 0.21 ± 0.06%/s; HSD + MEL: 0.21 ± 0.08%/s; p = 0.97) and TSI area under the curve (HSD + PL: 199899 ± 10,863 a.u.; HSD + MEL: 20315 ± 11,348 a.u.; p = 0.17) were similar at the end of each condition. Neither nitroxide molarity (HSD + PL: 7.8 × 10−5 ± 4.1 × 10−5 mol/L; HSD + MEL: 8.7 × 10−5 ± 5.1 × 10−5 mol/L; p = 0.55) nor free radical number (HSD + PL: 8.0 × 1015 ± 4.4 × 1015; HSD + MEL: 9.0 × 1015 ± 4.9 × 1015; p = 0.51) were different between conditions. Melatonin supplementation did not alter vascular function or ROS levels while on a HSD in this sample of young healthyItem Antecubital venous endothelial ETB receptor protein expression is preserved with aging in men(American Journal of Physiology - Heart and Circulatory Physiology, 2024-01-01) Tummala, Saumya; Kuczmarski, Andrew V.; Del Vecchio, Angelica R.; Schwab, Allyson I.; Edwards, David G.; Wenner, Megan M.Changes in endothelial function precede the development of cardiovascular disease (CVD). We have previously shown that age-related declines in endothelial function in women are due in part to a reduction in endothelial cell endothelin-B receptor (ETBR) protein expression. However, it is not known if ETBR protein expression changes with aging in men. The purpose of this study was to test the hypothesis that ETBR protein expression is attenuated in older men (OM) compared with younger men (YM). Primary endothelial cells were harvested from the antecubital vein of 14 OM (60 ± 6 yr; 26 ± 3 kg/m2) and 17 YM (24 ± 5 yr; 24 ± 2 kg/m2). Cells were stained with 4′,6-diamidino-2-phenylindole, vascular endothelial cadherin, and ETBR. Images were quantified using immunocytochemistry. Endothelial function was assessed using brachial artery flow-mediated dilation (FMD). Systolic BP was similar (OM, 123 ± 11 vs. YM, 122 ± 10 mmHg) whereas diastolic BP was higher in OM (OM, 77 ± 7 vs. YM, 70 ± 6 mmHg; P < 0.01). Total testosterone was lower in OM (OM, 6.28 ± 4.21 vs. YM, 9.10 ± 2.68 ng/mL; P = 0.03). As expected, FMD was lower in OM (OM, 3.85 ± 1.51 vs. YM, 6.40 ± 2.68%; P < 0.01). However, ETBR protein expression was similar between OM and YM (OM, 0.39 ± 0.17 vs. YM, 0.42 ± 0.17 AU; P = 0.66). These data suggest that ETBR protein expression is not altered with age in men. These findings contrast with our previous data in women and further support sex differences in the endothelin system. NEW & NOTEWORTHY Our laboratory has previously shown that age-related declines in endothelial function are associated with a reduction in endothelial cell ETBR protein expression in women. However, it is unclear if endothelial cell ETBR protein expression is reduced with aging in men. This study demonstrates that endothelial cell ETBR protein expression is preserved with aging in men, and provides additional evidence for sex differences in the endothelin system.Item Validating the measurement of upper limb sensorimotor behavior utilizing a tablet in neurologically intact controls and individuals with chronic stroke(Journal of NeuroEngineering and Rehabilitation, 2023-09-01) Austin, Devin Sean; Dixon, Makenna J.; Tulimieri, Duncan Thibodeau; Cashaback, Joshua G. A.; Semrau, Jennifer A.Background Intact sensorimotor function of the upper extremity is essential for successfully performing activities of daily living. After a stroke, upper limb function is often compromised and requires rehabilitation. To develop appropriate rehabilitation interventions, sensitive and objective assessments are required. Current clinical measures often lack precision and technological devices (e.g. robotics) that are objective and sensitive to small changes in sensorimotor function are often unsuitable and impractical for performing home-based assessments. Here we developed a portable, tablet-based application capable of quantifying upper limb sensorimotor function after stroke. Our goal was to validate the developed application and accompanying data analysis against previously validated robotic measures of upper limb function in stroke. Methods Twenty individuals with stroke, twenty age-matched older controls, and twenty younger controls completed an eight-target Visually Guided Reaching (VGR) task using a Kinarm Robotic Exoskeleton and a Samsung Galaxy Tablet. Participants completed eighty trials of the VGR task on each device, where each trial consisted of making a reaching movement to one of eight pseudorandomly appearing targets. We calculated several outcome parameters capturing various aspects of sensorimotor behavior (e.g., Reaction Time, Initial Direction Error, Max Speed, and Movement Time) from each reaching movement, and our analyses compared metric consistency between devices. We used the previously validated Kinarm Standard Analysis (KSA) and a custom in-house analysis to calculate each outcome parameter. Results We observed strong correlations between the KSA and our custom analysis for all outcome parameters within each participant group, indicating our custom analysis accurately replicates the KSA. Minimal differences were observed for between-device comparisons (tablet vs. robot) in our outcome parameters. Additionally, we observed similar correlations for each device when comparing the Fugl-Meyer Assessment (FMA) scores of individuals with stroke to tablet-derived metrics, demonstrating that the tablet can capture clinically-based elements of upper limb impairment. Conclusions Tablet devices can accurately assess upper limb sensorimotor function in neurologically intact individuals and individuals with stroke. Our findings validate the use of tablets as a cost-effective and efficient assessment tool for upper-limb function after stroke.Item Effects of a mitochondrial-targeted ubiquinol on vascular function and exercise capacity in chronic kidney disease: a randomized controlled pilot study(American Journal of Physiology - Renal Physiology, 2023-10-01) Kirkman, Danielle L.; Stock, ,Joseph M.; Shenouda, Ninette; Bohmke, Natalie J.; Kim, Youngdeok; Kidd, Jason; Townsend, Raymond R.; Edwards, David G.Mitochondria-derived oxidative stress has been implicated in vascular and skeletal muscle abnormalities in chronic kidney disease (CKD). The purpose of this study was to investigate the effects of a mitochondria-targeted ubiquinol (MitoQ) on vascular function and exercise capacity in CKD. In this randomized controlled trial, 18 patients with CKD (means ± SE, age: 62 ± 3 yr and estimated glomerular filtration rate: 45 ± 3 mL/min/1.73 m2) received 4 wk of 20 mg/day MitoQ (MTQ group) or placebo (PLB). Outcomes assessed at baseline and follow-up included macrovascular function measured by flow-mediated dilation, microvascular function assessed by laser-Doppler flowmetry combined with intradermal microdialysis, aortic hemodynamics assessed by oscillometry, and exercise capacity assessed by cardiopulmonary exercise testing. Compared with PLB, MitoQ improved flow-mediated dilation (baseline vs. follow-up: MTQ, 2.4 ± 0.3% vs. 4.0 ± 0.9%, and PLB, 4.2 ± 1.0% vs. 2.5 ± 1.0%, P = 0.04). MitoQ improved microvascular function (change in cutaneous vascular conductance: MTQ 4.50 ± 2.57% vs. PLB −2.22 ± 2.67%, P = 0.053). Central aortic systolic and pulse pressures were unchanged; however, MitoQ prevented increases in augmentation pressures that were observed in the PLB group (P = 0.026). MitoQ did not affect exercise capacity. In conclusion, this study demonstrates the potential for a MitoQ to improve vascular function in CKD. The findings hold promise for future investigations of mitochondria-targeted therapies in CKD. NEW & NOTEWORTHY In this randomized controlled pilot study, we investigated the effects of a mitochondria-targeted ubiquinol (MitoQ) on vascular function and exercise capacity in chronic kidney disease. Our novel findings showed that 4-wk supplementation of MitoQ was well tolerated and improved macrovascular endothelial function, arterial hemodynamics, and microvascular function in patients with stage 3–4 chronic kidney disease. Our mechanistic findings also suggest that MitoQ improved microvascular function in part by reducing the NADPH oxidase contribution to vascular dysfunction.Item Contact or Collision Sport History, Repetitive Neurotrauma, and Patient-Reported Outcomes in Early to Midadulthood(Journal of Athletic Training, 2023-12-18) Hunzinger, Katherine J.; Caccese, Jaclyn B.; Mannix, Rebekah; Meehan, William P.; Swanik, C. Buz; Buckley, Thomas A.Context Data on the early to midlife effects of repetitive neurotrauma on patient-reported outcomes have been delimited to homogeneous samples of male athletes without comparison groups or accounting for modifying factors such as physical activity. Objective To determine the effect of contact or collision sport participation and repetitive neurotrauma on patient-reported outcomes among early to middle-aged adults. Design Cross-sectional study. Setting Research laboratory. Patients or Other Participants A total of 113 adults (53 [46.9%] men, 60 [53.1%] women; age = 34.88 ± 11.80 years) in 4 groups: (1) physically inactive individuals with no repetitive head impact (RHI) exposure (NON); (2) noncontact sport athletes and nonathletes with no RHI exposure who were currently physically active (NCA); (3) former high-risk sport athletes with an RHI history who were physically active (HRS); and (4) former rugby players with prolonged RHI exposure who remained physically active. Main Outcome Measure(s) The 12-Item Short-Form Health Survey (SF-12), Apathy Evaluation Scale–self-rated version (AES-S), Satisfaction With Life Scale (SWLS), and Sport Concussion Assessment Tool–5th Edition (SCAT5) Symptom and Symptom Severity Checklist. Results The NON group had worse self-rated physical function than the NCA group as assessed by the SF-12 physical component summary (P = .03) and worse self-rated apathy (AES-S) and satisfaction with life (SWLS) than the NCA (P = .03 for both) and HRS groups (P = .03 and P = .040, respectively). We observed no group differences for self-rated mental health (SF-12 mental component summary; P = .26) or symptoms (SCAT5; P = .42). Career duration was not associated with any patient-reported outcomes. Conclusions A history of contact or collision sport participation and career duration did not negatively affect patient-reported outcomes in physically active, early to middle-aged adults. However, physical inactivity status was negatively associated with patient-reported outcomes in these individuals in the absence of an RHI history. Key Points - The midlife and later-life effects of repetitive head impacts paired with physical activity on patient-reported outcomes need to be elucidated. - Contact or collision sport participation and career duration were unrelated to worse patient-reported outcomes in early to midadulthood among physically active individuals. - Physical inactivity may be a more important modifier of patient-reported outcomes in early to midadulthood than repetitive neurotrauma exposure.Item Self-Reported Mental Health Measures of Incoming Collegiate Student-Athletes With a History of COVID-19(Journal of Athletic Training, 2023-11-16) Anderson, Melissa N.; Gallo, Caitlin A.; Passalugo, Scott W.; Nimeh, Jake M.; Buckley, Thomas A.Background People with a history of COVID-19 may experience persistent neuropsychological disruptions such as lower satisfaction with life, depression, and anxiety. Although student-athletes are at low risk for severe COVID-19 complications, the effect of COVID-19 on mental health has not been elucidated. Objective To compare patient-reported mental health outcomes for incoming collegiate athletes with (COVID+) or without (COVID−) a history of COVID-19. Design Case-control study. Setting Laboratory. Patients or Other Participants A total of 178 student-athletes, consisting of 79 in the COVID+ group (44.3%; age = 18.90 ± 0.16 years) and 99 in the COVID− group (55.6%; age = 18.95 ± 0.16 years). Main Outcome Measure(s) Participants completed the Satisfaction With Life Scale (SWLS), the Hospital Anxiety and Depression Scale (HADS), and the State-Trait Anxiety Inventory (STAI). Unadjusted 1-way analyses of variance were conducted across all patient-reported outcomes. Analyses of covariance were calculated to determine the interaction of COVID-19 group, sex, and race and ethnicity on outcomes. Post hoc Bonferroni testing was performed to identify specific differences between groups. A χ2 analysis was computed to compare the number of athletes in each group who met the standard clinical cut points. Results We observed a between-groups difference for HADS depression (P = .047), whereby athletes in the COVID+ group had higher ratings (2.86 ± 0.26). We found group differences for the SWLS (P = .02), HADS anxiety (P = .003), and STAI state anxiety (P = .01) such that all scores were higher for the COVID+ group in the adjusted model. Post hoc testing revealed that female student-athletes in the COVID+ group had worse HADS anxiety (P = .01) and STAI trait anxiety (P = .002) scores than individuals in all other groups. We did not demonstrate differences between groups in the percentage of responses below established diagnostic thresholds. Conclusions Incoming collegiate student-athletes who reported a previous COVID-19 diagnosis displayed higher depression scores, suggesting that clinicians may need to provide appropriate identification and referral for mental health conditions. However, we were encouraged that most participants, regardless of a history of COVID-19 diagnosis, had mental health scores that did not exceed established diagnostic threshold values. Key Points - Differences in mental health for student-athletes with and those without a history of COVID-19 were below the established clinical cut points for satisfaction with life, anxiety, and depression. - Female student-athletes reported worse anxiety than male student-athletes, regardless of their COVID-19 history.Item Effect of acute handgrip and aerobic exercise on wasted pressure effort and arterial wave reflections in healthy aging(American Journal of Physiology - Heart and Circulatory Physiology, 2023-10-01) Stock, Joseph M.; Shenouda, Ninette; Chouramanis, Nicholas; Patik, Jordan C.; Martens, Christopher R.; Farquhar, William B.; Chirinos, Julio A.; Edwards, David G.Aging increases arterial stiffness and wave reflections that augment left ventricular wasted pressure effort (WPE). A single bout of exercise may be effective at acutely reducing WPE via reductions in arterial wave reflections. In young adults (YA) acute aerobic exercise decreases, whereas handgrip increases, wave reflections. Whether acute exercise mitigates or exacerbates WPE and arterial wave reflection in healthy aging warrants further examination. The purpose of this study was to determine if there are age-related differences in WPE and wave reflection during acute handgrip and aerobic exercise. When compared with baseline, WPE increased substantially in older adults (OA) during handgrip (5,219 ± 2,396 vs. 7,019 ± 2,888 mmHg·ms, P < 0.001). When compared with baseline, there was a robust reduction in WPE in OA during moderate-intensity aerobic exercise (5,428 ± 2,084 vs. 3,290 ± 1,537 mmHg·ms, P < 0.001), despite absolute WPE remaining higher in OA compared with YA during moderate-intensity aerobic exercise (OA 3,290 ± 1,537 vs. YA 1,188 ± 962 mmHg·ms, P < 0.001). There was no change in wave reflection timing indexed to ejection duration in OA during handgrip (40 ± 6 vs. 38 ± 4%, P = 0.41) or moderate-intensity aerobic exercise (40 ± 5 vs. 42 ± 8%, P = 0.99). Conversely, there was an earlier return of wave reflection in YA during handgrip (60 ± 11 vs. 52 ± 6%, P < 0.001) and moderate-intensity aerobic exercise (59 ± 7 vs. 51 ± 9%, P < 0.001). Changes in stroke volume were not different between groups during handgrip (P = 0.08) or aerobic exercise (P = 0.47). The greater increase in WPE during handgrip and decrease in WPE during aerobic exercise suggest that aortic hemodynamic responses to acute exercise are exaggerated with healthy aging without affecting stroke volume. NEW & NOTEWORTHY We demonstrated that acute aerobic exercise attenuated, whereas handgrip augmented, left ventricular hemodynamic load from wave reflections more in healthy older (OA) compared with young adults (YA) without altering stroke volume. These findings suggest an exaggerated aortic hemodynamic response to acute exercise perturbations with aging. They also highlight the importance of considering exercise modality when examining aortic hemodynamic responses to acute exercise in older adults.Item Limitations in utilization and prioritization of standardized somatosensory assessments after stroke: A cross-sectional survey of neurorehabilitation clinicians(Topics in Stroke Rehabilitation, 2023-04-16) Hoh, Joanna Eskander; Borich, Michael R.; Kesar, Trisha M.; Reisman, Darcy S.; Semrau, Jennifer A.Background and Purpose Somatosensory impairments are common after stroke, but receive limited evaluation and intervention during neurorehabilitation, despite negatively impacting functional movement and recovery. Objectives Our objective was to understand the scope of somatosensory assessments used by clinicians in stroke rehabilitation, and barriers to increasing use in clinical practice. Methods An electronic survey was distributed to clinicians (physical therapists, occupational therapists, physicians, and nurses) who assessed at least one individual with stroke in the past 6 months. The survey included questions on evaluation procedures, type, and use of somatosensory assessments, as well as barriers and facilitators in clinical practice. Results Clinicians (N = 431) indicated greater familiarity with non-standardized assessments, and greater utilization compared to standardized assessments (p < 0.0001). Components of tactile sensation were the most commonly assessed modality of somatosensation (25%), while proprioception was rarely assessed (1%). Overall, assessments of motor function were prioritized over assessments of somatosensory function (p < 0.0001). Discussion Respondents reported assessing somatosensation less frequently than motor function and demonstrated a reliance on rapid and coarse non-standardized assessments that ineffectively capture multi-modal somatosensory impairments, particularly for proprioceptive deficits common post-stroke. In general, clinicians were not familiar with standardized somatosensory assessments, and this knowledge gap likely contributes to lack of translation of these assessments into practice. Conclusions Clinicians utilize somatosensory assessments that inadequately capture the multi-modal nature of somatosensory impairments in stroke survivors. Addressing barriers to clinical translation has the potential to increase utilization of standardized assessments to improve the characterization of somatosensory deficits that inform clinical decision-making toward enhancing stroke rehabilitation outcomes.Item Clinical Mental Health Measures and Prediction of Postconcussion Musculoskeletal Injury(Journal of Athletic Training, 2023-07-31) Buckley, Thomas A.; Bryk, Kelsey N.; Enrique, Alexander L.; Kaminski, Thomas W.; Hunzinger, Katherine J.; Oldham, Jessie R.Context The rate of lower extremity musculoskeletal injury (LE MSK) is elevated after concussion; however, the underlying mechanism has not been elucidated. Physical characteristics have been investigated despite poorer mental health being a common postconcussion complaint and linked to MSKs. Objective To evaluate the role of mental health as a predictor of postconcussion LE MSK. Design Case-control study. Setting Intercollegiate athletic training facility. Patients or Other Participants A total of 67 National Collegiate Athletic Association Division I student-athletes (n = 39 females) who had been diagnosed with a sport-related concussion. Main Outcome Measure(s) The Brief Symptom Inventory-18, Hospital Anxiety and Depression Scale, and Satisfaction With Life Scale (SWLS) measures were completed at baseline (preseason) and on the day participants were cleared for unrestricted return to play (RTP) after a concussion. Two binary logistic regressions were used to predict postconcussion LE MSK within a year, one for the baseline time point and the second for the RTP time point. A 2 (group: LE MSK, no LE MSK)-by-2 (time: baseline, RTP) repeated-measures analysis of variance compared performance between baseline and RTP. Results Subsequent LE MSKs were sustained by 44 participants (65.7%). The only significant predictor of postconcussion LE MSK was the SWLS score at RTP, with Exp(B) = 0.64, indicating that an increased (improved) SWLS score was associated with a lower LE MSK rate. No significant interactions were present between mental health measures and subsequent MSK (P values = .105–.885). Conclusions Limited associations were evident between postconcussion LE MSK and scores on commonly used measures of anxiety, depression, and satisfaction with life. Reported increased satisfaction with life was associated with a decreased injury risk, which warrants further attention. Our results suggest that these measures of anxiety, depression, and satisfaction with life have limited value in assisting sports medicine clinicians with determining which student-athletes are at elevated risk of postconcussion LE MSK. Key Points Measures of anxiety and depressive symptoms were not predictive of elevated postconcussion lower extremity musculoskeletal injury. Greater satisfaction with life was associated with a decreased risk of postconcussion lower extremity musculoskeletal injury.Item Temporal associations between nightly sleep with daytime eating and activity levels in free-living young adults(SLEEP, 2023-04-21) Hoopes, Elissa K.; Brewer, Benjamin; Robson, Shannon M.; Witman, Melissa A.; D’Agata, Michele N.; Malone, Susan K.; Edwards, David G.; Patterson, FredaStudy Objectives This study aimed to quantify the temporal associations between nightly sleep quantity and timing with daytime eating behavior and activity levels in free-living (i.e. non-experimental) settings. Methods Generally healthy young adults (N = 63; 28.9 ± 7.1 years) completed concurrent sleep (wrist actigraphy), eating (photo-assisted diet records), and activity (waist actigraphy) assessments over 14 days. Multilevel models quantified the associations between nightly sleep (total sleep time, timing of sleep and wake onset) with next-day eating behavior (diet quality, caloric intake, timing of eating onset/offset, eating window duration) and activity levels (total physical activity, sedentary time). Associations in the reverse direction (i.e. eating and activity predicting sleep) were explored. Models adjusted for demographic and behavioral confounders and accounted for multiple testing. Results At within- and between-subject levels, nights with greater-than-average total sleep time predicted a shorter eating window the next day (all p ≤ 0.002). Later-than-average sleep and wake timing predicted within- and between-subject delays in next-day eating onset and offset, and between-subject reductions in diet quality and caloric intake (all p ≤ 0.008). At within- and between-subject levels, total sleep time was bidirectionally, inversely associated with sedentary time (all p < 0.001), while later-than-average sleep and wake timing predicted lower next-day physical activity (all p ≤ 0.008). Conclusions These data underscore the complex interrelatedness between sleep, eating behavior, and activity levels in free-living settings. Findings also suggest that sleep exerts a greater influence on next-day behavior, rather than vice versa. While testing in more diverse samples is needed, these data have potential to enhance health behavior interventions and maximize health outcomes. Graphical Abstract: Available at https://doi.org/10.1093/sleep/zsad123
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