Open Access Publications

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

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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 Investigators
Context 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.
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 A
Concussions 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.
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, Freda
Background 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.
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 healthy
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.
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.
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.
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.
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.
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.
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.
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.
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, Freda
Study 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
Dietary Supplementation With NAD+-Boosting Compounds in Humans: Current Knowledge and Future Directions
(The Journals of Gerontology: Series A, 2023-05-05) Freeberg, Kaitlin A.; Udovich, Ce Ann C.; Martens, Christopher R.; Seals, Douglas R.; Craighead, Daniel H.
Advancing age and many disease states are associated with declines in nicotinamide adenine dinucleotide (NAD+) levels. Preclinical studies suggest that boosting NAD+ abundance with precursor compounds, such as nicotinamide riboside or nicotinamide mononucleotide, has profound effects on physiological function in models of aging and disease. Translation of these compounds for oral supplementation in humans has been increasingly studied within the last 10 years; however, the clinical evidence that raising NAD+ concentrations can improve physiological function is unclear. The goal of this review was to synthesize the published literature on the effects of chronic oral supplementation with NAD+ precursors on healthy aging and age-related chronic diseases. We identified nicotinamide riboside, nicotinamide riboside co-administered with pterostilbene, and nicotinamide mononucleotide as the most common candidates in investigations of NAD+-boosting compounds for improving physiological function in humans. Studies have been performed in generally healthy midlife and older adults, adults with cardiometabolic disease risk factors such as overweight and obesity, and numerous patient populations. Supplementation with these compounds is safe, tolerable, and can increase the abundance of NAD+ and related metabolites in multiple tissues. Dosing regimens and study durations vary greatly across interventions, and small sample sizes limit data interpretation of physiological outcomes. Limitations are identified and future research directions are suggested to further our understanding of the potential efficacy of NAD+-boosting compounds for improving physiological function and extending human health span.
Imaging the lower limb network in Parkinson’s disease
(NeuroImage: Clinical, 2023-04-13) Chung, Jae Woo; Bower, Abigail E.; Malik, Ibrahim; Martello, Justin P.; Knight, Christopher A.; Jeka, John J.; Burciu, Roxana G.
Background Despite the significant impact of lower limb symptoms on everyday life activities in Parkinson’s disease (PD), knowledge of the neural correlates of lower limb deficits is limited. Objective We ran an fMRI study to investigate the neural correlates of lower limb movements in individuals with and without PD. Methods Participants included 24 PD and 21 older adults who were scanned while performing a precisely controlled isometric force generation task by dorsiflexing their ankle. A novel MRI-compatible ankle dorsiflexion device that limits head motion during motor tasks was used. The PD were tested on their more affected side, whereas the side in controls was randomized. Importantly, PD were tested in the off-state, following overnight withdrawal from antiparkinsonian medication. Results The foot task revealed extensive functional brain changes in PD compared to controls, with reduced fMRI signal during ankle dorsiflexion within the contralateral putamen and M1 foot area, and ipsilateral cerebellum. The activity of M1 foot area was negatively correlated with the severity of foot symptoms based on the Movement Disorder Society‐Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS-III). Conclusion Overall, current findings provide new evidence of brain changes underlying motor symptoms in PD. Our results suggest that pathophysiology of lower limb symptoms in PD appears to involve both the cortico-basal ganglia and cortico-cerebellar motor circuits.
Effects of contact/collision sport history on gait in early- to mid-adulthood
(Journal of Sport and Health Science, 2023-05-01) Hunzinger, Katherine J.; Caccese, Jaclyn B.; Mannix, Rebekah; Meehan, William P. III; Hafer, Jocelyn F.; Swanik, C. Buz; Buckley, Thomas A.
Background: To determine the effect of contact/collision sport participation on measures of single-task (ST) and dual-task (DT) gait among early- to middle-aged adults. Methods: The study recruited 113 adults (34.88 ± 11.80 years, (mean ± SD); 53.0% female) representing 4 groups. Groups included (a) former non-contact/collision athletes and non-athletes who are not physically active (n = 28); (b) former non-contact/collision athletes who are physically active (n = 29); (c) former contact/collision sport athletes who participated in high-risk sports and are physically active (n = 29); and (d) former rugby players with prolonged repetitive head impact exposure history who are physically active (n = 27). Gait parameters were collected using inertial measurement units during ST and DT gait. DT cost was calculated for all gait parameters (double support, gait speed, and stride length). Groups were compared first using one-way analysis of covariance. Then a multiple regression was performed for participants in the high-risk sport athletes and repetitive head impact exposure athletes groups only to predict gait outcomes from contact/collision sport career duration. Results: There were no significant differences between groups on any ST, DT, or DT cost outcomes (p > 0.05). Contact/collision sport duration did not predict any ST, DT, or DT cost gait outcomes. Conclusion: Years and history of contact/collision sport participation does not appear to negatively affect or predict neurobehavioral function in early- to mid-adulthood among physically active individuals. Graphical abstract available at: https://doi.org/10.1016/j.jshs.2022.12.004
Oral nicotinamide riboside raises NAD+ and lowers biomarkers of neurodegenerative pathology in plasma extracellular vesicles enriched for neuronal origin
(Aging Cell, 2023-01-12) Vreones, Michael; Mustapic, Maja; Moaddel, Ruin; Pucha, Krishna A.; Lovett, Jacqueline; Seals, Douglas R.; Kapogiannis, Dimitrios; Martens, Christopher R.
Declining nicotinamide adenine dinucleotide (NAD+) concentration in the brain during aging contributes to metabolic and cellular dysfunction and is implicated in the pathogenesis of aging-associated neurological disorders. Experimental therapies aimed at boosting brain NAD+ levels normalize several neurodegenerative phenotypes in animal models, motivating their clinical translation. Dietary intake of NAD+ precursors, such as nicotinamide riboside (NR), is a safe and effective avenue for augmenting NAD+ levels in peripheral tissues in humans, yet evidence supporting their ability to raise NAD+ levels in the brain or engage neurodegenerative disease pathways is lacking. Here, we studied biomarkers in plasma extracellular vesicles enriched for neuronal origin (NEVs) from 22 healthy older adults who participated in a randomized, placebo-controlled crossover trial (NCT02921659) of oral NR supplementation (500 mg, 2x /day, 6 weeks). We demonstrate that oral NR supplementation increases NAD+ levels in NEVs and decreases NEV levels of Aβ42, pJNK, and pERK1/2 (kinases involved in insulin resistance and neuroinflammatory pathways). In addition, changes in NAD(H) correlated with changes in canonical insulin–Akt signaling proteins and changes in pERK1/2 and pJNK. These findings support the ability of orally administered NR to augment neuronal NAD+ levels and modify biomarkers related to neurodegenerative pathology in humans. Furthermore, NEVs offer a new blood-based window into monitoring the physiologic response of NR in the brain.
Stress deprivation of tendon explants or Tpm3.1 inhibition in tendon cells reduces F-actin to promote a tendinosis-like phenotype
(Molecular Biology of the Cell, 2022-12-01) Inguito, Kameron L.; Schofield, Mandy M.; Faghri, Arya D.; Bloom, Ellen T.; Heino, Marissa; West, Valerie C.; Ebron, Karl Matthew M.; Elliot, Dawn M.; Parreno, Justin
Actin is a central mediator between mechanical force and cellular phenotype. In tendons, it is speculated that mechanical stress deprivation regulates gene expression by reducing filamentous (F)-actin. However, the mechanisms regulating tenocyte F-actin remain unclear. Tropomyosins (Tpms) are master regulators of F-actin. There are more than 40 Tpm isoforms, each having the unique capability to stabilize F-actin subpopulations. We investigated F-actin polymerization in stress-deprived tendons and tested the hypothesis that stress fiber–associated Tpm(s) stabilize F-actin to regulate cellular phenotype. Stress deprivation of mouse tail tendon down-regulated tenogenic and up-regulated protease (matrix metalloproteinase-3) mRNA levels. Concomitant with mRNA modulation were increases in G/F-actin, confirming reduced F-actin by tendon stress deprivation. To investigate the molecular regulation of F-actin, we identified that tail, Achilles, and plantaris tendons express three isoforms in common: Tpm1.6, 3.1, and 4.2. Tpm3.1 associates with F-actin in native and primary tenocytes. Tpm3.1 inhibition reduces F-actin, leading to decreases in tenogenic expression, increases in chondrogenic expression, and enhancement of protease expression in mouse and human tenocytes. These expression changes by Tpm3.1 inhibition are consistent with tendinosis progression. A further understanding of F-actin regulation in musculoskeletal cells could lead to new therapeutic interventions to prevent alterations in cellular phenotype during disease progression.
Sex differences in microvascular function and arterial hemodynamics in nondialysis chronic kidney disease
(American Journal of Physiology - Heart and Circulatory Physiology, 2022-12-01) Kirkman, Danielle L.; Ramick, Meghan G.; Muth, Bryce J.; Stock, Joseph M.; Townsend, Raymond R.; Edwards, David G.
Cardiovascular disease (CVD) is the leading cause of death in chronic kidney disease (CKD). Abnormal arterial hemodynamics contribute to CVD, a relationship that can be mediated by microvascular dysfunction. The purpose of this study was to investigate potential sex differences in arterial hemodynamics and microvascular dysfunction in patients with stages 3 to 4 CKD. Vascular function was assessed in 22 male (mean ± SD; age, 56 ± 13 yr) and 10 female (age, 63 ± 9 yr) patients. Arterial hemodynamics were acquired with combined tonometry and oscillometry. Skin blood flow was used as a model of microvascular function. Participants were instrumented with three microdialysis fibers for the delivery of 1) Ringer’s solution; 2) superoxide dismutase mimetic, Tempol; and 3) nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, apocynin. Blood flow was measured via laser-Doppler flowmetry during standardized local heating (42°C). Central pulse pressure (mean ± SE; 62 ± 9 vs. 46 ± 3 mmHg; P = 0.01) and augmentation index (36 ± 3 vs. 26 ± 3%; P = 0.03) were higher in females. There was a trend for higher central systolic pressures in females (146 ± 9 vs. 131 ± 3 mmHg; P = 0.06). Females reported higher forward (39 ± 4 vs. 29 ± 2 mmHg; P = 0.004) and reflected (27 ± 3 vs. 19 ± 1 mmHg; P < 0.001) wave amplitudes. Cutaneous vascular function was impaired in females compared with males (77 ± 3 vs. 89 ± 1%, P = 0.001). Microvascular function was improved following the delivery of Tempol and apocynin in females but not in males. Female patients with CKD had poorer central hemodynamics and reduced microvascular function compared with their male counterparts. Oxidative stress may contribute to lower microvascular function observed in females. NEW & NOTEWORTHY There are limited data regarding the physiological mechanisms of potential sex differences in central hemodynamics and vascular function in chronic kidney disease (CKD). We report that older female patients with nondialysis CKD have higher central pulse pressures compared with male patients with CKD. In addition, older females with CKD have lower microvascular function compared with their male counterparts, and oxidative stress contributes to the lower microvascular function in older female patients with CKD.
Associations between noninvasive upper- and lower-limb vascular function assessments: extending the evidence to young women
(Journal of Applied Physiology, 2022-10-01) D'Agata, Michele N.; Hoopes, Elissa K.; Witman, Melissa A.
Brachial artery (BA) flow-mediated dilation (FMD) is a well-established measure of peripheral vascular function prognostic of future cardiovascular events. The vasodilatory response to FMD (FMD%) reflects upper-limb conduit artery function, whereas reactive hyperemia (RH) following cuff-occlusion release reflects upper-limb resistance artery function. Comparatively, passive leg movement (PLM) is a newer, increasingly utilized assessment of lower-limb resistance artery function. To increase its clinical utility, PLM-induced leg blood flow (LBF) responses have been compared with hemodynamic responses to FMD, but only in men. Therefore, the purpose of this study was to retrospectively compare LBF responses to FMD% and RH responses in women. We hypothesized that LBF responses would be positively associated with both FMD% and RH, but to a greater extent with RH. FMD and PLM were performed on 72 women (23 ± 4 yr). Arterial diameter and blood velocity were assessed using Doppler ultrasound. Pearson correlation coefficients were used to evaluate associations. Measures of resistance artery function were weakly positively associated: change in BA blood flow ΔBABF and ΔLBF (r = 0.33, P < 0.01), BABF area under the curve (BABF AUC) and LBF AUC (r = 0.33, P < 0.01), and BABFpeak and LBFpeak (r = 0.37, P < 0.01). However, FMD% was not associated with any index of PLM (all P > 0.30). In women, indices of resistance artery function in the upper- and lower limbs were positively associated. However, contrary to the previous work in men, upper-limb conduit artery function was not associated with lower-limb resistance artery function suggesting these assessments capture different aspects of vascular function and should not be used interchangeably in women. NEW & NOTEWORTHY: Upper- and lower-limb indices of resistance artery function are positively associated in young women when assessed by reactive hyperemia following brachial artery flow-mediated dilation (FMD) cuff-occlusion release and leg blood flow responses to passive leg movement (PLM), respectively. However, despite previous data demonstrating a positive association between upper-limb conduit artery function assessed by FMD and lower-limb resistance artery function assessed by PLM in young men, these measures do not appear to be related in young women.

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