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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Mechanical Properties of the Cortex in Older Adults and Relationships With Personality Traits
(Human Brain Mapping, 2025-02-06) Twohy, Kyra E.; Kramer, Mary K.; Diano, Alexa M.; Bailey, Olivia M.; Delgorio, Peyton L.; McIlvain, Grace; McGarry, Matthew D. J.; Martens, Christopher R.; Schwarb, Hillary; Hiscox, Lucy V.; Johnson, Curtis L.
Aging and neurodegeneration impact structural brain integrity and can result in changes to behavior and cognition. Personality, a relatively stable trait in adults as compared to behavior, in part relies on normative individual differences in cellular organization of the cerebral cortex, but links between brain structure and personality expression have been mixed. One key finding is that personality has been shown to be a risk factor in the development of Alzheimer's disease, highlighting a structure–trait relationship. Magnetic resonance elastography (MRE) has been used to noninvasively study age-related changes in tissue mechanical properties because of its high sensitivity to both the microstructural health and the structure–function relationship of the tissue. Recent advancements in MRE methodology have allowed for reliable property recovery of cortical subregions, which had previously presented challenges due to the complex geometry and overall thin structure. This study aimed to quantify age-related changes in cortical mechanical properties and the relationship of these properties to measures of personality in an older adult population (N = 57; age 60–85 years) for the first time. Mechanical properties including shear stiffness and damping ratio were calculated for 30 bilateral regions of the cortex across all four lobes, and the NEO Personality Inventory (NEO-PI) was used to measure neuroticism and conscientiousness in all participants. Shear stiffness and damping ratio were found to vary widely across regions of the cortex, upward of 1 kPa in stiffness and by 0.3 in damping ratio. Shear stiffness changed regionally with age, with some regions experiencing accelerated degradation compared to neighboring regions. Greater neuroticism (i.e., the tendency to experience negative emotions and vulnerability to stress) was associated with high damping ratio, indicative of poorer tissue integrity, in the rostral middle frontal cortex and the precentral gyrus. This study provides evidence of structure–trait correlates between physical mechanical properties and measures of personality in older adults and adds to the supporting literature that neurotic traits may impact brain health in cognitively normal aging.
Actin Polymerization Status Regulates Tenocyte Homeostasis Through Myocardin-Related Transcription Factor-A
(Cytoskeleton, 2024-11-27) West, Valerie C.; Owen, Kaelyn E.; Inguito, Kameron L.; Ebron, Karl Matthew M.; Reiner, Tori N.; Mirack, Chloe E.; Le, Christian H.; Marqueti, Rita de Cassia; Snipes, Steven; Mousavizadeh, Rouhollah; King, Rylee E.; Elliott, Dawn M.; Parreno, Justin
The actin cytoskeleton is a potent regulator of tenocyte homeostasis. However, the mechanisms by which actin regulates tendon homeostasis are not entirely known. This study examined the regulation of tenocyte molecule expression by actin polymerization via the globular (G-) actin-binding transcription factor, myocardin-related transcription factor-a (MRTF). We determined that decreasing the proportion of G-actin in tenocytes by treatment with TGFβ1 increases nuclear MRTF. These alterations in actin polymerization and MRTF localization coincided with favorable alterations to tenocyte gene expression. In contrast, latrunculin A increases the proportion of G-actin in tenocytes and reduces nuclear MRTF, causing cells to acquire a tendinosis-like phenotype. To parse out the effects of F-actin depolymerization from regulation by MRTF, we treated tenocytes with cytochalasin D. Exposure of cells to cytochalasin D increases the proportion of G-actin in tenocytes. However, as compared to latrunculin A, cytochalasin D has a differential effect on MRTF localization by increasing nuclear MRTF. This led to an opposing effect on the regulation of a subset of genes. The differential regulation of genes by latrunculin A and cytochalasin D suggests that actin signals through MRTF to regulate a specific subset of genes. By targeting the deactivation of MRTF through the inhibitor CCG1423, we verify that MRTF regulates Type I Collagen, Tenascin C, Scleraxis, and α-smooth muscle actin in tenocytes. Actin polymerization status is a potent regulator of tenocyte homeostasis through the modulation of several downstream pathways, including MRTF. Understanding the regulation of tenocyte homeostasis by actin may lead to new therapeutic interventions against tendinopathies, such as tendinosis.
Cerebral vasomotor reactivity to carbon dioxide using the rebreathe technique: assessment of within-day and between-day repeatability
(American Journal of Physiology - Regulatory, Integrative and Comparative Physiology, 2024-12-01) Nandadeva, Damsara; Skow, Rachel J.; Martin, Zachary T.; Patik, Jordan C.; Taherzadeh, Ziba; Ortiz, Alison; Kao, Yungfei; Fadel, Paul J.; Brothers, R. Matthew
The cerebral vasodilator response to increased arterial carbon dioxide (CO2) concentration, termed cerebral vasomotor reactivity (CVMR), is used to assess cerebral vascular function. We sought to assess the within-day and between-day repeatability of CVMR to rebreathing-induced hypercapnia. Twelve healthy adults performed a within-day short interval protocol (17 ± 2 min between trials), ten performed a within-day long interval protocol (145 ± 16 min between trials), and seventeen performed a between-day protocol (5 ± 2 days between visits). Repeatability of the slope of the percent change in middle cerebral artery mean blood velocity (%MCAvmean) and cerebral vascular conductance index (%CVCi), to the change in partial pressure of end-tidal CO2 (P⁢ETCO2) between the two trials/days was assessed. Within-day short interval, %MCAvmean slope demonstrated fair to excellent repeatability (intraclass correlation, ICC = 0.92 [95% confidence interval 0.72–0.98]; P < 0.001) while %CVCi slope showed more variability (ICC = 0.84 [0.47–0.95]; P = 0.002]). Within-day long interval, %MCAvmean (ICC = 0.95 [0.80–0.99]) and %CVCi (ICC = 0.94 [0.71–0.99]) slopes showed good to excellent and fair to excellent repeatability respectively (P < 0.001 for both). For between-day trials, better repeatability was observed for %CVCi (ICC = 0.85 [0.57–0.95]; P < 0.001) compared with %MCAvmean (ICC = 0.76 [0.33–0.91]; P = 0.004) slope. These findings indicate repeatable within- and between-day CVMR responses to rebreathe-induced hypercapnia. However, a longer interval may be better for within-day repeat trials, particularly for CVCi measures.
Six-year follow-up of a world record-breaking master marathon runner
(Journal of Applied Physiology, 2024-11-01) Romberger, Nathan T.; Stock, Joseph M.; McMillan, Ronald K.; Overstreet, Matthew L.; Lepers, Romuald; Joyner, Michael J.; Farquhar, William B.
Endurance performance declines with advancing age. Of the three main physiological factors that determine endurance running performance [maximal oxygen consumption (V̇o2max), lactate threshold, and running economy (RE)], V̇o2max appears to be most affected by age. Although endurance performance declines with age, recently, endurance performance has rapidly improved in master athletes as the number of master athletes competing in endurance events has increased. Master athletes represent an intriguing model to study healthy aging. In this case study, we reassessed the physiological profile of a 76-yr-old distance runner who broke the marathon world record for men over 70 yr of age in 2018. This runner was tested a few months before breaking the world record and retested in 2024. Between 2018 and 2024, his marathon running velocity decreased significantly. Therefore, the purpose of this case study was to determine the physiological changes that explain his performance decline. RE remained similar to 2018, and while there was not a clear breakpoint in blood lactate, he still likely runs marathons at a high percentage (∼90%) of his V̇o2max. However, V̇o2max declined by 15.1%. HRmax declined by 3.2% and maximal O2 pulse declined by 12.4%, suggesting that maximal stroke volume and/or arteriovenous O2 difference decreased. Altogether, although this marathoner continues to compete at an elite level, his performance has declined since his record-breaking marathon due to a reduction in V̇o2max. This is likely caused by reductions in maximal stroke volume and/or arteriovenous O2 difference. We speculate that these changes reflect primarily age-related processes. NEW & NOTEWORTHY We performed 6-yr follow-up testing on a world record-breaking master marathon runner. We determined that his performance declined since his record-breaking marathon in 2018 primarily due to a reduction in V̇o2max. His max heart rate (HR) changed minimally, but his peak O2 pulse decreased, suggesting that his maximal stroke volume and/or arteriovenous O2 difference decreased. These changes likely reflect primarily age-related effects in the absence of an overt pathological disease process.
Characterizing vascular and hormonal changes in women across the life span: a cross-sectional analysis
(American Journal of Physiology - Heart and Circulatory Physiology, 2024-11-01) Wenner, Megan M.; Shenouda, Ninette; Shoemaker, Leena; Kuczmarski, Andrew; Haigh, Katherine; Del Vecchio, Angelica; Schwab, Allyson; McGinty, Shane J.; Edwards, David G.; Pohlig, Ryan T.; Nuckols, Virginia R.; DuBose, Lyndsey; Moreau, Kerrie L.
Vascular dysfunction, marked by lower endothelial function and increased aortic stiffness, is a nontraditional risk factor that precedes the development of cardiovascular disease (CVD). However, the age at which these changes in vascular function occur in women and the degree to which reproductive hormones mediate these changes has not been characterized. Women free from major disease were enrolled across the adult life span (aged 18–70 yr, n = 140). Endothelial function was assessed as flow-mediated dilation (FMD) of the brachial artery during reactive hyperemia using duplex ultrasound and expressed as percent dilation. Aortic stiffness was measured by carotid-femoral pulse wave velocity (cfPWV). Blood samples were obtained to quantify reproductive hormone concentration. Regression models determined age-related breakpoints and mediating factors between age and vascular outcomes. FMD declined with age with a breakpoint and steeper decline occurring at 47 yr of age. Thereafter, age was independently associated with lower FMD (B = −0.13, P < 0.001). cfPWV was relatively stable until a breakpoint at age 48, and age was independently associated with higher cfPWV thereafter (B = 0.10, P < 0.001). Path analysis revealed that the association between age and FMD was partially mediated by follicle-stimulating hormone (abind = 0.051, P = 0.01) and progesterone (abind = 0.513, P < 0.001) but not estradiol (abind = −0.004, P = 0.08). No mediation was present for cfPWV. Age was associated with endothelial dysfunction and aortic stiffness in women beginning at 47 and 48 yr old, respectively, 3 to 4 yr before the average age of menopause. The association between age and endothelial dysfunction was explained in part by elevations in follicle-stimulating hormone and progesterone, but not declining estradiol. NEW & NOTEWORTHY We demonstrate that the age at which endothelial function declines and aortic stiffness increases in healthy women is 47 and 48, respectively. The inflection point in flow-mediated dilation (FMD) is 6 yr earlier than previously reported, and the association between age and FMD was mediated by follicle-stimulating hormone (FSH) and progesterone (P4) but not estradiol (E2). Graphical abstract available at: https://doi.org/10.1152/ajpheart.00373.2024
Youth Soccer Heading Exposure and Its Effects on Clinical Outcome Measures
(Sports, 2024-12-10) Wahlquist, Victoria E.; Buckley, Thomas A.; Caccese, Jaclyn B.; Glutting, Joseph J.; Royer, Todd D.; Kaminski, Thomas W.
Purposeful heading, in which players may use their heads to advance the ball in play, is a unique part of soccer. Clinical outcome measures used to aid in the diagnosis of a concussion have long been a cornerstone of the contemporary measurements associated with the short- and long-term effects of monitoring repetitive head impacts (RHI) and soccer heading exposure. The effects of RHI in the youth population are still unknown, therefore, the purpose of this study was to examine if heading exposure is predictive of changes in self-reported symptoms, neurocognitive functioning, gait, and balance in female youth soccer players over the course of one soccer season. Small improvements in neurocognitive functioning and gait and slight deficits in balance were observed from pre- to post-season. All changes were not clinically relevant and likely due to a practice effect. The low heading exposure in our cohort of youth soccer players was likely not enough to elicit any changes in clinical measures. In general, our clinical outcomes did not change after a season of soccer play and change scores were not predicted by heading exposure.
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.
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.
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.
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, Laurie
Research 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.
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 Chandra
Diabetic 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.
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.
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.
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.

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