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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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.
A Simple Adaptive Transfer Function for Deriving the Central Blood Pressure Waveform from a Radial Blood Pressure Waveform
(Nature Publishing Group, 9/14/16) Gao,Mingwu; Rose,William C.; Fetics,Barry; Kass,David A.; Chen,Chen-Huan; Mukkamala,Ramakrishna; Mingwu Gao, William C. Rose, Barry Fetics, David A. Kass, Chen-Huan Chen, Ramakrishna Mukkamala; Rose, William C
Generalized transfer functions (GTFs) are available to compute the more relevant central blood pressure (BP) waveform from a more easily measured radial BP waveform. However, GTFs are population averages and therefore may not adapt to variations in pulse pressure (PP) amplification (ratio of radial to central PP). A simple adaptive transfer function (ATF) was Developmenteloped. First, the transfer function is defined in terms of the wave travel time and reflection coefficient parameters of an arterial model. Then, the parameters are estimated from the radial BP waveform by exploiting the observation that central BP waveforms exhibit exponential diastolic decays. The ATF was assessed using the original data that helped popularize the GTF. These data included radial BP waveforms and invasive reference central BP waveforms from cardiac catheterization patients. The data were divided into low, middle, and high PP amplification groups. The ATF estimated central BP with greater accuracy than GTFs in the low PP amplification group (e.g., central systolic BP and PP root-mean-square-errors of 3.3 and 4.2 mm Hg versus 6.2 and 7.1 mm Hg; p <= 0.05) while showing similar accuracy in the higher PP amplification groups. The ATF may permit more accurate, non-invasive central BP monitoring in elderly and hypertensive patients.
Altered brain functional connectivity in the frontoparietal network following an ice hockey season
(European Journal of Sport Science, 2022-05-08) DiFabio, Melissa S.; Smith, Daniel R.; Breedlove, Katherine M.; Pohlig, Ryan T.; Buckley, Thomas A.; Johnson, Curtis L.
Sustaining sports-related head impacts has been reported to result in neurological changes that potentially lead to later-life neurological disease. Advanced neuroimaging techniques have been used to detect subtle neurological effects resulting from head impacts, even after a single competitive season. The current study used resting-state functional magnetic resonance imaging to assess changes in functional connectivity of the frontoparietal network, a brain network responsible for executive functioning, in collegiate club ice hockey players over one season. Each player was scanned before and after the season and wore accelerometers to measure head impacts at practices and home games throughout the season. We examined pre- to post-season differences in connectivity within the frontoparietal and default mode networks, as well as the relationship between the total number of head impacts sustained and changes in connectivity. We found a significant interaction between network region of interest and time point (p = .016), in which connectivity between the left and right posterior parietal cortex seed regions increased over the season (p < .01). Number of impacts had a significant effect on frontoparietal network connectivity, such that more impacts were related to greater connectivity differences over the season (p = .042). Overall, functional connectivity increased in ice hockey athletes over a season between regions involved in executive functioning, and sensory integration, in particular. Furthermore, those who sustained more impacts had the greatest changes in connectivity. Consistent with prior findings in resting-state sports-related head impact literature, these findings have been suggested to represent brain injury. Highlights: Functional connectivity of the frontoparietal network significantly increased between the pre- and post-season, which may be a compensatory mechanism driven by neural tissue injury caused by repetitive head impacts. Changes in frontoparietal network connectivity are related to head impact exposure, measured as the number of head impacts sustained in a single season. Functional connectivity of the default mode network did not change over an ice hockey season.
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.
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.
Biomechanical Analysis of Gait Termination in 11-17 Year Old Youth at Preferred and Fast Walking Speeds
(Elsevier, 2016-07-15) Ridge, Sarah Trager; Henley, John; Manal, Kurt; Miller, Freeman; Richards, James G.; Sarah Trager Ridge, John Henley, Kurt Manal, Freeman Miller, and James G. Richards; Ridge, Sarah Trager; Manal, Kurt; Richards, James G.
In populations where walking and/or stopping can be difficult, such as in children with cerebral palsy, the ability to quickly stop walking may be beyond the child’s capabilities. Gait termination may be improved with physical therapy. However, without a greater understanding of the mechanical requirements of this skill, treatment planning is difficult. The purpose of this study was to understand how healthy children successfully terminate gait in one step when walking quickly, which can be challenging even for healthy children. Lower extremity kinematic and kinetic data were collected from 15 youth as they performed walking, planned, and unplanned stopping tasks. Each stopping task was performed as the subject walked at his/her preferred speed and a fast speed. The most significant changes in mechanics between speed conditions (preferred and fast) of the same stopping task were greater knee flexion angles (unplanned: +16.49±.54°, p=.00; planned: +15.75±1.1°, p=.00) and knee extension moments (unplanned: +.67±.02 N/kgm, p=.00; planned: +.57±.23 N/kgm, p=.00) at faster speeds. The extra range of motion in the joints and extra muscle strength required to maintain the stopping position suggests that stretching and strengthening the muscles surrounding the joints of the lower extremity, particularly the knee, may be a useful intervention.
Brain Activation in the Prefrontal Cortex during Motor and Cognitive Tasks in Adults
(Scientific Research Publishing, 2016-11-03) Liang, Ling-Yin; Shewokis, Patricia A.; Getchell, Nancy; Ling-Yin Liang, Patricia A. Shewokis, Nancy Getchell; Getchell, Nancy
The prefrontal cortex (PFC) plays an important role in cognitive function, involved in Executive Functions (EFs) such as planning, working memory, and inhibition. Activation in the PFC also occurs during some motor activities. One commonly used tool to assess EF is the Tower of Hanoi, demonstrating sensitivity to PFC dysfunction. However, limited neuroimaging evidence is available to support the contribution of the PFC in the Tower of Hanoi task. In the current study, we use functional near infrared (fNIR) spectroscopy to examine hemodynamic responses associated with neural activity in the PFC in adults as they participate in the Tower of Hanoi task. We compared changes in cerebral oxygenation during resting, a motor task (tapping), and the Tower of Hanoi in 16 neurotypical adults, with measures of relative changes in concentration of oxygenated hemoglobin (Δoxy-Hb) and deoxygenated hemoglobin (Δdeoxy-Hb) taken throughout tasks, as well as total hemoglobin (ΔHbT) and oxygenation (Δoxy). Performance on the Tower of Hanoi was measured by the number of moves used to complete each level and the highest level of successful performance (3, 4, or 5 disks). We found a significant higher value of Δoxy-Hb and Δoxy in dorsolateral PFC (DLPFC) during the Tower of Hanoi as compared to tapping and resting. Significant changes in Δdeoxy-Hb and ΔHbT during the Tower of Hanoi were found in the right DLPFC only. These results support the notion that the Tower of Hanoi task requires higher levels of PFC activity than a similar motor task with low executive function demands.
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.
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.
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.
Concussion is not associated with elevated rates of lower-extremity musculoskeletal injuries in National Football League Players
(Physician and Sportsmedicine, 2022-05-27) Buckley, Thomas A.; Browne, Steven; Hunzinger, Katherine J.; Kaminski, Thomas W.; Swanik, Charles Buz
Objective: Emerging evidence has identified an ~2x elevated risk of musculoskeletal (MSK) injury in the year following a concussion. Most of these studies have examined a single college/university athletic department and may lack generalizability to professional sports. Therefore, the purpose of this study was to assess the odds of post-concussion MSK injury utilizing publicly available National Football League (NFL) injury reports. Methods: Concussions were identified through a review of published NFL injury reports during the 2015, 2016, and 2017 regular seasons. Concussed players were matched by team and position, and injuries were tracked for both groups for the remainder of the season. A chi-square analysis compared the frequency of MSK injury in both groups and a Cox Proportional Hazard model calculated the risk of sustaining a subsequent MSK injury. Results: There were 322 concussed NFL players who met inclusion criteria and were successfully matched. From the time of concussion through the remainder of the season, 21.4% of the concussed players were injured and 26.4% of control participants were injured. There was no difference in MSK injury rates (p = 0.166), and the relative risk ratio was 0.90 for subsequent injury in the concussion group. There was no difference in the time to event for subsequent MSK between the two groups (p = 0.123). Conclusion: The primary finding of this study was no elevated risk of post-concussion MSK in NFL football players.
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.
Control Strategy of Maximum Vertical Jumps: the Preferred Countermovement Depth May Not Be Fully Optimized for Jump Height
(De Gruyter Open, 2016-09-10) Mandic, Radivoj; Knezevic, Olivera M.; Mirkov, Dragan M.; Jaric, Slobodan; Radivoj Mandic, Olivera M. Knezevic, Dragan M. Mirkov, Slobodan Jaric; Jaric, Slobodan
The aim of the present study was to explore the control strategy of maximum countermovement jumps regarding the preferred countermovement depth preceding the concentric jump phase. Elite basketball players and physically active non-athletes were tested on the jumps performed with and without an arm swing, while the countermovement depth was varied within the interval of almost 30 cm around its preferred value. The results consistently revealed 5.1-11.2 cm smaller countermovement depth than the optimum one, but the same difference was more prominent in non-athletes. In addition, although the same differences revealed a marked effect on the recorded force and power output, they reduced jump height for only 0.1-1.2 cm. Therefore, the studied control strategy may not be based solely on the countermovement depth that maximizes jump height. In addition, the comparison of the two groups does not support the concept of a dual-task strategy based on the trade-off between maximizing jump height and minimizing the jumping quickness that should be more prominent in the athletes that routinely need to jump quickly. Further research could explore whether the observed phenomenon is based on other optimization principles, such as the minimization of effort and energy expenditure. Nevertheless, future routine testing procedures should take into account that the control strategy of maximum countermovement jumps is not fully based on maximizing the jump height, while the countermovement depth markedly confound the relationship between the jump height and the assessed force and power output of leg muscles.
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.
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.
Differential effects of obesity on visceral vs. subcutaneous adipose arteries: role of shear activated Kir2.1 and alterations to the glycocalyx
(American Journal of Physiology - Heart and Circulatory Physiology, 2022-01-07) Ahn, Sang Joon; Le Master, Elizabeth; Lee, James C.; Phillips, Shane A.; Levitan, Irena; Fancher, Ibra S.
Obesity imposes well-established deficits to endothelial function. We recently showed that obesity-induced endothelial dysfunction was mediated by disruption of the glycocalyx and a loss of Kir channel flow sensitivity. However, obesity-induced endothelial dysfunction is not observed in all vascular beds: visceral adipose arteries (VAAs), but not subcutaneous adipose arteries (SAAs), exhibit endothelial dysfunction. To determine whether differences in SAA versus VAA endothelial function observed in obesity are attributed to differential impairment of Kir channels and alterations to the glycocalyx, mice were fed a normal rodent diet, or a high-fat Western diet to induce obesity. Flow-induced vasodilation (FIV) was measured ex vivo. Functional downregulation of endothelial Kir2.1 was accomplished by transducing adipose arteries from mice and obese humans with adenovirus containing a dominant-negative Kir2.1 construct. Kir function was tested in freshly isolated endothelial cells seeded in a flow chamber for electrophysiological recordings under fluid shear. Atomic force microscopy was used to assess biophysical properties of the glycocalyx. Endothelial dysfunction was observed in VAAs of obese mice and humans. Downregulating Kir2.1 blunted FIV in SAAs, but had no effect on VAAs, from obese mice and humans. Obesity abolished Kir shear sensitivity in VAA endothelial cells and significantly altered the VAA glycocalyx. In contrast, Kir shear sensitivity was observed in SAA endothelial cells from obese mice and effects on SAA glycocalyx were less pronounced. We reveal distinct differences in Kir function and alterations to the glycocalyx that we propose contribute to the dichotomy in SAA versus VAA endothelial function with obesity. NEW & NOTEWORTHY: We identified a role for endothelial Kir2.1 in the differences observed in VAA versus SAA endothelial function with obesity. The endothelial glycocalyx, a regulator of Kir activation by shear, is unequally perturbed in VAAs as compared with SAAs, which we propose results in a near complete loss of VAA endothelial Kir shear sensitivity and endothelial dysfunction. We propose that these differences underly the preserved endothelial function of SAA in obese mice and humans.
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.
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.
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
Effects of Pre-Collegiate Sport Specialization on Cognitive, Postural, and Psychological Functions: Findings from the NCAA-DoD CARE Consortium
(International Journal of Environmental Research and Public Health, 2022-02-18) Chou, Tsung-Yeh; Caccese, Jaclyn B.; Huang, Yu-Lun; Glutting, Joseph J.; Buckley, Thomas A.; Broglio, Steven P.; McAllister, Thomas W.; McCrea, Michael A.; Pasquina, Paul F.; Kaminski, Thomas W.
Background: Early sport specialization has been associated with an increased risk of musculoskeletal injuries and unfavorable psychological outcomes; however, it is unknown whether sport specialization is associated with worse cognitive, postural, and psychological functions in first-year collegiate student-athletes. Methods: First-year collegiate multisport (MA) and single-sport (SA) student-athletes were identified using a pre-collegiate sport experience questionnaire. The cognitive, postural, and psychological functions were assessed by the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT), Standardized Assessment of Concussion (SAC), Balance Error Scoring System (BESS), and Brief Symptom Inventory 18 (BSI-18). Results: MA student-athletes performed higher in cognitive outcomes (e.g., higher ImPACT visual memory composite scores [ß = 0.056, p < 0.001]), but had higher psychological distress (e.g., higher BSI-18 global severity index [ß = 0.057, p < 0.001]) and no difference in postural stability (p > 0.05) than SA student-athletes. Conclusions: This study indicated first-year collegiate athletes with a history of sport specialization demonstrate lower cognitive performance but decreased psychological distress and no differences in static postural stability as compared to their MA counterparts. Future studies should consider involving different health measures to better understand the influence of sport specialization on overall physical and mental health.

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