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- ItemPersonalized physiologic flow waveforms improve wave reflection estimates compared to triangular flow waveforms in adults(American Journal of Physiology - Heart and Circulatory Physiology, 2021-04-21) Shenouda, Ninette; Stock, Joseph M.; Patik, Jordan C.; Chirinos, Julio A.; Edwards, David G.Central aortic pressure waveforms contain valuable prognostic information in addition to central systolic pressure. Using pressure-flow relations, wave separation analysis can be used to decompose aortic pressure waveforms into forward- (Pf) and backward-traveling (Pb) components. Reflection magnitude, the ratio of pressure amplitudes (RM = Pb/Pf), is a predictor of heart failure and all-cause mortality. Aortic flow can be measured via Doppler echocardiography or estimated using a triangular flow waveform; however, the latter may underestimate the flow waveform convexity and overestimate Pb and RM. We sought to determine the accuracy of a personalized synthetic physiologic flow waveform, compared with triangular and measured flow waveforms, for estimating wave reflection indices in 49 healthy young (27 ± 6 yr) and 29 older adults [66 ± 6 yr; 20 healthy, 9 chronic kidney disease (CKD)]. Aortic pressure and measured flow waveforms were acquired via radial tonometry and echocardiography, respectively. Triangular and physiologic flow waveforms were constructed from aortic pressure waveforms. Compared with the measured flow waveform, the triangular waveform underestimated Pf in older, but not young, adults and overestimated Pb and RM in both groups. The physiologic waveform was equivalent to measured flow in deriving all wave reflection indices and yielded smaller mean absolute biases than the triangular waveform in all instances (P < 0.05). Lastly, central pulse pressure was associated with triangular, but not physiologic, mean biases for Pb and RM independent of age or central arterial stiffness (P < 0.05). These findings support the use of personalized physiologic flow waveforms as a more robust alternative to triangular flow waveforms when true flow cannot be measured. NEW & NOTEWORTHY We demonstrate that triangular flow waveforms overestimate wave reflection indices, particularly at higher central pulse pressures independent of age or carotid-femoral pulse wave velocity. In contrast, personalized physiologic flow waveforms provide equivalent wave reflection estimates as measured flow waveforms, thereby offering a more robust alternative to triangulation when aortic flow cannot be measured.
- ItemMechanisms of injury for concussions in collegiate soccer: an NCAA/DoD CARE consortium study(Science and Medicine in Football, 2021-10-13) Kaminski, Thomas W.; Chrisman, Sara P. D.; Glutting, Joseph; Wahlquist, Victoria; Eagle, Shawn; Putukian, Margot; Tierney, Ryan; Broglio, Steven P.; McAllister, Thomas W.; McCrea, Michael A.; Pasquina, Paul F.; Kontos, Anthony P.; CARE Site InvestigatorsOver 9,000 concussions occur annually in intercollegiate soccer in the United States with little known about the incidence of mechanisms (e.g., collisions) and possible factors (e.g., sex) associated with each mechanism. Objective: The purpose of this study was to describe the mechanism of injury (MOI) and examine factors associated with greater risk for specific MOIs involving concussions in collegiate soccer players. Methods: Participants included 3,288 collegiate soccer players from 28 institutions across four competitive seasons, 2014–17. MOIs were documented for 262 soccer-related concussions during the study and placed into one of four categories: collisions, unintentional contact, aerial challenges, and others. Results: 70% of the concussions occurred in DI soccer players. Collisions and unintentional contact were the MOIs that resulted in 66.5% of all concussions. DI and DIII soccer players sustained more concussions by unintentional contact versus collisions and aerial challenges when compared to their DII counterparts. Defenders were more likely than midfielders to sustain concussions by aerial challenges than collisions. As expected, the field players experienced more concussions as a result of collisions, unintentional contact, and aerial challenges when compared to goalkeepers. Conclusions: Future research should explore preventive strategies for decreasing collisions, especially during aerial challenges while heading the soccer ball, and unintentional contacts from errant balls in soccer in order to decrease concussion risk.
- ItemEvidence of reduced peripheral microvascular function in young Black women across the menstrual cycle(Journal of Applied Physiology, 2021-12-01) D’Agata, Michele N.; Hoopes, Elissa K.; Berube, Felicia R.; Hirt, Alexandra E.; Kuczmarski, Andrew V.; Ranadive, Sushant M.; Wenner, Megan M.; Witman, Melissa A.Black women (BLW) have a higher prevalence of cardiovascular disease (CVD) morbidity and mortality compared with White women (WHW). A racial disparity in CVD risk has been identified early in life as young adult BLW demonstrate attenuated vascular function compared with WHW. Previous studies comparing vascular function between premenopausal WHW and BLW have been limited to the early follicular (EF) phase of the menstrual cycle, which may not reflect their vascular function during other menstrual phases. Therefore, we evaluated peripheral microvascular function in premenopausal WHW and BLW using passive leg movement (PLM) during three menstrual phases: EF, ovulation (OV), and mid-luteal (ML). We hypothesized that microvascular function would be augmented during the OV and ML phases compared with the EF phase in both groups, but would be attenuated in BLW compared with WHW at all three phases. PLM was performed on 26 apparently healthy premenopausal women not using hormonal contraceptives: 15 WHW (23 ± 3 yr), 11 BLW (24 ± 5 yr). There was a main effect of race on the overall change in leg blood flow (ΔLBF) (P = 0.01) and leg blood flow area under the curve (LBF AUC) (P = 0.02), such that LBF was lower in BLW. However, there was no effect of phase on ΔLBF (P = 0.69) or LBF AUC (P = 0.65), nor an interaction between race and phase on ΔLBF (P = 0.37) or LBF AUC (P = 0.75). Despite peripheral microvascular function being unchanged across the menstrual cycle, a racial disparity was apparent as microvascular function was attenuated in BLW compared with WHW across the menstrual cycle. NEW & NOTEWORTHY: This is the first study to compare peripheral microvascular function between young, otherwise healthy Black women and White women at multiple phases of the menstrual cycle. Our novel findings demonstrate a significant effect of race on peripheral microvascular function such that Black women exhibit significant attenuations in microvascular function across the menstrual cycle compared with White women.
- ItemKnee joint biomechanics during gait improve from 3 to 6 months after anterior cruciate ligament reconstruction(Journal of Orthopaedic Research, 2022-01-06) Neal, Kelsey; Williams, Jack R.; Alfayyadh, Abdulmajeed; Capin, Jacob J.; Khandha, Ashutosh; Manal, Kurt; Snyder‐Mackler, Lynn; Buchanan, Thomas S.Gait alterations after anterior cruciate ligament reconstruction (ACLR) are commonly reported and have been linked to posttraumatic osteoarthritis development. While knee gait alterations have been studied at several time points after ACLR, little is known about how these biomechanical variables change earlier than 6 months after surgery, nor is much known about how they differ over the entire stance phase of gait. The purpose of this study was to examine knee gait biomechanical variables over their entire movement pattern through stance at both 3 and 6 months after ACLR and to study the progression of interlimb asymmetry between the two postoperative time points. Thirty-five individuals underwent motion analysis during overground walking 3 (3.2 ± 0.5) and 6 (6.4 ± 0.7) months after ACLR. Knee biomechanical variables were compared between limbs and across time points through 100% of stance using statistical parametric mapping; this included a 2 × 2 (Limb × Time) repeated measures analysis of variance and two-tailed t-tests. Smaller knee joint angles, moments, extensor forces, and medial compartment forces were present in the involved versus uninvolved limb. Interlimb asymmetries were present at both time points but were less prevalent at 6 months. The uninvolved limb's biomechanical variables stayed relatively consistent over time, while the involved limb's trended toward that of the uninvolved limb. Statement of Clinical Significance: Interventions to correct asymmetrical gait patterns after ACLR may need to occur early after surgery and may need to focus on multiple parts of stance phase.
- ItemDifferential 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.
- ItemEffects 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.
- ItemImpact of angiotensin receptor–neprilysin inhibition on vascular function in heart failure with reduced ejection fraction: A pilot study(Physiological Reports, 2022-03-05) Nathaniel, Sangeetha; McGinty, Shane; Witman, Melissa A. H.; Edwards, David G.; Farquhar, William B.; Hosmane, Vinay; Wenner, Megan M.The mechanisms for the benefits of Angiotensin Receptor Neprilysin Inhibition (ARNi) in heart failure patients with reduced ejection fraction (HFrEF) are likely beyond blood pressure reduction. Measures of vascular function such as arterial stiffness and endothelial function are strong prognostic markers of cardiovascular outcomes in HFrEF, yet the impact of ARNi on vascular health remains to be explored. We hypothesized that arterial stiffness and endothelial function would improve after 12 weeks of ARNi in HFrEF. We tested 10 stable HFrEF patients at baseline and following 12 weeks of ARNi [64 ± 9 years, Men/Women: 9/1, left ventricular ejection fraction (EF): 28 ± 6%] as well as 10 stable HFrEF patients that remained on conventional treatment (CON: 60 ± 7 years, Men/Women: 6/4, EF: 31 ± 5%; all p = NS). Arterial stiffness was assessed via carotid-femoral pulse wave velocity (PWV) and endothelial function was assessed via brachial artery flow-mediated dilation (FMD). PWV decreased after 12 weeks of ARNi (9.0 ± 2.1 vs. 7.1 ± 1.2 m/s; p < 0.01) but not in CON (7.0 ± 2.4 vs. 7.5 ± 2.3 m/s; p = 0.35), an effect that remained when controlling for reductions in mean arterial pressure (p < 0.01). FMD increased after 12 weeks of ARNi (2.2 ± 1.9 vs. 5.5 ± 2.1%; p < 0.001) but not in CON (4.8 ± 3.8 vs. 5.4 ± 3.4%; p = 0.34). Baseline PWV (p = 0.06) and FMD (p = 0.07) were not different between groups. These preliminary data suggest that 12 weeks of ARNi therapy may reduce arterial stiffness and improve endothelial function in HFrEF. Thus, the findings from this pilot study suggest that the benefits of ARNi are beyond blood pressure reduction and include improvements in vascular function. New & Noteworthy: Twelve weeks of ARNi therapy may reduce arterial stiffness (assessed by carotid-femoral PWV) and improve endothelial function (assessed by brachial artery FMD) in HFrEF when compared to conventional treatment. Improvement in vascular function may be a physiological mechanism for the clinical benefit seen with ARNi in HFrEF. Moreover, these pleiotropic benefits of ARNi beyond BP lowering may be vital for the treatment of HFrEF and possibly other cardiovascular diseases.
- ItemRelationships between aggression, sensation seeking, brain stiffness, and head impact exposure: Implications for head impact prevention in ice hockey(Brain and Behavior, 2022-04-23) DiFabio, Melissa S.; Smith, Daniel R.; Breedlove, Katherine M.; Buckley, Thomas A.; Johnson, Curtis L.Objectives: The objectives of this study were to (1) examine the relationship between the number of head impacts sustained in a season of men's collegiate club ice hockey and behavioral traits of aggression and sensation seeking, and (2) explore the neural correlates of these behaviors using neuroimaging. Design: Retrospective cohort study. Methods: Participants (n = 18) completed baseline surveys to quantify self-reported aggression and sensation-seeking tendencies. Aggression related to playing style was quantified through penalty minutes accrued during a season. Participants wore head impact sensors throughout a season to quantify the number of head impacts sustained. Participants (n = 15) also completed baseline anatomical and magnetic elastography neuroimaging scans to measure brain volumetric and viscoelastic properties. Pearson correlation analyses were performed to examine relationships between (1) impacts, aggression, and sensation seeking, and (2) impacts, aggression, and sensation seeking and brain volume, stiffness, and damping ratio, as an exploratory analysis. Results: Number of head impacts sustained was significantly related to the number of penalty minutes accrued, normalized to number of games played (r = .62, p < .01). Our secondary, exploratory analysis revealed that number of impacts, sensation seeking, and aggression were related to stiffness or damping ratio of the thalamus, amygdala, hippocampus, and frontal cortex, but not volume. Conclusions: A more aggressive playing style was related to an increased number of head impacts sustained, which may provide evidence for future studies of head impact prevention. Further, magnetic resonance elastography may aid to monitor behavior or head impact exposure. Researchers should continue to examine this relationship and consider targeting behavioral modification programs of aggression to decrease head impact exposure in ice hockey.
- ItemAltered 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.
- ItemExamining the influence of the Get aHEAD Safely in Soccer™ program on head impact kinematics and neck strength in female youth soccer players(Research in Sports Medicine, 2022-05-24) Wahlquist, Victoria E.; Glutting, Joseph J.; Kaminski, Thomas W.The objective was to examine the efficacy of the Get aHEAD Safely in Soccer™ intervention on head impact kinematics and neck strength in female youth soccer players. The control group (CG) consisted of 13 players (age: 11.0 ± 0.4 yrs), while the experimental group (EG) consisted of 14 players (age: 10.6 ± 0.5 yrs). Head impact kinematics included peak linear acceleration (PLA), peak rotational acceleration (PRA), and peak rotational velocity (PRV). Pre- and post-season measures included strength measures of neck/torso flexion (NF/TF) and extension (NE/TE). Data were analysed using a multilevel linear model and ANOVA techniques. No differences in PLA, PRA, or PRV were observed between groups. The EG showed significant improvement in NF strength while the CG showed significant improvement in NE strength. Both groups significantly improved in TF pre- to post-season. The foundational strength components of the Get aHEAD Safely in Soccer program appear to show a benefit in youth soccer players beginning to learn the skill of purposeful heading.
- ItemConcussion 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 BuzObjective: 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.
- ItemNational Collegiate Athletic Association athletic trainers’ response to the Arrington settlement: management, compliance, and practice patterns(The Physician and Sportsmedicine, 2022-09-05) Buckley, Thomas A.; Bryk, Kelsey N.; Hunzinger, Katherine J.; Costantini, KatelynThe primary purpose of this study was to assess Athletic Trainers’ (ATs) report of NCAA member institution compliance with the Arrington settlement, the concussion lawsuit vs. the NCAA, and to elucidate compliance predictors. A secondary purpose was to provide a contemporary concussion management clinical practice pattern description among NCAA collegiate athletic trainers. Head Athletic Trainers from NCAA Division I, II, and III completed an electronic questionnaire in August 2020 regarding their institution’s response to the Arrington Settlement and their current concussion management clinical practice patterns. The 37-item questionnaire included AT and institution demographics, current concussion management policies, and response to the Arrington settlement with a specific focus on the five settlement requirements. An overall compliance score on the five requirements, compliance on the individual requirements, and concussion management practices are reported with descriptives. Regression was used to identify specific predictors of both overall and individual settlement requirements. An ANOVA compared compliance by NCAA division level. Being pressured to be non-compliant was assessed between sexes by a chi-square. There were 223 respondents (21.8%), and overall compliance was high (4.1 ± 0.7) with the five required Arrington Settlement components. Settlement requirement 1, pre-season baseline testing, and requirement 5, presence of trained personnel at all contact sport practices, had the lowest compliance rates at 44.8% and 73.3%, respectively. The number of sports the institution offered was the only significant predictor of each requirement. There was no difference in compliance between NCAA divisions. Although the overall rate of being non-compliant pressure was low (13.8%), females were 3.28x more likely report being pressured than males. NCAA institutions are generally compliant with the Arrington settlement; however, lack of clarity in the requirements, particularly requirement 1, raises potential concerns. Concussion management practices continue to incorporate multifaceted approaches and are largely consistent with current best practices.
- ItemMetatarsophalangeal Joint Dynamic Stiffness During Toe Rocker Changes With Walking Speed(Journal of Applied Biomechanics, 2022-09-12) Nigro, Luke; Arch, Elisa S.Dynamic joint stiffness (or simply “stiffness”) is a customization criteria used to tune mechanical properties of orthotic and prosthetic devices. This study examines metatarsophalangeal (MTP) joint stiffness during the toe-rocker phase of barefoot walking and establishes baseline characteristics of MTP joint stiffness. Ten healthy individuals walked at 4 speeds (0.4, 0.6, 0.8, and 1.0 statures·s−1) over level ground. MTP sagittal plane joint angles and moments were calculated during the toe-rocker phase of stance. Least-squares linear regressions were conducted on the MTP moment versus angle curve to determine joint stiffness during early toe rocker and late toe rocker. Multilevel linear models were used to test for statistically significant differences between conditions. Early toe rocker stiffness was positive, while late toe rocker was negative. Both early toe rocker and late toe rocker stiffness increased in magnitude significantly with speed. This study establishes baseline characteristics of MTP joint stiffness in healthy walking, which previously had not been examined through a range of controlled walking speeds. This information can be used in the future as design criteria for orthotic and prosthetic ankle and ankle–foot devices that can imitate, support, and facilitate natural human foot motion during walking better than existing devices.
- ItemAssociations 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.
- ItemStress deprivation of tendon explants or Tpm3.1 inhibition in tendon cells reduces F-actin to promote a tendinosis-like phenotype(Molecular Biology of the Cell, 2022-12-01) Inguito, Kameron L.; Schofield, Mandy M.; Faghri, Arya D.; Bloom, Ellen T.; Heino, Marissa; West, Valerie C.; Ebron, Karl Matthew M.; Elliot, Dawn M.; Parreno, JustinActin is a central mediator between mechanical force and cellular phenotype. In tendons, it is speculated that mechanical stress deprivation regulates gene expression by reducing filamentous (F)-actin. However, the mechanisms regulating tenocyte F-actin remain unclear. Tropomyosins (Tpms) are master regulators of F-actin. There are more than 40 Tpm isoforms, each having the unique capability to stabilize F-actin subpopulations. We investigated F-actin polymerization in stress-deprived tendons and tested the hypothesis that stress fiber–associated Tpm(s) stabilize F-actin to regulate cellular phenotype. Stress deprivation of mouse tail tendon down-regulated tenogenic and up-regulated protease (matrix metalloproteinase-3) mRNA levels. Concomitant with mRNA modulation were increases in G/F-actin, confirming reduced F-actin by tendon stress deprivation. To investigate the molecular regulation of F-actin, we identified that tail, Achilles, and plantaris tendons express three isoforms in common: Tpm1.6, 3.1, and 4.2. Tpm3.1 associates with F-actin in native and primary tenocytes. Tpm3.1 inhibition reduces F-actin, leading to decreases in tenogenic expression, increases in chondrogenic expression, and enhancement of protease expression in mouse and human tenocytes. These expression changes by Tpm3.1 inhibition are consistent with tendinosis progression. A further understanding of F-actin regulation in musculoskeletal cells could lead to new therapeutic interventions to prevent alterations in cellular phenotype during disease progression.
- ItemSex differences in microvascular function and arterial hemodynamics in nondialysis chronic kidney disease(American Journal of Physiology - Heart and Circulatory Physiology, 2022-12-01) Kirkman, Danielle L.; Ramick, Meghan G.; Muth, Bryce J.; Stock, Joseph M.; Townsend, Raymond R.; Edwards, David G.Cardiovascular disease (CVD) is the leading cause of death in chronic kidney disease (CKD). Abnormal arterial hemodynamics contribute to CVD, a relationship that can be mediated by microvascular dysfunction. The purpose of this study was to investigate potential sex differences in arterial hemodynamics and microvascular dysfunction in patients with stages 3 to 4 CKD. Vascular function was assessed in 22 male (mean ± SD; age, 56 ± 13 yr) and 10 female (age, 63 ± 9 yr) patients. Arterial hemodynamics were acquired with combined tonometry and oscillometry. Skin blood flow was used as a model of microvascular function. Participants were instrumented with three microdialysis fibers for the delivery of 1) Ringer’s solution; 2) superoxide dismutase mimetic, Tempol; and 3) nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, apocynin. Blood flow was measured via laser-Doppler flowmetry during standardized local heating (42°C). Central pulse pressure (mean ± SE; 62 ± 9 vs. 46 ± 3 mmHg; P = 0.01) and augmentation index (36 ± 3 vs. 26 ± 3%; P = 0.03) were higher in females. There was a trend for higher central systolic pressures in females (146 ± 9 vs. 131 ± 3 mmHg; P = 0.06). Females reported higher forward (39 ± 4 vs. 29 ± 2 mmHg; P = 0.004) and reflected (27 ± 3 vs. 19 ± 1 mmHg; P < 0.001) wave amplitudes. Cutaneous vascular function was impaired in females compared with males (77 ± 3 vs. 89 ± 1%, P = 0.001). Microvascular function was improved following the delivery of Tempol and apocynin in females but not in males. Female patients with CKD had poorer central hemodynamics and reduced microvascular function compared with their male counterparts. Oxidative stress may contribute to lower microvascular function observed in females. NEW & NOTEWORTHY There are limited data regarding the physiological mechanisms of potential sex differences in central hemodynamics and vascular function in chronic kidney disease (CKD). We report that older female patients with nondialysis CKD have higher central pulse pressures compared with male patients with CKD. In addition, older females with CKD have lower microvascular function compared with their male counterparts, and oxidative stress contributes to the lower microvascular function in older female patients with CKD.
- ItemOral nicotinamide riboside raises NAD+ and lowers biomarkers of neurodegenerative pathology in plasma extracellular vesicles enriched for neuronal origin(Aging Cell, 2023-01-12) Vreones, Michael; Mustapic, Maja; Moaddel, Ruin; Pucha, Krishna A.; Lovett, Jacqueline; Seals, Douglas R.; Kapogiannis, Dimitrios; Martens, Christopher R.Declining nicotinamide adenine dinucleotide (NAD+) concentration in the brain during aging contributes to metabolic and cellular dysfunction and is implicated in the pathogenesis of aging-associated neurological disorders. Experimental therapies aimed at boosting brain NAD+ levels normalize several neurodegenerative phenotypes in animal models, motivating their clinical translation. Dietary intake of NAD+ precursors, such as nicotinamide riboside (NR), is a safe and effective avenue for augmenting NAD+ levels in peripheral tissues in humans, yet evidence supporting their ability to raise NAD+ levels in the brain or engage neurodegenerative disease pathways is lacking. Here, we studied biomarkers in plasma extracellular vesicles enriched for neuronal origin (NEVs) from 22 healthy older adults who participated in a randomized, placebo-controlled crossover trial (NCT02921659) of oral NR supplementation (500 mg, 2x /day, 6 weeks). We demonstrate that oral NR supplementation increases NAD+ levels in NEVs and decreases NEV levels of Aβ42, pJNK, and pERK1/2 (kinases involved in insulin resistance and neuroinflammatory pathways). In addition, changes in NAD(H) correlated with changes in canonical insulin–Akt signaling proteins and changes in pERK1/2 and pJNK. These findings support the ability of orally administered NR to augment neuronal NAD+ levels and modify biomarkers related to neurodegenerative pathology in humans. Furthermore, NEVs offer a new blood-based window into monitoring the physiologic response of NR in the brain.