<p>  </p> <p>The disruption of homeostasis in tendon extracellular matrix and altered biomechanical properties lead to poor tendon healing, creating a significant clinical challenge for millions of diabetics. Furthermore, improving blood glucose levels doesn't normalize tendon properties in diabetics. Diabetes-related tendon complications are often associated with advanced glycation end products (AGEs) crosslinking with collagen. However, recent studies have found no evidence of higher collagen crosslinking in diabetics and no correlation between tendon AGE content and tensile strength. The interaction between serum AGEs and AGE receptors (RAGE) is a less explored mechanism of AGE-mediated effects. People with diabetes are more likely to accumulate AGEs in their serum as a result of hyperglycemia, the consumption of AGE-rich foods, and diminished kidney clearance of AGEs. In previous studies, advanced glycation end-products (AGEs) have been shown to inhibit cell proliferation and migration, both of which are critical to tendon healing. We hypothesized that serum AGEs and activation of RAGE represent a mechanism underlying impaired tendon properties with diabetes. The increasing serum AGE levels would impair tendon biomechanical properties and tendon healing, while inhibition of RAGE [Azeliragon (AZ)] would improve tendon mechanics.</p> <p>Db/db mice with naturally elevated serum AGEs and impaired tendon function were treated daily with a RAGE inhibitor [Azeliragon (AZ), n=9] or vehicle (n=10) for three weeks. Patellar tendon stiffness and modulus were greater (p<0.05) in mice receiving AZ (stiffness: 9.6±1.2 N/mm, modulus: 78.2±8.2 MPa) compared to vehicle (5.8±0.9 N/mm, modulus: 49.0±8.3 MPa). Maximum strain (vehicle: 0.9±0.1, AZ: 0.8±0.05) and toughness (vehicle: 6.1±1.4, AZ: 6.5±1.2 J·m−3) were not different between groups (p>0.05). Maximum stress tended to be greater in the AZ group (vehicle: 14.6±2.4, AZ: 23.3±2.9 N/mm2, p=0.156).</p> <p>Ten-week-old non-diabetic mice were assigned to receive daily injections of bovine serum albumin (BSA-only, n=6), BSA and AZ (BSA-AZ, n=5), 200 mg/ml glycated BSA (AGE-BSA, n=4), and AGE with AZ (AGE-AZ, n=6). A full-thickness, partial-width defect was created in both patellar tendons. Treatments were started one week before surgery and continued for three weeks after surgery. Three Tendon stiffness was lower in mice treated with AGEs (p<0.05, 10.8±1.4 N/mm) compared to BSA-only (17.6±1.3 N/mm). Further, tendon stiffness in AGE-treated mice given AZ was not different from AGE-BSA (p<0.05, 12.7±1.8 N/mm). Tendon modulus was lower in mice treated with AGEs (p<0.05, 28.0±7.0 MPa) compared to BSA-only (63.5±9.0 MPa). Additionally, modulus in AGE-treated mice given AZ was not different from AGE-BSA (p>0.05, 47.6±10.4 N/mm). </p> <p>We demonstrate that administering a RAGE inhibitor improves tendon properties in an established mouse model for type 2 diabetes. In healthy mice, serum AGE levels inhibit the recovery of tendon biomechanical properties after injury; RAGE inhibitors did not have an effect on mice given AGEs. Based on these data, we suggest elevated serum AGEs, as seen with diabetes, are associated with poor mechanical properties and delayed tendon healing.</p>

No description available.

The primary purpose of this dissertation is to evaluate the effectiveness of a questionnaire designed to assess coaches’ perceptions of an athlete monitoring program. There are four reasons for this examination of perceptions: 1) it may serve as a check for understanding of how the coach takes in the information presented to them, 2) identify any gaps in the knowledge of the coach which the sport scientist may help to fill, 3) can serve to open a dialog with the coach for ways in which the information may be better tailored to help them improve their decision-making, and 4) the feedback provided can shed insight towards the areas a sport scientist can make more robust (e.g., delivery of information or structure of a training program). Coaches participating in the athlete monitoring program at East Tennessee State University’s (ETSU) Sport Performance Enhancement Group (SPEG) were invited to participate. There were no statistically significant differences between the pre- vs post- questionnaire responses. The secondary purpose of this dissertation is to examine the outcomes from the questionnaire and develop an understanding of the present responses. Considering the range of responses submitted by coaches, this serves as an indicator for the sport scientist/Strength & Conditioning Coach to prompt a dialog with the coach of the team they work with to better understand what else they may contribute towards enhancing the coach’s experience with such services. The tertiary goal of dissertation section is to provide practitioners who are interested in developing a sport scientist program for assessment of athletes with resources to better approach the logistics for developing their own system. Considerations included applying evidence-based practice, implementing precursor methods leading up to data collection (e.g., pre-testing certifications, lab set up, data collection, and testing protocols), approaching data collection (e.g., factors related to assessments, athletes, and additional considerations cover aspects of assessment validity and reliability), and potential assessment methods to consider (e.g., hydration, body composition, vertical jump height (VJH), and maximal strength).

Consumption of β-hydroxy β-methylbutyrate (HBM), a leucine metabolite, alters muscle composition and metabolism leading to strength and agility improvements in human athletes. To determine if HMB affects athletic performance and muscle function in horses, Thoroughbred geldings were fed a control (CON; n=5) or HMB (n=6) supplement (30 mg/kg/day) for 6 weeks prior to completing a standardized exercise test (SET). Gluteus medius (GM) muscle samples were obtained before the SET for fiber-typing and venous blood was collected before and immediately upon completion of the SET for lactate measurements. Heart rate (HR), biceps femoris (BF) and semitendinosus (ST) surface electromyograms, and fore- and hindlimb metacarpophalangeal joint angles were captured for the duration of the SET. Results demonstrate that HMB supplementation increased (P < 0.05) the percentage of type IIA muscle fibers in the GM with a corresponding decrease (P < 0.05) in type IIX fibers. The percentage of type I fibers was unaffected by diet. Supplementation with HMB did not result in any significant effects on performance, muscle function or biomechanical properties by comparison to CON. Increasing treadmill speed resulted in an increase (P < 0.05) in stride length and maximal extension angle of the fore fetlock, and a shortening (P < 0.05) of the stance phase of the gait cycle. Integrated EMG (iEMG) increased (P < 0.05) with increasing treadmill speeds for both the BF and ST, with the BF exhibiting greater iEMG values than the ST. In summary, HMB increased the percentage of type IIA fibers which did not translate into immediate, improved athletic performance / Master of Science / Muscles depend on their fibers, innervation, energy supply, and blood flow to contract. Failure to meet one or more of these requirements precludes muscle tissue from performing work, situation termed fatigue. Identification of fatigue indicators is of interest to the horse industry for a number of reasons, including horse and human safety, prevention of unnecessary expenses, and general public opinion of the sport disciplines. Diet supplementation with legal, performanceenhancing compounds is of interest to riders and horse owners alike. Molecules such as betahydroxy beta-methylbutyrate (HMB) improve muscle function, protein synthesis, and muscle tissue repair. Assessment of the athletic capacity and performance of horses by evaluating fatigue indicators favors responsible training regimes. Techniques to achieve this goal include muscle sampling, biochemical, electromyographic, and biomechanical analysis. We hypothesized that dietary supplementation of HMB would have positive effects on the athletic performance of horses. This study evaluated the effects of 45-day HMB supplementation on muscle fiber composition, muscle performance, and rates of fatigue in adult Thoroughbred horses by use of a high-speed treadmill. Muscle biopsies, blood lactate, high-speed video captures, and electromyography were analyzed. These analyses revealed that HMB supplementation increased the number of fatigue-resistant fibers in muscles but caused no substantial, immediate improvements on the athletic performance of horses.

<p>Functional limitations place youth with cerebral palsy (CP) at an increased risk of physical inactivity and cardiovascular disease. The structure and function of the cardiovascular system of these adolescents has not been previously investigated. In the current cross-sectional study, endothelial function was assessed using flow-mediated dilation (FMD) in eleven adolescents with CP (age 13.2 ± 2.1 y) and compared to eleven healthy, age-and gender-matched control participants (12.4 ± 2.3 y). All participants with CP were ambulatory or ambulatory with assistive devices (lower leg brace) and classified as levels I-II according to the Gross Motor Function Classification System (GMFCS). Baseline arterial stiffness was examined through assessment of central and peripheral pulse wave velocity (cPWV, pPWV,) as well as carotid distensibility, a direct measure of central artery stiffness. A combination of B-mode ultrasound imaging and applanation tonometry was used to calculate carotid distensibility. Carotid intima-media thickness (IMT), a measure of vascular structure, was also quantified using B-mode ultrasound images and a semi-automated edge detection software program. cPWV was calculated using the distance (carotid to femoral via the subtraction method) and time delay between ventricular depolarization and the foot of the femoral waveform. pPWV was calculated from the femoral to dorsalis pedis artery using the distance between each site and time delay between the arrival of the foot of each corresponding waveform. Physical activity (PA) levels were assessed using a 7-day recall questionnaire. Anthropometric measurements as well as measures of resting systolic, diastolic and mean arterial blood pressures were similar in both groups. There were no group differences (p>0.05) in ivabsolute, relative or normalized FMD responses. Both groups also had similar values of carotid IMT as well as all measures of arterial stiffness including carotid distensibility, cPWV and pPWV (p>0.05). No group differences were found in the amount of time spent in light and moderate intensity PA; however, the control group participated in a significantly greater amount of vigorous intensity PA (CON: 196 ± 174 min. vs. CP: 38 ± 80 min). Pearson correlation coefficients with all participants revealed a significant positive relationship between age and cPWV (r=0.485 p=0.026) and negative relationship with carotid compliance (r=-0.436, p=0.048). These findings indicate that the arterial structure and function of youth with CP (GMFCS level I-II), examined in this study are not different from a healthy control group. Future research should include youth with CP of GMFCS levels III-V to gain further insight into the potential consequences of severe mobility impairments and functional limitations on levels of habitual PA and arterial health in this young, clinical population.</p> / Master of Science (MSc)

<p>Chronic resistance training leads to muscle hypotrophy in a wide range of populations however most resistance training studies are relatively small in sample size</p> <p>Three studies were conducted to better understand the sources of this variability. The first study employed a unilateral resistance training model to test the effects of relative training load and volume on the magnitude of hypertrophy and strength gains. This study showed that high relative training loads were no better than low training loads at inducing muscle hypertrophy provided that each set was performed to the point of muscular exhaustion. In agreement with previous finding, strength gains were greatest with the highest loads.</p> <p>The next two studies attempted to correlate various putative regulators of muscle hypertrophy with the magnitude of hypertrophy after 16 weeks of training in 23 subjects. Study two showed no association between the acute responses of testosterone, GH or IGF-1 and muscle hypertrophy but did show associations with androgen receptor content and acute phosphorylation of p70S6K. This suggests that local rather than systemic processes are the most important regulators of muscle hypertrophy.</p> <p>The third study tested whether the acute post exercise protein synthetic response to a single bout of resistance exercise is related to the magnitude of hypertrophy following training in the same subjects. Although previous work has shown that acute post exercise protein synthetic response is qualitatively similar to the magnitude of hypertrophy after chronic training with similar manipulations in different subjects, we did not see any relationship.</p> / Doctor of Philosophy (PhD)

The aim of this study was to measure the degree of dehydration experienced during surf practice and examine the effect this might have on surfing performance, cognitive function and muscular endurance of elite surfers. Twelve male national and international level surfers volunteered to take part in the study. Their mean (± SD) age, body mass, height and surfing experience were 27.0 ± 3.3 years, 73.2 ± 7.1 kg, 1.7 ± 0.05 m and 21.0 ± 3.1 years, respectively. The participants were randomly assigned to one of two trials: no fluid ingestion (NF) or fluid ingestion (FI) during 100 min of surf practice in a steamer wetsuit. The experiment was designed to emulate not only the physical and cognitive demands of surfing but also the ambient environment in which it takes place. Before and immediately after surf practice, the participants had their hydration status measured, completed a cognitive test battery and upper and lower-body muscular endurance tests. Surfing performance was assessed during the first and last 20 min of practice. At the conclusion of the NF trial, participants showed a 3.9 ± 0.7% body mass (BM) loss, this was significantly greater (P < 0.05) than the 1.6 ± 0.7% BM loss seen at the end of the FI trial. In the NF trial, surfing performance decreased by 20.3 ± 7.1%, but showed a slight improvement in the FI trial (1.9 ± 10.2%). Of the six cognitive domains assessed (short-term memory, information processing speed, working memory, attention, visuomotor skill and visual acuity) all were significantly impaired when at a 3.9 ± 0.7% BM loss (P < 0.05) yet were unaffected at a 1.6 ± 0.7% BM loss. Information processing speed and working memory were the most strongly correlated to surfing performance (r = 0.74; P < 0.05). At the conclusion of the NF trial upper and lower-body muscular endurance were diminished by 21.2 ± 5.5% and 4.4 ± 5.8%, respectively. At the conclusion of the FI trial upper-body muscular endurance was reduced by 17.0 ± 4.1% while lower-body muscular endurance was marginally better (1 ± 3%). There was a significant difference in muscular endurance capacity between trials yet no significant correlation was observed between muscular endurance and surfing performance. The findings of this study suggest that surf practice for 100 min in a steamer wetsuit results in BM loss severe enough to significantly impair surfing performance, cognitive function and muscular endurance. Yet, when water is consumed during surf practice, surfing performance, cognitive function and lower body (but not upper-body) muscular endurance is maintained. Keywords: fluid ingestion, surf training, steamer wetsuit, hypohydration.

<p>Oxygen (O2) plays a crucial role in the energy metabolism of complex multicellular life on earth. Due to the small and finite energy stores in the body, fine-tuned changes within the body are required to meet metabolic demand during skeletal muscle contractions, such as during exercise and activities of daily living. The skeletal muscle microcirculation is one of the last steps in the O2 transport pathway from the lungs to muscle cells and represents the largest surface area for O2 and substrate exchange. When skeletal muscle O2 uptake increases during contractions to meet metabolic demand, there must be an increase in muscle O2 delivery. To achieve these elevations in O2 delivery, vessel (arteriole) diameter in the microcirculation is increased, known as vasodilation. This process in the skeletal muscle microcirculation is regulated by several factors, such as neurohumoral, mechanical, endothelial, paracrine, and metabolic influences, which are imperative in properly regulating O2 delivery at rest and during muscular contractions. Two vasodilatory pathways of interest in this dissertation are the cyclooxygenase (COX) and nitric oxide (NO) vasodilatory pathways.</p> <p>The primary aim of my dissertation studies was to determine the mechanisms that modulate skeletal muscle oxygenation in health and to define the impact of a potentially effective intervention, whole-body chronic heat therapy (HT), to treat heart failure with preserved ejection fraction (HFpEF). In Chapter 2, we report that acute selective COX-2 inhibition had no effect on resting or exercising skeletal muscle microvascular oxygenation, pulmonary oxygen uptake, or exercise tolerance in healthy young humans. In Chapter 3, we report that NO, via phosphodiesterase type 5 inhibition, regulates myocyte O2 transport at rest and during recovery from muscle contractions in healthy young rats. In Chapter 4, we show that whole-body chronic HT promotes central and peripheral adaptations, which impact positively exercise tolerance in a pre-clinical rat model of HFpEF. Specifically, whole-body chronic HT had beneficial influences on exercise tolerance, skeletal muscle oxygenation from rest to contractions (driven, at least in part, by enhanced NO bioavailability), body composition, and cardiac function. Chapter 5 is a summary of the results and limitations of the projects presented in Chapters 2-4, with a brief discussion of potential future research directions. </p>

<p>It is well established that physical activity can improve aspects of physical fitness in individuals with spinal cord injury (SCI). Despite reports of declining health and fitness post-discharge from rehabilitation, there is a limited amount of research exploring exercise status or interventions during this period. The purpose of this dissertation was to investigate the integration of structured exercise into the rehabilitation process following SCI, and to optimize the exercise prescription in the community setting. Findings from the first study indicated that exercise is well tolerated among individuals with sub-acute SCI; performance of a peak exercise test on an arm ergometer was feasible for all injury types. At this stage post-injury, interventions should be mindful of the greater risk of orthostatic intolerance in individuals with complete tetraplegia and focus on building task specific self-efficacy. The second study involved a direct referral and physical activity counselling intervention post-discharge. Adherence rates were excellent among those participants who received the intervention suggesting that this model of care can facilitate adherence to community exercise after discharge.</p> <p>The final two studies took place in the community. Several modes of adapted exercise were compared and findings indicated that while there were no differences in measures of physiological intensity or enjoyment between the different modes, arm-only exercise was perceived as safer than passive hybrid (arm and leg) exercise. Further, the validity of using ratings of perceived exertion (RPE) to attain prescribed exercise intensity was established. The efficacy of the physical activity guidelines for improving fitness in adults with SCI were evaluated in a community-based randomized controlled trial and the results revealed that the guidelines were effective in improving both aerobic capacity and muscle strength. Taken together, this series of studies describes a model of care that links rehabilitation with community exercise and suggests options for sustained engagement.</p> / Doctor of Philosophy (PhD)

Hyperkalemic periodic paralysis is characterized by myotonic discharges followed by paralysis. Caused by a mutation in the gene encoding for NaV1.4 channel, patients do not experience symptoms during infancy, but the onset starts between 1-10 years of age. The symptoms severity then increases with age until adolescence. A large increase in gene expression marked by an increase in oxidative capacity of muscles has also been reported in HyperKPP. It is possible that the onset of symptoms is related solely to NaV1.4 channel content/activity reaching a critical level. It is also possible that the onset of some symptoms are due to defective NaV1.4, while other symptoms and the increase in severity with age are related to changes in membrane components as a result of changes in gene expression. To test these possibilities, the progression of paralysis and changes in fiber types were followed with age in HyperKPP mice in relation to changes in NaV1.4 content and activity. Changes in fiber types (index of changes in gene expression), started after the onset of paralysis was observed, which coincided with NaV1.4 channels reaching maximum expression. Therefore, the onset of symptoms was related to defective NaV1.4 channels.