Spatial coordination of bimanual movements is important when performing daily activities. Whereas, older adults and individuals with Parkinsons disease (PD) commonly show difficulties in temporally coordinating the hands in bimanual coordination tasks, the effects of aging and Parkinsons disease on the quality of spatial coordination between the hands are unclear. Thus, the present work investigated the impact of older age and PD on the spatial interference in a bimanual task in which 48 right hand-dominant participants (16 young adults, 16 older adults and 16 individuals with PD) drew simultaneously two lines with both hands with varied movement amplitudes (3 and 6 cm) and/or directions (horizontal and vertical). The dependent variables were amplitude error of the line drawn with the right hand (A-error-R), amplitude error of the line drawn with the left hand (A-error-L), directional error of the line drawn with the right hand (D-error-R) and directional error of the line drawn with the left hand (D-error-L). The results showed that older adults were able to maintain a similar level of spatial accuracy on the dominant side as young adults, but they showed reduced spatial accuracy when using the non-dominant hand. Furthermore, advanced age altered the control of movement direction in the bimanual coordination task, but not the control of movement amplitude. These results indicate that, the effects of the use of a longer standard spatial code for movement amplitude did not change in older adults, but older age does alter the control of direction in bimanual movements. Individuals with Parkinsons disease and older adults showed similar levels of spatial accuracy, except for the directional accuracy of the lines drawn with the dominant hand; these lines showed angles with the target direction were increased about two degree in the PD group as compared to older control group. In summary, the quality of spatial coordination declined only in part in older adults, and the decline in the quality of spatial coordination was not exacerbated in individuals with PD, indicating the divergent role of basal ganglia for the control of temporal and spatial aspects.

Scholars have argued that athletics are utilized by universities to advertise their school to all individuals (Collins, 2012; Dwyer, Eddy, Havard, & Braa, 2010; Toma & Cross, 1998; Washington & Ventresca, 2004; Weaver, 2010). Expectedly, university officials are willing to contribute resources in order to develop an effective athletics program to establish an institutions legitimacy among other universities (Collins, 2012; Toma & Cross, 1998; Washington & Ventresca, 2004). One tactic employed by schools focuses on the process of athletic association reclassification into the National Collegiate Athletic Association (NCAA) from other member associations (e.g., National Association for Intercollegiate Athletics). Officials consider this move due to the NCAAs identity as the premiere intercollegiate athletic association. As such, studies on college movement recognized that universities are more likely to move to the NCAA if other universities with shared characteristics have reclassified in order to become legitimate among peers (Smith, Williams, Soebbing, & Washington, 2013; Washington, 2004; 2004-05). However, research has not been conducted to estimate the quantity and duration of a potential 'reclassification' effect. The purpose of this dissertation is to determine if a change in athletic association will increase the number of application receives after reclassification. The dissertation analyzes this phenomenon through the movement of former NAIA member schools from 1959 to 2012 to the NCAA.

Abstract Purpose: To determine effects of 8 wks of progressive whole-body training preceded by 4 wks of regional specific (RSTS) or aerobic training (AT), on bone mineral density (BMD). Methods: Subjects were over age 70 y, with a 6-min walk score of 218-490 m. Subjects were randomized to AT or RSTS for the first 4 wks (Phase 1). AT consisted of ~45 min of walking/biking (50-85% HR reserve), 3 d/wk. RSTS consisted of 8 exercises specific to major muscle groups and was performed for 3-5 min, at ~40-70% of max voluntary strength for ~45 min, 3 d/wk. After 4 wks, all subjects were advanced to a whole-body program using established guidelines (Phase 2). Bone mineral density of the lumbar and thoracic spine and pelvis was examined before training, after 4 wks, and after 12 wks, using Dual-energy X-ray absorptiometry (DXA). Results Analysis showed a significant time effect for lumbar, thoracic, and pelvis BMD (p<0.05, 0.05, and 0.01, respectively); however, group by time interactions were found only for thoracic and lumbar BMD (p<0.05, p<0.10, respectively). Post hoc analysis revealed a significant difference for thoracic BMD at 12 wks compared to 4 wks and baseline for RSTS while AT showed no significant changes in thoracic or lumbar BMD. A significant increase of 3.2% from baseline for RSTS was found for lumbar BMD after only 4 wks. Conclusion Preceding well-rounded training with RSTS proved beneficial with respect to thoracic and lumbar BMD. The rapid time course for change in lumbar BMD may support the use of RSTS when trying to reduce fracture risk in a short time frame.

Effect of a Specific Respiratory Warm-up on Run Performance, Pulmonary Functions, and Rating of Perceived Breathing The purpose of this study was to evaluate the effect of a respiratory warm-up for five minutes using an inspiratory/expiratory (IEC) device on pulmonary function (PFT) (FVC, FEV©û, FEF 25-75%, PEF), rate of perceived exertional (RPE) breathing, and performance time [300 yard shuttle run (300y) and 1.5 mile run (1.5m)] in asthmatics and non-asthmatics. Ten non-asthmatics males (22.6¡¾7.4 years) participated in phase I, twenty non-asthmatic males (24.2¡¾9.8 years) in phase II, and five asthmatics (20.8¡¾3.2 years) in phase III of this study. The Phase I pilot study examined three breathing warm-up (inspiratory only, expiratory only, and combined IEC). Results suggest the IEC produced the most favorable responses (greatest system stress, highest recovery data). In phase II and III, subjects performed initial resting PFT (asthmatics performed an additional five-minute post medication resting PFT), followed by five-minutes of a no-warm-up controlled condition (CC) or five-minutes of IEC. After completion of the CC or the IEC, subjects rested for five-minutes and then performed either a 300y or a 1.5m for time. After the runs, subjects performed one-minute recovery intervals of PF and RPE up to 15-minutes as well as five-minute intervals of PFT up to 15-minutes. Paired sample t-tests were calculated to compare CC to IEC across the two runs with statistical significance for these correlations set at p ¡Â 0.05*. The results indicated that non-asthmatics benefited from the IEC and improved performance by 3.2% (average of 25 seconds) in the 1.5m over the CC [M=13.1075 v. 12.6830, SD=2.19429 v. 1.85474, p= 0.044*]. Asthmatics increased their FEV©û at five-minutes of recovery after the IEC verses the CC for the 1.5m [M=3.3120 v. 3.4280, SD=0.51339 v. 0.54929, p= 0.019*]. The results suggest that a respiratory warm-up could be beneficial by improved performance and increased pulmonary functions to asthmatics and non-asthmatics alike.

Background/Objectives: Low areal bone mineral density (aBMD) of the hip and knee region has been associated with fracture risk in individuals with SCI; however the contribution of bone micro-architecture to fracture risk has not been evaluated. The primary objective of this study was to determine whether a relationship exists between indices of bone strength (aBMD at the distal femur and proximal tibia; trabecular vBMD; average hole size, HA; cortical thickness, CTh; buckling ratio, BR; cross-sectional moment of inertia, CSMI; and polar moment of inertia, PMI) and potential fracture risk factors (gender, age, bisphosphonate use, time post-injury, fractures, and completeness of injury). The secondary objectives were to 1) determine whether indices of bone strength can discriminate between SCI patients with and without fragility fractures; 2) determine if these indices of bone strength correlate with the number of fractures sustained; and 3) determine the proportion of individuals with SCI who have a trabecular vBMD at the ultra-distal tibia that is below 72mg/cm3. Materials and Methods: A nested case-control study was performed. Forty seven men (n=33) and women (n=14) with chronic SCI (C2-T12 AIS A-D) with a duration of paralysis of at least two years were included in this study. Subjects with SCI were questioned about the cause, location, and time of the lower extremity fragility fractures. Fracture presence was verified by x-rays. aBMD of the distal femur and proximal tibia were determined using dual energy x-ray absorptiometry (DXA). Trabecular volumetric bone mineral density (vBMD) and HA were measured at 4% of the tibia length, and CTh, BR, CSMI, and PMI were measured at 66% of the tibia length of individuals with chronic SCI using peripheral quantitative computed tomography (pQCT). Linear and multiple regression models were used to determine significant correlates (age, gender, completeness of injury, duration of injury, bisphosphonate use, and fractures) of indices of bone strength, while logistic regression was used to assess the relationship between indices of bone strength and fragility fractures. To assess the relationship between multiple fragility fractures and indices of bone strength, a poisson regression analysis was performed. Results: Risk factors found to be related to the indices of bone strength include gender, completeness of injury, duration of injury, bisphosponate use, and prior fractures. An increase in HA (OR=1.081, 95% CI=1.001-1.166, p=0.0470), a decrease in aBMD in the distal femur (OR=0.988, 95% CI=0.978-0.998, p=0.0226), and a decrease in CSMI (OR=0.098, 95% CI=0.012-0.838), p=0.0338) were associated with fractures. Fractures were not associated with aBMD at the proximal tibia, trabecular vBMD, CTh, or BR. The poisson regression model predicting the number of fragility fractures sustained among individuals with chronic SCI from aBMD, vBMD, HA, CTh, CSMI, PMI, and BR were each statistically significant. Finally, only 7.7% of our population had a trabecular vBMD fracture threshold of less than or equal to 72mg/cm3. We found a trabecular vBMD fracture breaking point of approximately 126mg/cm3 and 115mg/cm3 at the ultra distal tibia in individuals with complete and incomplete SCI, respectively. Conclusion: Specific bone strength measures, specifically aBMD at the distal femur, HA, and CSMI are associated with fracture risk and may improve our ability to identify individuals with SCI at high risk of fracture. Larger population based studies are needed to determine the most appropriate risk factors that contribute to bone loss and understand the role and importance of these and other indices of bone strength on skeletal fragility in individuals with SCI.

Essential hypertension is a disease involving impaired endothelium-dependant vasomotor function which is partially mediated through an increase in reactive oxygen species. Recent evidence has demonstrated that resveratrol (RSV), a polyphenol with antioxidant capabilities, alleviates this impaired endothelium-dependant vasomotor function and can provide cardiovascular health benefits. The aim of this study was to examine the effects of chronic resveratrol treatment for 28 days on the endothelium-dependant vasomotor function and hemodynamic measures of the common carotid artery (CCA) of Spontaneously Hypertensive rat (SHR) aged 20-22 weeks at a high (2.7 mg per day, equivalent to a 500mg dose in humans) and a low (0.027mg per day, equivalent to moderate red wine consumption in humans) dose. The 20-22 week old SHR (n=9) demonstrated an elevated mean arterial blood pressure compared to the normotensive control, Wistar Kyoto rats (WKY) (n=9) (p<0.001). The SHR also demonstrated decreased endothelium-dependant vasorelaxation and increased endothelium-dependant contraction, indicating impaired endothelium-dependant vasomotor function. Following chronic treatment with resveratrol for 28 days at a high dose maximal relaxation to acetylcholine (ACh) of phenylephrine (PE) pre-contracted CCA vessels was increased when compared to SHR CON (High 100.4 + 5.2%, CON 53.6 + 6%) (p<0.001). This difference is possibly mediated by improved nitric oxide (NO) bioavailability. This study also confirmed that SHR demonstrate increased endothelium-dependant contractions in quiescent, non pre-contracted rings of the CCA (P<0.001). High dose resveratrol treatment reduced SHR endothelium-dependant contraction in the CCA compared to SHR CON (High 55 + 5.4%, CON 68 + 5%) (p<0.05). This effect was likely mediated by an observed reduction in prostacyclin (PGI2) production, when compared to the SHR CON (p<0.05). This result is likely to be cause by inhibition of cycloxygenase 1 (COX 1) since reversal of SHR endothelium-dependant contraction is demonstrated following inhibition of COX 1, an interpretation supported by the observation that resveratrol treatment had no effect on the sensitivity of the thromboxane-prostaglandin receptor, and no effect on the protein expression of COX 1. This study indicates that chronic treatment with resveratrol at a high dose improves CCA endothelium- dependent vasomotor function in SHR via improved NO bioavailability and a reduction in endothelium-dependant PGI2-mediated contraction. These improvements in vasomotor function produced an alteration in vascular tone to a less contracted state. If these observations extend to the resistance vasculature they could contribute to the explanation for resveratrol-dependant reduction in mean arterial blood pressure.

Background, Rationale and General Purpose: Several seminal observations suggest that AMPK mediates vascular tone: 1) in endothelial cell culture and in vitro isolated protein experiments, activation of AMPK stimulates nitric oxide (NO) production via phosphorylation of endothelial nitric oxide synthase (eNOS), 2) stimuli associated with AMPK activation relax isolated vascular smooth muscle preparations from healthy animals, and 3) acute activation of AMPK in vivo induces hypotension in normotensive animals, an effect that could be indicative of reduced vascular tone. Together these findings prompt the logical hypothesis that acute activation of AMPK induces relaxation that is both endothelium-, NO-dependent and also vascular smooth muscle dependent; however the direct effects of AMPK activation on the regulation of vascular tone in the context of intact healthy arteries in vitro or in situ have not been tested. AMPK activation is dysregulated in essential hypertension and aging, conditions both characterized by vasomotor dysfunction. The integrity of AMPK-mediated vasomotor effects has not been evaluated in any model of vascular dysfunction or in the presence of AMPK dysregulation, and so it is unknown if or to what extent, activation of AMPK alters vascular tone in vessels with these impairments. The mechanisms of AMPK-mediated vasomotor effects have also not been delineating in healthy or dysfunctional arteries. Studying basic vascular signalling mechanisms in both healthy and dysfunctional models is important for understanding physiological function and regulation of vascular tissue, as well as to understand vascular pathology and aid in the development of therapeutic interventions. Collectively these considerations present compelling reasons to investigate the role of AMPK in vasomotor function in health and disease. The unifying purpose of this thesis was therefore to investigate the role of AMP-activated protein kinase in regulating vascular tone in arteries of healthy, hypertensive and aged rats. Experimental Approach and Main Findings: The global objective of the thesis is satisfied by four main studies that utilize a combination of in vitro isolated artery preparations to assess vasomotor function, biochemical analyses and in vivo hemodynamic assessments. In Study 1, we characterize the basic nature of the vasomotor response generated acutely by the pharmacological AMPK activator AICAR in vitro in isolated aorta of normotensive (Wistar-Kyoto rats; WKY) and hypertensive rats (Spontaneously Hypertensive rats; SHR), and the mechanisms mediating these responses. In these experiments, acute activation of AMPK using AICAR induced dose-dependent relaxation of isolated, precontracted arteries from WKY and SHR that was dependent in part on both the endothelium and vascular smooth muscle, and vasorelaxation to AICAR was enhanced in aortic rings of SHR versus those of WKY. In WKY, the endothelium-dependent component of relaxation to AICAR was solely NO-mediated, while in SHR it was dependent on both elevated NO-bioactivity and blunted COX-dependent contraction. In Study 2, we investigate the mechanisms responsible for AMPK-mediated inhibition of endothelium- and cyclooxygenase-dependent vasocontraction in aorta from WKY and SHR (a response enhanced in arteries of hypertensive rats that contributes to vasomotor dysfunction). Pre-activation of AMPK blunted endothelium-dependent contractions to acetylcholine in isolated, non-precontracted WKY and SHR aortic rings. The mechanisms accounting for this effect of AICAR were endothelium-specific, occurring via inhibition of the ACh-stimulated production/release of 6-keto-prostaglandin F1α, the major product of prostacyclin, which is the key prostanoid responsible for endothelium-dependent contractions in aorta of WKY and SHR. AMPK activation had no effect on vascular smooth muscle responsiveness to TP-receptor agonists, ruling out a contribution of vascular smooth muscle mechanisms. In Study 3, we examine responses and mechanisms associated with acute pharmacological AMPK activation on vascular tone of isolated mesenteric resistance arteries in vitro, and on in vivo hemodynamics in WKY and SHR. These experiments revealed that administration of AICAR acutely in vivo acutely reduced blood pressure by ~70mmHg in SHR and this effect was partly NO-dependent. In contrast, AICAR had no effect on blood pressure in WKY. Activation of AMPK also produced vasodilation of isolated, precontracted WKY and SHR resistance mesenteric arteries in vitro, and this was dependent on NO to a greater extent in SHR than in WKY. Together, the parallel reductions in blood pressure in vivo and relaxation of isolated arteries in vitro support reduced vascular resistance as a potential explanation for the in vivo blood pressure effects. Finally, Study 4 characterizes the basic vasodilatory responses to acute AMPK activation and mechanisms associated with these responses in aorta from aged animals and their young counterparts (male Sprague Dawley rats) to glean insight using an additional model of vasomotor dysfunction. In this study, acute activation of AMPK using AICAR generates relaxation in a dose-dependent manner that is partly endothelium-, NO-dependent and partly reliant on vascular smooth muscle in precontracted aorta of both young and aged rats. Similar to the findings of Study 1 in SHR versus WKY, vasodilatory response to AICAR were also enhanced in dysfunctional aorta of aged rats versus healthy aorta of young animals. Other agents shown to activate AMPK in other tissues and models, the anti-diabetic drug metformin and the polyphenol resveratrol, generated varying amounts of relaxation in vascular smooth muscle of young and aged aortic rings. These effects were only associated with AMPK activation in rings treated with metformin but not resveratrol. Conclusions and Perspectives: These findings are the first to characterize the vasomotor responses generated by acutely activating AMPK in intact arteries of any hypertensive or aging model, and to delineate mechanisms mediating these responses in healthy and dysfunctional vessels. Despite vasomotor dysfunction and dysregulated AMPK activity in arteries of hypertensive and aged rats, acute AMPK activation still generates robust relaxation responses via endothelium- and NO-dependent relaxation, inhibition of enhanced endothelium-dependent contractions in SHR, and direct relaxation of the vascular smooth muscle; effects that would aid in reversing the dysfunctional characteristics of arteries from these animals, and may recommend AMPK as a useful therapeutic target for interventions aimed at improving vasomotor function. Future studies will be necessary to reveal whether AMPK plays a role in generating acute changes in vessel tone induced by AMPK-activating physiological stimuli in situ (i.e. such as shear stress during exercise). Together these data continue to support AMPK as a novel regulator of vascular tone, yield valuable, novel, mechanistic insight into AMPK-mediated regulation of vasomotor function in arteries during health, disease and aging, and highlight the need for continued investigation into a vasoregulatory function for AMPK in health and disease.

Background: Exercise interventions reduce falls in older adults. Methods for enhancing uptake and adherence to exercise programs in at-risk individuals are needed. Objectives: This pilot study evaluated feasibility of recruitment, short-term retention and adherence to PEPTEAM (Prescribe Exercise for Prevention of Falls and Fractures), an exercise plus behaviour change intervention. Methods: Patients > 65 years old plus ≥ 1 additional risk factor for falls/fractures (≥2 falls in 6 months, age 75+, high CAROC fracture risk, difficulty walking/balance, acute fall, fragility fracture) were identified by nursing staff at the Center for Family Medicine. The intervention was delivered in two visits, with two follow-up calls, and included: a) physician telling the patient they are at risk; b) exercise prescription provided by a physical therapist; c) motivational interviewing, action and coping planning delivered by a kinesiologist. The primary outcome was change in minutes per day of moderate to vigorous physical activity (MVPA) from baseline to six-week follow-up, measured using X2 mini accelerometers. Secondary outcomes included: feasibility of recruitment and retention, an action planning questionnaire, EQ-5D-5L, Short Physical Performance Battery, and the Timed Up and Go. Adherence to exercise was determined using activity logs. Results: 92 patients were screened, 22 were eligible and 11 were recruited (mean [SD] age 72.64 [6.47] years). All participants returned at 6 weeks. Adherence to exercise was 52%. Mean [SD] minutes of MVPA were 24.7 [22.8] at baseline and 21.6 [15.8] at six weeks (p=0.722). Participant action planning and coping planning abilities were significantly improved (P=0.008), (P=0.012) respectively. Patient-rated health at 6 weeks also significantly improved (P=0.010). Conclusion: Many but not all patients demonstrated positive changes in intensity-specific MVPA. The feasibility information collected from this study in addition to practical recommendations identified for future work could be used to inform a future multicenter randomized controlled trial.

Cellular maturation (differentiation) and cell death (apoptosis) are two vital processes shared by virtually all mammalian cells types. Although these two events have disparate outcomes, recent evidence indicates their execution may involve similar cellular mechanisms. Considered the primary effectors of apoptosis, a family of proteolytic enzymes known as caspases become activated in response to upstream apoptotic signalling, and are responsible for cleavage of structural and regulatory proteins, nuclear degradation and DNA fragmentation, and cell blebbing. While these enzymes have a well-defined role in death, current research suggests their activity is necessary during the differentiation of several cell types including skeletal muscle. However, it is currently unknown how this pro-apoptotic environment is regulated to promote differentiation. A long known mediator of apoptotic signalling, the mitochondria, has recently been shown to affect apoptosis through changes to its morphology. Mitochondrial division (fission) and fusion are necessary for maintaining normal cellular function, although fission contributes to apoptotic signalling. In this study, we examined the mechanisms which lead to caspase activation during skeletal muscle differentiation, and determined the importance of mitochondrial fission to this process. It was hypothesized that typical mitochondrial-mediated apoptotic signalling would be responsible for activating caspases during myogenesis, partly due to increased fission. C2C12 mouse skeletal myoblasts maintained in culture were induced to differentiate by switching to low growth-factor media and collected at various time points during the differentiation process. Activity levels of caspases-2 and -3 transiently increased 51% and 2.5-fold, respectively, 1.5 days after inducing differentiation (p<0.05). No changes were observed in the activity levels of caspases-8 and -9. Although whole-cell levels of Bax and PUMA increased 16% and 21% (p<0.05), respectively, prior to the spike in caspase activity, levels of mitochondrial-Bax were matched by Bcl-2, resulting in no change to the mitochondrial Bax:Bcl-2 ratio early during differentiation. This ratio indicates the susceptibility of the mitochondria to release pro-apoptotic factors, and was associated with decreased cytosolic levels of Smac and cytochrome c by 63% and 75%, respectively, early during differentiation (p<0.05). Levels of the anti-apoptotic proteins Bcl-2 and ARC increased (p<0.05) as caspase activity diminished, possibly supporting their role in ensuring temporary caspase activation. Pharmacological inhibition of caspase-3 resulted in reduced differentiation as indicated by decreased myotube development and cell fusion events. These morphological changes were associated with decreased protein expression levels of the myogenic transcription factor myogenin (p<0.05), and the mature-muscle marker myosin (p<0.05). Likewise, chemical inhibition of caspase-2 activity impaired myotube development, cell fusion, as well as expression of myogenin (p<0.05) and myosin (p<0.05) similar to the inhibition of caspase-3. Finally, reducing mitochondrial fission with a chemical inhibitor of Drp1 function (mdivi-1) also prevented myotube development, resulting in undetectable levels of myosin expression and a 94% drop in cell fusion events. However, these effects were not due to decreased caspase activation. In contrast to our hypothesis, these results support the notion that mitochondrial apoptotic signalling is likely not responsible for inducing caspase activity during myogenesis. Furthermore, we report that mitochondrial fission is necessary for proper skeletal muscle differentiation, likely through its contribution to mitochondrial network morphological changes associated with myotube formation.

Glycogen is the storage polysaccharide in a spectrum of organisms ranging from yeast to humans. Glycogen has a highly branched structure somewhat resembling a tree or shrub, with the branch points formed by glucose molecules being joined by α 1,6-glycosidic linkages. These linkages are formed by the action of branching enzyme. Branching of glycogen is critical to health, with a lack of branching causing glycogen storage disease type IV, which is fatal in humans by age 2. While glycogen branching enzyme has been studied in clinical medicine, modulation of the enzyme has received comparatively little attention. This dissertation undertook three experiments to address whether or not branching enzyme changes in response to dietary intervention and supplementation in mouse liver. Experiment one focused on the application and refinement of a quantitative assay technique for the measurement of branching enzyme activity. The experiment tested the reliability of the assay for the first time on a large number (n=68) of subjects. Intraclass correlation coefficients revealed that the technique demonstrated high reliability (ICCs of 0.848, 0.925, 0.99, and 0.998) for the various assay components. A simplification of the assay method was also introduced that increases the economy of the testing protocol. Experiment two examined whether or not a dietary intervention resulted in different degrees of branching in the liver glycogen of two groups of mice. The results did not show a significant difference between mice fed on low-carbohydrate versus high-carbohydrate diets. The third experiment investigated whether diet combined with quercetin supplementation had an effect on the degree of branching of mouse liver glycogen. Of the nine cohorts under study, only two groups were significantly different from one another statistically (p = .049). These two groups differed only in the time of day the animals were euthanized. Glycogen concentration was not different between the two groups. Taken together, the experiments provide data indicating that the assay technique is reliable. New data pertaining to norms in the degree of branching in mouse liver glycogen are reported as well. Future experiments could apply the assay to other tissues such as skeletal muscle in conjunction with exercise.