Hamm et al., 2021 reported that voluntary wheel running (R) was complementary to micro-dystrophin gene therapy (GT) in mdx mice, a model of Duchenne muscular dystrophy (DMD). After 21 weeks of running, time to fatigue on a treadmill for the mdxRGT mice was increased 1.8-fold compared to mdxGT mice (no run) and ~5-fold compared to mdx mice (no micro-dystrophin, no run). Fatigue times for mdxRGT were similar to wild type runners (WTR), while mdxGT and WT (no run) were also similar. The diaphragm is an important muscle for endurance exercise. Remarkably, diaphragm power in mdxRGT was depressed compared to mdxGT, suggesting a negative impact of running on GT. To explore mechanisms to explain this decrease, transcriptome profiles for each of the study groups were assessed. RNASeq data revealed differentially expressed genes (DEGs) from groupwise comparisons. Transcripts identified using the Jackson Labs' Gene Expression Database and extensive literature review were organized into a master signaling pathway composed of two sub-pathways: muscle regeneration and fast-slow fiber type shift. Both sub-pathways were hypothesized to explain the improved treadmill performance despite decreased diaphragm power in mdxRGT as potential adaptive mechanisms. Analysis revealed that GT alone (mdxGT) rescued transcriptome expression to WT values in the mdx phenotype more than GT and running combined (mdxRGT). This outcome indicates that, at the 26-week timepoint of sacrifice, the signaling of the transcripts in the muscle regeneration and fast-slow fiber type shift sub-pathways was likely not responsible for the observed improved running performance of mdxRGT compared to mdx. / Master of Science / Muscular dystrophy is a group of diseases characterized by progressive muscle wasting and loss of function. Duchenne muscular dystrophy (DMD) is the most common of these conditions, with an occurrence of 18 per 100,000 live births. The muscles of people with DMD lack a protein called dystrophin, which provides structural integrity for muscle fibers during contraction. This lack of dystrophin leads to muscle deterioration over time, leading to people with DMD typically being wheelchair-bound by ten years of age. Animal models of DMD have been created over time to help study this condition. One such model, the mdx mouse, was used in the study that led to this thesis project. In this study, Hamm et al., 2021, some of these mdx mice were given a micro-dystrophin gene therapy (GT). This GT aimed to deliver a smaller, but still functional version of the missing dystrophin protein to the mice, which has been shown to be beneficial in other studies. This study aimed to measure the effect of this GT when combined with voluntary wheel running. As people with DMD cannot exercise under current clinical guidelines, measuring the response of mdx mice to GT and running combined is an important step in determining the safety of such a treatment in human patients. In the study conducted by Hamm et al., 2021, the mice that received the micro-dystrophin GT and access to running wheels (mdxRGT) performed almost twice as well on a treadmill running test than the mice that received GT alone (mdxGT). Despite this positive result, the mdxRGT mice showed decreased diaphragm power generation compared to mdxGT mice. As the diaphragm is the most important breathing muscle, it is also very important for running performance; therefore, the decreased diaphragm power generation seen in mdxRGT mice is apparently contrary to their improved running performance. To explain this discrepancy, this thesis project examined the diaphragm transcriptome of the different groups in Hamm et al., 2021. The transcriptome is the sum total of messenger ribonucleic acid (mRNA) expressed in a given tissue. Deoxyribonucleic acid, or DNA, is transcribed into mRNA, which is then translated into protein. As such, this thesis project looked at the mRNA expressed in the diaphragm of the mice in the various groups of Hamm et al., 2021, specifically comparing the mdxGT and mdxRGT groups. Important mRNA transcripts, or genes, were identified and assembled into signaling pathways, cascades that highlight how transcripts affect each other and ultimately lead to function once they are translated into their corresponding proteins. Two such signaling pathways were generated based on mechanisms that were thought to contribute to the improved running performance-decreased diaphragm power discrepancy in mdxRGT mice -slow fiber type shifting, and muscle fiber regeneration. The expression of many of the mRNA transcripts in these resulting pathways was closer to the control group in mdxGT compared to mdxRGT. The control group was made up of healthy mice, and as such, their transcript expression level is seen as normal. This outcome of mdxGT having more similar expression to the control group than mdxRGT suggests that the expression of the transcripts included in the two signaling pathways (fast-slow fiber type shift and muscle fiber regeneration) likely did not explain the improved running performance despite decreased diaphragm power in mdxRGT mice. As such, future studies are warranted.

No description available.

In light of the current global prevalence of overweight and obesity, the associated health risks, and the continuing adoption of sedentary lifestyle, this thesis investigated some of the factors that contribute to exercise adherence, directly comparing high-intensity whole body interval training and continuous endurance training. 68 inactive university aged adults (Age: 21.4±3.4 yrs, BMI: 25.6±4.6 kg/m2, VO2peak 40.1±5.7 ml/kg/min) were randomized into one of three groups; a non-exercise control, whole body high intensity training, or continuous endurance training. Aerobic capacity measurements, time to completion trials, muscular endurance, and core strength measures were taken at pre, post and follow up testing sessions. Psychological questionnaires were also administered during exercise as well as throughout the study. Following the intervention both exercise groups demonstrated equivalent improvements in aerobic performance, with only the interval group experiencing improved muscular and core endurance. After the 2-month follow up testing sessions the interval group lost all aerobic and core adaptation, with endurance only experiencing a partial loss. This finding indicates that the interval group did not adhere to exercise at a level that was high enough to preserve the adaptations associated with training. This finding is further supported by the psychological factors measured throughout this study, including acute affect, enjoyment and intentions to engage in future exercise. / Thesis (Master, Kinesiology & Health Studies) -- Queen's University, 2013-10-31 15:08:15.524

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Master of Science / Department of Kinesiology / Steven W. Copp / Cancer patients have a reduced exercise capacity compared to age-matched healthy counterparts which contributes to premature fatigue. The reductions in exercise capacity are multifactorial and vary depending on the type of treatments and the specific cancer. Given that cancer treatments have been shown to impair cardiovascular and/or skeletal muscle function, it is difficult to determine if cancer itself reduces exercise capacity. We used a rat prostate tumor model to test the hypothesis that cancer independently reduces endurance exercise capacity. Methods: In male Copenhagen rats (COP/CrCrl), an initial treadmill test to exhaustion was used to determine endurance exercise capacity. Subsequently, the prostates of the rats were injected with either prostate carcinoma cells (R-3327 AT-1) in Matrigel (cancer: n = 9) or Matrigel only (sham: n = 7). Treadmill tests to exhaustion were repeated four and eight weeks post-surgery. Results: Time to exhaustion decreased over the course of the experimental protocol in both the sham and cancer groups. However, the overall reduction in time to exhaustion in the cancer group (-16.7 ± 1.9 min) was significantly greater (p = 0.038) than the sham group (-10.1 ± 2.2 min). Despite no differences in total body mass at the end of the experimental protocol, heart, left ventricle, and gastrocnemius muscle mass were significantly lower in the cancer group compared to the sham group (p < 0.05 for all). Moreover, within the cancer group heart and left ventricle mass, but not gastrocnemius mass, were significantly inversely correlated with prostate tumor mass. Conclusion: Endurance exercise capacity was reduced in rats with untreated prostate cancer to a greater extent than it was reduced in sham operated rats. Although multiple mechanisms likely contributed to the reduced exercise capacity, reductions in heart and gastrocnemius muscle mass likely played an important role.

MSc (Physiotherapy), Faculty of Health Sciences, University of the Witwatersrand / In South Africa, the concept of Developmental Co-ordination Disorder (DCD) is relatively unfamiliar and not well understood. The exact epidemiology is unknown, but the Diagnostic and Statistical Manual of Mental Disorders (DSM IV, 2000) indicate that the value could be between five and ten percent of the American population. Many studies on DCD have been conducted and most highlight the immense difficulties these children experience with motor activities, both in sport and daily tasks. However, few studies specifically investigated endurance and the impact it has on the child’s ability to function normally without too much effort and fatigue due to the condition. The main aim of this study was to determine the difference in submaximal endurance levels between children diagnosed with DCD and normally developing children. Children between the ages of seven and ten years were included in the study. The Six Minute Walk Test (6MWT) was employed to determine the average distance covered by each of two groups that were selected to participate in the study and thus, the submaximal endurance levels of each group. The first group of participants consisted of children having a diagnosis of DCD (n=31) and the second comparative group consisted of normally developing children (n=17). The results were analysed and compared using the Student t-test. Anthropometric data of height, age, gender and weight as well as baseline data of breathing rate, heart rate and peak flow were taken. These were compared to normative data as determined by the growth charts of the Centre for Disease Control and Prevention (CDC) as well as previous research on the various topics. The average distance covered by the DCD group was 375.89 metres with a standard deviation of ±73.33 and the mean distance covered by the normal comparative group was 430.48 metres with a standard deviation of ±60.85. When the two groups were compared it produced a p-value of 0.0086 which was a statistically significant difference. The normally developing group covered on average 54.6 metres more distance than the group with co-ordination difficulties. In comparison to studies that determined normal age (Lammers et al, 2008) and height (Li et al, 2007) reference values, the children within the eight-year age band for the normally developing group fell within the determined values. The other age bands fell below average for both the DCD and normally developing groups. The finding of the current study is important as it highlights the discrepancy in the submaximal endurance levels of children with DCD when compared to normally developing children of the same age. This is important when considering that most of the activities of daily living are performed at submaximal endurance levels and it is particularly important to note that these are the activities that children with DCD find challenging. The 6MWT can be performed by children as young as four years of age, with explanation and encouragement. This is particularly helpful in the clinical setting, as other tests of physical fitness require more time, equipment and generally good co-ordination in the individual being tested. The 6MWT is easy to apply and requires few tools, making it a cost and time effective means of testing submaximal fitness in children. It is thus a useful measure to determine whether therapeutic intervention has impacted endurance for activities of daily living.

The metabolic heat generated by exercise must be dissipated to maintain body temperature within narrow physiological limits; during exercise and heat exposure, body water is lost via sweating to enable evaporative cooling of the body. When sweating takes place, total body water is reduced (without the intake of additional fluids) from each fluid compartment due to the free exchange of water between compartments with a concomitant loss of electrolytes, primarily sodium. A series of three investigations were undertaken to evaluate: 1) the efficacy of acute sodium citrate-chloride loading on endurance trained males and females as a viable means to expand extracellular fluid volume, 2) any menstrual cycle effects on renal handling of this sodium load at rest, and 3) if any subsequent hypervolaemia reduces the physiological strain of exercise in warm conditions in both genders. The first investigation examined eight endurance-trained (VO₂[max]: 58 ml�kg⁻��min⁻� (SD 5); 36 y (SD 11)) runners in a randomized double-blind crossover study. The participants ingested a high-sodium (HighNa⁺: 164 mmol Na⁺�L⁻�) or low-sodium (LowNa⁺: 10 mmol Na⁺�L⁻�) beverage (10 ml�kg⁻�) before running to exhaustion at 70% VO₂[max] in warm conditions (32�C, 50% RH, V[a]~1.5 m�s⁻�). Results indicate that HighNa⁺ increased PV before exercise (4.5% (SD 3.7)), calculated from Hct and [Hb]), whereas LowNa⁺ didn�t (0.0% (SD 0.5); P = 0.04), and involved greater time to exercise termination in those who were stopped due to ethical end point of 39.5�C and volitional exhaustion (39.5�C: 57.9 min (SD 6) vs. 46.4 min (SD 4); n = 5, P = 0.04; EXH: 96.1 min (SD 22) vs. 75.3 min (SD 21); n = 3, P = 0.03; HighNa⁺ vs. LowNa⁺ respectively). At equivalent times before exercise termination, HighNa⁺ also involved lower core temperature (38.9 vs. 39.3�C; P = 0.00) and perceived exertion (P = 0.01), and a tendency for lower heart rate (164 vs. 174 bpm; P = 0.08). The main purpose of the second investigation was to investigate the efficacy of an acute sodium load on endurance trained women�s plasma volume and renal mechanisms across the menstrual cycle at rest. This was evaluated by inducing a sodium-mediated plasma volume expansion using HighNa⁺ at rest during the last high hormone week of the OCP cycle (HH[ocp]) or the late-luteal phase of the natural cycle (LUT[nat]) and during the low hormone sugar pill week of the OCP cycle (SUG[ocp]) or during the early follicular phase of the natural cycle (FOL[nat]. Thirteen women completed the study with one woman on a progestin-only pill (results were used for case study, not statistical analyses) and were assigned to one of two groups: 1) control (NAT, n = 6, 24 y (SD 5), 53 ml�kg�ml⁻� (SD 3)) or oral contraceptive pill (OCP, n = 6, progestin only n = 1, 29 y (SD 6), 51 ml�kg�ml⁻� (SD 2)) group according to their usage status. Across the four-hour post loading time there was greater plasma volume expansion in SUG[ocp] and FOL[nat] vs. LUT[nat] and HH[ocp] (5.06% (SD1.16) vs. 3.35% (SD 0.23), P = 0.02). OCP usage did not reliably alter the hypervolaemic response (P = 0.27), and this was not dependent on phase of cycle (P = 0.32). Plasma volume expansion occurred across both types and phases of the menstrual cycle with evidence that estradiol interactions with AVP, P[osm] and body water retention are stronger in the low hormone phase of the OCP than in the follicular phase of the natural cycle; illustrated by greater overall water retention after an acute sodium+water load. The third investigation was conducted during the high hormone phase of both OCP and NAT menstrual cycles to further examine sodium-loading effects on the physiological capacity of exhaustive cycling in warm conditions. Thirteen endurance-trained (VO₂[peak] 52 ml�kg⁻��min⁻� (SD 2); 26 y (SD 6), 60.8 kg (SD 5), mean (SD)) cyclists completed this double-blind, crossover experiment during the high hormone phase of the menstrual cycle. Cyclists ingested a concentrated sodium (HighNa⁺: 164 mmol Na⁺�L⁻�) or low-sodium (LowNa⁺: 10 mmol Na⁺�L⁻�) beverage (10 ml�kg⁻�) before cycling to exhaustion at 70% VO₂[max] in warm conditions (32�C, 50% RH, V[a]~5.6 m�s⁻�). HighNa⁺ increased PV before exercise, similar to that of the men in the first investigation, whereas LowNa⁺ didn�t (4.4% (SD 1.2) vs. -1.9% (SD 1.3); P < 0.0001), and involved greater time to exhaustion (98.6 min (SD 25.6) vs. 78.5 min (SD 24.6); P < 0.0001). There was a higher baseline core temperature and faster rate of change for HH[ocp] for both beverage conditions (HighNa⁺: 37.15 (SD 0.6) vs. 36.92�C (SD 0.4); P = 0.05, LowNa⁺: 37.04 (SD 0.6) vs. 36.90�C (SD 0.4), P = 0.05; HH[ocp] vs. LUT[nat], respectively). Through this series of investigations a greater understanding was achieved of fluid balance and the effect of pre-exercise hypervolaemia between genders; pre-exercise ingestion of a concentrated sodium beverage increased plasma volume before exercise and involved less thermoregulatory and the actual and perceived physiological strain during exercise and increased endurance in warm conditions.

This thesis proposes that the concept 'permanence' is relevant at the beginning of the twenty first century. It examines why the term, while perhaps pertinent in addressing the disposability of architecture in Western society, seems anachronistic. The study reviews the seeming inaccessibility of the term in its contested and plural interpretations, and reviews problems in its definition and relevance. <br /><br /> A close examination of definitions, interpretations and contemporary approaches is provided in order to create a conceptual framework that reveals complex implications of the term. Four strategies for understanding the concept are offered: 'realms versus modes', definitions, a distillation of four positions relating to permanence, and an inquiry into contemporary issues relating to the concept. 'Absolute' and 'relative' realms illuminate a scope for permanence, and 'static' and 'dynamic' modes are discussed. A series of definitions are reviewed that reveal nuance in implications. An analysis of four essays on permanence is included, one from the beginning of the twentieth century and three from the end. This section reveals a series of conflicts relating to the way contemporary Western society uses and understands the term. <br /><br /> Permanence within architecture is widely associated with the Vitruvian definition of <em>firmitas</em>: mass and solidity crafted to endure eternally. Vitruvius' employment of 'permanence' is used as a grounding definition and a fundamental reference for the term's evolution into contemporary usage. In observing the endurance of the original Vitruvian term today, a disconnect becomes evident: absolutism in a society defined by relativity. This thesis argues for the critical significance of the term at a pivotal point in history in addressing the problem of disposable architecture on both a cultural and ecological level. Final open-ended questions are raised that consider staggering construction and demolition waste statistics, implying that permanence could play a significant role in effective responses to a global environmental crisis.

This thesis proposes that the concept 'permanence' is relevant at the beginning of the twenty first century. It examines why the term, while perhaps pertinent in addressing the disposability of architecture in Western society, seems anachronistic. The study reviews the seeming inaccessibility of the term in its contested and plural interpretations, and reviews problems in its definition and relevance. <br /><br /> A close examination of definitions, interpretations and contemporary approaches is provided in order to create a conceptual framework that reveals complex implications of the term. Four strategies for understanding the concept are offered: 'realms versus modes', definitions, a distillation of four positions relating to permanence, and an inquiry into contemporary issues relating to the concept. 'Absolute' and 'relative' realms illuminate a scope for permanence, and 'static' and 'dynamic' modes are discussed. A series of definitions are reviewed that reveal nuance in implications. An analysis of four essays on permanence is included, one from the beginning of the twentieth century and three from the end. This section reveals a series of conflicts relating to the way contemporary Western society uses and understands the term. <br /><br /> Permanence within architecture is widely associated with the Vitruvian definition of <em>firmitas</em>: mass and solidity crafted to endure eternally. Vitruvius' employment of 'permanence' is used as a grounding definition and a fundamental reference for the term's evolution into contemporary usage. In observing the endurance of the original Vitruvian term today, a disconnect becomes evident: absolutism in a society defined by relativity. This thesis argues for the critical significance of the term at a pivotal point in history in addressing the problem of disposable architecture on both a cultural and ecological level. Final open-ended questions are raised that consider staggering construction and demolition waste statistics, implying that permanence could play a significant role in effective responses to a global environmental crisis.

ABSTRACT Asthma exemplifies a major medical concern and is a considerable cause of morbidity and mortality in Western society. Controversy still exists regarding the most effective mode and intensity of exercise training for asthmatics. Thus, the purpose of the study was to determine whether walking or jogging at 60% of age-predicted heart rate maximum can increase effort-dependent pulmonary function parameters in moderate, persistent asthmatics. Forty-four sedentary asthmatics were randomly assigned to either a non-exercising control (NE) group (n = 22) or an eight-week moderate-intensity aerobic exercise (AE) group (n = 22). Results indicated that the subjects in the AE training group significantly (p = 0.05) increased their forced vital capacity (FVC), forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), maximal voluntary ventilation (MVV) and inspiratory vital capacity (IVC). The NE group did not exhibit any significant changes in any of the measured variables. Therefore, walking or jogging at 60% heart rate maximum for 30 minutes three times a week for eight weeks can effectively improve the effort-dependent pulmonary parameters in moderate, persistent asthmatics. This represents a strong argument to support the inclusion of this mode of aerobic training in the treatment of moderate, persistent asthma due to its effectiveness, inexpensiveness and lowrisk.