Endothelial cells (EC) are essential regulator of vascular homeostasis through the generation and release of various bioactive agents, including nitric oxide (NO). NO modulates several vascular functions such as vascular tone and permeability, through the stimulation of soluble guanylate cyclase (sGC) leading to the production of cGMP. Conversely, phosphodiesterases (PDEs) are enzymes metabolizing cyclic nucleotides (cGMP and cAMP) and are therefore major regulatory players for cGMP and cAMP signalling pathways. Although ECs are the main source of NO, little is known on the endothelial NO-cGMP signalling pathway and cellular outcomes. It was then hypothesized that a specific population of cGMP-phosphodiesterases allows ECs to stabilize cGMP levels despite the elevated production of NO. Expression of cGMP-phosphodiesterases was initially studied in resistance mesenteric arteries from mice. PDE5 and PDE6 were both found at mRNA and protein levels in native arteries but PDE6 is not found in cultured ECs. Interestingly, subcellular distributions of both enzymes were distinct. PDE5 appeared to be homogeneously distributed whilst PDE6 catalytic subunits (PDE6 and PDE6) showed a preferential staining in the perinuclear region. These results suggest that PDE6 might be involved in the regulation of cGMP microdomains. Based on these findings, a mathematical model was developed. Simulations of dynamic cGMP levels in ECs support the notion of cGMP microdomains dependent on PDE6 expression and localization. In the absence of PDE6, application of NO either as a single bolus or repetitive pulses led to a homogeneous increase in cGMP levels in ECs despite PDE5 homogeneous distribution. However, PDE6 subcellular targeting to the perinuclear membrane generated a cGMP-depleted perinuclear space. The findings from this study provide the first evidence of the expression and specific intracellular distribution of PDE6 in native endothelial cells that strongly support their involvement in the generation of cGMP microdomains / Les cellules endothéliales (CEs) participent au maintien de l’homéostasie vasculaire en générant et libérant de nombreux agents bioactifs, incluant l’oxyde nitrique (NO). Le NO module plusieurs fonctions vasculaires telles que le tonus et la perméabilité vasculaire via la stimulation de la guanylate cyclase soluble (GCs) provoquant la formation de GMPc. D’autre part, les phosphodiestérases (PDEs) sont des enzymes métabolisant les nucléotides cycliques (GMPc et AMPc) et participent donc à des étapes essentielles du contrôle des voies de signalisation du GMPc et de l’AMPc. Bien que les CEs soient la source principale de NO, la voie de signalisation NO-GMPc endothéliale et les répercussions fonctionnelles demeurent méconnues. Nous avons alors émis l’hypothèse qu’une population spécifique de PDEs ciblant le GMPc (PDEs-GMPc) permettrait aux CEs de maintenir des niveaux de GMPc faible malgré l’importante production de NO. L’expression des isoformes de PDEs-GMPc dans les artères mésentériques de souris fut initialement déterminée. PDE5 et PDE6 furent détectées tant sous la forme d’ARNm que de protéines dans les artères natives alors que PDE6 est absente de lignées de CEs en culture. La distribution intracellulaire des deux enzymes est distincte. Alors que PDE5 est distribué uniformément dans le cytoplasme des cellules endothéliales, les sousunités catalytiques de PDE6 ( et ) sont préférentiellement présentes dans la région périnucléaire. Ces résultats suggèrent que PDE6 puisse être impliqué dans le contrôle de microdomaines de GMPc. Des simulations effectuées à l’aide d’un modèle mathématique développé sur la base de ces données sont en accords avec la notion selon laquelle l’expression et la distribution subcellulaire de PDE6 sont responsables de microdomaines de GMPc dans l’endothélium. En absence de PDE6, l’ajout de NO sous forme de bolus unique ou répétée mène à une augmentation homogène de la concentration cytoplasmique en GMPc malgré la présence de PDE5. Toutefois, la présence de PDE6 à la membrane péri-nucléaire crée un espace péri-nucléaire pauvre en GMPc. Les résultats de cette étude forment les premières évidences de l’expression et de la distribution intracellulaire hétérogène de PDE6 dans les cellules endothéliales natives et suggèrent leur implication dans la génération de microdomaines.

Master of Public Health / Department of Human Nutrition / Sandra B. Procter / Family meals and meals with caregivers can be sources of social support. Current literature indicates that social support is important for physical and psychological health and well-being. There has been no published research looking at the role of communal meals in collegiate dining centers as sources of social support. This study investigated the possibility that communal meals in a collegiate dining center and eating with other people in these settings may be related to perceived social support, academic success, frequency of family meals, and/or degree of involvement in college extracurricular activities. To investigate these relationships, first-year Kansas State University students living in the residence halls of the Derby Complex (Ford, Haymaker, Moore, and West Halls) were administered a survey about dining center usage habits. The survey included the previously tested Interpersonal Relationship Inventory Short Form by V.P. Tilden (n.d.) as a measure of perceived social support. Participants granted access to their first semester Kansas State University grade point average and semester dining center usage data. Surveys were completed online (n=216) and in paper format (n=89) for a total of 303 participants. There was no significant difference between the demographics of those that completed the online versus paper formats of the survey. Therefore, the online and paper formats of the survey were analyzed together. The data were analyzed for all participants and for males (n=94) and females (n=209) separately. Results revealed multiple significant relationships (p<0.05). Results related to grade point average and perceived social support revealed a significant positive relationship between frequency of eating in the dining center and grade point average for all participants combined. This relationship was also noted for males and females analyzed separately. Frequency of eating with others was found to be significantly positively correlated to perceived social support score for all participants combined, and for males and females analyzed separately. Frequency of eating with others was significantly positively correlated with grade point average for males alone and females alone, but not all participants combined. Further research is needed to determine if the relationships are causal and if so, the direction of causality in the relationships.

No description available.

No description available.

This qualitative research study examined the patient education experience from the point of view of health care professionals, namely doctors of chiropractic in the Greater Toronto Area practicing for up to ten years. Health care professionals’ views and beliefs of this important aspect of health care have not been well studied. Patient education is defined as, “the process by which patients learn or acquire knowledge about his/her health status or condition and may involve learning in the cognitive, affective, and/or psychomotor domains.” The study explored eight participants’ views on the nature of patient education in their early and current practices by examining their feelings, beliefs, and use of patient education, its role in their practices, as well as the perceptions of their roles as patient educators. Two semi-structured interviews were conducted with each of the participants. The transcribed interviews underwent detailed qualitative analysis to determine response trends and consensus. The key findings revealed that the participants felt that, while they were well prepared in their undergraduate curricula to diagnose and treat patients, they were not as well prepared to be effective patient educators when they entered practice. Early in their careers, they did not understand or appreciate patient education’s importance and value as a component of their practice. Over time, their beliefs and understanding of patient education changed and participants reported that with experience, they began to value patient education to a greater extent. Changing values reflected changing behaviours. For example, participants increased their time and efforts related to patient education with increased clinical experience. A variety of teaching aids were used with wall charts/posters, three dimensional anatomical models, printed materials and images from textbooks being among the most common. Most of the teaching described by the participants would be characterized as transmission with a one-way flow of information from the doctor to the patient. To a great extent, patient education involved speaking with individual patients. Participants reported encountering, throughout their careers, intrinsic and extrinsic barriers that interfered with the effectiveness of their patient education. The findings suggest that curricular planners for health care professional programs, and specifically for chiropractors, might consider developing content aimed at improving students’ patient education knowledge and skills.

Acute demyelination in children may be a monophasic illness or the sentinel attack of multiple sclerosis (MS) – a chronic inflammatory neurodegenerative demyelinating disease. MS risk is largely determined during childhood and vitamin D may protect against MS. The primary objective of this thesis was to evaluate vitamin D status in children presenting with acute demyelinating syndromes (ADS) as a potential contributor to MS outcome. The LIAISON “25 OH Vitamin D TOTAL” assay was validated to assess the biomarker of vitamin D status – serum 25-hydroxyvitamin D (25(OH)D) concentrations. Consecutive patients (<16 y) were enrolled at presentation with ADS and prospectively evaluated at 23 Canadian centres. MS was defined by a second clinical demyelinating event or by MRI evidence of new lesions over time. Cox proportional hazards regression models assessed risk of MS outcome as a function of serum 25(OH)D tertiles, accounting for factors associated with either MS risk or vitamin D status – age, sex, season, and HLA-DRB1*15 status. Of 211 children with 25(OH)D measured in sera obtained a median of 9 days from onset (interquartile range, 5 – 17 d; maximum 36 days), 20% (n = 41) were diagnosed with MS after 3.7 mos. (3.1 – 7.3 mos.). Risk of MS was lower in children with 25(OH)D levels in the highest tertile (≥ 74 nmol/L) at ADS versus those in the lowest tertile (<50 nmol/L) (HR 0.41; 95% CI 0.18 to 0.97, adjusted model). Children with higher circulating 25(OH)D concentrations at ADS have a lower risk of MS. Further evidence for a role of vitamin D insufficiency during childhood and adolescence contributing to MS risk comes from three MS patients with suboptimally managed pseudo-vitamin D deficiency rickets. Finally, a sun exposure questionnaire was validated in the latter part of this thesis for use in future research into determinants of vitamin D status and their association with risk of MS.

Although androgens are known to exert anabolic effects in skeletal muscle, overexpression of androgen receptor (AR) selectively in this tissue causes androgen dependent motor deficits and muscular atrophy. The cellular and subcellular changes underlying this phenotype are unknown. Therefore, this study aimed to elucidate the ultrastructural and histologic changes accompanying myopathy and to determine the importance of androgens and overexpression level for myopathic features. Transmission electron microscopy revealed augmented mitochondrial content and reduced myofibril width in androgen exposed transgenics. Additionally, male transgenics demonstrated increased glycogen content. Histochemical analyses confirmed sex-specific changes in glycogen content and revealed a surprising loss in the proportion of oxidative fibers in symptomatic animals. However, increased mitochondrial content was confirmed by the presence of ragged red fibers. Overexpression of AR in muscle fiber results in mitochondrial pathology and dysregulation of glycogen metabolism, possibly reflecting normal but exaggerated function of androgens in skeletal muscle fibers.

Many healthcare providers are at risk of compassion fatigue and burnout from prolonged occupational stress, which can adversely affect workers, patients, and the healthcare system. This qualitative research project inquired into eight female healthcare providers’ experiences of sustaining their own wellbeing. Participants (27 to 60 years old) engaged in semi-structured interviews and participant observation of a self-care activity. Themes were found relating to the variety of self-care strategies used, challenges and supports in the work context, and the important role of authenticity in health promotion practice. Self-care strategies included: social support, pacing, taking breaks, exercise, nutrition, emotional self-care, adapting self-care routines over time, goal setting and prioritization. Supports to wellbeing included: flexible scheduling, taking personal responsibility for wellness, workplace wellness programs, and positive relationships with supervisors, colleagues, friends and family. This arts-informed research project is presented in graphic novel form to enhance its accessibility.

Communication of hospital discharge instructions between patient and provider is an important component of hospital discharge to ensure that patients have the information they need to manage their post-acute care. Patient perception of this interaction is a key indicator of the quality of services provided. This study examined whether there is a correlation between hospital continuity and transition scores (a measure of patient perceptions of hospital discharge instructions) and hospital readmissions in Ontario. The final regression model for the outcome of all medical readmissions within three days of hospital discharge, showed a significant positive relationship (coefficient=0.0090, p=0.011). The estimate was smaller and not significant once the data was restricted to only community hospitals located outside of Toronto (coefficient=0.0085, p=0.060), and when restricted to urban community hospitals outside of Toronto (coefficient=0.0041, p=0.384). For the outcome of specific medical readmissions within 28 days of hospital discharge, no statistically significant relationship was found.

Programs that use the arts to engage older people promote health, foster community, and give voice and legacy to participants. Creative practice in health care settings facilitates emotional, mental, and physical wellness for participants and staff, while improving the culture of care. Yet there is resistance to arts-in-medicine as a legitimate tool of health care. The predominant biomedical paradigm privileges quantitative assessment methods over qualitative studies which may accept anecdotal, arts-informed, or “common sense” evidence. Successful creative programs face challenges translating their benefits when evaluated inappropriately. This arts-informed inquiry uses creative writing to address multiple dimensions of knowing, integrating autoethnographical insights from work as a caregiver, artist, educator, and administrator of collaborative art. Serendipity and imagination in research were employed to explore how collaborating artists can facilitate creative engagement for elders, embodying preventative, community-based medicine to successfully address and transform myriad challenges and opportunities as the population continues to age.