Medicine and Health Sciences Commons^™

Improving Developing Countries’ Health Information Systems Capacity For Infectious Disease Pandemic Responses: A Case Study Of The Ebola Virus Disease And The Coronavirus Disease Pandemics, Uche Ikenyei

Electronic Thesis and Dissertation Repository

There is increasing evidence to demonstrate that current information system theoretical models meant to assess the success of the health information systems (HIS) lack the applicable theoretical underpinning suitable for developing countries. This stems partly from a theory-evidence gap where theoretical models developed in the West are applied in developing country contexts but lack tailoring to localized, contextual realities. Therefore, this study addresses this gap by enhancing the DeLeon and McLean's information system success model with six contextual factors peculiar to the infectious disease HISs in a developing country context.

This study took place in two developing countries, Liberia and …

Effect Of Levodopa On Eeg Connectivity In Parkinson's Patients, Sepehr Torab Parhiz

Electronic Thesis and Dissertation Repository

Levodopa is a dopamine replacement medication administered to patients with Parkinson’s disease (PD) to alleviate their motor symptoms. However, its long-term use can cause adverse side effects, including involuntary motor movements. We studied 16 PD patients before and after taking Levodopa based on resting-state electroencephalography (EEG) recordings to determine how Levodopa affects the functional connectivity of their brain networks. We used several metrics from graph theory, in particular the minimum spanning tree (MST) metric, and analyzed how they change after subjects take Levodopa. We observed significant changes in the lower alpha band toward a more path-like and less globally efficient …

Effects Of Annexin A5 On Endothelial Inflammation Induced By Lipopolysaccharide-Activated Platelets And Extracellular Vesicles, Brent Jeffrey Tschirhart

Electronic Thesis and Dissertation Repository

Sepsis is a dysregulated immune response to infection and the leading cause of mortality globally, accounting for 11 million deaths in 2017. To date, no therapeutics are available to treat the underlying septic response. Previous research from our laboratory has shown that annexin A5 (Anx5) treatment increased survival by 40% in mice with endotoxemia, a model of sepsis. During sepsis, activated platelets release membrane fragments called extracellular vesicles (EVs) with externalization of phosphatidylserine to which annexin A5 binds with a high affinity. We hypothesized that annexin A5 will block the pro-inflammatory response induced by activated platelets and EVs in vascular …

Kindlin-1 Is Involved In Spreading, Migration, And Protein Regulation In Epidermal Scc-13 Cells, Naomi Mishan

Electronic Thesis and Dissertation Repository

Kindlin-1 is a scaffold protein linking the cytoskeleton to the extracellular matrix. Loss of function mutations in the FERMT1 gene (encoding Kindlin-1) cause gastrointestinal and skin defects associated with increased susceptibility to aggressive epidermal squamous cell carcinoma (SCC). This study investigated the consequences of targeted FERMT1 inactivation in the SCC-13 cell line of epidermal SCC. My studies demonstrate Kindlin-1 is not essential for SCC-13 proliferation or clonogenic potential in culture. Kindlin-1 was required for cell spreading on collagen I, but not on laminin-332, and its absence enhanced SCC-13 directional migration. Finally, I identified several proteins involved in tumor formation and …

Assessment Of Executive Function Using A Series Of Operant Conditioning Based Tasks In T1dm Rodents, Kevin T. Murphy

Electronic Thesis and Dissertation Repository

This study examined the impact of Type 1 Diabetes Mellitus (T1DM) on executive function using a series of operant conditioning based tasks in rats. Sprague Dawley rats were randomized to either non-diabetic (n = 12; 6 male) or diabetic (n = 14; 6 male) groups. Diabetes was induced using multiple low-dose streptozotocin injections. All diabetic rodents were insulin-treated using subcutaneous insulin pellet implants. At week 14 of the study, rats were placed on a food restricted diet to induce 5 - 10% weight loss. Rodents were familiarized and tested on a series of tasks that required continuous adjustments to novel …

Mechanisms Underlying Enhanced Bone Marrow Adipogenesis In Diabetes, Jina J.Y. Kum

Electronic Thesis and Dissertation Repository

Morbidity and mortality associated with diabetes are due to secondary vascular complications that include both micro- and macro-vascular organ dysfunctions. Our recent studies show that vascular dysfunction and inadequate vessel repair in diabetes may potentially be due to impaired vasculogenesis (de novo vessel formation). Specifically, we have shown that diabetes enhances adipogenesis in the bone marrow and reduces the number of marrow-resident vascular regenerative stem cells. In this study, I have determined the mechanisms of deleterious bone marrow adipogenesis, which may alter the cellular composition of the marrow and lead to the depletion of vascular regenerative stem cells.

My …

Endothelial Cell-Specific Loss Of Breast Cancer Susceptibility Gene 2 Exacerbates Atherosclerosis, David C.R. Michels

Electronic Thesis and Dissertation Repository

Despite mounting concern over the increased risk of cardiovascular disease in breast cancer patients, studies evaluating the common genetic/molecular link between these diseases are limited. Mutations in the breast cancer susceptibility genes (BRCA1&2) predispose carriers to breast and ovarian cancers due to compromised DNA damage repair capacity leading to DNA damage accumulation; in cancer cells, and in other cell-types including endothelial cells, causing atherosclerotic hallmarks of endothelial dysfunction/apoptosis. We present a new understanding of BRCA2’s protective functionality in the setting of atherosclerosis. Studies have thus far demonstrated that while loss of endothelial BRCA2 in mice does not affect a molecular …

Effects Of Ergothioneine On Endothelial Cell And Macrophage Characteristics, And Markers Of Atherosclerosis Risk Under High Lipid Conditions, Daniel Lam-Sidun

Electronic Thesis and Dissertation Repository

Ergothioneine (EGT) is an antioxidant and potential anti-inflammatory molecule that may have protective effects against the lipid-induced oxidative stress and inflammation that occurs in the vasculature of individuals with obesity and metabolic syndrome. This thesis addresses the hypothesis that EGT supplementation decreases endothelial cell dysfunction and macrophage inflammatory characteristics under high lipid conditions, and markers of atherosclerotic risk in diet-induced obese mice. Results showed that EGT did not influence endothelial tube formation or stability but reduced nitric oxide production in endothelial cells. Moreover, EGT decreased the production of reactive oxygen species, and potentially nitric oxide, by macrophages. In diet-induced obese …

Fishing For The Right Probiotic: Investigating The Mechanism Of Mucosal-Bacterial Interactions At The Interface Of Health And Productivity In Salmonid Aquaculture, Luana Langlois

Electronic Thesis and Dissertation Repository

Aquaculture is vital for the global food supply, but the high incidence of infectious diseases threatens the industry’s productivity. The intestinal mucosa is a key port of entry for pathogens and provides an extensive interface for host-microbe interactions. Tight junctions are at the core of gut barrier function and the mucosal health of finfish. Disruption of these complexes gives rise to sepsis, which leads to systemic inflammation and death. The present study employs a combinatorial approach that integrates in vitro and in vivo analyses to gain actionable insights into the mechanism of microbial-mediated modulation of host health. The experiments outlined …

Establishing Intratumoral Modulation Therapy As A New Treatment Modality For High Grade Gliomas, Andrew M.A. Deweyert

Electronic Thesis and Dissertation Repository

Glioblastoma (GBM) is the most common and lethal primary brain cancer in adults despite aggressive treatments with surgery and chemo-radiation. Advances in electrotherapeutics offer a foundation for developing new treatment modalities that exploit an innate vulnerability of glioblastoma (GBM). Low intensity, non-ablative electric fields are innocuous to normal neural structure, but incite GBM cell apoptosis by putatively disrupting cytokinesis and transmembrane ion homeostasis. Our collaborative research group is pioneering a new electrotherapeutic technology for GBM called Intratumoral Modulation Therapy (IMT) which uses customized, implanted bioelectrodes to deliver sustained, titratable and focused therapeutic electric fields into tumor-affected brain regions. My work …

The Regulation Of Pannexin1 And Pannexin2 In The Skin In Health And Disease, Rafael E. Sanchez Pupo

Electronic Thesis and Dissertation Repository

Pannexins (PANX1, 2, 3) are a family of channel-forming glycoproteins that mediate intracellular and paracrine signaling. In contrast to PANX2, PANX1 has been extensively investigated in the skin, modulating cell differentiation, wound healing, and melanoma development. PANX1 and PANX2 can co-exist in the same cell and form mixed channels where their glycosylation seems to regulate their intermixing. N-glycosylation and caspase cleavage have been proposed as modulators of the function of PANX1, but their effects on PANX2 are unknown. We explored the PANX2 expression in mouse skin and showed that a Panx2 splice variant (PANX2-202) is continuously expressed throughout aging skin. …

Health Concerns Of Adolescents And Adults With Spina Bifida, Jessica A. Starowicz

Electronic Thesis and Dissertation Repository

The Transitional and Lifelong Care (TLC) program is a multidisciplinary clinical service providing comprehensive, coordinated care to adolescents and adults with spina bifida (SB). This study sought to identify the most common health concerns among this population at initial consultation and identify patient factors related to these concerns to ultimately improve health care delivery. A retrospective chart review was performed. Descriptive analyses were completed and associations between concerns and patient factors were determined using Spearman’s rho correlation coefficients. A multiple linear regression was performed to estimate the relationship between patient factors and total number of concerns reported. Ninety-four patient charts …

Incidence Of Cancer And Stage At Diagnosis Among People With Recent-Onset Psychotic Disorders, Jared C. Wootten

Electronic Thesis and Dissertation Repository

Evidence on cancer incidence in people with psychotic disorders, compared to the general population, is equivocal, although those with psychotic disorders so have more advanced stage of cancer at the time of diagnosis. The objective of this thesis was to compare cancer incidence and stage at diagnosis for people with psychotic disorders, relative to the general population. Our systematic review did not observe a significant difference in overall cancer incidence among people diagnosed with psychotic disorders (RR = 1.08, 95% CI: 1.00 to 1.16), however people with psychotic disorders were more likely to be present with advanced stage cancer at …

Genetic Approaches For The Study Of Complex Human Diseases, Julieta Lazarte

Electronic Thesis and Dissertation Repository

The field of human genetics has evolved from its initial narrow focus on single-gene Mendelian disorders, which largely affect children, to our current understanding that for most diseases there is continuum of rare to common variants which can exert a range of phenotypic effects. Despite advances in sequencing capabilities and our overall understanding of diseases, there remains a large proportion of heritability unexplained. Through the use of next-generation sequencing technologies and DNA microarray, I have explored a spectrum of genetic variations from rare, single and structural variants to common variants in individuals with i) “lone” atrial fibrillation; ii) familial hypercholesterolemia; …

Characterizing The Cellular, Molecular, And Behavioural Pathology Of Repetitive Mtbi In A Human Tau Transgenic Mouse, Morgan A. Walker

Electronic Thesis and Dissertation Repository

After an episode of repetitive mild traumatic brain injury (rmTBI), many cellular and molecular cascades are initiated that result in the disruption of the structural and chemical integrity of the components in the brain, leading to the development of various cognitive deficits. The goal of this thesis was to evaluate a mouse model of concussion in order to study the relationship between rmTBI, GSK3β and tau phosphorylation, and behavioural outcomes in a transgenic mouse line expressing solely human tau. We found that there was increased phosphorylation of the two main regulatory sites on GSK3β, Tyr216 and Ser9, in the C57BL/6 …

Addressing Bias In Non-Experimental Studies Assessing Treatment Outcomes In Prostate Cancer, David E. Guy

Electronic Thesis and Dissertation Repository

We evaluated the ability of matching techniques to balance baseline characteristics between treatment groups using non-experimental data. We identified a set of balance diagnostics that assessed key differences in baseline covariates with potential for confounding. These diagnostics were used in a novel systematic approach to developing and evaluating models for use in propensity score matching that optimized balance and data retention. We then compared the performance of propensity score and coarsened exact matching strategies in optimizing balance and data retention, using non-experimental data from a pan-Canadian prostate cancer database. Both matching techniques balanced baseline covariates adequately and retained approximately 70% …

Characterization Of The Ang/Tie2 Signaling Pathway In The Skeletal Muscle Of Dmd, Yiming Lin

Electronic Thesis and Dissertation Repository

In Duchenne muscular dystrophy (DMD), angiogenesis appears to be attenuated. Local administration of angiopoietin 1 (Ang1) has been shown to reduce inflammation, ischemia, and fibrosis in DMD mice. Ang1 is a vital vascular stabilizing factor that activates the endothelial cell receptor Tie2, leading to downstream pro-survival PI3K/Akt pathway activation and eNOS phosphorylation. In this study, we aim to characterize the Ang/Tie2 signaling pathway within the skeletal muscle of mouse models of DMD. Utilizing immunoblots and RT-qPCR, we show that Ang1 is downregulated, while the antagonist angiopoietin 2 (Ang2) is upregulated, leading to a decreased Ang1/Ang2 ratio. This correlates with a …

Three-Dimensional Ultrasound Imaging For Quantifying Knee Cartilage Volume, Samuel Papernick

Electronic Thesis and Dissertation Repository

Arthritis is the most common chronic health condition in Canada, with the most common form being osteoarthritis (OA). There is a great clinical need for an objective imaging-based point-of-care tool to assess OA status, progression, and response to treatment. This thesis aims to validate a handheld mechanical three-dimensional (3D) ultrasound (US) device against the current clinical standard of magnetic resonance imaging (MRI) for quantifying femoral articular cartilage (FAC) volume. Knee images of 25 healthy volunteers were acquired using 3D US and 3.0 Tesla MRI scans. Two raters manually segmented the trochlear FAC during separate sessions to assess intra- and inter-rater …

Measuring The Impact Of Atrial Fibrillation On Patients, Justine Chang

Electronic Thesis and Dissertation Repository

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Patients experience the effects of AF from early symptom onset to treatment and beyond. A previous qualitative study found AF to substantially affect patients’ emotional wellbeing, social relationships, employment, and finances. Existing quality of life questionnaires do not adequately assess the AF impact. In this thesis, a new patient-reported questionnaire was developed to measure the impact of AF as experienced by patients. An exploratory factor analysis was conducted on the new questionnaire, revealing five domains: “Affect”, “Social Support”, “Major Life Events”, “Financial Impact”, and “Diagnostic Experience”. Age, marital status, educational …

Spinal Excitability Changes Following Sensory Electrical Stimulation Of The Forearm, Devin K. Box

Electronic Thesis and Dissertation Repository

Sensory electrical stimulation can be used to suppress tremor in Parkinson’s disease. This study investigated the central mechanism underlying this suppression in healthy participants. Reciprocal inhibition (RI) of the wrist flexors before and after a session of sensory electrical stimulation (SES) applied to the antagonistic extensor muscles was assessed using electromyography. It was hypothesized that a 15-minute session of SES, rated by participants as a 3 on a 0-10 pain scale, would produce an increase in RI. Seven of the 18 participants experienced an increase in RI at 0-5 minutes post stimulation, which returned to baseline at 10-15 minutes. The …

Testing A Novel Peptide-Infused Cream For Treatment Of Rheumatoid Arthritis In Dr4tg Mice, Alisha J. Moynahan

Electronic Thesis and Dissertation Repository

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes joint pain and damage. Studies have shown that inducing immune tolerance towards RA-specific proteins/peptides in RA mouse models can reduce arthritis severity and pro-inflammatory responses. The objectives of this study were to determine if a novel peptide cream treatment could modify RA-specific immune responses and reduce joint swelling in a humanized mouse model expressing the HLA-DRB1*0401 allele (known as DR4tg mice), the strongest genetic risk-factor for RA. Hyaluronan-Phosphatidylethanolamine cream infused with synthetic peptides HomoCitJED and CitJED was applied to HomoCitJED-immunized DR4tg mice before or after arthritis induction. Knee joint …

Exploring The Burden Experiences Of Care Partners For People With Parkinson's Disease Living In Southwestern Ontario, Lisa A. Moszczynski

Electronic Thesis and Dissertation Repository

This thesis quantitatively explored the burden experiences of care partners of people with Parkinson’s Disease in Southwestern Ontario. Thirty-five complete responses (27 females, 8 males) and three partial responses to an online survey were obtained. The survey included a demographic section (41 items), two measures of burden and a quality of life measure. Care partner data were stratified based on Zarit Burden Inventory scores for analysis. Of the Little to No Burden (n=4), Mild Burden (n=15), Moderate Burden (n=8), and Severe Burden (n=4) groups, weekly hours spent on care duties and years in the care partner role were similar. The …

Hiv-1 Drug Resistance To Integrase Strand Transfer Inhibitors In Hiv-1 Non-B Subtypes, Emmanuel Ndashimye

Electronic Thesis and Dissertation Repository

Human immunodeficiency syndrome (HIV-1) has infected over 75 million people and over 35 million have succumbed to virus related illnesses. Despite access to a variety of antiretroviral therapy (ART) options, ART programs have been disproportionally spread in the world with low-and middle-income countries (LMICs) facing challenges to access the most potent ART options. With less potent ART remaining in use in LMICs, HIV-1 drug resistance (HIVDR) presents a growing challenge in LMICs. Since approval of the first-generation integrase strand transfer inhibitor (INSTIs), Raltegravir (RAL) in 2007, INSTIs remain the best choice as a backbone of ART. Access to second generation …

Trna Regulation In Humans: The Cellular Effect Of A Pathological Hars Y454s Mutation, Rosan Kenana

Electronic Thesis and Dissertation Repository

tRNAs are the adapter molecules involved in translating the genetic code into functional protein in a living cell. tRNAs are charged with their cognate amino acids - by aminoacyl-tRNA synthetases (aaRS or ARS) - which are then transferred to a growing peptide in a process called mRNA translation. The efficiency of translation is dependent on the ratio of ARS enzymes to their cognate tRNAs and the availability of correctly amino acylated tRNAs. Disruptions of this process, caused by mutations in ARS genes, in particular, have been linked to complex inherited diseases. USH3B syndrome, a recessively inherited disorder among consanguineous families …

Novel Imaging Tools Reveal The Dynamics Of The Myocardial Growth Hormone Secretagogue Receptor In Heart Disease And Heart Failure, Rebecca Sullivan

Electronic Thesis and Dissertation Repository

Heart disease (HD) is the leading cause of mortality worldwide. Currently, diagnosis is based on clinical features, imaging, and circulating cardiac biomarkers. Cardiac imaging technologies, such as echocardiography and cardiac magnetic resonance imaging (cMRI), enable the non-invasive detection of changes in heart function. Although these modalities can detect changes in structure and anatomy, it is usually at later stages, where prevention may not be possible. In conjunction with imaging, circulating biomarkers of heart failure (HF), notably B-type natriuretic peptide (BNP) and cardiac troponin I and T, can be detected with increased levels in the blood. These biomarkers are associated with …