Medicine and Health Sciences Commons^™

Characterizing The Function Of B Cells That Accumulate In The Inflamed Central Nervous System In Anti-Myelin Autoimmunity, Lika Chowdhury

Electronic Thesis and Dissertation Repository

While the role of autoimmune T cells has been extensively studied in anti-myelin

autoimmunity, little is known about the function of B cells in multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system (CNS). B cells form clusters with T cells in the meninges directly adjacent to demyelinating lesions. Previous studies have shown that disease progression is dependent on the depletion of specific populations of B cells, but it is not clear which contributes to pathology or how. The purpose of this thesis is to characterize the population of meningeal B cells to determine how they differ …

Monitoring Intraventricular Hemorrhage In Preterm Infants, Lilian Mn Kebaya

Electronic Thesis and Dissertation Repository

Germinal Matrix-Intraventricular hemorrhage (GMH-IVH) remains a significant cause of adverse neurodevelopmental outcomes in preterm infants. Current management options for GMH-IVH rely on serial 2-dimensional cranial ultrasound (2D cUS) ventricular measurements and clinical signs. A need exists for reliable biomarkers to aid in the early detection of posthemorrhagic ventricular dilatation (PHVD) and cerebral palsy (CP). We incorporated 3-dimensional cranial US (3D cUS) and functional infrared spectroscopy (fNIRS) to monitor ventricle volumes (VV) and spontaneous functional connectivity (sFC) in preterm infants with GMH-IVH. Infants with severe GMH-IVH who underwent cerebrospinal fluid diversion showed larger VV, which correlated with decreased sFC. Our findings …

Noninvasive Quantification Of Tissue Sodium Concentration In The Kidney Disease Spectrum Using 23na Magnetic Resonance Imaging, Fabio R. Salerno

Electronic Thesis and Dissertation Repository

Chronic kidney disease (CKD), especially when requiring kidney replacement therapy (hemodialysis (HD) and peritoneal dialysis (PD)), is associated with extracellular water expansion with increased total body sodium. Sodium can also be accumulated in tissues independently of extracellular water. Sodium-23 magnetic resonance imaging (²³Na MRI) can quantify the concentration of sodium nuclei in tissues. Applied to the human leg, quantification of tissue sodium concentrations mainly at the skin and muscle level is possible. We hypothesized that increased tissue sodium concentrations exert toxic effects in CKD and dialysis. We aimed to (1) compare tissue sodium concentrations in adults, children and …

The Effect Of Oral And Topical Antibiotics On Foreskin Inflammation And Hiv Target Cells In Ugandan Men., Zhongtian (Eric) Shao

Electronic Thesis and Dissertation Repository

Penile circumcision reduces HIV susceptibility by up to 60% in men; however, many men prefer to remain uncircumcised for personal or cultural reasons. Penile circumcision protects against HIV by reducing anaerobic bacteria on the penis. Penile anaerobes cause local inflammation and the recruitment of HIV-susceptible CD4+CCR5+ cells, increasing the likelihood that exposure to HIV during intercourse results in infection. To determine if a non-surgical intervention can reduce penile anaerobes and HIV target cells, we randomized men to antimicrobial treatment prior to circumcision. To be able to quantify the effect of antimicrobials, we developed a novel deep-learning algorithm to quantify HIV …

Exploration Of The Pathophysiological Mechanisms Underlying Hemodialysis Associated Cardiac Ischemic Injury, Lisa Yun Jeong Hur

Electronic Thesis and Dissertation Repository

Hemodialysis (HD) provides life-saving treatment in individuals with kidney failure. However, HD is associated with poor quality of life and extremely high mortality rates mainly caused by cardiovascular disease due to heart failure and sudden cardiac death. Standard pharmacological treatment developed within the non-kidney disease community are largely ineffective in HD patients because of the difference in pathophysiology of cardiovascular mortality. HD treatment causes hypotension and recurrent ischemic injury to multiple vascular beds including the heart, leading to heart failure. These injuries can be abrogated by improving the patient’s tolerability of the treatment. To apply interventions that may improve hemodynamic …

Western Diet-Like Culture Conditions And Oxidative Stress On A Cell Model Of Non-Alcoholic Fatty Liver Disease, Celina M. Valvano

Electronic Thesis and Dissertation Repository

Non-alcoholic fatty liver disease (NAFLD) is a major health burden in the Western world, as the Western diet (WD) appears to be the driving force of this disease. However, the individual contributions of the diet and the impacts of their individual metabolism are currently ill-defined. This study used HepG2 cells to understand the impact of the individual components of WD in early NAFLD development under basal insulin levels. Specifically, nutrient-induced changes in reactive oxygen species (ROS) and signaling pathways, such as sterol regulatory element binding proteins (SREBPs), were examined to identify the root cause of steatosis development. High-fat and WD-exposed …

Technical Adaptations For Cardiac Sodium Mri, Taylor L. Marcus

Electronic Thesis and Dissertation Repository

Cardiac sodium (Na⁺) MRI has the potential to unveil relationships between chronic kidney disease (CKD) and cardiovascular disease (CVD). Unfortunately, this modality requires many technical adaptations before it’s possible to extract and compare image data between individuals. This study investigated whether cardiac electrocardiogram (ECG) gating could improve image quality, and whether a uniform phantom could increase signal uniformity if a surface coil is used to acquire the image. Healthy participants were imaged with a custom-built surface coil and 3.0-T MR system. Cardiac gated images presented with a decreased signal-to-noise ratio (SNR), but intensity correction significantly increased image signal …

Role Of Decorin At The Fetal-Maternal Interface, Chidambra D. Halari

Electronic Thesis and Dissertation Repository

The human placenta is an invasive tumor-like structure, this invasion being physiological. A subset of placental trophoblast called extra-villous trophoblast invades the uterine decidua and remodels uterine arteries into low-resistance, high-flow tubes to permit adequate flow of maternal blood to nourish the fetus. A poor extra-villous trophoblast invasion and uterine arterial remodeling can lead to fetal growth restriction and a serious pregnancy-associated maternal disease preeclampsia. Decorin, a leucine-rich proteoglycan produced by uterine decidual cells restrains multiple trophoblast functions: self-renewal and differentiation of trophoblast stem cells, migration, invasion, proliferation and endovascular differentiation. Additionally, decidual overproduction of decorin was associated with preeclampsia, …

Using A One Health Approach For The Assessment Of Rabies Control In Rural Victoria Falls, Zimbabwe, Ryan Lapenna

Electronic Thesis and Dissertation Repository

Rabies, a viral zoonotic disease, is widespread in Zimbabwe, with human fatalities reported annually in the country. To supplement the Government’s effort on rabies control, the Victoria Falls Wildlife Trust and Veterinarians for Animal Welfare Zimbabwe have joined forces to carry out dog rabies vaccinations in rural communities adjacent to the major tourist attraction of The Victoria Falls. A One Health approach was used to 1) determine the level of protective rabies antibodies among a sample of rural dogs and 2) collect information and describe the knowledge, attitudes, and practices related to rabies among dog owners. In 2020, blood was …

Ex-Smokers With And Without Copd: Investigating Ct Pulmonary Vascular, Airway, Pulmonary Artery And Aorta Measurements, Vedanth Desaigoudar, Paulina V. Wyszkiewicz, Alexander M. Matheson, Maksym Sharma, Marrissa J. Mcintosh, Harkiran K. Kooner, David G. Mccormack, Grace Parraga

Undergraduate Student Research Internships Conference

RATIONALE: Pulmonary hypertension is characterized by increased pressure in the pulmonary artery, and is a key contributor to worsening symptoms in individuals with chronic obstructive pulmonary disease (COPD). The pulmonary artery to aorta diameter ratio (PA:Ao), measured using computed tomography (CT), is a biomarker of pulmonary hypertension; however, longitudinal changes in this measurement and its relationship to pulmonary vascular and airway structural changes is not well understood. Our objective was to investigate longitudinal changes in PA:Ao and its relationship with CT pulmonary vascular and airway abnormalities, airflow limitation and exercise-capacity.

Resistance Training Improves White Matter Structural Connectivity In Older Adults At-Risk For Cognitive Decline, Ryu Lien

Undergraduate Student Research Internships Conference

Diabetes is a global health concern that impacts 415 million people worldwide. Individuals who are at-risk for diabetes (characterized by high blood glucose and/or being overweight) have white matter atrophy, decreased cognitive function, and an increased risk of Alzheimer’s disease (AD). Recently, resistance training (RT) has been shown to lower white matter atrophy and white matter lesion volume. However, investigating changes in white matter tracts is complex, hence previous findings remain inconclusive. Diffusion tensor imaging (DTI) serves as a highly sensitive tool that enables visualization and characterization of white matter tracts and has the potential to combat this complexity. The …

Rna Isolation In Duchenne Muscular Dystrophy (Dmd) Mice Models, Salem Abu Al-Burak

Undergraduate Student Research Internships Conference

Fibrosis is a progressive and typically irreversible disease process characterized by the excessive deposition of collagen in organs and in tissues of the musculoskeletal (MSK) system^1,2. This process, which causes loss of organ and tissue function, can be initiated by micro-traumas³, an excessive and/or prolonged immune response¹, the activation and proliferation of fibrosis-inducing progenitor cells⁴, and a pro-fibrotic extra-cellular microenvironment⁵. In parallel with the events that initiate fibrosis, genetic or environmental influences may cause cells and tissues to become predisposed to fibrosis development prior to initiation. This suggests that these …

Intracranial Eeg Patient Analysis: Seizure Reduction In Refractory Epilepsy Following Depth Electrode Insertion, Shreyashish Roy-Chowdhury

Undergraduate Student Research Internships Conference

Rationale: The implantation effect describes an immediate reduction in seizure frequency following the insertion of intracranial electrodes. There is limited information regarding which patients will experience a reduction of seizures and the reason for the implantation effect. This study focuses on describing predictor factors for the reduction in seizure frequency in patients with medically resistant epilepsy implanted with depth electrodes.

Methods: We conducted a retrospective chart review of 89 patients who underwent intracranial electroencephalography (iEEG) monitoring with depth electrodes. Sixty-five of these patients had no subsequent therapeutic interventions and had a 3-6 month follow-up. Patients were grouped as either responders …

Wellness Study: Functional Visual Outcomes In Eye Disease Patients Following The Covid-19 Pandemic, Andrew Maher

Undergraduate Student Research Internships Conference

The COVID-19 pandemic has caused delays in health services and medical appointments, affecting approximately one in three Canadian adults. Elderly eye disease patients experienced delays in treatment for eye conditions including cataracts, glaucoma, and retinal diseases. The impact of these delays on functional visual outcomes and general health rating of elderly patients is not well understood. As part of the Wellness Study, we aimed to investigate the pandemic-related impacts on functional vision and general health rating in an elderly eye patient population in London, Ontario.

Assessing Cognitive Health Outcomes In Anca-Associated Vasculitis Patients, Ruo Yan Chen

Undergraduate Student Research Internships Conference

Anti-neutrophilic cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare and life-threatening autoimmune disease with severe complications. Central nervous system (CNS) involvement is thought to be rare, however, the prevalence of neuropsychiatric complications have been reported in 30-60% of AAV cases. Studies looking at the cognitive health outcomes of AAV patients with CNS involvement have noted cognitive impairment as a significant contributor to reduced quality of life with unique challenges in care and treatment. The data collected from this primary output could be combined with global assessments of cognitive function as well as the application of advanced imaging tools to study …

The Effect Of Type 1 Diabetes On The Metabolic Response To Exercise, Theres Tijo

Undergraduate Student Research Internships Conference

Type 1 Diabetes Mellitus (T1DM) is an autoimmune disorder that results in insufficient endogenous insulin production. Regular exercise has numerous health benefits for individuals with T1DM, however, most insulin-dependent diabetics avoid physical activity due to the fear of exercise-induced hypoglycemia (low blood glucose/BG).

The risk of hypoglycemia in this population may be partly due to lower liver glycogen stores which is a major source of blood glucose during exercise. However, the mechanism that leads to lower glycogen stores in T1DM is unknown.

The purpose of this study was to determine the effect of an acute bout of moderate-intensity aerobic exercise …

The Coping Strategies Of Older Adults With Age Related Vision Loss (Arvl) – A Narrative Account, Zakara J. Stampp

Electronic Thesis and Dissertation Repository

The goal of this study was to share the stories of older adults with age-related vision loss (ARVL) and how they have coped to maintain meaningful occupational engagement. Grounded in a constructivist paradigm, data collection and analysis were guided by the narrative inquiry methodology. The participants consisted of six older adults aged 60 or older, diagnosed with one of the following ARVL conditions: macular degeneration, diabetic retinopathy, and/or glaucoma. Participants were recruited from vision loss non-profit organizations such as the Canadian National Institute for the Blind (CNIB) and the Alliance for Equity of Blind Canadians (AEBC). One older adult was …

The Quality Of Life Of Patients With Eye Diseases, Brian Edward Yu

Electronic Thesis and Dissertation Repository

Background: Health-related Quality of Life (HRQoL) values determined using direct elicitation methods and generic preference-based measures are important for economic evaluations of healthcare interventions. The ophthalmology clientele is vulnerable to psychological stressors in the context of the coronavirus disease 2019 (COVID-19) pandemic.

Objectives: To systematically identify and summarize the quality of life (QoL) of eye disease patients in general in North America and seniors with eye diseases during the COVID-19 pandemic.

Methods: A systematic review identified North American studies that quantified HRQoL of eye disease patients. A cross-sectional study was conducted among seniors with eye diseases and backwards stepwise regression …

Feasibility And Clinical Value Of 3-Dimensional Myocardial Deformation Analysis By Computed Tomography In Transcatheter Aortic Valve Replacement Patients, Mohamad Rabbani

Electronic Thesis and Dissertation Repository

Purpose: Multi-phase computed tomography angiography (CTA) for the pre-procedural planning of TAVR presents a unique opportunity to assess 3D myocardial biomechanics. This study aimed to assess the feasibility and predictive utility of 3D myocardial deformation analysis (3D-MDA) based principal strain to predict heart failure or death following TAVR using pre-procedural, multi-phase computed tomography angiography (CTA) datasets.

Methods: Two hundred and five patients undergoing pre-TAVR multi-phase gated CTA followed by successful TAVR were retrospectively identified. Whole heart 3D mesh chamber models were generated followed by 3D-MDA of the left ventricle (LV) to determine global LV minimum principal strain (minPS) for endocardial, …

A Theoretical Perspective On Parasite-Host Coevolution With Alternative Modes Of Infection, George N. Shillcock

Electronic Thesis and Dissertation Repository

We investigate how natural selection shapes the coevolution of parasitism. We discuss the antagonism fuelled by parasites’ necessity to transmit to novel hosts, and host’s desire to minimise virulence. In support, we build a mathematical model which considers the epidemiology and life-history trade-offs faced by an obligate microparasite and its host. Our model allows parasites to be transmitted to new hosts via direct contact (horizontally) or from parent to offspring during birth (vertically). We test the hypothesis that vertical transmission causes virulence to diminish in the long run, and contrary to widely accepted views, find that vertical transmission need not …

Advancing Type 2 Diabetes As A Condition For Primary Referral To Physiotherapy In Canada, Sarah M. Janssen

Electronic Thesis and Dissertation Repository

Obesity and sedentary lifestyle are increasingly prevalent risk factors for type 2 diabetes (T2D), characterized by high blood glucose levels. Adoption and maintenance of healthy eating, physical activity, and exercise is recommended for lowering blood glucose and weight management. Physiotherapists are experts in prescribing safe, effective exercise to optimize health for people with co-morbid health conditions. However, T2D is not a primary condition for referral to physiotherapy services in Canada. The overall question guiding a series of three related studies was, What is the current education and perspectives of Canadian physiotherapists about their role in managing T2D? Study one surveyed …

The Role Of Reactive Oxygen Species In The Accumulation Of Driver Mutations In B Cell Acute Lymphoblastic Leukemia, Mia P. Sams

Electronic Thesis and Dissertation Repository

B cell acute lymphoblastic leukemia (B-ALL) is the most prevalent type of cancer in young children and is associated with recurrent mutations and high levels of reactive oxygen species (ROS). The antioxidant N-acetylcysteine was tested for its ability to prolong lifespan of a mouse model of B-ALL and reduce frequency of mutations. Mice treated with 1g/L of N-acetylcysteine in drinking water were found to have delayed onset of B-ALL at 11 weeks of age and changes in gene expression relating to B cell development, calcium-apoptosis signaling, and pathways in cancer, although no differences in lifespan were observed. Tumours from treated …

Increased Lipid Metabolism In Response To Repetitive Aerobic Exercise During Proestrus In Type 1 Diabetes Mellitus Rats, Silar Gardy

Electronic Thesis and Dissertation Repository

In response to repetitive bouts of aerobic exercise, type I diabetes mellitus (T1DM) female rats demonstrate greater post-exercise blood glucose (BG) recovery during proestrus than T1DM males. Fuel selection differences may explain sex-related differences in the blunted counterregulatory responses to subsequent exercise and estrogen (E2) has shown to mediate fuel metabolism. Evidence of E2’s activation of AMP-kinase (AMPK) may mediate the metabolic actions of E2. This study aimed to examine sex-related differences in lipid and glucose metabolism in response to a 4-day aerobic exercise protocol in skeletal muscle and liver tissue of male and female T1DM-induced (n = 5) and …

The Streptococcus Pyogenes Hyaluronic Acid Capsule Prevents Neutrophil Clearance, And Greater Insights Into The Streptococcal M Protein As A Vaccine Candidate And Driver Of Heart Dysfunction, Jacklyn Hurst

Electronic Thesis and Dissertation Repository

Streptococcus pyogenes is a human-specific opportunistic pathogen that exploits an assortment of surface molecules to overcome host clearing mechanisms and cause a substantial burden of acute and chronic diseases worldwide. In the present work we utilize the M18 serotype S. pyogenes strain MGAS8232 to demonstrate that genomic deletion of thehyaluronic acid capsule significantly reduces bacterial densities in murine models of experimental nasopharyngeal and skin infections. We show that anti-Ly6G administration recovers the deteriorated burden by unencapsulated bacteria at both infection sites, indicating that capsule expression promotes resistance to neutrophil-mediated clearance during acute infections. We also evaluated the efficacy of serotype-specific …

The Role Of Coagulase-Negative Staphylococcal Secreted Products On Staphylococcus Aureus And Staphylococcus Lugdunensis Infections, Denny Chin

Electronic Thesis and Dissertation Repository

The Staphylococcus genus is comprised of over 40 bacterial species. The most well-studied species in this genus is the notorious human pathogen Staphylococcus aureus, a bacterium that produces coagulase among many other virulence factors. Since S. aureus is a major health burden and causes a plethora of diseases in humans, it has received significant attention and much research has been done to understand its biology to treat diseases caused by this pathogen. However, the coagulase-negative staphylococci (CoNS) make up most of the staphylococcal species and have received less attention since they are thought to have a lesser impact on …