Digital Commons Network^™

A Bioinformatics Approach To Understanding The Pathogenesis Of Ectopic Spine Calcification, Fang Chi Wang

Electronic Thesis and Dissertation Repository

This study used mice lacking equilibrative nucleoside transporter 1 (ENT1^-/-) as a preclinical model to study pathogenesis of ectopic spine mineralization in diffuse idiopathic skeletal hyperostosis (DISH). We hypothesized that mineralization of the annulus fibrosus (AF), was driven by dysregulation of cellular processes and pathways associated with apoptosis, S100A9 proteins, the PI3K-Akt pathway, and lipid metabolism. Target pathways and processes were assessed using in situ localization and quantitative analyses. Metabolomic analysis of AF and plasma data was conducted to identify altered metabolites. Results demonstrate increased caspase-3 activity in the AF of ENT1^-/- mice at both timepoints …

Trauma Systems In Canada: Evolution, Challenges, And Strategies For Improving Trauma Care For Rural Patients, Richard C. Chaulk

Electronic Thesis and Dissertation Repository

This thesis explores the development and current state of trauma systems in Canada, emphasizing the challenges and disparities faced by patients who are injured in rural areas. With trauma being the leading cause of death for Canadians under 40, effective trauma systems are crucial. However, patients injured in rural and remote areas face significant barriers to timely and adequate trauma care, resulting in increased morbidity and mortality. This body of work aims to evaluate some of these disparities and propose strategies for improvement.

The concept of organized trauma systems has its roots in ancient wartime practices, evolving significantly over centuries. …

Therapeutic Promise And Insights For Parkinson's Disease From The Living Brain, Simon M. Benoit

Electronic Thesis and Dissertation Repository

Background: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the brain. To date, no disease-modifying treatments for PD are available and novel insights and therapeutics are essential. This thesis explores a novel substrate for cell-based therapies for PD, brain-derived progenitor cells (BDPCs), derived from living PD brain samples obtained during deep-brain stimulation surgery, while also utilizing this unique tissue source to gain important insights into the molecular underpinnings of the disease. Methods: In Chapter 2, human and rat BDPCs were compared, and the latter engineered for longitudinal tracking in vivo using bioluminescence …

Investigating Synergistic Effects Of Mild Traumatic Brain Injury And Reduced Cholinergic Tone On Attentional Deficits And Alzheimer's-Like Pathology In Haβ And Htau Mice, Elizabeth M. Teasell

Electronic Thesis and Dissertation Repository

Mild traumatic brain injury (mTBI) increases the risk of Alzheimer’s disease. The early cholinergic decline in Alzheimer’s disease and cholinergic damage observed after TBI suggest a distinct role of this neural system in vulnerability to Alzheimer’s disease following TBI. This thesis evaluated the role of repetitive mTBI and cholinergic dysfunction in the development of cognitive deficits, specifically attentional deficits, and Alzheimer’s-related pathology in mice expressing humanized amyloid-beta and tau and a vesicular acetylcholine transporter knockdown to induce a mild cholinergic deficit. Using the rodent continuous performance test, it was shown that repetitive mTBI in the presence of an already vulnerable …

How Different Insulin Administration Routes Affect Hepatic Glycogen Levels After An Aerobic Exercise Bout In Male Rats With Type 1 Diabetes, Amit P. Sayal Mr.

Electronic Thesis and Dissertation Repository

Type 1 diabetes mellitus (T1DM) is an autoimmune disease resulting in the destruction of pancreatic beta cells leading to deficient insulin production. Insulin plays a crucial role in regulating glucose metabolism, facilitating the utilization of dietary energy. Individuals with T1DM exhibit dysregulated blood glucose concentration and necessitate exogenous insulin administration. Intensive insulin therapy (IIT) is employed commonly, typically via subcutaneous (SQ) injections to treat individuals with T1DM. However, SQ insulin delivery fails to mimic endogenous insulin secretion, particularly its physiological distribution directly to the liver via the hepatic portal vein. Insulin concentration in the liver contributes significantly to glucose homeostasis, …

Quantifying Resting-State Functional Connectivity In Critically Brain-Injured Patients: A Graph-Theoretical Approach With Fnirs, Ira Gupta

Electronic Thesis and Dissertation Repository

Assessment of consciousness in behaviourally unresponsive patients with critical brain injuries continues to be a challenge. There remains a need for robust tools that can accurately characterize preserved cortical function and predict patient outcomes. In the present study, functional near-infrared spectroscopy is employed in conjunction with graph theory and machine learning to quantify resting-state functional connectivity in 16 acutely brain-injured patients and 23 healthy controls. Results revealed significant channel-level differences between the groups for three graph metrics, including degree, clustering coefficient, and local efficiency. Further investigation using machine learning algorithms revealed that these metrics can be used to distinguish between …

The Impact Of Simulated Image Acquisition Time Reduction On Image Quality And Parameters Of Myocardial Perfusion Imaging Using A Dedicated Cardiac Camera, Alireza Khatami

Electronic Thesis and Dissertation Repository

Heart disease is the second leading cause of death in Canada, highlighting the crucial role of early diagnosis in disease management. Myocardial perfusion imaging (MPI), is widely employed for this purpose, involves injecting a radiopharmaceutical into the body, imaging its distribution with a gamma camera, and revealing cardiac blood flow patterns. A significant challenge in MPI is the lengthy 8 to 10 minutes required for stress and rest imaging, potentially causing patient discomfort and compromising image quality due to movement. In a clinical study with 26 patients, post-processed data manipulation simulated a reduction in MPI imaging time. The findings indicated …

Interaction Of Circularrna And Microrna-9-5p In The Mediation Of Cardiac Fibrosis In Diabetic Cardiomyopathy, Honglin Wang

Electronic Thesis and Dissertation Repository

Diabetic cardiomyopathy (DCM) is a chronic diabetic complication affecting the heart. It is a significant and independent contributor to heart failure and characterized by cardiac fibrosis and left ventricular hypertrophy. Endothelial cells are the first cells to be damaged by hyperglycemia, leading to epigenetic modifications and subsequent signaling and transcription derangements that lead to endothelial dysfunction and therefore cardiac fibrosis. The role of the two noncoding RNA microRNA-9-5p and circRNA_012164 are investigated using in vivo and in vitro models of hyperglycemia. CircRNA_012164 is upregulated in the hearts of diabetic mice and in cells exposed to high glucose. This results in …

Multi-Arm Randomized Control Trials In Inflammatory Bowel Disease: A Literature Review And An Illustration Of Methods For Analysis, Sahiba Saini

Electronic Thesis and Dissertation Repository

This thesis aimed to review the literature on multiple-arm randomized control trials in inflammatory bowel disease (IBD) and to illustrate how to analyze these trials, focusing on appropriately controlling the type 1 error rates. The literature review found 247 trials published from the inception of each database to April 2014, of which 122 (49%) trials were multiple-arm trials and of those, 59 (48%) trials were on ulcerative colitis and 63 (52%) on Crohn’s disease. A published assessment tool was adopted to assess whether controlling of Type I error rates was needed. Despite the common use of this trial design and …

Assessing Copd Care Quality In A Rural Ontario Primary Care Clinic: A Retrospective Chart Review, Daniel Henke

Electronic Thesis and Dissertation Repository

Background: Primary chronic obstructive pulmonary disease (COPD) care may be worse in rural versus more urban environments.

Purpose: To evaluate the quality of COPD care in a rural Ontario primary care clinic.

Methods: A 12-month retrospective chart review study was conducted between June 2022 and January 2023 at a Goderich, Ontario primary care clinic. Electronic medical records (EMRs) were randomly selected for inclusion. Baseline sociodemographic (e.g., occupation) and health (e.g., smoking status) characteristics were extracted as well as information regarding COPD care received (i.e., Health Quality Ontario [HQO] Quality Standard [QS] indicators; n=33. The primary study outcome was overall proportion …

The Impact Of Access To Oral Health Care On Inadequate Oral Health And Multimorbidity, Luis Limo

Electronic Thesis and Dissertation Repository

The connection between oral health and other non-communicable chronic conditions—commonly referred in the dental literature as the oral-systemic health connection—emphasizes the role of oral health care on both oral diseases and chronic conditions, particularly in vulnerable populations like the elderly. This thesis comprises 2 studies: the first is a systematic review on the impact of oral health care interventions, as an indicator of access to oral health care, on chronic conditions of which their co-existence would result in multimorbidity; the second study is a cross-sectional investigation of the associations between oral health, access to oral health care, and multimorbidity among …

Exploring The Experience Of Sexuality And Gender During The Healthcare Transition Of The Youth With Cerebral Palsy, Umma Salma

Electronic Thesis and Dissertation Repository

Background: Transition from the pediatric to adult health care system is an important phase of healthcare for youth with cerebral palsy (CP). Sexuality and gender are two very important components of health that are mostly ignored in the healthcare transition process. It is possible that health care providers only see a client’s disability, and therefore, key aspects of sexuality and gender diversity may be ignored, or deemed irrelevant as a result of their disability status. Therefore, the purpose of our study is to explore how gender and sexuality may influence the experience of health care transition for youth with cerebral …

Optimizing Dynamic Treatment Regimes With Q-Learning: Complications Due To Error-Prone Data And Applications To Covid-19 Data, Yasin Khadem Charvadeh

Electronic Thesis and Dissertation Repository

In this thesis, we employ statistical modeling and methods to examine COVID-19 data, and we develop new methods to address new issues that invalidate some standard methods.

In the first study, we employ semiparametric and nonparametric survival models as well as data visualization techniques to examine the epidemiological features of COVID-19. Based on our numerical results, the median incubation time is about 5 days, and the elders are more likely to have longer incubation periods.

In the second study, we use data from 175 countries and investigate possible factors associated with the case fatality rate (CFR) of COVID-19. The Q-learning …

Role Of Circular Rna Asph In Macrophage Polarization And Response In Sepsis, Tan Ze Wang

Electronic Thesis and Dissertation Repository

Circular RNAs (circRNAs), a novel non-coding RNA species generated by back-splicing, has been shown to participate in gene regulation of leukocytes. Our previous RNA sequencing results show circular RNA ASPH (circASPH) to be highly expressed in peripheral blood mononuclear cells of sepsis patients at the start of intensive care. Macrophages, as ubiquitous innate immune cells, are responsible for the recruitment of other immune cells at sepsis onset. This work investigates the role of circASPH in the regulation of macrophage polarization in sepsis. Using an in vitro THP-1 cell model, it was found that circASPH levels peaked after 24 h of …

Sex Differences In Mood And Anxiety-Related Outcomes In Response To Adolescent Nicotine Exposure, Tsun Hay Jason Ng

Electronic Thesis and Dissertation Repository

Nicotine dependence is causally linked to increased risk of mood/anxiety disorders in later life. Females are reported to experience a higher prevalence of anxiety/depressive disorders and challenges in smoking cessation therapies, suggesting a potential sex-specific response to nicotine exposure and mood/anxiety disorder risk. However, pre-clinical evidence of sex-specific responses to adolescent nicotine exposure is unclear. Thus, to determine any sex differences in anxiety/depressive-related outcomes, adolescent male and female Sprague Dawley rats received nicotine (0.4 mg/kg; 3x daily) or saline injections for 10 consecutive days, followed by behavioural testing, in-vivo electrophysiology and Western Blot analyses. Our results revealed that adolescent nicotine …

Pannexin3 In Exercise, Obesity, And Osteoarthritis, Brent Wakefield

Electronic Thesis and Dissertation Repository

Pannexin 3 (PANX3), is a glycoprotein that oligomerizes to form mechano-sensitive channels expressed in musculoskeletal tissues, and has been identified as a potential target for the treatment of obesity and osteoarthritis (OA). Obesity and OA are two of the most prevalent diseases worldwide, leading to disability and even death. These conditions are thought to originate from a complex interaction between genetics, aging, sex, and modifiable lifestyle factors, such as exercise. Investigating the interactions between genetic and exercise may provide a more comprehensive, context-specific understanding of gene function. This thesis aimed to understand the interactions between PANX3 and exercise interventions on …

Imaging Features Characterizing The Continuum Of Diffuse Idiopathic Skeletal Hyperostosis, Dale E. Fournier

Electronic Thesis and Dissertation Repository

Problem: Diffuse idiopathic skeletal hyperostosis (DISH) is a common musculoskeletal condition yet its etiology, early and progressive disease features, and clinical implications are poorly understood. The purpose of this dissertation was to investigate the imaging features associated with the continuum of DISH.

Methods: A retrospective study design was used to evaluate thoracic computed tomography scans from a population in Minnesota, United States. Female and male individuals ≥20 years of age were examined for imaging features of DISH and early-phase DISH. The extent of ectopic bridging between each vertebrae was scored. Subsequently, the individuals with repeated computed tomography scans of the …

The Combined Effects Of Physical Exercise And Cognitive Training On Gait Speed And Primary Motor Cortex Metabolism In Individuals With Mild Cognitive Impairment: A 1h-Mrs Analysis, Jack Thomas Emsey Elkas

Electronic Thesis and Dissertation Repository

Mild cognitive impairment (MCI) is a transitional stage before dementia. Altered gait in MCI has been associated with progression to dementia. Using magnetic resonance spectroscopy, a relationship between primary motor cortex (M1) neurochemistry and dual task gait speed has been reported in MCI. Interventional research suggests exercise, cognitive training, and vitamin D supplementation may benefit MCI, yet the combined effect of these treatments on gait speed and M1 metabolism is unknown. Participants with MCI (N=75) were assigned to one of five intervention arms and dual task cost on gait speed and M1 metabolism was assessed before and five months after …

Do Clinical Exercise Tests Permit Exercise Threshold Identification In Patients Referred To Cardiac Rehabilitation?, Randi R. Keltz

Electronic Thesis and Dissertation Repository

The purpose of this thesis was to quantify the proportion of patients whose clinical cardiopulmonary exercise test (CPET) permitted identification of estimated lactate threshold (θ_LT) and respiratory compensation point (RCP) and to characterize the variability at which these thresholds occur to evaluate the feasibility of “threshold-based” aerobic exercise prescription. We retrospectively analyzed CPET data of 1102 patients (65±12 yrs; 306 females) referred to cardiac rehabilitation. θ_LT and RCP were identified and reported as oxygen uptake (V̇O₂), heart rate (HR), %V̇O_2peak, and %HR_peak. Patients were grouped by threshold identification: group 0) neither …

Assessing The Neurological Sequelae Of Covid-19 And Acute Respiratory Distress Syndrome, Rachel Wagner

Electronic Thesis and Dissertation Repository

COVID-19 infection leading to acute respiratory distress syndrome (ARDS) has been associated with impaired neurocognitive function and is known to increase the risk for endothelial dysfunction and coagulopathy affecting the vasculature of the brain. Recent studies have reported a higher concentration of cytokine and glutamate receptors along white matter tracts which may increase susceptibility to inflammatory-induced damage, further affected by hypoxemia due to direct and indirect lung damage. We conducted a systematic review and meta-analysis which suggests that the combination of ARDS and COVID-19 doubles the risk of developing intracranial hemorrhage and increases vulnerability to cerebral white matter injury as …

Mining Sars-Cov-2 Phylogenetic Trees To Estimate Circulating Infections And Patterns Of Migration, Erin V. Brintnell

Electronic Thesis and Dissertation Repository

The SARS-CoV-2 pandemic led to the formation of very large databases of genomic viral data. These databases contain information on transmission dynamics, emergence and evolution of SARS-CoV-2. However, extracting this information from sequences is difficult, as most methods of analyzing viral genomes were developed for smaller data sets. Therefore, my objective was to develop new fast estimators of the number of infections (I) and the rate of migration based on simple features of SARS-CoV-2 phylogenies.

I simulated pathogen evolution using a susceptible-exposed-infectious-recovered (SEIR) model of pathogen spread, reconstructing evolution using CoVizu. For simulations of I, I varied the total number …

Assessing Inflammation In The Pathology Of Knee Osteoarthritis, Zachary J. Koudys

Electronic Thesis and Dissertation Repository

Osteoarthritis (OA) is a joint disease that causes pain, stiffness, and loss of function. Inflammation of the synovium plays a role in the pathology of OA. Macrophages are the dominant immune cells in synovial tissue. Activated macrophages over-express the translocator protein (TSPO). [¹⁸F]FEPPA is a 2^nd generation positron emission tomography (PET) tracer that can target TSPO with high specificity. Hybrid [¹⁸F]FEPPA PET/MRI may enable accurate quantification of macrophage activity in vivo. In this work, [¹⁸F]FEPPA tracer uptake in knee synovial tissue was measured ex vivo using autoradiography and was validated to correlate to …

Transferring Organelles Into Native Neurons: A Disease-Modifying Therapy For Neurodegenerative Disorders, Lohiny Balendran

Electronic Thesis and Dissertation Repository

Currently, there are no disease-modifying therapies to counter the progression of neurodegenerative diseases that are associated with mitochondrial dysfunction in the early stages. In this study, we have used a novel strategy of cell fusion to transfer mitochondria from one cell to another using fusogens (syncytin 1 and syncytin 2). Syncytins are placental proteins encoded by endogenous retroviral envelope genes that promote cellular fusion. In this study, we have proposed that donor cells engineered to stably express syncytin when cocultured with recipient cells will allow fusion and facilitate the transfer of mitochondria into recipient cells. Syncytin-mediated systems revealed about 16.6-18.5% …

Sarcopenia In Head And Neck Cancer: A Prognostic Analysis, Nedeljko Jovanovic

Electronic Thesis and Dissertation Repository

Introduction: In head and neck cancer (HNC), loss of skeletal muscle mass (SMM), or sarcopenia, is a strong prognostic factor for outcomes. However, inconsistencies in its assessment limit our understanding of the relationship between sarcopenia and nutrition-related outcomes. This project evaluated the significance of sarcopenia as described in the literature and as demonstrated in a cohort of HNC patients.

Methods: A scoping review was first conducted followed by a retrospective cohort study with data collected from 194 oropharyngeal carcinoma patients treated with definitive radiation/chemoradiation. Sarcopenia was assessed from computed tomography (CT) imaging at the third cervical vertebra (C3) and the …

Lipoprotein(A), Oxidized Phospholipids, And Vascular Smooth Muscle Cell Phenotype And Viability, Michael Dunphy

Electronic Thesis and Dissertation Repository

Genetic studies have shown elevated plasma lipoprotein(a) (Lp(a)) levels to be an independent and causal risk factor for atherosclerotic cardiovascular disease and calcific aortic valve disease, however a definite mechanism for this pathogenicity has yet to be clearly identified. Oxidized phospholipids (oxPLs) have been implicated in facilitating atherogenic changes in the gene expression of vascular cells. As the primary carrier of oxPLs in the plasma, we hypothesize that Lp(a) contributes to vascular diseases by its enhanced ability to bind to and deliver oxPLs to tissue through a strong lysine binding site on its apolipoprotein(a) (apo(a)) component. Using a cultured primary …

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 …