Medical Sciences Commons^™

White Matter Inflammation And Executive Dysfunction: Implications For Alzheimer Disease And Vascular Cognitive Impairment, Alexander Levit

Electronic Thesis and Dissertation Repository

White matter integrity is crucial to healthy executive function, the cognitive domain that enables functional independence. However, in the ageing brain, white matter is highly vulnerable. White matter inflammation increases with age and Alzheimer disease (AD), which disrupts the normal function of white matter. This may contribute to executive dysfunction, but the relationship between white matter inflammation and executive function has not been directly evaluated in ageing nor AD. White matter is also particularly vulnerable to cerebrovascular disease, corresponding with the common presentation of executive dysfunction in vascular cognitive impairment (VCI). Thus, white matter may be an important substrate by …

Wearable Sensors And Total Knee Arthroplasty: Assessing Quantitative Function To Improve The Patient Experience, Megan Fennema

Electronic Thesis and Dissertation Repository

Osteoarthritis (OA) is a chronic degenerative disease for which the only long-term solution is total knee arthroplasty (TKA), though many patients are not satisfied with their TKA. Satisfaction in TKA patients is not well understood. Subjective questionnaires and objective functional tests have been previously used to assess TKA outcomes, but both have disadvantages. Wearable sensors have facilitated affordable biomechanical measurement in OA and TKA populations. The objective of this work was to use wearable sensors alongside functional tests with TKA patients to identify quantitative function that related to subjective function and satisfaction. A wearable sensor-setup was validated before implementation in …

Effects Of Maternal Protein Restriction On The Pulmonary Surfactant System During The Early Life And Adulthood, Reza Khazaee

Electronic Thesis and Dissertation Repository

Fetal growth restriction (FGR) is defined by low birth weight and contributes to a variety of adult-onset diseases with different severities between males and females. However, the effects of FGR on the pulmonary surfactant are not fully elucidated. In this thesis, first, we investigated the FGR effects on the lung function and the surfactant system at the early postnatal life. It was hypothesized that FGR contributes to alterations of lung mechanics and the surfactant system during the neonatal period. Second, we assessed the FGR effects on the surfactant system in response to sepsis in adulthood. It was hypothesized that FGR …

The Epidemiology Of Infective Endocarditis Among People Who Inject Drugs In London, Ontario., Brian Hallam

Electronic Thesis and Dissertation Repository

Infective endocarditis is an infectious disease that affects the valves of the heart. Injection drug use is currently a leading risk factor among patients with endocarditis. We conducted a prospective study using data from hospital chart records among patients with endocarditis in London, Ontario, which has a relatively high prevalence of people who inject drugs to assess the severity of the issue and the major risk factors of mortality pertaining to this population. This study had a sample size of 353 and included a review of the incidence of admissions of endocarditis, as well as a survival analysis, using both …

Drug Response And Metabolism In Crohn's Disease, Aze Wilson

Electronic Thesis and Dissertation Repository

Inflammatory bowel disease (IBD) is an illness of chronic intestinal inflammation comprised of Crohn's disease (CD) and ulcerative colitis (UC). Specialists rely heavily on drugs that target a dysregulated immune system. There is a staggering degree of variation in drug response in CD. Our understanding of drug metabolism and response in IBD is limited. Gaining new insights into IBD-specific modifications of drug metabolism may allow for improved drug efficacy and reduced toxicity. Cytochrome P450 (CYP) 3A4 is the most relevant determinant of drug metabolism and exposure for medications prescribed today. CYP3A4 is highly expressed in the liver, but is also …

Head Injury Risk And Car Seat Use For Children In Collisions, Peyton A. Schroeder, M.J. Skhurm, D. Fraser, K. Mcclafferty

Western Research Forum

Background: Motor vehicle collisions (MVCs) are the leading cause of death for people under the age of 17 years. Almost 80% of rear seat motor vehicle passengers are children. Previous studies have shown that a large fraction of injuries to children in MVCs involved the head and chest. In this study, the hypothesis that children under the age of eight using a forward-facing child restraint system (FFCRS) will have more severe head injuries than children using any other type of restraints in an MVC was tested.

Methods: Several datasets obtained from Transport Canada and Level 1 Pediatric Trauma Centre emergency …

Kallikrein-Related Peptidases Are Dysregulated In Pleomorphic Adenoma, Matthew D. Morrison

Electronic Thesis and Dissertation Repository

Objectives: Pleomorphic adenoma (PA) is the most common benign salivary gland tumor. Kallikrein-related peptidases (KLKs) have been identified as biomarkers in many human tumors and may influence tumor behavior. We investigated KLK1-15 messenger ribonucleic acid (mRNA) and proteins in PA specimens to determine a KLK expression profile for this tumor.

Methods: Fresh frozen PA tissue specimens (n = 26) and matched controls were subjected to RT-qPCR to detect KLK1-15 mRNA. Expression of KLK1, KLK12, KLK13 and KLK8 proteins were then evaluated via immunostaining techniques. Statistical analyses were performed with the level of significance set at P < .05.

Results: We observed downregulation …

Acute Pharmacologic Modulation Of Glioblastoma Ph Monitored By Chemical Exchange Saturation Transfer Magnetic Resonance Imaging, Mohammed Albatany

Electronic Thesis and Dissertation Repository

The response of tumor intracellular pH (pH_i) to a pharmacological challenge could help identify aggressive cancer. In addition, tumor pH_i may influence cell proliferation, apoptosis, chemotherapy resistance, and thermosensitivity. Chemical exchange saturation transfer (CEST) is a novel MRI contrast mechanism that is sensitive to cellular pH. More specifically, a CEST method called amine and amide concentration-independent detection (AACID) produces images weighted by intracellular pH (pH_i) and can be used to study pharmacologic pH modulation in tumours.

The overall goal of this thesis was to maximize the magnitude of intracellular tumour acidification using pharmacologic agents. Several …

Characterization Of Urinary Microbiome And Their Association With Health And Disease, Yige Bao

Electronic Thesis and Dissertation Repository

There has been a growing interest in human microbiome studies in the past decade, with the development of high-throughput sequencing techniques. These microorganisms interact and respond to the host as an entity, and are involved in various homeostatic functions including nutrition digestion, immune response, metabolism and endocrine regulation. The urinary microbiome, however, remains relatively under-investigated.

One of the technical challenges of urinary microbiome studies is the samples usually contain a large number of host cells and low microbial biomass. These samples with the high host, low microbial abundance (“high-low” samples) are associated with increased risk of compromised quality of …