Digital Commons Network^™

Producing A Subunit Vaccine For Porcine Epidemic Diarrhea Virus, Zayn Khamis

Electronic Thesis and Dissertation Repository

Porcine epidemic diarrhea virus (PEDv) causes disease and mortality to piglets worldwide. Most vaccines used to combat the disease have been ineffective live attenuated virus vaccines. The goal of this project was to produce a plant-made subunit vaccine based off the membrane protein of the virus. This is the first time this protein has been produced in plants. An elastin-like polypeptide fusion membrane protein accumulated up to 0.8 mg/g of fresh leaf weight when transiently expressed in Nicotiana benthamiana. Virus-like particles were also produced for the first time for PEDv, and were able to form with just the membrane …

Behavioural Inflexibility And White Matter Inflammation In An Aged Happ Rat With Subcortical Stroke, Aaron M. Regis

Electronic Thesis and Dissertation Repository

The interactions between Alzheimer’s disease (AD) and ischemic stroke pathology are of key interest in the development of post-stroke cognitive decline. While clinical and experimental studies have suggested an interaction, the mechanisms whereby these conditions interact to worsen cognition haven’t been fully revealed. This study aimed to combine rodent models of AD and stroke in an aged rat and assess the behavioural and histological outcomes. An injection of endothelin-1 (ET-1), a potent vasoconstrictor into the basal ganglia of a rat with human amyloid precursor protein (hAPP) overexpression (F344Tg) was followed up 3 months later to assess behavioural flexibility, memory and …

Signal Transduction Mechanisms Mediating The Regulation Of Vascular G Protein-Coupled Receptors, Elena Tutunea-Fatan

Electronic Thesis and Dissertation Repository

Blood pressure homeostasis is controlled via a complex network of cell signaling mechanisms. Among the broad network of receptors and signaling molecules regulating blood vessel reactivity, members of the G protein-coupled receptor (GPCR) family are known to play a central role. GPCR activity represents a delicate, but coordinated balance between molecular mechanisms governing receptor signaling, desensitization, and re-sensitization. GPCR kinase 2 (GRK2) modulates multiple cellular responses through GPCR desensitization and alterations in GRK2 activity are considered to play an important role in the development of hypertension. The main premise of our study was to test whether the inhibition of GRK2 …

Cost-Effectiveness Of Selective Laser Trabeculoplasty (Slt) Versus Argon Laser Trabeculoplasty (Alt) In Uncontrolled Open Angle Glaucoma Patients Having At Least One Full Previous Slt: An Economic Evaluation Alongside An Ongoing Randomized Controlled Clinical Trial, Muhammad Rakibuz-Zaman

Electronic Thesis and Dissertation Repository

Background and objective: ALT and SLT are both safe and effective for glaucoma treatment. We performed a cost-effectiveness analysis (CEA) of SLT versus ALT for a six-month follow-up period in uncontrolled open angle glaucoma patients having at least one full previous SLT from an ongoing RCT. Methods: Trial based treatment costing and IOP reduction at 6-month follow-up from baseline for both intervention arms were calculated. A decision tree model was developed considering possible clinical pathways of patients undergoing repeat laser trabeculoplasty. CEA among ALT and SLT was done, and ICERs were calculated from both societal and ministry perspective. One way …

The Long Non-Coding Rna Malat1 Regulates Inflammatory Cytokine Production In Chronic Diabetic Complications, Andrew D. Gordon

Electronic Thesis and Dissertation Repository

We examined the role of MALAT1, a highly conserved nuclear lncRNA, in chronic diabetic complications affecting the heart and kidneys, specifically with respect to inflammatory cytokine production. Endothelial cells, exposed to various glucose levels, and MALAT1 knockout mice and controls, with or without streptozotocin-induced diabetes were examined. Endothelial cells cultured with high glucose, and renal and cardiac tissue from diabetic mice showed increased inflammatory cytokine (eg. IL-6, IL1β, TNFα) production along with transient MALAT1 upregulation. This was confirmed by both transcript and protein analyses, and such changes were prevented in the MALAT1 knockout diabetic animals. In the malat1 knockout animals, …

The Effect Of A Square-Stepping Exercise Intervention On Heart Rate Variability In Older Individuals With Type 2 Diabetes And Subjective Cognitive Complaints, Claire E. Riley

Electronic Thesis and Dissertation Repository

Aging is associated with increased onset of diseases such as type 2 diabetes (T2D) and cognitive impairment. Heart rate variability (HRV), a measure of autonomic function, is reduced in T2D and may have the potential to indicate cognitive decline in this population. Square-stepping exercise (SSE) is a novel cognitive exercise recently implemented in cognitive research, which may have the potential to improve global cognitive function in T2D individuals. Participants with T2D (N=25, aged ≥ 50y) and self-reported cognitive complaints were randomized into either an SSE intervention or a wait-list (WL) control group for 24-weeks. HRV parameters (time and frequency domain) …

Disability And Return To Work Following Musculoskeletal Injury, Qiyun Shi

Electronic Thesis and Dissertation Repository

Musculoskeletal disorders (MSDs) are injuries, damage or disorders affecting the musculoskeletal system including muscles, ligaments, nerves, tendons, bones or cartilage etc. MSDs are highly prevalent and associated with sickness absence, reduced work efficiency, job changes and earlier retirement.. They also affect daily activity and social functioning. Although many MSDs are accompanied by minor symptoms and settled spontaneously, approximately 10% of the workforce with MSDs have difficulty resuming their original work or exit the workforce permanently. Return to work after MSDs is complex, and is influenced by many factors including physical, psychological, economic and social factors.

Although there are extensive studies …

Expression Of Kallikrein-Related Peptidases (Klks) In Adenoid Cystic Carcinoma, Zachary R. Kerr

Electronic Thesis and Dissertation Repository

Adenoid cystic carcinoma (ACC) of salivary glands is a malignancy known for its slow growth pattern, but poor long-term survival despite aggressive treatment. This highlights the need for an improved approach to its management.

It has been suggested that kallikrein-related peptidases (KLKs), a group of 15 serine proteases, may serve as biomarkers for salivary gland tumors. KLKs are involved in numerous biological processes and have been linked to several cancers.

This study evaluated KLK gene expression in ACC and normal salivary gland tissue (NSGT). Total RNA was isolated from 40 formalin-fixed, paraffin-embedded samples, which included 25 ACCs and 15 NSGTs. …

Is Online Motor Control Really Impaired In Parkinson's Disease?, Kate E. Merritt

Electronic Thesis and Dissertation Repository

Patients with Parkinson’s disease (PD) are thought to be selectively impaired in consciously-mediated online automatic motor control, whereas the ability to perform subconscious online adjustments remains intact. This present study evaluates the hypothesis that the previously alleged deficits in online motor control in PD are not due to the consciousness of the correction, but rather are attributable to aspects of the prior experimental designs disproportionately penalizing patients for PD-related bradykinesia. Here, we implemented a modified traditional double-step paradigm to investigate consciously-mediated online motor control in PD, in a manner that would be unconfounded by disease-related bradykinesia. Further, we investigated the …

Panx1 And Panx3 Regulate Adipocyte Development And Fat Accumulation In Vivo, Vanessa R. Lee

Electronic Thesis and Dissertation Repository

The obesity epidemic is a growing concern due to its various comorbidities and associated risk factors. Pannexins 1 and 3 (Panx1 and Panx3), are members of a family of channel-forming glycoproteins that have been reported to be important in paracrine signaling and development. Panx1 and Panx3 are homologous and are regulated in many different cell types, mediating cell proliferation and differentiation. We have shown that Panx1 and Panx3 are expressed in adipocytes and adipose-derived stromal cells (ASCs) throughout the process of differentiation. Mice globally lacking Panx1 (Panx1 KO) have significantly greater total fat mass compared to wildtype (WT) mice under …

Characterization And Personalization Of Botulinum Toxin Type A Therapy For Upper Limb Tremor In Parkinson Disease And Essential Tremor Patients Using Multi-Sensor Kinematic Technology, Olivia Samotus

Electronic Thesis and Dissertation Repository

Tremor commonly affects the upper extremities in essential tremor (ET) and Parkinson disease (PD) patients where many experience functional disability and ultimately seek therapy. As ET and PD tremor features overlap and clinical assessment is challenging due to its highly complex nature, misdiagnosis is common resulting in unsuitable therapies and prognosis. Current treatment options for ET and PD tremor include pharmacotherapy, focal therapy with botulinum toxin type A (BoNT-A) injections, and surgical interventions which provide modest relief of tremor. However, such therapies are commonly associated with significant adverse events and lack long-term efficacy and tolerability. Hence lack of standardized, objective …

Investigating Stromal Contributions To The Regulation Of Cancer Progression, Krista M. Vincent

Electronic Thesis and Dissertation Repository

Tumours are not insular masses of proliferating cells, rather tumour cells evolve within a complex local environment complete with matrix, stromal, and immune components. Therefore, successful tumour growth and eventual metastasis is not determined solely by tumour cells themselves, but also by the fitness advantage or disadvantage conferred by their local environment. However, many of our current cancer models are composed solely of tumour cell isolates. As tumour fitness is dependent on the entire local cellular context, we were interested in characterizing the accuracy of cell lines as models of the tumour microenvironment, with a focus on the secreted Frizzled-related …

The Effect Of Ast-120 On Hepatic Metabolism And Transport In Chronic Kidney Disease, Andrew S. Kucey

Electronic Thesis and Dissertation Repository

Chronic kidney disease (CKD) is characterized by a progressive and irreversible decline in renal function. Patients are at high risk for adverse drug events since they are typically administered multiple medications concurrently and pharmacokinetic changes in the diseased state are relatively unexplored. Recent studies point towards molecules known as uremic toxins for playing a mechanistic role in altering the expression and function of drug metabolizing enzymes and drug transporter proteins. To further investigate this hypothesis an adenine-induced model of CKD was used in male wistar rats. AST-120 was administered to remove uremic toxins in an attempt to recover metabolic enzyme …

Beta Blocker Dialyzability And Effectiveness In Chronic Hemodialysis Patients, Alvin Tieu

Electronic Thesis and Dissertation Repository

Of the minimal information describing drug dialyzability, the majority was obtained prior to modern hemodialysis membranes. This study characterized the dialyzability of the most commonly prescribed beta blockers in patients undergoing high-flux hemodialysis. Eight subjects were recruited to a pharmacokinetic, 4-way crossover trial. Drug concentrations were measured using mass spectrometry and dialyzability determined by the arterial-venous difference and recovery clearance methods. A provincial-wide retrospective cohort study was designed to determine the effect of dialyzability on adverse clinical outcomes. Beta blocker efficacy can be hindered if substantial clearance occurs during dialysis. Our results demonstrate atenolol and metoprolol are extensively cleared during …

Inpatient Versus Outpatient Total Hip Arthroplasty, Michael Pollock

Electronic Thesis and Dissertation Repository

We conducted a randomized controlled trial to evaluate patients undergoing a total hip arthroplasty (THA) who were discharged from the hospital either on the day of surgery (outpatient) or were admitted overnight following surgery (inpatient). Our primary outcome was the rate of serious adverse events during the first three months postoperatively. Secondary outcome measures included cost, patient satisfaction, functional outcomes, quality of life and pain. We found no statistically significant difference between the two groups in serious adverse events. We found that outpatient THA was less expensive from the perspectives of the hospital and ministry of health; but the difference …

Peroxisome Proliferator Activated Receptor Delta In Osteoarthritis, Anusha Ratneswaran

Electronic Thesis and Dissertation Repository

Osteoarthritis (OA) affects 1 in 10 Canadians and is a leading cause of mobility disability worldwide. This condition is characterized by cartilage degeneration, subchondral bone damage and inflammation of the synovium, resulting in pain and joint failure. No treatments exist to stop the progression of this disease, and its underlying molecular mechanisms remain largely unknown. We previously identified the peroxisome proliferator activated receptor (PPAR) nuclear receptor pathway as altered in OA cartilage. In-vitro studies identified PPARd as a promoter of catabolic activity in chondrocytes, providing the foundation for my overarching hypothesis that PPARd inhibition is protective in OA.

I commenced …

Effects Of Prenatal Exposure To Bisphenol A On Fetal Lung Development, Ayten Hijazi

Electronic Thesis and Dissertation Repository

Prenatal exposure to bisphenol A (BPA), one of the most prevalent endocrine disrupting chemicals, is associated with lung dysfunction and diseases in later life. However, it is unknown if this association has a fetal origin. In this thesis, a series of in vivo and in vitro experiments were conducted to determine the effects of prenatal exposure to BPA on fetal lung development, and define the underlying molecular mechanisms. Environmentally relevant doses of BPA were administered to pregnant mice via diet from embryonic day (E) 7.5 to 18.5. Fetal lungs were analyzed at E18.5 for changes in structure and expression of …

The Development Of Novel Imaging Modalities & High-Throughput Drug Screening Platforms In The Drosophila Melanogaster Model Of Human Calcium Oxalate Nephrolithiasis, Sohrab Naushad Ali

Electronic Thesis and Dissertation Repository

Nephrolithiasis is a common urological disorder. Despite advances in the surgical treatment of kidney stone disease, research into its prevention and medical management remain stagnant. This is due to lack of viable pre-clinical models to study the disorder. In this project, we develop and characterize a robust Drosophila melanogaster model for human calcium oxalate nephrolithiasis. Using this model, we have developed intravital imaging techniques to study stone formation and novel high-throughput drug screening platforms. We successfully demonstrate calcium oxalate stone formation by sodium oxalate and ethylene glycol supplementation, with subsequent intravital imaging using bisphosphonate based fluorescent probes. Screening of 360 …

A Link Between Paediatric Asthma And Obesity: Are They Caused By The Same Environmental Conditions?, Phylicia Gonsalves

Electronic Thesis and Dissertation Repository

The highly associated paediatric conditions of asthma and overweight have seen dramatic increases over the past few decades. This thesis explored air pollution exposure as a potential underlying mechanism of co-morbid asthma and overweight among adolescents aged 12 to 18 years. Data from the Canadian Community Health Survey were merged with a database containing estimates of air pollution as assessed by particulate matter ≤ 2.5 microns (PM_2.5) concentrations at the postal code centroid in southwestern Ontario. Logistic regression was used to conduct the analysis. Adolescents were more likely to be overweight as PM_2.5 concentrations increased. There was …