Characterizing The Human Vaginal Microbiome Using High-Throughput Sequencing, Jean Megan E. Macklaim

Electronic Thesis and Dissertation Repository

The human vaginal microbiome undoubtedly has a significant role in reproductive health and for protection from infectious organisms. Recent efforts to characterize the bacterial species of the vagina using molecular techniques have uncovered an unexpected diversity. Using high-throughput sequencing I sought to describe the structure and function of the vaginal microbiome under different physiological states including healthy, bacterial vaginosis (BV), post-menopausal vaginal atrophy, and acute vulvovaginal candidiasis (VVC).

Partial 16S rRNA gene sequencing revealed that healthy, asymptomatic women most often have vaginal biotas dominated by Lactobacillus iners or L. crispatus. In contrast, BV is a heterogeneous, highly diversified condition …

Exploring The Structure And Biochemistry Of Oxidation-Mediated Inhibitation Of The Peptidyl-Prolyl Isomerase Pin1, Brendan T. Innes

Electronic Thesis and Dissertation Repository

Pin1 is a phosphorylation-dependent peptidyl-prolyl isomerase that has been shown to be neuroprotective in aging-related neurodegenerative diseases such as Alzheimer's disease (AD). However, it is not active in AD brain, and a recent proteomic screen of Mild Cognitive Impairment (MCI) brain samples revealed that Pin1 is oxidized in the brains of these pre-AD patients. This suggests that this oxidation may be the cause of the loss of the neuroprotective Pin1 function in AD. The Pin1 active site contains a functionally critical cysteine residue (Cys113) with a low predicted pKa, making it highly susceptible to oxidation. We hypothesize that Pin1 is …

A Pilot Study To Investigate Concerns In Patients Undergoing Neck Dissection Surgery, Daniel Sundar Raj Arulananda Doss

Electronic Thesis and Dissertation Repository

Abstract:

This study investigates concerns in patients undergoing neck dissection surgery. Forty patients were recruited at Pre-surgery, Discharge and 1-month Post-surgery. The Patient Concerns Inventory - Level of Importance questionnaire (PCI-LOI), Shoulder Pain and Disability Index (SPADI), Neck Dissection Impairment Index (NDII) and the University of Washington - Quality of Life questionnaire (UWQOL) were used.

The study identified "Anxiety" at Pre-surgery and "Appearance" at Discharge and 1-month Post-surgery as the important patient concerns. Patients’ concerns were found to change over time. Support for cross-sectional convergent validity of the PCI-LOI was evidenced by significant correlations between the PCI-LOI and the UWQOL …

Prenatal Programming Of Hepatic Glucose And Cholesterol Regulation In Male Rat Offspring By Chronic Intermittent Hypoxia, Waseem Iqbal

Electronic Thesis and Dissertation Repository

Obstructive sleep apnea (OSA) is a chronic disorder involving repetitive interruptions in breathing during sleep. Sufferers of OSA are exposed to chronic intermittent hypoxia (CIH), characterized by cyclical reductions in oxygen availability. A number of studies have established a link between OSA and various cardiovascular and metabolic comorbidities in adulthood, including hypertension, obesity, and type II diabetes. While the consequences of OSA in adults have been well described, the cross-generational impact of this condition and potential effects on fetal development are not known. Epidemiological and animal studies have demonstrated that physiological insults during pregnancy lead to diminished growth of offspring …

Measuring The Sixth Vital Sign: A Descriptive Analysis Of Distress In Individuals With Head And Neck Cancer And Their Caregivers, Catherine C. Bornbaum

Electronic Thesis and Dissertation Repository

Introduction: Distress has become so problematic in oncology that it has been recognized as the “sixth vital sign” implying that distress monitoring should occur as routinely as the monitoring of one’s temperature or blood pressure. The research reported herein investigated the impact of head and neck cancer on levels of distress, commonly reported problems, and perceptions of quality of life in individuals with head and neck cancer and their caregivers.

Method: Two distinct studies were conducted; the first explored the patient experience of distress and quality of life while the second assessed the caregiver experience of these same constructs. A …

Image Quality Of Energy-Dependent Approaches For X-Ray Angiography, Jesse Evan Tanguay

Electronic Thesis and Dissertation Repository

Digital subtraction angiography (DSA) is an x-ray-based imaging method widely used for diagnosis and treatment of patients with vascular disease. This technique uses subtraction of images acquired before and after injection of an iodinated contrast agent to generate iodine-specific images. While it is extremely successful at imaging structures that are near-stationary over a period of several seconds, motion artifacts can result in poor image quality with uncooperative patients and DSA is rarely used for coronary applications.

Alternative methods of generating iodine-specific images with reduced motion artifacts might exploit the energy-dependence of x-ray attenuation in a patient. This could be performed …

The Role Of Il-22 Produced By Th17 Cells In Type 1 Diabetes, Stacey M. Bellemore

Electronic Thesis and Dissertation Repository

Interleukin-22 (IL-22) is produced by T helper 17 (Th17) cells. Th17 cells have been shown to be pathogenic in autoimmune diseases, however their role in type 1 diabetes (T1D) remains controversial. We have shown that Th17-differentiation of naïve T cells can be driven by IL-23 + IL-6 to produce large amounts of IL-22 and induce T1D. Conversely, polarizing T cells using TGF-β + IL-6 led to nonpathogenic Th17 cells that produced lower IL-22 levels. We have shown that neutralizing IFN-γ during polarization leads to a drastic increase in IL-22. We have also found IL-22-producing cells in the pancreas of diabetic …

Vascular Stem Cells In Diabetic Complications, Emily C. Keats

Electronic Thesis and Dissertation Repository

Diabetes leads to a variety of secondary complications. At the heart of these complications lies endothelial cells (ECs) – cells that take up unregulated plasma glucose, experience various biochemical alterations, and provide the basis for whole organ vascular dysfunctions. With the purpose of generating new vascular networks for the treatment of these chronic complications, my initial work focused on vascular stem cells (VSCs). VSCs have the ability to differentiate into both endothelial (EPC) and mesenchymal (MPC) progenitor cells, both of which are necessary for the creation of stable and functional blood vessels. To establish whether these progenitor populations retain their …

Risk Factors For Diabetes Mellitus: A Comparative Analysis Of Subpopulation Differences In A Large Canadian Sample, Michael James Taylor

Electronic Thesis and Dissertation Repository

Objectives: Certain Canadian subpopulations observe numerous modifiable and non-modifiable risk factors for diabetes. This study compares immigrants and Aboriginals (First Nations, Inuit, and Métis) with Canada-born individuals at higher risks for diabetes, and deciphers the determinant differences between them.

Methods: Pooled Canadian Community Health Survey data (2001-2010) were used. Time trends for diabetes within each subsample were calculated using individual survey year prevalence rates; diabetes diagnoses were self-reported (N=33,565). Various risk factors were also examined using logistic regression.

Results: Diabetes prevalence rates significantly increased from 2001 to 2010 for each subpopulation, as well as the total sample: Canada-Born individuals (3.9% …

Evaluation Of Matricellular Proteins As Potential Therapeutics For The Treatment Of Human Chronic Skin Wounds, Christopher G. Elliott

Electronic Thesis and Dissertation Repository

There is currently an unmet need for treatments to enhance healing of human chronic skin wounds. Previously, therapy development has focused on growth factors and physical matrices, often resulting in disappointing clinical outcomes. In this thesis, we approached chronic skin wound treatment with a focus on fibrosis and matricellular proteins. Fibrosis is a pathological condition where tissue repair continues, unchecked, resulting in excess contraction, matrix accumulation and fibrogenic growth factor activity; features critically reduced in chronic skin wounds. Identifying factors that promote fibrosis may offer new therapeutic targets for use in chronic skin wounds. Two such factors are the matricellular …

Imaging Breast Cancer Progression And Lymph Node Metastases In Murine Models Using Mri And Magnetic Nanoparticles, Vasiliki Economopoulos

Electronic Thesis and Dissertation Repository

Most breast cancer related deaths are caused by the spread or metastasis of the primary tumor to distant sites in the body. The lymph nodes are one of the first places where metastases can be detected and are frequently examined for macroscopic metastases to help determine course of treatment for patients. However, little is known about the significance of microscopic metastases and disseminated individual cancer cells within the nodes. The goal of this work was to use MRI to monitor the development of primary tumors and lymphatic metastases in models of breast cancer.

In this thesis, we examined the MRI …

Role Of Inos In Septic Pulmonary Microvascular Endothelial Cell Activation, Zahra Asad

Electronic Thesis and Dissertation Repository

Abstract

Background. Neutrophils and nitric oxide (NO) derived from inducible NO synthase (iNOS) contributes importantly to the pathophysiology of acute lung injury (ALI) and pulmonary microvascular endothelial cell (PMVEC) injury. However, the mechanism of neutrophil and neutrophil iNOS dependent PMVEC injury has not been addressed. In our studies, we assessed PMVEC activation under septic conditions, and defined the role of PMVEC vs. bone-marrow polymorphonuclear leukocytes (PMN) iNOS in this septic PMVEC activation.

Methods and Results. We isolated PMVEC from iNOS+/+ and iNOS-/- mice lungs magnetically by microbeads attached to anti-PECAM antibodies, sorted by flow cytometry (FACS) by DiI-acetylated low density …

Magnetic Resonance Imaging Of Iron In Early Multiple Sclerosis At 3 Tesla, Matthew P. Quinn

Electronic Thesis and Dissertation Repository

Multiple sclerosis (MS) is the most common neurological disease in young Canadians, yet its etiology remains obscure. Two possibly related findings in MS are brain iron deposition and the presence of small veins in white matter lesions. This thesis concerns the development and application of 3 Tesla magnetic resonance imaging tools to image iron and veins in early multiple sclerosis.

To facilitate measurements of iron concentration as well as production of cerebral venograms, we first optimized multi-echo susceptibility weighted imaging (SWI), using numerical simulations and input from physicians. We validated measurements of R2*, an MRI parameter that scales linearly with …

Exploring The Iranian-Canadian Family Experience Of Dementia Caregiving: A Phenomenological Study, Sevil Deljavan

Electronic Thesis and Dissertation Repository

Presently in Canada, there are approximately 500,000 individuals living with dementia, which is expected to increase to over one million by 2038. With Canada’s minority elderly population growing, the number of Iranian-Canadian older adults living with dementia is expected to rise as well. Family caregivers are a significant source of help among Iranian-Canadians and the provision of informal care by adult children for parents with dementia in the Iranian culture is an expression of love and dedication.

This study explored the meaning of the experience of Iranian adult children in Canada caring for a parent with Alzheimer’s disease, the values …

Effects Of Niacin In Human Vascular Endothelial Cells During Lipotoxicity, Jennifer M. Hughes-Large

Electronic Thesis and Dissertation Repository

Nicotinic acid (NA) can improve vascular function and regeneration independent of correcting dyslipidemia. NA, as a potential biosynthetic precursor for NAD⁺, may elicit these vascular benefits through SIRT-mediated NAD⁺-dependent responses. We hypothesized that NA improves endothelial cell function under lipotoxic conditions through NAD⁺-dependent pathways. Angiogenic function in excess palmitate was assessed by tube formation assay following treatment of human microvascular endothelial cells (HMVEC) with NA or nicotinamide mononucleotide (NMN; a direct NAD⁺ precursor). Both NA and NMN improved HMVEC angiogenic function during palmitate overload. Only NMN increased cellular NAD⁺ and SIRT1 activity, …

Causes Of Post Stroke Falls Along The Care Continuum: Implications For Improving Patient Safety, Mona Madady

Electronic Thesis and Dissertation Repository

In Western countries stroke is responsible for 10-12% of all deaths. In 2000, strokes cost $3.6 billion for the Canadian healthcare system and lost productivity due to premature death and long-term disability. Falls are a frequent occurrence at all stages of post-stroke recovery and can have significant negative impacts. While information about the incidence and risk factors of falling among stroke survivors is available, considerably less is known about the specific factors contributing to falls and the circumstances surrounding these adverse events. The purpose of this project was to identify similarities between systemic factors of falls in stroke survivors across …

Human Adenovirus E1a Binds And Retasks Cellular Hbre1, Blocking Interferon Signalling And Activating Virus Early Gene Transcription, Gregory J. Fonseca

Electronic Thesis and Dissertation Repository

Upon infection, human adenovirus (HAdV) must block interferon signaling and activate the expression of its early genes to reprogram the cellular environment to support virus replication. During the initial phase of infection, these processes are orchestrated by the first HAdV gene expressed during infection, early region 1A (E1A). E1A binds and appropriates components of the cellular transcriptional machinery to modulate cellular gene transcription and activate viral early genes transcription. We have identified hBre1/RNF20 as a novel target of E1A. hBre1 is an E3 ubiquitin ligase which acts with the Ube2b E2 conjugase and accessory factors RNF40 and WAC1 to monoubiquitinate …

Regulation Of Lipid Homeostasis, Inflammatory Signalling And Atherosclerosis By The Peroxisome Proliferator-Activated Receptor Delta, Lazar A. Bojic

Electronic Thesis and Dissertation Repository

The peroxisome proliferator-activated receptor (PPAR) δ is a ligand-dependent transcription factor that has been implicated in metabolic and inflammatory regulation. The molecular and physiological mechanisms by which PPARδ activation regulates lipid metabolism, inflammatory signaling and protection from atherosclerosis in states of metabolic disturbance such as insulin resistance and dyslipidemia, were investigated in a series of in vitro and in vivo studies. In vitro experiments demonstrated that PPARδ activation inhibits atherogenic lipoprotein-induced lipid accumulation and the associated proinflammatory responses. The primary mechanisms for these effects were increased fatty acid β-oxidation, decreased lipoprotein lipase (LPL) activity, reduced MAPK signaling and improved insulin …

Amyloid Beta Resistance And The Warburg Effect: Re-Examining Alzheimer's Disease, Jordan Taylor Newington

Electronic Thesis and Dissertation Repository

Alzheimer’s disease (AD) is characterized by deposition of the amyloid beta (Ab) peptide in the brain, an event which frequently but not universally correlates with nerve cell death. Although most nerve cells die in response to Ab, small populations of cells are able to survive by becoming resistant to Ab toxicity. Understanding the mechanisms by which cells become resistant to Ab may reveal novel treatments for AD. Interestingly, nerve cell lines selected for resistance against Ab exhibit increased glucose uptake and glycolytic flux. Here I show that these metabolic changes are mediated through an upregulation of pyruvate dehydrogenase kinase 1 …

Genetic Approaches To Studying Complex Human Disease, Joseph B. Dube

Electronic Thesis and Dissertation Repository

Common, complex diseases such as cardiovascular disease (CVD) represent an intricate interaction between environmental and genetic factors and now account for the leading causes of mortality in western society. By investigating the genetic component of complex disease etiology, we have gained a better understanding of the biological pathways underlying complex disease and the heterogeneity of complex disease risk. However, the development of high throughput genomic technologies and large well-phenotyped multi-ethnic cohorts has opened the door towards more in-depth and trans-disciplinary approaches to studying the genetics of complex disease pathogenesis. Accordingly, we sought to investigate select complex traits and diseases using …

Characterizing Stomatin-Like Protein 2 And Its Role In Neuron Survival, Lisa A. Foris

Electronic Thesis and Dissertation Repository

Stomatin-like Protein 2 (SLP-2) has been identified as a stress-inducible transcript and has been shown to interact with and stabilize mitochondrial proteins. Since mitochondria are critical for neuronal function, we hypothesized that SLP-2 regulates neuron survival in response to stressful stimuli. A conditional SLP-2 knockout mouse (deletion) and the SN56 cell line (upregulation) were employed to study the role of SLP-2 in mitochondrial dynamics and neuron survival. SLP-2 deficient primary cortical neurons displayed significantly decreased levels of various mitochondrial respiratory chain proteins, indicating SLP-2 contributes to maintenance of mitochondrial membrane integrity. SLP-2 was up-regulated in response to oxidative stress and …

Elongation Factor 1a-1 And Hepatocyte Response To Fatty Acid Excess, Alexandra M. Stoianov

Electronic Thesis and Dissertation Repository

Obesity is associated with elevated levels of serum fatty acids, which accumulate in nonadipose tissues including the liver. Elongation factor 1A-1 (EF1A-1) has previously been shown to participate in the cell stress and death response of cardiomyocytes to excess saturated fatty exposure, and in steatotic mouse myocardium. In this thesis, the hypothesis that the hepatocyte response to fatty acid overload involves EF1A-1 was tested. EF1A-1 expression was induced in the livers of obese mice in association with severe hepatic steatosis, and in HepG2 human hepatoma cells in response to excess palmitate. Partial translocation of EF1A-1 from the ER to polymerized …

Systematic Assessment Of The Contribution Of Superantigens To Nasopharyngeal Colonization In A Mouse Model Of Streptococcal Infection, Katherine J. Kasper

Electronic Thesis and Dissertation Repository

Streptococcus pyogenes is adapted for persistence in humans. It typically colonizes the tonsils and skin, and humans are the only known reservoir. S. pyogenes can cause a wide range of mild to serious infections. Most streptococci-related deaths are due to complications of rheumatic fever and invasive infections. S. pyogenes produces virulence factors that contribute to the pathogen’s ability to colonize and cause disease, including streptococcal superantigens (SAgs), also known as streptococcal pyrogenic exotoxins (Spes). SAgs function by cross-linking T cells and antigen presenting cells (APC) which may cause a massive inflammatory response, and as such have been found to contribute …