Medicine and Health Sciences Commons^™

Does An Acute Achilles Tendon Rupture Become A Patient's Achilles Heel In The Long-Term?, Michaela Cm Khan

Electronic Thesis and Dissertation Repository

It is unknown if deficits in the involved limb following acute Achilles tendon rupture (AATR) persist in the long-term, or differ between patients treated operatively or non-operatively. This study investigated 43 patients 15±1 years post-AATR from a previous randomized controlled trial (RCT) that compared operative and non-operative treatment. Structural characteristics in the Achilles tendon and surrounding musculature were assessed using magnetic resonance imaging. We also performed physical examinations and evaluated performance-based and patient-reported outcomes. Overall, there were substantial differences between the involved and uninvolved limbs in most outcomes. Some outcomes improved over time from the initial RCT to the final …

The Difference In A1c Of Children And Adolescents With Type 1 Diabetes Mellitus Using Carbohydrate Counting Compared To Those Using A Structured Meal Plan, Alia El Kubbe

Electronic Thesis and Dissertation Repository

Carbohydrate counting (CHO) is a nutrition education tool used by patients with type 1 diabetes mellitus (T1DM). The primary objective was to assess glycated hemoglobin (A1C) in participants with T1DM using CHO counting vs. those using a structured meal plan (SMP). The secondary objectives were to determine if BMI-for-age, parental income, parental involvement, and mothers’ educational level were associated with their children’s glycemic control. A cross sectional study was conducted, where participants aged 4-18 years, or their parents completed a survey. Total sample size was 88 participants (77 in the CHO counting group and 11 in the SMP group). There …

Recovery Following Proximal Humerus Fracture, Azar Varahrami Vigeh

Electronic Thesis and Dissertation Repository

There is currently a glaring gap in the existing knowledge to address individuals’ experiences while recovering from a proximal humeral fracture (PHF). The main objective of this dissertation was to understand better how recovery is perceived by individuals after PHF. This overarching objective aligned well with the broad conceptualization of the issue at hand as those provided by the International Classification of Functioning, Disability and Health (ICF). Three inter-linked studies were conducted to provide a broader picture of recovery after PHF. The first study was a systematic review of prognostic factors predicting recovery after PHF in adults. This review demonstrated …

Utilizing Fiv (Feline Immunodeficiency Virus) To Develop A Novel Animal Model To Study Hiv (Human Immunodeficiency Virus), Ankita Suryakant Kambli

Electronic Thesis and Dissertation Repository

This project sought to perform the in vitro work needed to accomplish the long-term vision of harnessing the similarities between HIV (Human Immunodeficiency Virus) and FIV (Feline Immunodeficiency Virus) to develop an animal model whereby cats can be used to study HIV pathogenesis and therapeutics. We transfected CRFK (Crandell Rees Feline Kidney) fibroblasts with plasmids that could express human or feline CD4, CCR5, or both, and determined receptor surface expression through flow cytometry. We discovered that HIV envelope expressed on 293T can fuse with huCD4/huCCR5 on CRFK. These cat cell lines were also capable of supporting HIV infection. Additionally, we …

Discovery Of Novel Mechanisms Regulating Cancer Extravasation In The Chorioallantoic Membrane Model, Yohan Kim

Electronic Thesis and Dissertation Repository

Cancer metastasis is a multistep process that begins with the invasion of tumour cells into the stroma and migration towards the blood vessels. Tumour cells that have entered the bloodstream must then survive and leave by a process known as extravasation. Finally, extravasated cells proliferate and establish the secondary site in the metastatic cascade. Although extravasation encompasses key events during cancer cell invasion to aid in the development of effective treatments, an in vivo model that rapidly, reproducibly and economically recapitulates cancer cell extravasation is needed. Therefore, the objectives of my research were to 1) establish and validate an in …

Effect Of N-Acetyl-L-Cysteine Prevention Or Intervention On Diet Induced Beta Cell Compensation And Dysfunction, Madison Wallace

Electronic Thesis and Dissertation Repository

Type 2 diabetes mellitus (T2DM) progression increases oxidative stress which contributes to beta cell compensation and eventual dysfunction. To investigate the role of antioxidant N-acetyl-L-cysteine (NAC) on beta cell function and pancreatic stellate cell activation (aSMA⁺) during early and late stages of compensation, NAC was used for preventative (p) and intervention (i) treatments in C57BL/6N mice fed a 60% kcal high-fat diet (HFD) for 8 or 22 weeks. Significantly improved glucose tolerance was observed at 22 weeks following pNAC treatment in HFD mice. Although 22-week HFD mice displayed hyperinsulinemia, beta cell hypertrophy, decreased beta cell PDX-1 nuclear localization, …

In Search Of Psychiatric Kinds: Natural Kinds And Natural Classification In Psychiatry, Nicholas Slothouber

Electronic Thesis and Dissertation Repository

In recent years both philosophers and scientists have asked whether or not our current kinds of mental disorder—e.g., schizophrenia, depression, bipolar disorder—are natural kinds; and, moreover, whether or not the search for natural kinds of mental disorder is a realistic desideratum for psychiatry. In this dissertation I clarify the sense in which a kind can be said to be “natural” or “real” and argue that, despite a few notable exceptions, kinds of mental disorder cannot be considered natural kinds. Furthermore, I contend that psychopathological phenomena do not cluster together into kinds in the way that paradigmatic natural kinds (e.g., chemical …

Determining The Relative Transmission Fitness Of Hiv-1 Subtypes A, B, C, And D, Spencer Yeung

Electronic Thesis and Dissertation Repository

There is in vivo evidence that suggests the genetic diversity of HIV-1 subtypes influence heterosexual transmission efficiency. To recapitulate sexual transmission in vitro, blocks of genital tissue were exposed to mixtures of genetically different subtype viruses. Migrating immune cells were collected and co-cultured with a CD4+ T-cell line permissive to HIV infection (PM1) to measure dendritic cell virus transfer; HIV-exposed tissues were cultured separately. Next generation sequencing (NGS) of HIV-1 DNA was used to quantify relative infection rates of the various challenge viruses, and to assess fitness differences in infection of the tissue vs. migratory/T cell co-cultures. Our results …

Using Meditation To Improve Measures Of Attention In Older Adults, Sabrina Ford

Electronic Thesis and Dissertation Repository

Age-related cognitive decline greatly impacts quality of life for older adults. Previous research has indicated that meditation may act as a neuroprotective factor to prevent age-related cognitive decline. This thesis sought to replicate previous findings and investigate if a four-week meditation intervention would improve sustained attention. Participants 60 years and older (n=27, 17 female) were recruited and assigned to a focused-attention (FA) meditation or relaxation group which met for four weeks, three times a week. Resting-state EEG was used to collect individual alpha peak frequency (iAPF) and frontal alpha asymmetry (FAA). The Sustained Attention to Response Task (SART) was also …

Assessing The Structure-Function Relationships Of The Apolipoprotein(A) Kringle Iv Sub-Type 10 Domain, Matthew J. Borrelli

Electronic Thesis and Dissertation Repository

Elevated plasma lipoprotein(a) (Lp(a)) is the most prevalent heritable risk factor in the development of cardiovascular disease. The apolipoprotein(a) (apo(a)) component of Lp(a) is strongly implicated in the pathogenicity of Lp(a). It is hypothesized that the inflammatory potential of Lp(a)/apo(a) is mediated by the lysine binding ability of the apo(a) kringle IV10 (KIV10) domain, along with its covalently bound oxidized phospholipid (oxPL). Using targeted mutagenesis, two novel null alleles for the LPA gene that generate non-secretable apo(a) species have been identified, resulting from amino acid substitutions in the KIV10 domain. A potential mechanism by which KIV10 oxPL modification is enriched …

Investigating The Relationship Between Subcortical And Cortical Auditory Processing, Sonia Varma

Electronic Thesis and Dissertation Repository

The auditory system is highly integrative, with feedforward and feedback connections from periphery to cortex (and stages in between). In order to understand how the different levels of the human auditory system interact, it is necessary to simultaneously measure responses from multiple auditory levels. A novel stimulus was paired with electroencephalography (EEG) in 29 young, normal-hearing participants (17-34 years) to examine interactions among stages of the auditory pathway. Temporal regularity was manipulated by continuously accelerating and decelerating the rate of a click-train stimulus (i.e., ~3.5 Hz frequency modulation of the click rate). Adaptation of the brainstem (cochlear nucleus and inferior …

Neurodevelopmental Outcomes Of Infantile Hydrocephalus: An Fmri Case Study, Ikhlas Ahmed Hashi

Electronic Thesis and Dissertation Repository

Ventricle dilatation caused by infantile hydrocephalus may result in extensive damage of the posterior cortex (parietal and occipital lobes). We hypothesize that pathological changes in the development of the posterior cortex can be linked to non-verbal learning disabilities in children with previous infantile hydrocephalus. This case study will investigate the neurodevelopmental outcomes of 3 treated hydrocephalus patients, when compared to a group of healthy control children (n = 12). Within the hydrocephalus group, patients displayed differences in non-verbal test performance as well as parietal brain activation during an fMRI number comparison task. We associated these differences with clinical variables such …

Pregestational Diabetes Induced Congenital Heart Defects And Coronary Artery Malformations; Mechanisms And Preventative Therapies, Anish Engineer

Electronic Thesis and Dissertation Repository

Congenital heart defects (CHDs) arise from perturbations in complex molecular and cellular processes underlying normal embryonic heart development. CHDs are the most common congenital malformation, occurring in 1 to 5% of live births, and are the leading cause of pediatric mortality. Adverse genetic and environmental factors can impede normal cardiogenesis and increase the likelihood of CHDs. Pregestational maternal diabetes increases the risk of CHDs in children by more than four-fold. As the prevalence of diabetes rapidly rises among women of childbearing age, there is a need to investigate the mechanisms and potential preventative strategies for these defects. The aim of …

Microvascular Stenosis In Critical Limb Ischemia: Role Of Partial Endothelial To Mesenchymal Transition, Jacqueline M. Chevalier

Electronic Thesis and Dissertation Repository

Critical limb ischemia (CLI) is a widespread and debilitating manifestation of atherosclerosis. Unfortunately, revascularization strategies are often precluded or unsuccessful, resulting in amputation. A major reason for treatment failure is likely co-existing abnormalities in ­­the microvasculature. However, the specific microvascular defects present in end-stage PAD in humans remain unknown.

The purpose of this study was to delineate abnormalities in the microvascular wall in the critically ischemic skeletal muscle of patients with CLI.

To elucidate the microvascular landscape in CLI, we studied human tibialis anterior and gastrocnemius muscles harvested from below-knee amputations of 10 individuals with CLI. Control muscles are from …

Maternal Nicotine Exposure Induces Congenital Heart Defects In The Offspring Of Mice, Elizabeth Greco

Electronic Thesis and Dissertation Repository

Congenital heart defects are the most prevalent birth defect, and maternal cigarette smoking is a known risk factor. Nicotine replacement therapies are recommended to pregnant women who smoke to aid in smoking cessation, as this alternative is thought to be much safer compared to cigarette smoking. However, these products contain nicotine, and the safety of nicotine on the developing heart is not well known. In this thesis, a mouse model was used to test the hypothesis that maternal nicotine exposure (MNE) during pregnancy leads to congenital heart defects and coronary artery defects in the offspring of mice. MNE resulted in …

Resedent Study- Reducing Sedentary Behaviour May Slow Cognitive Decline In Older Adults With Mild Cognitive Impairment: A Pilot Study, Kirsten B. Dillon

Electronic Thesis and Dissertation Repository

Physical activity (PA) has been shown to slow down dementia. Unfortunately, older adults spend most of their day in sedentary behaviours (SB). Breaking up prolonged bouts of sitting with intermittent bouts of light intensity PA may reduce glycemic variability in the brain; potentially mitigating cognitive decline. This study investigated how interrupting SB with 10 min bouts of light intensity PA 3x a day would affect mild to moderate cognitive impairment progression (primary outcome) in older adults residing in an assisted living facility. Participants (n=25) were assigned in clusters into a two arm 10-week single site pilot randomized controlled trial. Secondary …

Measuring Quality Of Life In Patients With Rotator Cuff Disorders, Rochelle Furtado

Electronic Thesis and Dissertation Repository

Rotator cuff disorders (RCDs) are a common musculoskeletal problem with a higher prevalence in women and after the age of 60. Due to the increasing need for patient-centered care, researchers have been directed towards the use of patient reported outcomes (PROs) to evaluate the progress of patient recovery, as the experience varies across individuals.

Recently, the Western Ontario Rotator Cuff Index was reduced in items to create the shortened version of the Western Ontario Rotator Cuff Index (Short-WORC). However, the Short-WORC’s psychometrics have yet to be evaluated. Therefore, this mixed-methods thesis aimed to evaluate the psychometric properties of the Short-WORC …

Synthesis And Characterization Of American Ginseng Polysaccharides Nanoparticles, Vincent Lee

Electronic Thesis and Dissertation Repository

This project was concerned with the synthesis of nanoparticles (NPs) by microfluidics from bulk ginseng polysaccharides (PS) isolated from American ginseng to design a new delivery system to improve the bioavailability of PS. Physicochemical analyses showed products of nanosizing as unimodal spheres with a diameter of ~19 nm. Pharmacological characterization studies in vitro of these nanoparticles of PS (NPPS) have demonstrated heightened immunostimulatory activity, and enhanced penetration across skin cell monolayer, which could be considered as evidence of increased bioavailability. Studies using PS sub-fractions with different molecular weights for NPPS synthesis showed that molecular weights is one of the parameters …

Hiv-1 Group M Subtype Fitness, Disease Progression, And Entry Efficiency, Colin M. Venner

Electronic Thesis and Dissertation Repository

Human immunodeficiency virus type 1 (HIV-1) emerged in the human population shortly after the turn of the 19th century. Distribution of HIV-1 across the globe over the past 30–35 years can be traced to founder events with primordial HIV strains from sub-Saharan Africa. Even considering the burden of HIV in Africa, our knowledge of HIV-1 disease is still largely limited to subtype B HIV-1, a strain responsible for 3 million infections in North America and Europe as compared to the 33 million that are infected with HIV-1 subtypes A, C, D, and circulating and unique recombinant forms.

This dissertation analyzes …

Ultra-High Field Magnetic Resonance Imaging For Stereotactic Neurosurgery, Jonathan Lau

Electronic Thesis and Dissertation Repository

Stereotactic neurosurgery is a subspecialty within neurosurgery concerned with accurate targeting of brain structures. Deep brain stimulation (DBS) is a specific type of stereotaxy in which electrodes are implanted in deep brain structures. It has proven therapeutic efficacy in Parkinson’s disease and Essential Tremor, but with an expanding number of indications under evaluation including Alzheimer’s disease, depression, epilepsy, and obesity, many more Canadians with chronic health conditions may benefit. Accurate surgical targeting is crucial with millimeter deviations resulting in unwanted side effects including muscle contractions, or worse, vessel injury. Lack of adequate visualization of surgical targets with conventional lower field …

Mass Spectrometry-Based Proteomics Analysis Of Bioactive Proteins In Emd That Modulate Adhesion Of Gingival Fibroblast To Improve Bio-Integration Of Dental Implants, David Zuanazzi Machado Jr

Electronic Thesis and Dissertation Repository

Titanium implants are used in dental practice to replace damaged or lost teeth. The implant needs to integrate with the surrounding gingiva to protect it against bacterial invasion that leads to implant loss. The biointegration is dependent on the implant surface that interacts with proteins from biological fluids to modulate tissues response. Tailoring the surface with specific proteins from the enamel matrix derivative (EMD) would be beneficial to improve the implant-gingiva interface since EMD can affect various cells including gingival fibroblasts. A surface-affinity approach using three different titanium surfaces and saliva was utilized as a model in combination with tandem …

Translational Control Of Stress Induced Breast Cancer Plasticity, Michael Jewer

Electronic Thesis and Dissertation Repository

Cancer cell plasticity, whereby stem-cell-like properties are acquired in response to stress, represents a major challenge in cancer treatment. Using cell line and patient-derived xenograft (PDX) models, we demonstrate that translational reprogramming occurs in response to stresses such as hypoxia and chemotherapy which elicits stem cell properties in breast cancer. Other stresses like chemotherapy demonstrate the translational inhibition that has been well characterized as an integral hypoxic cellular response. The inhibition of translation is primarily regulated at initiation by mTOR/4E-BP1 and PERK/eIF2α signalling. We identify previously undescribed 5’ untranslated regions (5’UTRs) of plasticity-associated genes like NANOG, SNAIL and NODAL. …

The Group A Streptococci Bacteriocins Facilitate A Competitive Advantage During Nasopharyngeal Infection, Lana Estafanos

Electronic Thesis and Dissertation Repository

Pathogenic streptococci have evolved specific systems to eliminate bacterial competitors within their biological niche. In microbial environments, niche competition is often driven by the production of short antimicrobial peptides called bacteriocins; this provides a mechanism by which Streptococcus pyogenes may compete for ecological stability and establish infection. Recent findings from our laboratory have identified two novel Class IIb bacteriocin systems – Streptococcus pyogenes bacteriocin (Spb) JK and MN in the M18 serotype S. pyogenes strain MGAS8232 – that may contribute to nasopharyngeal infection. Here, we show that galactose and CO₂ are distinct regulatory cues which induce antimicrobial activity. Under …