Diseases Commons^™

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 …

Role Of Decorin At The Fetal-Maternal Interface, Chidambra D. Halari

Electronic Thesis and Dissertation Repository

The human placenta is an invasive tumor-like structure, this invasion being physiological. A subset of placental trophoblast called extra-villous trophoblast invades the uterine decidua and remodels uterine arteries into low-resistance, high-flow tubes to permit adequate flow of maternal blood to nourish the fetus. A poor extra-villous trophoblast invasion and uterine arterial remodeling can lead to fetal growth restriction and a serious pregnancy-associated maternal disease preeclampsia. Decorin, a leucine-rich proteoglycan produced by uterine decidual cells restrains multiple trophoblast functions: self-renewal and differentiation of trophoblast stem cells, migration, invasion, proliferation and endovascular differentiation. Additionally, decidual overproduction of decorin was associated with preeclampsia, …

Rna Isolation In Duchenne Muscular Dystrophy (Dmd) Mice Models, Salem Abu Al-Burak

Undergraduate Student Research Internships Conference

Fibrosis is a progressive and typically irreversible disease process characterized by the excessive deposition of collagen in organs and in tissues of the musculoskeletal (MSK) system^1,2. This process, which causes loss of organ and tissue function, can be initiated by micro-traumas³, an excessive and/or prolonged immune response¹, the activation and proliferation of fibrosis-inducing progenitor cells⁴, and a pro-fibrotic extra-cellular microenvironment⁵. In parallel with the events that initiate fibrosis, genetic or environmental influences may cause cells and tissues to become predisposed to fibrosis development prior to initiation. This suggests that these …

Establishing Intratumoral Modulation Therapy As A New Treatment Modality For High Grade Gliomas, Andrew M.A. Deweyert

Electronic Thesis and Dissertation Repository

Glioblastoma (GBM) is the most common and lethal primary brain cancer in adults despite aggressive treatments with surgery and chemo-radiation. Advances in electrotherapeutics offer a foundation for developing new treatment modalities that exploit an innate vulnerability of glioblastoma (GBM). Low intensity, non-ablative electric fields are innocuous to normal neural structure, but incite GBM cell apoptosis by putatively disrupting cytokinesis and transmembrane ion homeostasis. Our collaborative research group is pioneering a new electrotherapeutic technology for GBM called Intratumoral Modulation Therapy (IMT) which uses customized, implanted bioelectrodes to deliver sustained, titratable and focused therapeutic electric fields into tumor-affected brain regions. My work …

Novel Imaging Tools Reveal The Dynamics Of The Myocardial Growth Hormone Secretagogue Receptor In Heart Disease And Heart Failure, Rebecca Sullivan

Electronic Thesis and Dissertation Repository

Heart disease (HD) is the leading cause of mortality worldwide. Currently, diagnosis is based on clinical features, imaging, and circulating cardiac biomarkers. Cardiac imaging technologies, such as echocardiography and cardiac magnetic resonance imaging (cMRI), enable the non-invasive detection of changes in heart function. Although these modalities can detect changes in structure and anatomy, it is usually at later stages, where prevention may not be possible. In conjunction with imaging, circulating biomarkers of heart failure (HF), notably B-type natriuretic peptide (BNP) and cardiac troponin I and T, can be detected with increased levels in the blood. These biomarkers are associated with …

Investigating The Role Of Nuclear Receptor Peroxisome Proliferator-Activated Receptor Δ In Obesity-Associated Osteoarthritis, Bethia C. To

Electronic Thesis and Dissertation Repository

Osteoarthritis (OA) is a heterogeneous disease, differentiated based by risk factors that drive joint damage. Peroxisome proliferator-activated receptor delta (PPARd) is a nuclear receptor previously implicated in cartilage damage in OA. Given its deleterious role in post-traumatic OA and in regulating metabolism, we hypothesized that PPARd inhibition will protect against obesity-associated OA. Diet-induced obesity was used to induce OA in mice. Mice fed the western diet for 40 weeks exhibited mild OA, with subchondral bone remodelling occurring alongside cartilage damage. Cartilage-specific Ppard knockout (KO) mice were generated to study its role in metabolic OA. Both wildtype and PPARd KO mice …

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 …

Improving Material Mapping In Glenohumeral Finite Element Models: A Multi-Level Evaluation, Nikolas K. Knowles

Electronic Thesis and Dissertation Repository

An improved understanding of glenohumeral bone mechanics can be elucidated using computational models derived from computed tomography data. Although computational tools, such as finite element analysis, provide a powerful quantitative technique to evaluate and answer a variety of biomechanical and clinical questions, glenohumeral finite element models (FEMs) have not kept pace with improvements in modeling techniques or model validation methods seen in other anatomic locations. The present work describes the use of multi-level computational modeling to compare, develop and validate FEMs of the glenohumeral joint.

Common density-modulus relationships within the literature were evaluated using a multi-level comparative testing methodology to …

The Use Of Current Steering During Subthalamic Deep Brain Stimulation To Alleviate Upper Limb Symptoms Of Parkinson's Disease, Shabna Iftikar Mohideen

Electronic Thesis and Dissertation Repository

Subthalamic (STN) deep brain stimulation (DBS) is an established treatment to alleviate the appendicular motor symptoms of Parkinson's Disease (PD). Current steering during DBS allows the unequal fractionation of current between two electrodes on the lead, resulting in a non-spherical electrical field. It is hypothesized that the way the electrical field is shaped will affect a patient’s upper limb symptom alleviation. Seven PD patients who underwent bilateral STN-DBS were tested over four weeks post-operation. 16 current fractionation settings were tested each week at an amplitude that increased weekly. Optimal setting was defined as the setting that provided the best …

The Role Of Cholinergic Signaling In Cardiac Function, Rachel Reingold

Electronic Thesis and Dissertation Repository

Cardiovascular disease is one of the leading causes of death in Canada. Treatment currently focuses on preventing the increase of sympathetic signaling seen in heart failure. However, it has recently been noted that cardiac function is dependent on parasympathetic tone. Previous studies have demonstrated the development of heart failure when cholinergic targets are knocked out in cardiomyocytes. Transgenic mouse models that have increased cholinergic transmission show protection against cardiovascular insults. We have shown that transgenic mice overexpressing vesicular acetylcholine transporter in cholinergic cells show cardiovascular protection in response to ex vivo insults. As well, this protection is seen when cholinergic …

The Effects Of Tracheal Occlusion On Wnt Signaling In A Rabbit Model Of Congenital Diaphragmatic Hernia, Martina M. Mudri

Electronic Thesis and Dissertation Repository

Purpose: Tracheal occlusion (TO) reverses pulmonary hypoplasia (PH) in congenital diaphragmatic hernia (CDH), but its effect on epithelial-mesenchymal transition (EMT) in lung development remains poorly understood. The purpose of this study was to a) confirm the CDH rabbit model produced PH which was reversed by TO and b) determine the effects of CDH +/- TO on EMT pathways.

Methods: CDH was created at 23 days, TO at 28 days and lung collection at 31 days gestation in fetal rabbits. Lung body weight ratio (LBWR), mean terminal bronchiole density (MTBD), and expression of mRNA and micro-RNA was determined.

Results: Fifteen CDH, …

Measurement And Protection Of Lung Health In Poultry Farmers Of Southwestern Ontario, Rose-Marie Doyon Dolinar

Electronic Thesis and Dissertation Repository

Chronic obstructive lung disease (COPD), develops gradually, and tends to be noticed by farmers only after there has been a significant loss of lung function. People with symptoms of COPD often present for health care in later stages of disease, because they accept cough or breathlessness as “normal”.

Measurement of lung health for those at risk of developing COPD provides an opportunity for early detection of lung disease, and deter the progression toward irreversible damage to the lungs. COPD is, however, under-diagnosed.

The importance of bringing primary care providers and farmers together, and acknowledging the high-risk nature of occupational exposures, …

Pulmonary Imaging To Better Understand Asthma, Sarah Svenningsen

Electronic Thesis and Dissertation Repository

Asthma is characterized using the spirometry measurement of the forced expiratory volume in one second (FEV₁). Simple and inexpensive, FEV₁ provides a global estimate of lung function but this metric cannot regionally identify airways responsible for airflow limitation, asthma symptoms or control. Work that brought about an understanding that airway abnormalities are heterogeneously distributed within the lung in asthma patients has motivated the development of pulmonary imaging approaches, such as hyperpolarized helium-3 (³He) and xenon-129 (¹²⁹Xe) magnetic resonance imaging (MRI). These methods provide a way to visualize and quantify lung regions accessed by …

Evaluating The Pathological And Behavioural Consequences Of Injecting Amyloid Beta Oligomers In The Rat, Ryan S. Wong

Electronic Thesis and Dissertation Repository

Alzheimer’s disease (AD) is the most common form of dementia and is characterized by progressive neuronal loss and cognitive decline. Currently, no therapeutic treatments are available and our understanding of the disease progression is still unclear. Amyloid beta oligomers (AβO) are potent neurotoxic proteins and may be a potential initiator of the progression of AD. The purpose of this project was to identify the spatial and temporal consequences of injecting AβO into the rat brain by evaluating pathological and behavioural outcomes. We hypothesized that injecting AβO into the rat brain will result in microglial response as well as behavioural and …

Non-Invasive Quantification Of Alveolar Morphometry Measurements In Older Never-Smokers, Gregory A. Paulin

Electronic Thesis and Dissertation Repository

Diffusion-weighted noble gas pulmonary magnetic resonance imaging (MRI) provides in vivo images with a contrast uniquely sensitive to molecular displacement at cellular and sub-cellular length scales. We estimated the external airway radius (R) and internal airway radius (r) of the alveolar dimensions to evaluate potential differences in acinar duct morphometries in healthy older never-smokers and compared those with a group of ex-smokers. The acinar duct and alveolar MRI morphometry results were within the physiologically-valid range of parameters. Estimated values of internal (r) and external (R) airway radius as well as alveolar sheath (h) and …