Diseases Commons^™

The Impact Of Simulated Image Acquisition Time Reduction On Image Quality And Parameters Of Myocardial Perfusion Imaging Using A Dedicated Cardiac Camera, Alireza Khatami

Electronic Thesis and Dissertation Repository

Heart disease is the second leading cause of death in Canada, highlighting the crucial role of early diagnosis in disease management. Myocardial perfusion imaging (MPI), is widely employed for this purpose, involves injecting a radiopharmaceutical into the body, imaging its distribution with a gamma camera, and revealing cardiac blood flow patterns. A significant challenge in MPI is the lengthy 8 to 10 minutes required for stress and rest imaging, potentially causing patient discomfort and compromising image quality due to movement. In a clinical study with 26 patients, post-processed data manipulation simulated a reduction in MPI imaging time. The findings indicated …

The Impact Of Access To Oral Health Care On Inadequate Oral Health And Multimorbidity, Luis Limo

Electronic Thesis and Dissertation Repository

The connection between oral health and other non-communicable chronic conditions—commonly referred in the dental literature as the oral-systemic health connection—emphasizes the role of oral health care on both oral diseases and chronic conditions, particularly in vulnerable populations like the elderly. This thesis comprises 2 studies: the first is a systematic review on the impact of oral health care interventions, as an indicator of access to oral health care, on chronic conditions of which their co-existence would result in multimorbidity; the second study is a cross-sectional investigation of the associations between oral health, access to oral health care, and multimorbidity among …

Role Of Circular Rna Asph In Macrophage Polarization And Response In Sepsis, Tan Ze Wang

Electronic Thesis and Dissertation Repository

Circular RNAs (circRNAs), a novel non-coding RNA species generated by back-splicing, has been shown to participate in gene regulation of leukocytes. Our previous RNA sequencing results show circular RNA ASPH (circASPH) to be highly expressed in peripheral blood mononuclear cells of sepsis patients at the start of intensive care. Macrophages, as ubiquitous innate immune cells, are responsible for the recruitment of other immune cells at sepsis onset. This work investigates the role of circASPH in the regulation of macrophage polarization in sepsis. Using an in vitro THP-1 cell model, it was found that circASPH levels peaked after 24 h of …

Sex Differences In Mood And Anxiety-Related Outcomes In Response To Adolescent Nicotine Exposure, Tsun Hay Jason Ng

Electronic Thesis and Dissertation Repository

Nicotine dependence is causally linked to increased risk of mood/anxiety disorders in later life. Females are reported to experience a higher prevalence of anxiety/depressive disorders and challenges in smoking cessation therapies, suggesting a potential sex-specific response to nicotine exposure and mood/anxiety disorder risk. However, pre-clinical evidence of sex-specific responses to adolescent nicotine exposure is unclear. Thus, to determine any sex differences in anxiety/depressive-related outcomes, adolescent male and female Sprague Dawley rats received nicotine (0.4 mg/kg; 3x daily) or saline injections for 10 consecutive days, followed by behavioural testing, in-vivo electrophysiology and Western Blot analyses. Our results revealed that adolescent nicotine …

The Combined Effects Of Physical Exercise And Cognitive Training On Gait Speed And Primary Motor Cortex Metabolism In Individuals With Mild Cognitive Impairment: A 1h-Mrs Analysis, Jack Thomas Emsey Elkas

Electronic Thesis and Dissertation Repository

Mild cognitive impairment (MCI) is a transitional stage before dementia. Altered gait in MCI has been associated with progression to dementia. Using magnetic resonance spectroscopy, a relationship between primary motor cortex (M1) neurochemistry and dual task gait speed has been reported in MCI. Interventional research suggests exercise, cognitive training, and vitamin D supplementation may benefit MCI, yet the combined effect of these treatments on gait speed and M1 metabolism is unknown. Participants with MCI (N=75) were assigned to one of five intervention arms and dual task cost on gait speed and M1 metabolism was assessed before and five months after …

Assessing Inflammation In The Pathology Of Knee Osteoarthritis, Zachary J. Koudys

Electronic Thesis and Dissertation Repository

Osteoarthritis (OA) is a joint disease that causes pain, stiffness, and loss of function. Inflammation of the synovium plays a role in the pathology of OA. Macrophages are the dominant immune cells in synovial tissue. Activated macrophages over-express the translocator protein (TSPO). [¹⁸F]FEPPA is a 2^nd generation positron emission tomography (PET) tracer that can target TSPO with high specificity. Hybrid [¹⁸F]FEPPA PET/MRI may enable accurate quantification of macrophage activity in vivo. In this work, [¹⁸F]FEPPA tracer uptake in knee synovial tissue was measured ex vivo using autoradiography and was validated to correlate to …

Transferring Organelles Into Native Neurons: A Disease-Modifying Therapy For Neurodegenerative Disorders, Lohiny Balendran

Electronic Thesis and Dissertation Repository

Currently, there are no disease-modifying therapies to counter the progression of neurodegenerative diseases that are associated with mitochondrial dysfunction in the early stages. In this study, we have used a novel strategy of cell fusion to transfer mitochondria from one cell to another using fusogens (syncytin 1 and syncytin 2). Syncytins are placental proteins encoded by endogenous retroviral envelope genes that promote cellular fusion. In this study, we have proposed that donor cells engineered to stably express syncytin when cocultured with recipient cells will allow fusion and facilitate the transfer of mitochondria into recipient cells. Syncytin-mediated systems revealed about 16.6-18.5% …

Monitoring Intraventricular Hemorrhage In Preterm Infants, Lilian Mn Kebaya

Electronic Thesis and Dissertation Repository

Germinal Matrix-Intraventricular hemorrhage (GMH-IVH) remains a significant cause of adverse neurodevelopmental outcomes in preterm infants. Current management options for GMH-IVH rely on serial 2-dimensional cranial ultrasound (2D cUS) ventricular measurements and clinical signs. A need exists for reliable biomarkers to aid in the early detection of posthemorrhagic ventricular dilatation (PHVD) and cerebral palsy (CP). We incorporated 3-dimensional cranial US (3D cUS) and functional infrared spectroscopy (fNIRS) to monitor ventricle volumes (VV) and spontaneous functional connectivity (sFC) in preterm infants with GMH-IVH. Infants with severe GMH-IVH who underwent cerebrospinal fluid diversion showed larger VV, which correlated with decreased sFC. Our findings …

Noninvasive Quantification Of Tissue Sodium Concentration In The Kidney Disease Spectrum Using 23na Magnetic Resonance Imaging, Fabio R. Salerno

Electronic Thesis and Dissertation Repository

Chronic kidney disease (CKD), especially when requiring kidney replacement therapy (hemodialysis (HD) and peritoneal dialysis (PD)), is associated with extracellular water expansion with increased total body sodium. Sodium can also be accumulated in tissues independently of extracellular water. Sodium-23 magnetic resonance imaging (²³Na MRI) can quantify the concentration of sodium nuclei in tissues. Applied to the human leg, quantification of tissue sodium concentrations mainly at the skin and muscle level is possible. We hypothesized that increased tissue sodium concentrations exert toxic effects in CKD and dialysis. We aimed to (1) compare tissue sodium concentrations in adults, children and …

Exploration Of The Pathophysiological Mechanisms Underlying Hemodialysis Associated Cardiac Ischemic Injury, Lisa Yun Jeong Hur

Electronic Thesis and Dissertation Repository

Hemodialysis (HD) provides life-saving treatment in individuals with kidney failure. However, HD is associated with poor quality of life and extremely high mortality rates mainly caused by cardiovascular disease due to heart failure and sudden cardiac death. Standard pharmacological treatment developed within the non-kidney disease community are largely ineffective in HD patients because of the difference in pathophysiology of cardiovascular mortality. HD treatment causes hypotension and recurrent ischemic injury to multiple vascular beds including the heart, leading to heart failure. These injuries can be abrogated by improving the patient’s tolerability of the treatment. To apply interventions that may improve hemodynamic …

Technical Adaptations For Cardiac Sodium Mri, Taylor L. Marcus

Electronic Thesis and Dissertation Repository

Cardiac sodium (Na⁺) MRI has the potential to unveil relationships between chronic kidney disease (CKD) and cardiovascular disease (CVD). Unfortunately, this modality requires many technical adaptations before it’s possible to extract and compare image data between individuals. This study investigated whether cardiac electrocardiogram (ECG) gating could improve image quality, and whether a uniform phantom could increase signal uniformity if a surface coil is used to acquire the image. Healthy participants were imaged with a custom-built surface coil and 3.0-T MR system. Cardiac gated images presented with a decreased signal-to-noise ratio (SNR), but intensity correction significantly increased image signal …

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, …

Ex-Smokers With And Without Copd: Investigating Ct Pulmonary Vascular, Airway, Pulmonary Artery And Aorta Measurements, Vedanth Desaigoudar, Paulina V. Wyszkiewicz, Alexander M. Matheson, Maksym Sharma, Marrissa J. Mcintosh, Harkiran K. Kooner, David G. Mccormack, Grace Parraga

Undergraduate Student Research Internships Conference

RATIONALE: Pulmonary hypertension is characterized by increased pressure in the pulmonary artery, and is a key contributor to worsening symptoms in individuals with chronic obstructive pulmonary disease (COPD). The pulmonary artery to aorta diameter ratio (PA:Ao), measured using computed tomography (CT), is a biomarker of pulmonary hypertension; however, longitudinal changes in this measurement and its relationship to pulmonary vascular and airway structural changes is not well understood. Our objective was to investigate longitudinal changes in PA:Ao and its relationship with CT pulmonary vascular and airway abnormalities, airflow limitation and exercise-capacity.

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 …

The Effect Of Type 1 Diabetes On The Metabolic Response To Exercise, Theres Tijo

Undergraduate Student Research Internships Conference

Type 1 Diabetes Mellitus (T1DM) is an autoimmune disorder that results in insufficient endogenous insulin production. Regular exercise has numerous health benefits for individuals with T1DM, however, most insulin-dependent diabetics avoid physical activity due to the fear of exercise-induced hypoglycemia (low blood glucose/BG).

The risk of hypoglycemia in this population may be partly due to lower liver glycogen stores which is a major source of blood glucose during exercise. However, the mechanism that leads to lower glycogen stores in T1DM is unknown.

The purpose of this study was to determine the effect of an acute bout of moderate-intensity aerobic exercise …

The Role Of Coagulase-Negative Staphylococcal Secreted Products On Staphylococcus Aureus And Staphylococcus Lugdunensis Infections, Denny Chin

Electronic Thesis and Dissertation Repository

The Staphylococcus genus is comprised of over 40 bacterial species. The most well-studied species in this genus is the notorious human pathogen Staphylococcus aureus, a bacterium that produces coagulase among many other virulence factors. Since S. aureus is a major health burden and causes a plethora of diseases in humans, it has received significant attention and much research has been done to understand its biology to treat diseases caused by this pathogen. However, the coagulase-negative staphylococci (CoNS) make up most of the staphylococcal species and have received less attention since they are thought to have a lesser impact on …

Mechanisms Underlying Enhanced Bone Marrow Adipogenesis In Diabetes, Jina J.Y. Kum

Electronic Thesis and Dissertation Repository

Morbidity and mortality associated with diabetes are due to secondary vascular complications that include both micro- and macro-vascular organ dysfunctions. Our recent studies show that vascular dysfunction and inadequate vessel repair in diabetes may potentially be due to impaired vasculogenesis (de novo vessel formation). Specifically, we have shown that diabetes enhances adipogenesis in the bone marrow and reduces the number of marrow-resident vascular regenerative stem cells. In this study, I have determined the mechanisms of deleterious bone marrow adipogenesis, which may alter the cellular composition of the marrow and lead to the depletion of vascular regenerative stem cells.

My …

Scrna Seq Analysis Of Ebv+ Associated Gastric Cancer, Eric Wang

Undergraduate Student Research Internships Conference

No abstract provided.

The Effects Of Estrogen In The Glucoregulatory Response To Exercise In Type 1 Diabetes, Mitchell James Sammut

Undergraduate Student Research Internships Conference

Regular exercise has shown to benefit the health of individuals with type 1 diabetes mellitus (T1DM). However, a barrier to regular exercise for this population is the fear of low blood glucose (BG) levels, also known as hypoglycemia. Hypoglycemia can result in short and long-term side-effects, such as recurring loss of consciousness or in severe cases death.

In non-diabetics, sex-related differences in fuel selection during exercise are well established. Women shift towards using fats as fuel whereas men rely mostly on sugars (i.e., carbohydrates) for energy production. Exercise during the luteal phase of the female menstrual cycle, where estrogen levels …

Characterizing The Heterogeneity Of Adult-Onset Leukoencephalopathy With Axonal Spheroids: A Digital Spatial Profiling Study, Peter Liu

Undergraduate Student Research Internships Conference

Adult-onset leukoencephalopathy with axonal spheroids (ALAS) is a group of hereditary, progressive, neurodegenerative disorders involving primarily the central nervous system white matter (WM). ALAS is characterized by patchy, asymmetrical myelin loss and axonal destruction in the WM, predominantly involving the frontoparietal regions. However, the asymmetrical and heterogenous involvement of different brain regions remains poorly characterized.

In this study, digital spatial profiling was performed to investigate the region-specific expressions of 60 proteins. Conventional immunohistochemistry methods was used validate intrepretation of probes. Using a high-plex and high-throughput method, we provide evidence of regional heterogeneity in ALAS, particularly involving key markers of microglia …

Generating Cisplatin Resistant Hpv-Positive Hnscc Cell Lines, Temitope Akintola

Undergraduate Student Research Internships Conference

Acquired or innate resistance to chemotherapy poses a significant challenge in the treatment of head and neck squamous cell carcinomas (HNSCC). HNSCCs are often treated with a combination of surgery, radiation and chemotherapy, with cisplatin being a standard-of-care chemotherapy drug. Human Papillomavirus (HPV) associated HNSCCs have better treatment outcomes and prognosis when compared to HPV- HNSCCs. However, a subset (15-20%) of HPV+ patients develop treatment resistant diseases. The purpose of this study is to generate in-vitro models of cisplatin resistance in five HNSCC cell lines. We aim to characterize the generated cells in order to identify target genes that may …

Three-Dimensional Ultrasound Imaging For Quantifying Knee Cartilage Volume, Samuel Papernick

Electronic Thesis and Dissertation Repository

Arthritis is the most common chronic health condition in Canada, with the most common form being osteoarthritis (OA). There is a great clinical need for an objective imaging-based point-of-care tool to assess OA status, progression, and response to treatment. This thesis aims to validate a handheld mechanical three-dimensional (3D) ultrasound (US) device against the current clinical standard of magnetic resonance imaging (MRI) for quantifying femoral articular cartilage (FAC) volume. Knee images of 25 healthy volunteers were acquired using 3D US and 3.0 Tesla MRI scans. Two raters manually segmented the trochlear FAC during separate sessions to assess intra- and inter-rater …

Testing A Novel Peptide-Infused Cream For Treatment Of Rheumatoid Arthritis In Dr4tg Mice, Alisha J. Moynahan

Electronic Thesis and Dissertation Repository

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes joint pain and damage. Studies have shown that inducing immune tolerance towards RA-specific proteins/peptides in RA mouse models can reduce arthritis severity and pro-inflammatory responses. The objectives of this study were to determine if a novel peptide cream treatment could modify RA-specific immune responses and reduce joint swelling in a humanized mouse model expressing the HLA-DRB1*0401 allele (known as DR4tg mice), the strongest genetic risk-factor for RA. Hyaluronan-Phosphatidylethanolamine cream infused with synthetic peptides HomoCitJED and CitJED was applied to HomoCitJED-immunized DR4tg mice before or after arthritis induction. Knee joint …

Hiv-1 Drug Resistance To Integrase Strand Transfer Inhibitors In Hiv-1 Non-B Subtypes, Emmanuel Ndashimye

Electronic Thesis and Dissertation Repository

Human immunodeficiency syndrome (HIV-1) has infected over 75 million people and over 35 million have succumbed to virus related illnesses. Despite access to a variety of antiretroviral therapy (ART) options, ART programs have been disproportionally spread in the world with low-and middle-income countries (LMICs) facing challenges to access the most potent ART options. With less potent ART remaining in use in LMICs, HIV-1 drug resistance (HIVDR) presents a growing challenge in LMICs. Since approval of the first-generation integrase strand transfer inhibitor (INSTIs), Raltegravir (RAL) in 2007, INSTIs remain the best choice as a backbone of ART. Access to second generation …

Trna Regulation In Humans: The Cellular Effect Of A Pathological Hars Y454s Mutation, Rosan Kenana

Electronic Thesis and Dissertation Repository

tRNAs are the adapter molecules involved in translating the genetic code into functional protein in a living cell. tRNAs are charged with their cognate amino acids - by aminoacyl-tRNA synthetases (aaRS or ARS) - which are then transferred to a growing peptide in a process called mRNA translation. The efficiency of translation is dependent on the ratio of ARS enzymes to their cognate tRNAs and the availability of correctly amino acylated tRNAs. Disruptions of this process, caused by mutations in ARS genes, in particular, have been linked to complex inherited diseases. USH3B syndrome, a recessively inherited disorder among consanguineous families …

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 …

An Approach For The In-Vivo Characterization Of Brain And Heart Inflammation In Duchenne Muscular Dystrophy, Joanne Tang

Electronic Thesis and Dissertation Repository

Duchenne muscular dystrophy (DMD) is a neuromuscular disorder caused by dystrophin loss—notably within muscles and CNS neurons. DMD presents as cognitive weakness, progressive skeletal and cardiac muscle degeneration until pre-mature death from cardiac or respiratory failure. Innovative therapies improved life expectancy, but this is accompanied by increased late-onset heart failure and emergent cognitive degeneration. Thus, there is an increasing need to both better understand and track disease pathophysiology in the dystrophic heart and brain prior to onset of severe degenerative symptoms. Chronic inflammation is strongly associated with skeletal and cardiac muscle degeneration, however chronic neuroinflammation’s role is largely unknown in …

Implications Of Long Non-Coding Rnas In The Pathogenesis Of Diabetic Retinopathy: A Novel Epigenetic Paradigm., Saumik Biswas

Electronic Thesis and Dissertation Repository

With the rising incidence of diabetic retinopathy (DR), there is an urgent need for novel therapies. Presently, several altered metabolic pathways have been implicated in the pathogenesis of DR. Recent advances in genomic technologies have identified considerable epigenetic alterations that also contribute to DR progression. Long non-coding RNAs (lncRNAs; >200 nucleotides), critical regulators of gene expression, are aberrantly expressed in DR and have not been comprehensively characterized. Our microarray analyses using human retinal endothelial cells (HRECs) revealed thousands of differentially expressed lncRNAs following high glucose (HG) exposure, with profound increases in the lncRNAs MALAT1 and HOTAIR. Using multiple techniques, …

Development And Evaluation Of A Heterogenous Virus-Like Particle (Vlp) Formulation To Achieve Hiv-1 Latency Reversal And Cure., Joshua P. Pankrac

Electronic Thesis and Dissertation Repository

HIV-1 is the etiological agent behind acquired immune deficiency syndrome (AIDS) – a chronic, life-threatening condition that compromises host immune function. After nearly four decades and despite ongoing global efforts, HIV-1 persists in nearly 38 million individuals worldwide. Of this population, only 60% have access to life-saving combination antiretroviral therapy (cART), clearly emphasizing the need to realize a cure. Unfortunately, the establishment of replication-competent provirus in resting CD4+ T lymphocytes represents a significant barrier to HIV-1 curative research. The viral reservoir is highly stable and has a half-life of ~44 months. Therefore, it is unlikely that infection will naturally exhaust …

Assessment Of Intrinsic Hand Neuromuscular Physiology, Philemon Tsang

Electronic Thesis and Dissertation Repository

Alterations to the peripheral nervous system and neuromuscular physiology may impact hand function in a typical or clinical population, such as individuals with ulnar neuropathy. The mechanisms that influence these positive and negative changes are still not well understood. The three studies within my thesis aim to validate the reliability of decomposition-based quantitative electromyography (DQEMG) measurements and explore the changes in intrinsic hand neuromuscular physiology in a typical aging population and individuals recovering from a surgical intervention for severe ulnar neuropathy.

The purpose of the first study was to determine the test-retest reliability of near-fibre (NF) jiggle, a measure of …