Translational Medical Research Commons^™

Shedding Light On Hearing In Coma: Investigating The Applicability Of Functional Near-Infrared Spectroscopy For Assessing Auditory Function And Aiding Prognosis In Patients With Acute Disorders Of Consciousness, Reza Moulavi Ardakani

Electronic Thesis and Dissertation Repository

There is a critical need for a bedside neuroimaging tool to aid in the prediction of functional recovery outcomes for patients with acute disorders of consciousness (DoC) in the early days following severe brain injury. Current neurobehavioral examinations and prognosis tools have limitations in predicting good outcomes, leading to potential mistreatment or premature withdrawal of life support. Functional near-infrared spectroscopy (fNIRS) is a viable candidate for such purposes due to its portability and cost-effectiveness. Auditory processing, viewed as a multi-level and multifaceted brain function, could provide a sensitive and specific marker of residual cognitive function in unresponsive patients. This study …

Differential Effects Of Kim-1 In Subcutaneous And Orthotopic Renca Models Of Kidney Cancer, Demitra M. Yotis Dy

Electronic Thesis and Dissertation Repository

Renal Cell Carcinoma (RCC) is the most common and fatal type of kidney cancer. Over 30% of patients that are diagnosed with RCC exhibit metastases. Almost 88% of patients with distant metastases succumb to the disease within 5 years of diagnosis. Kidney Injury Molecule-1 (KIM-1) is a cell surface glycoprotein that is not expressed in a healthy kidney but becomes highly expressed on proximal tubular epithelial cells (PTECs) following injury. Data from the Cancer Genome Atlas (TCGA) reveals that >90% of RCC tumours express KIM-1 mRNA and that higher expression levels correlate with increased overall survival rates of patients. The …

Functional Role Of Dream And Dyrk1a In High-Grade Serous Ovarian Cancer Cell Dormancy, Pirunthan Perampalam

Electronic Thesis and Dissertation Repository

High-grade serous ovarian cancer (HGSOC) is the most common form of ovarian cancer. The majority of women are disproportionately diagnosed at an advanced stage (stage III-IV) of the disease when tumours have progressed beyond the ovaries or fallopian tubes and into the peritoneal cavity. Survival rates at late-stage are as low as 25% and chemoresistant disease recurrence is common, affecting up to 90% of patients. Multicellular clusters called spheroids contribute to dormancy, chemoresistance, and metastases and are a major challenge to treatment of HGSOC. Spheroid cells undergo reversible quiescence to evade chemotherapy in a process mediated by the mammalian DREAM …

Targeting Cd5 To Enhance Immune T Cell Activation And Function In Treatment Of Solid Tumours, Faizah Alotaibi

Electronic Thesis and Dissertation Repository

CD5 is a member of scavenger receptor cysteine-rich superfamily that is expressed primarily on T cells. It can attenuate T-cell receptor signaling and impair cytotoxic T lymphocyte (CTL) activation and is a therapeutic targetable tumour antigen expressed on leukemic T and B cells. However, the potential therapeutic effect of functionally blocking CD5 to increase T cell anti-tumour activity against tumours (including solid tumours) has not been explored. CD5^- solid tumours in CD5 knockout mice display increased in anti-tumour immunity. Hence, blocking CD5 function may have a potential therapeutic effect by enhancing CTL function. Here, I assessed CD5 levels in …

Drug Response And Metabolism In Crohn's Disease, Aze Wilson

Electronic Thesis and Dissertation Repository

Inflammatory bowel disease (IBD) is an illness of chronic intestinal inflammation comprised of Crohn's disease (CD) and ulcerative colitis (UC). Specialists rely heavily on drugs that target a dysregulated immune system. There is a staggering degree of variation in drug response in CD. Our understanding of drug metabolism and response in IBD is limited. Gaining new insights into IBD-specific modifications of drug metabolism may allow for improved drug efficacy and reduced toxicity. Cytochrome P450 (CYP) 3A4 is the most relevant determinant of drug metabolism and exposure for medications prescribed today. CYP3A4 is highly expressed in the liver, but is also …

Clinical And Pharmacogenetic Determinants Of Plasma Factor Xa Inhibitor Systemic Exposure, Markus Gulilat

Electronic Thesis and Dissertation Repository

Inhibition of blood coagulation via oral anticoagulant therapy is the mainstay for preventing a cardioembolic stroke in patients with atrial fibrillation (AF). Factor Xa inhibitors (FXaIs), rivaroxaban and apixaban, represent a new class of oral anticoagulants that are now widely prescribed in AF patients as an alternative to traditional warfarin therapy. An important advantage of these drugs is that routine monitoring of anticoagulation response is not necessary. Nevertheless, because of their mechanism of action, FXaI antithrombotic effect can be inferred based on the observed drug plasma concentration, with prolonged periods of elevated FXaI systemic exposure associated with increased risk for …

Prostate Cancer Microparticles In Men Undergoing Radical Prostatectomy, Malcolm James Dewar

Electronic Thesis and Dissertation Repository

Objectives: To determine changes in prostate microparticle (PMP) concentrations in men with prostate cancer (PCa) after digital rectal examination (DRE), after radical prostatectomy (RP), and at follow-up.

Materials and Methods: 22 men were recruited before RP. Four blood specimens were collected – baseline (specimen 1), post-DRE (specimen 2), immediately post-RP (specimen 3), and follow-up (specimen 4). Pre- and post-DRE urine was collected (Specimen A and B respectively). Flow cytometric analysis of biofluids was performed with fluorescent-labeled antibodies against prostate-specific membrane antigen (PSMA) and polysialic acid. Total MP (TMP) and dual positive (PMP) events per µl of plasma or urine were …

A Clinico-Pathological Study Of The Structural And Functional Changes In The Retina And Optic Nerve Following Diabetic Retinopathy Treatments, Richard Filek

Electronic Thesis and Dissertation Repository

Diabetic retinopathy (DR) is the result of microvascular changes in the retina due to hyperglycemia which alter the blood-retinal barrier (BRB). The increased permeability of BRB results in the accumulation of extracellular fluid, the development of diabetic macular edema (DME) and capillary occlusion. Capillary occlusion results in retinal ischemia which increases vascular endothelial growth factor (VEGF) levels, increases vascular permeability and results in neovascularization in proliferative diabetic retinopathy (PDR) patients. The treatments clinically used for DR are panretinal photocoagulation (PRP) for PDR and injectable vascular endothelial growth factor inhibitors (anti-VEGFs) for DME.

The safety of PRP and anti-VEGF therapy on …

Protective Benefits Of Hydrogen Sulfide Treatment During Renal Transplantation, Ian Lobb

Electronic Thesis and Dissertation Repository

Ischemia/reperfusion injury (IRI) is inherent to renal transplantation (RTx) and is initiated when blood supply is necessarily removed during organ procurement (ischemia) and subsequently restored upon engraftment (reperfusion). During renal ischemia, ATP depletion causes tubular epithelial cell (TEC) injury and subsequent release of pro-inflammatory mediators. Upon reperfusion, influx of O₂ causes reactive oxygen species (ROS) production and infiltration of innate immune cells which release damaging ROS and proteases. Prolonged periods of IRI are associated with increased risk of delayed graft function (DGF) and decreased long-term graft survival. The endogenously produced gasotransmitter, hydrogen sulfide (H₂S), has recently been …

A Clinically Relevant Relevant Post-Traumatic Osteoarthritis Mouse Model, Chantel P. Arce

Electronic Thesis and Dissertation Repository

Osteoarthritis affects 13-20% of Canadians with the majority being under 65years of age. Post-traumatic osteoarthritis (PTOA) is of great concern in young athletes following knee injury. Current research attempts at modeling the disease fall short. This study aimed to incorporate two important aspects of injury, the nature of the injury and the post-injury standard of care in humans, to a model of PTOA in mice. The study validated a non-invasive protocol to elicit an anterior cruciate ligament (ACL) injury at varying loading speeds addressing the closed capsule nature of an ACL injury that occurs in humans. Secondly, we proposed a …

Gender Does Not Influence The Relationship Between Posterior Cruciate Ligament Design And Patient-Reported Outcomes In Patients Receiving Primary Unilateral Total Knee Arthroplasty, Ryan Milan

Electronic Thesis and Dissertation Repository

The effect of the interaction between gender and posterior cruciate ligament (PCL) prosthesis design on patient-reported outcomes is an understudied area of research. We evaluated 1613 patients, from the Ontario Joint Replacement Registry (2001-2006), who underwent primary total knee replacement. This study investigated the impact of the gender-PCL design interaction on Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) change scores and patient satisfaction, by performing linear regression analysis, using full-adjusted models that also included the gender-PCL prosthesis design interaction variable. PCL prosthesis design did not affect WOMAC change scores or satisfaction (p>0.05). Moreover, Gender did not influence either …

Hearts And Minds: Examining The Evolution Of The Egyptian Excerebration And Evisceration Traditions Through The Impact Mummy Database, Andrew D. Wade

Electronic Thesis and Dissertation Repository

Egyptian mummification and funerary rituals were a transformative process, making the deceased a pure being; free of disease, injury, and disfigurements, as well as ethical and moral impurities. Consequently, the features of mummification available to specific categories of individuals hold social and ideological significance. This study refutes long-held classical stereotypes, particularly dogmatic class associations; demonstrates the apocryphal nature of universal heart retention; and expands on the purposes of excerebration and evisceration implied by synthetic and radiological analyses.

Features of the embalming traditions, specifically the variable excerebration and evisceration traditions, represented the Egyptian view of death. Fine-grain analyses, through primary imaging …