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 …

Genetic Approaches For The Study Of Complex Human Diseases, Julieta Lazarte

Electronic Thesis and Dissertation Repository

The field of human genetics has evolved from its initial narrow focus on single-gene Mendelian disorders, which largely affect children, to our current understanding that for most diseases there is continuum of rare to common variants which can exert a range of phenotypic effects. Despite advances in sequencing capabilities and our overall understanding of diseases, there remains a large proportion of heritability unexplained. Through the use of next-generation sequencing technologies and DNA microarray, I have explored a spectrum of genetic variations from rare, single and structural variants to common variants in individuals with i) “lone” atrial fibrillation; ii) familial hypercholesterolemia; …

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 …

Cell-Free Dna Release During Programmed Cell Death In Ischemia Reperfusion Injury, Alexander Dionne, Anthony M. Jevnikar, Zhu-Xu Zhang

Western Research Forum

Transplantation is invariably associated with acute allograft injury caused by ischemia reperfusion injury (IRI). This injury causes cells of the allograft to undergo various forms of programmed cell death including apoptosis and necroptosis. During programmed cell death, immunogenic molecules are released from cells, one of which is cell-free DNA (cfDNA). We hypothesize that cfDNA is released by microvascular endothelial cells (MVECs) during programmed cell death of IRI and that cfDNA acts as both a biomarker for cellular injury as well as a biologically active molecule capable of amplifying inflammation and organ injury.

Our results indicate that cfDNA is released by …

Quantifying The Effects Of Systematic Stn-Dbs Programming On Rest And Postural Tremor In Idiopathic Parkinson Disease Patients, Kristina Ognjanovic

Electronic Thesis and Dissertation Repository

Parkinson’s disease (PD) is a complex neurodegenerative disorder that encompasses both motor and non-motor symptoms. These symptoms and their severity are typically assessed by scale based measures in a clinical setting. Scale- based assessments of PD patients undergoing bilateral subthalamic nucleus deep brain stimulation surgery (STN-DBS) such as the Unified Parkinson Disease Rating Scale (UPDRS) are commonly used in a clinical setting to assess symptom severity and progression. However, the subjective nature of these and other clinical scales call into question both the sensitivity and accuracy of patient assessment over time. An objective quantification of rest and postural tremor of …