The Significance Of Injuries And Anatomical Patterns Of Trauma In Pedestrian And Cyclist Fatalities And Their Association With Motor Vehicle Collision Dynamics And Post-Collision Kinematics, Moheem M. Halari

Electronic Thesis and Dissertation Repository

Deaths from motor vehicle collisions (MVCs) are a major global health concern, with over 1.35 million fatalities reported annually by the United Nations. More than half involve pedestrians, cyclists, and motorcyclists. Post-mortem examinations by pathologists determine the cause of death and mechanisms of injury and play a significant role in the investigation of the deaths of vulnerable road users.

The purpose of this study was to understand the injury patterns sustained by pedestrians and cyclists fatally injured in motor vehicle impacts.

This study reviews the development of injury patterns described in the medical literature and identifies their limitations in the …

The Role Of Dlc1Β In Attenuating Cardiac Ischemia-Reperfusion Injury During Heart Transplantation, Samantha L. Collings

Electronic Thesis and Dissertation Repository

Cardiac ischemia-reperfusion injury (IRI) occurs intra-operatively during heart transplantation (HTx), underpinning graft survival. Past research implicated the PI3K/Akt1 & RhoA/ROCK pathways in IRI. Rho-GTPase activity/Akt regulates Deleted-in-liver-cancer 1 protein’s beta-isoform (DLC1β). Therefore, we hypothesized that DLC1β overexpression (OE) had anti-apoptotic effects. In vitro, HL-1 cells (mouse cardiomyocytes) received chamber hypoxia-oxygenation reperfusion (H/R) for 24H4R with/without DLC1β plasmid, before collection for protein/mRNA analyses. DLC1β-OE resulted in downregulated pro-apoptotic mRNA expression (Bax/Cycs/Casp3), upregulated protective mRNA targets (BCl2/Akt1) and less late/early apoptosis via flow cytometry. Results were confirmed via H9C2 (rat cardiomyocyte) cell lines. In vivo, C57/BL6 mice received heterotopic HTx with/without DLC1β-OE …

Synovial Histopathology Across A Spectrum Of Hip Disorders: From Pre-Arthritic Femoroacetabular Impingement To Advanced Osteoarthritis, Ronan James Anderson

Electronic Thesis and Dissertation Repository

Objective: The objective of this thesis was to provide insight into early changes in osteoarthritis pathogenesis. Histopathology of synovium was investigated in femoroacetabular impingement (FAI), FAI with early hip osteoarthritis, and advanced hip osteoarthritis.

Methods: Synovium biopsies were collected from ten FAI, fourteen FAI with early osteoarthritis, and twelve advanced osteoarthritis patients. Histopathological grading allowed assessment of osteoarthritis-associated features. Microvessel density and maturity were determined through immunofluorescent labelling of CD31 and a-smooth muscle actin. Immunohistochemical staining was applied to calculate CD105⁺ microvessel density.

Results: In all groups, vascularization was prominent, with a mean [95% confidence interval] of 1.66 [1.41, …

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 …

Acidic Ph Environment Alters Cell Death And Regulates Aif Translocation In Endothelial Cells, Laura Xu

Electronic Thesis and Dissertation Repository

Cardiac transplantations are the golden standard treatment for end-stage heart failure but issues like ischemia-reperfusion injury (IRI) and graft rejection persist. Prolonged ischemia induces anaerobic metabolism, lactic acid accumulation, and intracellular acidosis. IRI is associated with programmed cell death, of which necroptosis is significant. We have shown that in hypoxia-reoxygenation, targeting necroptosis prevents murine microvascular endothelial cell (MVEC) death through cyclophilin D inhibition in vitro and apoptosis-inducing factor (AIF) is implicated in DNA damage. Here, we investigated AIF and the impact of acidic pH on cell death. Acidic pH conditions altered MVEC necroptosis to an apoptosis-like pattern. AIF nuclear translocation …

Evaluating The Utility Of S100a7 In Identifying Oral Dysplastic Lesions That Will Progress To Oral Squamous Cell Carcinoma, Jeff Soparlo

Electronic Thesis and Dissertation Repository

Title: Evaluating the utility of S100A7 in identifying oral dysplastic lesions that will progress to oral squamous cell carcinoma Introduction: Recently, S100A7 has been shown to be a potential useful marker for identifying oral lesions at risk of transformation from dysplasia to squamous cell carcinoma. Our hypothesis is that high S100A7 protein expression predicts the transformation of oral epithelial dysplasia to malignancy. The objective of our study is to semi-quantitatively evaluate the level of S100A7 expression in dysplastic lesions which have transformed into oral squamous cell carcinoma using immunohistochemistry, and correlate these results with other methods of analysis including the …

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 …

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 …

The Role Of Tbx3 In Early Breast Cancer Progression, Milica Krstic

Electronic Thesis and Dissertation Repository

TBX3 is a transcriptional regulator involved in embryonic development and in tumorigenesis of several cancer types. There are two isoforms of TBX3 (TBX3iso1 and TBX3iso2) with different DNA binding domains. The large-scale functional roles of TBX3iso1 and TBX3iso2 were characterized in a breast cancer context. Both TBX3 isoforms induced invasiveness and an epithelial-to-mesenchymal (EMT) phenotype. Coupling data from genome-wide ChIP-array and RNA-Seq studies provided a novel list of genes regulated by each isoform. Both TBX3 isoforms regulate expression of several EMT-related genes, including SLUG and TWIST1. Importantly, TBX3 is a direct regulator of SLUG, and SLUG expression is required for …

White Matter Inflammation And Executive Dysfunction: Implications For Alzheimer Disease And Vascular Cognitive Impairment, Alexander Levit

Electronic Thesis and Dissertation Repository

White matter integrity is crucial to healthy executive function, the cognitive domain that enables functional independence. However, in the ageing brain, white matter is highly vulnerable. White matter inflammation increases with age and Alzheimer disease (AD), which disrupts the normal function of white matter. This may contribute to executive dysfunction, but the relationship between white matter inflammation and executive function has not been directly evaluated in ageing nor AD. White matter is also particularly vulnerable to cerebrovascular disease, corresponding with the common presentation of executive dysfunction in vascular cognitive impairment (VCI). Thus, white matter may be an important substrate by …

The Effects Of Child Restraint System Use And Motor Vehicle Collision Severity On Injury Patterns And Severity In Children 8 Years Old And Younger., Peyton A. Schroeder

Electronic Thesis and Dissertation Repository

Motor vehicle collisions (MVCs) are a leading cause of injury and death for children under the age of 14 years in North America. Children, eight years old or younger, are required to use a child restraint system (CRS) when travelling in a vehicle in Canada. In the present study, the hypothesis that head injury severity of children in this age group, seated in rear rows of vehicles in MVCs, will be influenced by the types of restraint systems used was not supported by the data; however, other secondary aspects of collision data were explored. There were injury patterns that involved …

Non-Cancerous Abnormalities That Could Mimic Prostate Cancer Like Signal In Multi-Parametric Mri Images, Mena Gaed

Electronic Thesis and Dissertation Repository

Prostate Cancer (PCa) is the most common non-cutaneous cancer in North American men. Multi-parametric magnatic resonance imaging (mpMRI) has the potential to be used as a non-invasive procedure to predict locations and prognosis of PCa. This study aims to examine non-cancerous pathology lesions and normal histology that could mimic cancer in mpMRI signals. This study includes 19 radical prostatectomy specimens from the London Health Science Centre (LHSC) that were marked with 10 strand-shaped fiducials per specimen which were used as landmarks in histology processing and ex vivo MRI. Initial registration between fiducials on histology and MR images was performed followed …

Body And Organ Measurements In Infants And Neonates: An Autopsy Study, Audrey-Ann M. Evetts

Electronic Thesis and Dissertation Repository

Abstract

Introduction: A pathologist doing a pediatric autopsy will commonly assess child’s development by comparing the postmortem data to standardized population parameters using body and organ measurement charts. Although a number of resources are available, many are outdated and have significant limitations.

Objectives: To create Ontario population-specific organ and body measurement mean charts for infants and to explore relationships between body measurements/organ weights and cause of death, age, and gender of the deceased.

Methods: A database of 900 cases of infant and neonatal deaths that were investigated by Ontario coroners from 2000 to 2010 was retrospectively analyzed.

Results and Conclusions: …

Expression Of Human Kallikrein Protein And Mrna In Maxillofacial Cysts And Tumours, Karl Kevin Cuddy

Electronic Thesis and Dissertation Repository

Non-inflammatory odontogenic cysts and tumours vary in clinical appearance and can cause widespread destruction and deformation of the face. Proteases may play a role in the differing pathogenesis of these cysts and tumours. Human kallikrein proteins (KLKs) are a group of 15 serine proteases implicated in a variety of signaling and regulatory roles. This study evaluated the ameloblastoma, keratocystic odontogenic tumour (KOT), dentigerous cyst, lateral periodontal cyst, nasopalatine duct cyst and odontoma for the presence of KLK 3, 4, 5, 9 and 11 utilizing immunohistochemistry. Secondarily, we evaluated ameloblastoma for expression of KLK 1-15 mRNA using reverse transcription-polymerase chain reaction. …

Epithelial To Mesenchymal Transition In The Metastatic Progression Of Gastroenteropancreatic Neuroendocrine Tumours, Stephanie Mok

Electronic Thesis and Dissertation Repository

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a rare type of malignant epithelial cancer arising from the diffuse neuroendocrine system. In this study, we have performed gene expression profiling along with immunohistochemistry (IHC) to highlight key molecular pathways underlying the pathogenesis of GEP-NETs. We used formalin-fixed paraffin-embedded archived tissue samples of NETs arising from small intestine (SI-NETs), pancreas (P-NETs), and distal colon/rectal region (R-NETs) to extract RNA for real-time PCR-based gene profiling, and to construct tissue microarrays (TMAs) for high-throughput immunohistochemistry. Our results show evidence of epithelial to mesenchymal transition (EMT) at the mRNA and protein levels. From the genes highlighted by …

Role Of Sirt1 In Vascular Complications Of Diabetes, Rokhsana Mortuza

Electronic Thesis and Dissertation Repository

Chronic diabetic complications are significant causes of morbidity. In diabetes, as the cellular changes are similar to aging, we investigated the role of sirtuins (SIRTs) in chronic diabetic complications.

We examined glucose and aging-induced changes in the endothelial cells (ECs), the primary targets of chronic diabetic complications. ECs in high glucose showed evidences of early senescence, being more pronounced in microvascular ECs in association with decreased SIRT1 and FOXO1-dependent reduction in antioxidant gene expressions. A regulatory relationship of deacetylator SIRT1 and histone acetylator p300 was identified. Renal and retinal tissues of diabetic animals showed similar results.

Having established such changes, …