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Mouse Models Of Intervertebral Disc Development, Degeneration And Mechanical Loading, Matthew R. Mccann

Electronic Thesis and Dissertation Repository

Intervertebral disc (IVD) degeneration is a complex and multi-factorial process that is influenced by aging, genetic predispositions and environmental influences, such as altered mechanical loading. While recent studies have begun to characterize changes in the IVD associated with degeneration, the underlying etiology remains elusive. It is thought that the loss of notochord cells from the nucleus pulposus (NP) is one initiating factor contributing to the cascade of disc degeneration. However, questions remain about the function of notochord cells within the disc, including their capacity as tissue specific progenitor cells for the nucleus pulposus. We have demonstrated, with the use of …

Regulation Of Crfr1 And 5-Ht2ar By Pdz Domain-Containing Proteins Sap97 And Psd-95, Henry A. Dunn

Electronic Thesis and Dissertation Repository

Previous studies identified a crosstalk mechanism whereby CRFR1 sensitized 5-HT_2AR-mediated signaling via interactions with PDZ domain-containing proteins: a mechanism that may underlie stress-induced anxiety and depression. This prompted an investigation into uncovering which PDZ domain-containing proteins could regulate the crosstalk between these two receptors, and how they could be regulated individually. In the current studies, a subset of PDZ domain-containing proteins were identified that may interact with CRFR1 and 5-HT_2AR. The focus narrowed to two candidates previously implicated in psychiatric disease: SAP97 and PSD-95. We confirmed SAP97 and PSD-95 as interacting partners of CRFR1 in adult …

Influence Of Polycaprolactone And Basic Fibroblast Growth Factor On Gingival Fibroblasts, Sarah Michelsons

Electronic Thesis and Dissertation Repository

Guided tissue regeneration (GTR) to regenerate periodontal tissue involves placement of a cell-occlusive barrier membrane functionally excluding the gingiva and associated oral epithelium from the periodontal defect. Gingival connective tissue (CT) contains a rich vascular plexus and is a source of progenitor cells which could contribute to periodontal regeneration. We propose the use of a novel biodegradable and bioactive electrospun fibrous polycaprolactone (PCL) scaffold loaded with microspheres releasing basic fibroblast growth factor (bFGF) to promote gingival CT growth while maintaining a barrier to the oral epithelium. Scaffolds supported human gingival fibroblast proliferation and mesenchymal cell infiltration in a bFGF dose …

Exploring Communication Apprehension And Its Relationship To Communication Attitude And Socio-Communicative Functioning In Children With Velopharyngeal Insufficiency, Agnieszka Dzioba

Electronic Thesis and Dissertation Repository

Myriad findings on children with velopharyngeal insufficiency (VPI) indicate the potential for this population of children to experience feelings of apprehension specific to communication and the potential for other psychological and social difficulties. The purpose of the present investigation was to explore the construct of communication apprehension (CA) and its potential relationship to social and communicative functioning in a diverse group of children with VPI. Potential linkages between CA and multiple socio-communicative constructs including attitude, speech satisfaction, speech and language skill, social competence, and speech severity were explored in a cohort of children with and without VPI, followed by an …

Comparison Of Housed And Homeless Patients With An Orthopedic Diagnosis, Susan M. Williams

Electronic Thesis and Dissertation Repository

Studies on homelessness have shown that people who are homeless are admitted to hospital more frequently, for longer periods of time, and at a younger age than people who are housed. Once admitted to hospital, discharge planning is difficult and resource intensive, often leading to discharge back to the streets or a shelter. This puts this population at risk for complications and readmission. Although people who are homeless are prone to orthopedic injuries, there is no research on the outcomes of patients who are homeless with orthopedic injuries. This retrospective, case control study, based on the social determinants of health, …

The Effect Of Fixation Plate Length On Spinal Instability Following Anterior Cervical Plate Fixation For The Repair Of In Vitro Flexion-Distraction Injuries, Abdulaziz J. Al-Kuwari

Electronic Thesis and Dissertation Repository

Abstract:

The Effect of Fixation Plate Length on Spinal Instability Following Anterior Cervical Plate Fixation for the Repair of in Vitro Flexion-Distraction Injuries

Introduction: Anterior cervical decompression and fusion with a plate (ACDFP) is a commonly performed treatment following a traumatic injury to the subaxial cervical spine. The purpose of the presented work was to determine the biomechanical effect of plate length on cervical spine kinematic stability following ACDFP stabilization for a simulated traumatic injury.

Methods: Eleven fresh-frozen cadaveric C5-C6 and C6-C7 motion segments were examined in this study. To assess kinematics, flexibility testing was performed on each specimen …

The Expression And Potential Significance Of Human Kallikreins 6, 7, 8, 10, 13, And 14 In The Epithelium Of Selected Odontogenic Cysts And Tumors Of Variably Aggressive Biological Behaviour, Rebecca Woodford

Electronic Thesis and Dissertation Repository

ABSTRACT

This study analyzed the immunohistochemical staining, localization and relative concentrations of human kallikreins (KLKs) 6,7,8,10,13,14 to determine if there is a predilection for odontogenic epithelium and if differential staining could predict biological behavior of selected odontogenic lesions.

We found that all KLKs studied were present in the epithelium of all lesions examined. However, there were significant differences in location of intra-epithelial staining and staining scores between the lesions. There was no significant, unexplainable difference in staining between odontogenic cysts and the control cyst indicating no specific role in odontogenic cystogenesis. However, the odontogenic neoplasms showed statistically significant increased expression …

Transcriptional Regulation Of Peptidylarginine Deiminase Type Iv: Implications For Rheumatoid Arthritis, Ali Abbas

Electronic Thesis and Dissertation Repository

High titers of anti-citrullinated protein antibodies have been detected in sera of rheumatoid arthritis (RA) patients, implicating citrullinating enzymes in the pathogenesis of RA. Peptidylarginine deiminase type IV (PAD4) is a member of the PAD family of enzymes that catalyze the post- translational modification of arginine to citrulline and has been linked with RA. However, little is known about its transcriptional regulation. Therefore, our aim was to determine how transcription of PAD4 is activated in the myeloid lineage. Using bioinformatics, a potential nuclear factor kappa B (NF-kB) binding site was identified on the PAD4 promoter. Luciferase assays were used to …

The Development Of A Digital X-Ray Imaging System For The Characterization Of Transmission Of Whole-Body Vibration In Mice, Zhengyi Hu

Electronic Thesis and Dissertation Repository

Mechanical stimulus such as whole-body vibration (WBV) has shown to promote bone formation both in humans and animals. WBV has been hypothesized as a potentially useful osteoporosis intervention. While the transmission of WBV has been well characterized in humans, there is currently a lack of knowledge in the transmission of vibration in small animal models, such as mice, due to the lack of an implantable accelerometer appropriate to make such measurements. This thesis introduces an imaging-based method to quantify transmission of vibration in mice using x-ray imaging. Specifically, it utilizes motion blur of fiducial markers, which are implanted into the …

Investigation Of Β-Catenin-Mediated Regulation Of Igfbp-6 And The Roles Of Igfbp-6 And Igf-Ii In Dupuytren's Disease, Christina N. Raykha

Electronic Thesis and Dissertation Repository

Dupuytren’s Disease (DD) is a benign and heritable connective tissue fibrosis that affects the palmar fascia and typically results in permanent finger contracture(s). Similar to other fibroses, DD is characterized by increased fibroblast proliferation, myofibroblast differentiation and excess collagen deposition. Currently, there are no truly effective treatment options for connective tissue fibroses.

Increased levels of β-catenin, an intracellular trans-regulator of gene transcription, have been previously reported in DD. Genes that are associated with, and therefore potentially transcriptionally regulated by, β-catenin during DD development were identified in this thesis. One of these gene targets, IGFBP6, was shown to consistently be …

Cell Biology Of The Entry Of Bdellovibrio And Like Organisms, Ryan M. Chanyi

Electronic Thesis and Dissertation Repository

Bdellovibrio and like organisms (BALOs) are obligate predators of Gram negative bacteria. Predation occurs via a periplasmic or epibiotic life cycle. A periplasmic predator invades the periplasmic space of a prey while an epibiotic predator remains on the exterior.

An analysis of the genome sequences of periplasmic predators, Bdellovibrio bacteriovorus and Bacteriovorax marinus, and epibiotic predators, Bdellovibrio exovorus and Micavibrio aeruginosavorus determined that the genome size of epibiotic predators was smaller, while the metabolic networks were highly conserved. No core set of invasion-specific genes was identified.

Both life cycles were characterized by cryoelectron microscopy. The periplasmic predator, Bd. bacteriovorus …

The Effect Of Botulinum Toxin Type A On Speech Intelligibility In Oromandibular Dystonia, Beatriz Ysabel Domingo

Electronic Thesis and Dissertation Repository

Speech intelligibility of 10 individuals with OMD was measured before and after receiving BoNT-A injections. Intelligibility was assessed using the PIT (single-word intelligibility), SIT (sentence intelligibility), and a conversational speech task. Five listeners rated the speech intelligibility of these three intelligibility tasks via orthographic transcription and visual analogue scaling (VAS) techniques. BoNT-A was not associated with significant differences in speech intelligibility. Further analysis revealed a significant difference on the PIT VAS intelligibility ratings based on order of presentation, suggesting that listeners rated the first half of words on the PIT (words 1-29) as more intelligible than the second half of …

Probiotic Therapy For Heart Failure: Investigating The Potential Anti-Hypertrophic Properties Of Probiotics, Grace L. Ettinger

Electronic Thesis and Dissertation Repository

Heart failure patients face a five-year 50% mortality rate, due to impaired cardiac function and hypertrophy of the heart. Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. Considering the established cardiovascular benefits of some probiotics, including reduction of cholesterol and hypertension, it was hypothesized that probiotics can improve outcomes of heart failure. Probiotics or controls were administered orally to an animal model for heart failure. Those receiving probiotics showed a significant improvement in cardiac hypertrophy and an attenuation of heart failure compared to control. No changes in gut microbial composition occurred. …

Through The Eyes Of Children: First Nations Children's Perceptions Of Health, Kyla Annui Ursa English

Electronic Thesis and Dissertation Repository

Few studies addressing Indigenous children’s health have incorporated the voices of children or integrated an occupational science perspective. In partnership with the Southwest Ontario Aboriginal Health Access Centre, this community-based study used artwork and sharing circles to understand First Nations children’s perceptions of health during a week-long culture camp. The objectives were: (1) to understand how First Nations children view their health, and (2) to explore how children connect health and culture. Findings demonstrated that children’s perceptions (n=20, aged 10 to 12) focused on physical aspects of health, such as diet and fitness. Children attended much less to spiritual, mental, …

Analysis Of Invariant Natural Killer T Cells In Intra-Abdominal Sepsis, Ram Venkatesh Anantha

Electronic Thesis and Dissertation Repository

Sepsis is characterized by a severe systemic inflammatory response to infection that is associated with high morbidity and mortality despite optimal care. Invariant natural killer T (iNKT) cells are potent regulatory lymphocytes that can produce pro- and/or anti-inflammatory cytokines, thus shaping the course and nature of immune responses; however, little is known about their role in sepsis. We demonstrate here that patients with sepsis/severe sepsis have significantly elevated proportions of circulating iNKT cells in their peripheral blood, as compared to non-septic patients. We therefore investigated iNKT cells in mice with intra-abdominal sepsis (IAS). Our data show that iNKT cells are …

Investigating Risk Factors For Pediatric Opioid Morbidity And Mortality, Lauren E. Kelly

Electronic Thesis and Dissertation Repository

Young children are sometimes prescribed opioids and may be exposed to opioids in utero and through breast milk. Clinical and genetic factors create large inter- individual variability in opioid response and have been associated with life threatening and often fatal adverse drug reactions in young children. Genetic factors have been studied in adults but there is little clinical evidence in young children. The focus of this thesis is on three commonly prescribed opioids: codeine, morphine and methadone. The objective of this work was to investigate risk factors associated with opioid related morbidity and mortality in young children. Risk factors were …

Reinforcement Of Flowable Dental Composites With Titanium Dioxide Nanotubes, Manal Dafar

Electronic Thesis and Dissertation Repository

Flowable composites are widely used in dentistry. However, they suffer from poor mechanical properties. The aim of this study was to reinforce a flowable composite with TiO₂ nanotubes (n-TiO₂), which were synthesized using an alkaline hydrothermal technique then functionalized with silane or methacrylic acid (MA). The synthesized n-TiO₂ was characterized using X-ray diffraction, energy-dispersive X-ray spectroscopy and Fourier transform infrared spectroscopy. Electron microscopy revealed a tubular morphology of n-TiO₂. Commercially available flowable composite was reinforced with varying amounts of nanotubes (0-5%). Dynamic Young’s moduli (E) and fracture toughness (K_IC) of composites reinforced …

Validation Of A Novel Methodology For Evaluating Surgical Tissue Plane Identification, Syed T. Ali

Electronic Thesis and Dissertation Repository

Introduction: The ability to identify tissues planes is a fundamental surgical skill. This study attempts to validate a previously developed test for assessing this ability.

Methods: 48 video captured images from laparoscopic right hemicolectomies were presented on an iPad to 18 surgeons who were grouped based on experience (Consultants (C), Senior trainees (S), and the Junior trainees (J)). Subjects were asked to draw a line indicating the tissue plane of dissection. Lines were compared by a modified Hausdorff measure. Within group variability represented group precision and trainee accuracy was determined from comparison to Consultants.

Results: Within group comparisons demonstrated Consultants …

Effect Of Ascorbate On Coagulation And Fibrinolytic Factors In The Septic Microvasculature, Scott Swarbreck

Electronic Thesis and Dissertation Repository

Sepsis, a systemic inflammatory response to an infection, is a significant cause of morbidity and mortality worldwide. The microcirculation during sepsis fails, in part, due to microthrombosis and the resulting plugging of capillaries, precipitating organ failure. Intravenous injection of ascorbate has been shown to reduce capillary plugging, however the mechanism of this protective effect is unclear. We hypothesized that ascorbate-mediated destabilization of the microthrombi through promoting fibrinolysis could contribute to this protection.

We showed that streptokinase, a pro-fibrinolytic agent, reduced the capillary plugging to a similar degree as ascorbate. This similarity provided the impetus for studying the effect of ascorbate …

Pathophysiology Of Compartment Syndrome, Abdel-Rahman Lawendy

Electronic Thesis and Dissertation Repository

Acute limb compartment syndrome (CS), a potentially devastating complication of musculoskeletal trauma, is characterized by increased pressure within a closed osseofascial compartment, resulting in muscle-threatening and ultimately limb-threatening ischemia. Urgent fasciotomy remains the only effective treatment and a current gold-standard surgical therapy. Despite a large body of literature dedicated to understanding the pathophysiology of CS, the mechanisms of CS-induced tissue damage are rather poorly understood. The established view is that increasing compartmental pressure compromises microcirculatory perfusion, restricting oxygen and nutrient delivery to vital tissues, resulting in cellular anoxia and severe tissue necrosis. However, unlike complete ischemia, CS causes myonecrosis in …

Development Of Non-Covalent Functionalization Of Carbon Nanotubes For Sirna Delivery, King Sun Siu

Electronic Thesis and Dissertation Repository

RNA interference (RNAi) therapy is promising for treating various diseases but the delivery of small interfering RNA (siRNA) is difficult. To overcome the technical difficulties of siRNA delivery, an efficient and targeted delivery of siRNA is required for efficient RNAi therapy. Single-walled carbon nanotubes (CNT) has been used for nucleic acid delivery such as siRNA delivery. It has been found that CNT can gain entry into the cells by a diffusion-like mechanism which was called “nano-needle”. However, the solubility of CNT is low in most of the solvents including water. Functionalization of CNT can be carried out to enhance the …

Indoleamine 2,3-Dioxygenase Confers Resistance To Chemotherapy And Γ Radiation To Cancer Cells, Independent Of Direct Immune Involvement, Saman Maleki Vareki

Electronic Thesis and Dissertation Repository

Indoleamine 2,3-dioxygenase-1 (IDO) is an immunosuppressive molecule expressed by most human tumours. IDO levels correlate with poor prognosis in cancer patients and IDO inhibitors are under investigation to enhance endogenous anticancer immunosurveillance. Little is known regarding the immune-independent functions of IDO relevant to cancer therapy. In this thesis I show, for the first time, that IDO mediates human tumour cell resistance, in a cell-autonomous fashion, to single and combination treatment with a diverse group of chemotherapy drugs and g radiation. These drugs include a PARP inhibitor (olaparib), a DNA cross-linking agent (cisplatin), a folate antimetabolite (pemetrexed), a nucleoside analogue (gemcitabine), …