Medicine and Health Sciences Commons^™

Low Birth Weight Followed By Postnatal Over-Nutrition In The Guinea Pig Exposes A Predominant Player In The Development Of Vascular Dysfunction., Jennifer A Thompson, Ousseynou Sarr, Karolina Piorkowska, Robert Gros, Timothy Regnault

Paediatrics Publications

The association between intrauterine growth restriction (IUGR) and hypertension is well established, yet the interaction between IUGR and other pathogenic contributors remains ill-defined. This study examined the independent and interactive effects of fetal growth reduction resulting in low birth weight (LBW), and postnatal Western diet (WD) on vascular function. Growth reduction was induced in pregnant guinea pigs by uterine artery ablation. LBW and normal birth weight (NBW) offspring were randomly assigned to a control diet (CD) or a WD. In young adulthood, length-tension curves were generated in aortic rings and responses to methacholine (MCh) were evaluated in the carotid and …

Assessing The Structural Validity Of The Measure Of Processes Of Care (Mpoc-20) In Children With Epilepsy, Kariym Christopher Joachim

Electronic Thesis and Dissertation Repository

The goal of this thesis was to determine whether the 20-item Measure of Processes of Care (MPOC-20) questionnaire remains structurally/factorially valid among children with epilepsy, and to propose adaptations if it did not. Establishing the MPOC-20’s structural validity in this population makes it possible to draw conclusions on the potential effects of parent-perceived Family-Centred Care (FCC) on health outcomes within this population. Data came from the Health-related Quality of Life for Children with Epilepsy Study (HERQULES). Confirmatory Factor Analysis (CFA) indicated that the original five factor model fit poorly in children with epilepsy. An exploratory analysis within a CFA framework …

A Comparison Of Clinical Trial And Model-Based Cost Estimates In Glaucoma – The Case Of Repeat Laser Trabeculoplasty In Ontario, Omar Akhtar

Electronic Thesis and Dissertation Repository

Background and objective: For cost-effectiveness analyses (CEA) of glaucoma interventions to be of use they require valid and accurate cost and effectiveness data. Costs remain understudied relative to effectiveness. The impact of cost estimation methods on resultant estimates is unknown in glaucoma. Direct measurement of costs is labour-intensive and expensive. Decision-analytic modelling of costs using literature sources, expert opinion, institutional experience and assumptions provides a quicker, less laborious alternative to empirical costing. A lack of long-term effectiveness data in chronic diseases like glaucoma means that modelling is widespread and inevitable, both for CEAs and budget impact projections. The same problem …

Propranolol Therapy For Infantile Hemangioma Is Less Toxic But Longer In Duration Than Corticosteroid Therapy, Kathryn Sawa, Arjang Yazdani, Michael J. Rieder, Guido Filler

Paediatrics Publications

BACKGROUND: Infantile hemangioma is the most common benign, self-limiting tumour of childhood. Treatment is reserved for hemangiomas that obstruct vital structures or cause significant disfigurement. Traditionally, corticosteroids have been the medical treatment of choice. Since 2008, however, propranolol has been rapidly adopted as an effective pharmacological treatment for infantile hemangioma. Published data regarding the long-term side effects of propranolol are currently lacking. OBJECTIVE: To describe the long-term effects of propranolol and corticosteroids on anthropometric measurements (height, body mass index [BMI]) and blood pressure in children. METHODS: A prospective database analysis of all infantile hemangioma patient visits to the pediatric vascular …

The Health Initiative Program For Kids (Hip Kids): Effects Of A 1-Year Multidisciplinary Lifestyle Intervention On Adiposity And Quality Of Life In Obese Children And Adolescents -- A Longitudinal Pilot Intervention Study, Dirk E. Bock, Tracy Robinson, Jamie A Seabrook, Meghan Rombeek, Kambiz Norozi, Guido Filler, Ralf Rauch, Cheril L Clarson

Paediatrics Publications

BACKGROUND: Though recent data suggest that multidisciplinary outpatient interventions can have a positive effect on childhood obesity, it is still unclear which program components are most beneficial and how they affect quality of life (QoL). The aim of this study was to determine if a 1-year multidisciplinary, family-centered outpatient intervention based on social cognitive theory would be effective in (i) preventing further increases in BMI and BMI z-score, and (ii) improving QoL in obese children and adolescents.

METHODS: Obese children and adolescents 8-17 years of age and their families participated in this 1-year longitudinal pilot intervention study. The intervention consisted …

Quality Of Life And Health-Related Quality Of Life In Children With Duchenne Muscular Dystrophy, Yi Wei

Electronic Thesis and Dissertation Repository

Quality of life studies in Duchenne Muscular Dystrophy are scarce. This study explores the relationship between the broad concept of quality of life and the more focused concept of health-related quality of life and examines the relationships between patient and family characteristics and health-related quality of life. Participants were recruited from the Canadian Neuromuscular Disease Registry, 98 parents and 85 children completed the Quality of My Life and Pediatric Quality of Life Inventory questionnaires. Simple regression was used to examine the relationship between quality of life and health-related quality of life. Multivariable linear regressions were used to determine child and …

Bmp4 And Lgl1 Are Down Regulated In An Ovine Model Of Congenital Diaphragmatic Hernia, Heather M A Emmerton-Coughlin, K Kathryn Martin, Jacky S S Chiu, Lin Zhao, Leslie A Scott, Timothy R H Regnault, Andreana Bütter

Surgery Publications

BACKGROUND/PURPOSE: The molecular pathophysiology of lung hypoplasia in congenital diaphragmatic hernia (CDH) remains poorly understood. The Wnt signaling pathway and downstream targets, such as bone morphogenetic proteins (BMP) 4 and other factors such as late gestation lung protein 1 (LGL1), are essential to normal lung development. Nitrofen-induced hypoplastic CDH rodent lungs demonstrate down regulation of the Wnt pathway including BMP4 and reduced LGL1 expression. The aim of the current study was to examine the molecular pathophysiology associated with a surgically induced CDH in an ovine model.

METHODS: Left thoracotomy was performed at 80 days in 14 fetal sheep; CDH was …

Atrx Is Required For Maintenance Of The Neuroprogenitor Cell Pool In The Embryonic Mouse Brain, Kieran Ritchie, L Ashley Watson, Benjamin Davidson, Yan Jiang, Nathalie G. Bérubé

Paediatrics Publications

Mutations in the alpha-thalassemia mental retardation X-linked (ATRX) gene cause a spectrum of abnormalities including intellectual disability, developmental delay, seizures, and microcephaly. The ATRX protein is highly enriched at heterochromatic repetitive sequences adjacent to the centromere, and ATRX depletion results in chromosome congression, segregation, and cohesion defects. Here, we show that Cre-mediated inactivation of Atrx in the embryonic mouse (Mus musculus) brain results in expansion of cerebral cortical layer VI, and a concurrent thinning of layers II-IV. We observed increased cell cycle exit during early-mid neurogenesis, and a depletion of apical progenitors by late neurogenesis in the Atrx-null neocortex, explaining …

Exploiting High-Throughput Cell Line Drug Screening Studies To Identify Candidate Therapeutic Agents In Head And Neck Cancer, Anthony C Nichols, Morgan Black, John Yoo, Nicole Pinto, Andrew Fernandes, Benjamin Haibe-Kains, Paul C Boutros, John W Barrett

Oncology Publications

BACKGROUND: There is an urgent need for better therapeutics in head and neck squamous cell cancer (HNSCC) to improve survival and decrease treatment morbidity. Recent advances in high-throughput drug screening techniques and next-generation sequencing have identified new therapeutic targets in other cancer types, but an HNSCC-specific study has not yet been carried out. We have exploited data from two large-scale cell line projects to clearly describe the mutational and copy number status of HNSCC cell lines and identify candidate drugs with elevated efficacy in HNSCC.

METHODS: The genetic landscape of 42 HNSCC cell lines including mutational and copy number data …

Quantitative Mri Correlates Of Hippocampal And Neocortical Pathology In Intractable Temporal Lobe Epilepsy, Maged Goubran

Electronic Thesis and Dissertation Repository

Intractable or drug-resistant epilepsy occurs in over 30% of epilepsy patients, with many of these patients undergoing surgical excision of the affected brain region to achieve seizure control. Advances in MRI have the potential to improve surgical treatment of epilepsy through improved identification and delineation of lesions. However, validation is currently needed to investigate histopathological correlates of these new imaging techniques. The purpose of this work is to investigate histopathological correlates of quantitative relaxometry and DTI from hippocampal and neocortical specimens of intractable TLE patients. To achieve this goal I developed and evaluated a pipeline for histology to in-vivo MRI …

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 …

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, …

Blood Conservation In Total Hip Arthroplasty: Interim Analysis Of The Tranexamic Acid Comparison In Hip Replacement (Teach-R) Trial, Richard P. Nadeau

Electronic Thesis and Dissertation Repository

Intravenous tranexamic acid (TEA) is used in total hip arthroplasty (THA) to reduce blood loss. Concern of increased thromboembolic risk has prompted the search for treatment alternatives. The Tranexamic Acid Comparison in Hip Replacement (TeACH-R) trial is a prospective randomized controlled trial comparing the efficacy of intravenous and topical TEA in reducing perioperative blood loss. For interim data analysis, 52 of the planned 144 participants had completed the initial phase of the TeACH-R trial. No significant differences were identified between the intravenous and topical TEA treatment arms for delta-hemoglobin (ΔHgb; 34.81±13.78 vs. 35.65±15.54 mg/dL; p=0.840), calculated blood loss (1548±509 …

Cell Death Regulates Injury And Inflammation During Renal Allograft Transplantation, Arthur Lau

Electronic Thesis and Dissertation Repository

Renal transplantation invariably results in tissue injury resulting from ischemia reperfusion injury (IRI), inflammation, drug toxicity, and rejection. Tubular epithelial cells (TEC) comprise the majority of renal parenchyma and are susceptible to cell death and injury during diverse forms of inflammation, which has direct and indirect effects on long term allograft function. Renal TEC have the unique ability to attenuate inflammation and alloimmune injury through the expression of various mediators of cell death and inflammatory molecules. Inhibition of cell death pathways in renal allografts may influence outcomes of alloimmune responses and graft survival. In this body of investigation, alteration of …

Investigating Barriers To Access And Delivery Of Palliative Care For Persons With Dementia In London, Ontario, Emily M. Hill

Electronic Thesis and Dissertation Repository

Dementia is a syndrome that is progressive, degenerative and terminal. The palliative care philosophy aims to maximize quality of life for the dying individual and has been recognized in the literature as being both beneficial and under-used in persons dying with dementia. The purpose of this study was to investigate the experiences of staff delivering palliative care to individuals with dementia to determine how care was delivered, to learn which assessment tools were used, and whether policies were affected the delivery of palliative care. Twenty-two staff participants were interviewed. Data were interpreted using phenomenological methodology. Findings yielded three themes: confusion, …

Functional Assessment And Potential Therapeutic Role Of Carbon Monoxide Releasing Molecule-­‐3 In A Rodent Model Of Compartment Syndrome, Al Walid Hamam

Electronic Thesis and Dissertation Repository

Compartment syndrome (CS) is a life and limb threatening condition resulting in long term morbidity. Gold standard treatment of CS is surgical fasciotomy. Long-term morbidity is common post fasciotomy. We tested a gait analysis system (CatWalk™) to see if we could detect functional effects of CS in our rodent model. We also investigated the effects of carbon monoxide releasing molecule-3 (CORM-3) on the function of gait in rodents post CS.

The CatWalkTM system was able to detect abnormalities in a rodent’s gait post CS. CORM-3 was also found to alleviate the functional deficits following CS. Multiple dose but not single …

Introduction Of A Mobile Device Based Tertiary Survey Application Reduces Missed Injuries: A Multi-Center Prospective Study, Bradley S. Moffat

Electronic Thesis and Dissertation Repository

Missed injuries in trauma patients are a significant source of preventable morbidity. The tertiary survey is a head-to-toe physical exam performed within 24 hours of admission to identify any injuries which may have been missed during initial assessment and resuscitation. The Physician Assist Trauma Software (PATS) is an electronic program designed to guide users through a thorough tertiary survey and document the results. This thesis project was designed to study the impact of implementing this novel mobile device based electronic tertiary survey program on missed injuries. The first phase of this study involved quantifying and characterizing the missed injury rate …

Efficacy Of Novel Antifouling/Antimicrobial Coatings For The Prevention Of Urinary Device Associated Infection And Encrustation, Thomas O. Tailly

Electronic Thesis and Dissertation Repository

Device associated urinary tract infections are a very important healthcare issue. Despite best efforts in preventing and treating these infections, many patients and physicians are still confronted with this problem. Our research group is involved in testing and evaluating new stent coatings for the prevention of device associated infections and device encrustation. In the current project, we tested two new coating copolymers, both based on a long chain polymer backbone and mussel adhesive protein to this purpose in a rabbit and porcine model. The results demonstrate efficiency of one copolymer in preventing infections in the rabbit model. Interestingly there is …

Implantation Failure In Female Kiss1-/- Mice Is Independent Of Their Hypogonadic State And Can Be Partially Rescued By Leukemia Inhibitory Factor., Michele Calder, Yee-Ming Chan, Renju Raj, Macarena Pampillo, Adrienne Elbert, Michelle Noonan, Carolina Gillio-Meina, Claudia Caligioni, Nathalie G Bérubé, Moshmi Bhattacharya, Andrew J Watson, Stephanie B Seminara, Andy V Babwah

Obstetrics & Gynaecology Publications

The hypothalamic kisspeptin signaling system is a major positive regulator of the reproductive neuroendocrine axis, and loss of Kiss1 in the mouse results in infertility, a condition generally attributed to its hypogonadotropic hypogonadism. We demonstrate that in Kiss1(-/-) female mice, acute replacement of gonadotropins and estradiol restores ovulation, mating, and fertilization; however, these mice are still unable to achieve pregnancy because embryos fail to implant. Progesterone treatment did not overcome this defect. Kiss1(+/-) embryos transferred to a wild-type female mouse can successfully implant, demonstrating the defect is due to maternal factors. Kisspeptin and its receptor are expressed in the mouse …

Overall Survival And Biochemical Failure-Free Survival Comparison Of Brachytherapy Treatment Options Versus External Beam Radiation Therapy For Both Low And Intermediate-Risk Prostate Cancer: A Propensity-Score Matched Analysis, Graham D. Smith

Electronic Thesis and Dissertation Repository

Purpose: This study compares overall survival (OS) and biochemical failure-free survival (bFFS) in low- and intermediate-risk prostate cancer patients that received brachytherapy [low-dose-rate brachytherapy (LDR-BT) or high-dose-rate brachytherapy with external beam radiation therapy (HDR-BT+EBRT)] versus external beam radiation therapy (EBRT) alone.

Materials/Methods: Patient data was obtained from the ProCaRS database, which contains 7974 prostate cancer patients treated at four Canadian institutions. Propensity score (PS) matching was used to generate matched cohorts with balanced baseline prognostic factors.

Results/Conclusions: Final PS matches included two 1:1 intermediate-risk patient matches, LDR-BT vs. EBRT (total n = 254) and HDR-BT+EBRT vs. EBRT (total n=388), and …

Analysis Of Neonatal Brain Lacking Atrx Or Mecp2 Reveals Changes In Nucleosome Density, Ctcf Binding And Chromatin Looping, Kristin D Kernohan, Douglas Vernimmen, Gregory B Gloor, Nathalie G. Bérubé

Paediatrics Publications

ATRX and MeCP2 belong to an expanding group of chromatin-associated proteins implicated in human neurodevelopmental disorders, although their gene-regulatory activities are not fully resolved. Loss of ATRX prevents full repression of an imprinted gene network in the postnatal brain and in this study we address the mechanistic aspects of this regulation. We show that ATRX binds many imprinted domains individually but that transient co-localization between imprinted domains in the nuclei of neurons does not require ATRX. We demonstrate that MeCP2 is required for ATRX recruitment and that deficiency of either ATRX or MeCP2 causes decreased frequency of long-range chromatin interactions …

Polycomb Repressive Complex 2 Regulates Mir-200b In Retinal Endothelial Cells: Possible Implications In Diabetic Retinopathy, Michael A. Ruiz

Electronic Thesis and Dissertation Repository

Glucose-induced augmented vascular endothelial growth factor (VEGF) production is a key event in diabetic retinopathy. We have previously demonstrated that downregulation of miR-200b increases VEGF, mediating structural and functional changes in the retina in diabetes. However, mechanisms regulating miR-200b in diabetes are not known. Histone methyltransferase complex, Polycomb Repressive Complex 2 (PRC2), has been shown to repress miRNAs in neoplastic process. We hypothesized that, in diabetes, PRC2 represses miR-200b through its histone H3 lysine-27 trimethylation mark. We show that human retinal microvascular endothelial cells exposed to high levels of glucose regulate miR-200b repression through histone methylation, and that inhibition of …

The Repair, Reconstruction And Replacement Of The Coronoid Process, Bashar Alolabi

Electronic Thesis and Dissertation Repository

The coronoid process is the most important articular stabilizer of the elbow. While most large coronoid fractures are treated surgically with open reduction and internal fixation, there is limited data on the most effective fixation method. The strengths of five different coronoid fixation methods were assessed using a materials testing machine. Plate fixation proved to be stronger than screw fixation; two screws, regardless of the orientation, were stronger than one; and suture fixation was unreliable. In the setting of an unfixable coronoid fracture, reconstruction of the coronoid using the tip of the olecranon has been described. However, this technique has …

Mri Relaxation Rates: A Quantitative Approach To Track Tumour Cells Expressing Maga, Anindita Sengupta

Electronic Thesis and Dissertation Repository

Using magnetic resonance imaging, relaxation rate measurements were

performed in cancer cells overexpressing a magnetotactic bacterial gene, MagA.

Measurements of magnetic resonance relaxation rates in this expression

system is important for optimizing cell detection and specificity, for developing

quantification methods, and for refinement of gene-based iron contrast using

magnetosome associated genes. We measured the total transverse

relaxation rate (R2^*), its irreversible and reversible components (R2 and R2^′,

respectively) and the longitudinal relaxation rate (R1) in MDA-MB-435 tumor cells.

Clonal lines overexpressing MagA were cultured in the presence and absence of

iron supplementation, and mounted in a …

Managing Uncertainty In Young-Onset Parkinson's Disease, Michael J. Ravenek

Electronic Thesis and Dissertation Repository

Typically considered a disease of old-age, Parkinson’s disease can affect those younger in life, i.e., before the age of 55, when it is referred to as young-onset Parkinson’s disease (YOPD). Using constructionist grounded theory, this research sought to understand how, and why, individuals with YOPD became informed about their disease over time. A total of 39 individuals, who self-identified as living with YOPD, took part in this study which was organized according to four cycles of data collection. These cycles utilized focus groups, in-depth interviews and a private online discussion board, supplemented by 14 autobiographies written by individuals living with …

The Role Of Rotator Interval Closure In Bankart Lesion Repair, Lauren L. Rainsford

Electronic Thesis and Dissertation Repository

Twenty-nine patients who had sustained an anterior shoulder dislocation were randomly assigned to receive Bankart lesion repair, or Bankart lesion repair with rotator interval closure. External rotation range of motion with 90° of abduction external rotation range of motion with no abduction, and forward flexion range of motion were measured preoperatively, and at three and six months postoperatively. Quality of life, function, and pain were measured preoperatively, and at three, six, 12 and 24 weeks postoperatively. We found no significant differences between groups for any outcome but the confidence intervals were wide and definitive conclusions could not be made. This …

Three Dimensional Dual Labelled Dna Fluorescent In Situ Hybridization Analysis In Fixed Tissue Sections, Kristin D Kernohan, Nathalie G. Bérubé

Paediatrics Publications

Emerging studies demonstrate that three-dimensional organization of chromatin in the nucleus plays a vital role in regulating the genome. DNA fluorescent in situ hybridization (FISH) is a common molecular technique used to visualize the location of DNA sequences. The vast majority of DNA FISH studies are conducted on cultured cells due to the technical difficulties encountered using fixed tissue sections. However, the use of cultured cells poses important limitations that could yield misleading results, making in vivo analysis a far superior approach. Here we present a protocol for multiplexed three dimensional DNA FISH in mouse brain sections, which is also …

Cortisol And Testosterone In Hair As Biological Markers Of Systolic Heart Failure, Justin Chan

Electronic Thesis and Dissertation Repository

Congestive heart failure (CHF) is associated with increased stress and alterations in metabolism, favoring catabolism over anabolism. Hormonal profiles of patients with heart failure have been assessed using serum and saliva as matrices, which are only point measurements and do not provide long-term information. Scalp hair is a novel matrix that allows for measurement of hormones over a period of several months. We aimed to evaluate whether levels of cortisol and testosterone and their ratio (C/T) in hair correlate with severity of heart failure. We conducted a prospective study in ambulatory male patients with a left ventricular ejection fraction (LVEF) …

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 …

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 …