Loss Of Atrx Does Not Confer Susceptibility To Osteoarthritis, Lauren A. Solomon, Bailey A. Russell, David Makar, Nathalie G. Bérubé, Frank Beier

Paediatrics Publications

The chromatin remodelling protein ATRX is associated with the rare genetic disorder ATR-X syndrome. This syndrome includes developmental delay, cognitive impairment, and a variety of skeletal deformities. ATRX plays a role in several basic chromatin-mediated cellular events including DNA replication, telomere stability, gene transcription, and chromosome congression and cohesion during cell division. We have used a loss-of-function approach to directly investigate the role of Atrx in the adult skeleton in three different models of selective Atrx loss. We specifically targeted deletion of Atrx to the forelimb mesenchyme, to cartilage and to bone-forming osteoblasts. We previously demonstrated that loss of ATRX …

Prenatal Programming Of Hepatic Glucose And Cholesterol Regulation In Male Rat Offspring By Chronic Intermittent Hypoxia, Waseem Iqbal

Electronic Thesis and Dissertation Repository

Obstructive sleep apnea (OSA) is a chronic disorder involving repetitive interruptions in breathing during sleep. Sufferers of OSA are exposed to chronic intermittent hypoxia (CIH), characterized by cyclical reductions in oxygen availability. A number of studies have established a link between OSA and various cardiovascular and metabolic comorbidities in adulthood, including hypertension, obesity, and type II diabetes. While the consequences of OSA in adults have been well described, the cross-generational impact of this condition and potential effects on fetal development are not known. Epidemiological and animal studies have demonstrated that physiological insults during pregnancy lead to diminished growth of offspring …

The Centre Of The Brain: Topographical Model Of Motor, Cognitive, Affective, And Somatosensory Functions Of The Basal Ganglia, Marie Arsalidou, Emma G. Duerden, Margot J. Taylor

Paediatrics Publications

The basal ganglia have traditionally been viewed as motor processing nuclei; however, functional neuroimaging evidence has implicated these structures in more complex cognitive and affective processes that are fundamental for a range of human activities. Using quantitative meta-analysis methods we assessed the functional subdivisions of basal ganglia nuclei in relation to motor (body and eye movements), cognitive (working-memory and executive), affective (emotion and reward) and somatosensory functions in healthy participants. We document affective processes in the anterior parts of the caudate head with the most overlap within the left hemisphere. Cognitive processes showed the most widespread response, whereas motor processes …

Techniques For The Isolation Of High-Quality Rna From Cells Encapsulated In Chitosan Hydrogels, Claire Yu, Stuart Young, Valerio Russo, Brian G. Amsden, Lauren E. Flynn

Paediatrics Publications

Extracting high-quality RNA from hydrogels containing polysaccharide components is challenging, as traditional RNA isolation techniques designed for cells and tissues can have limited yields and purity due to physiochemical interactions between the nucleic acids and the biomaterials. In this study, a comparative analysis of several different RNA isolation methods was performed on human adipose-derived stem cells photo-encapsulated within methacrylated glycol chitosan hydrogels. The results demonstrated that RNA isolation methods with cetyl trimethylammonium bromide (CTAB) buffer followed by purification with an RNeasy® mini kit resulted in low yields of RNA, except when the samples were preminced directly within the buffer. In …

Measuring The Sixth Vital Sign: A Descriptive Analysis Of Distress In Individuals With Head And Neck Cancer And Their Caregivers, Catherine C. Bornbaum

Electronic Thesis and Dissertation Repository

Introduction: Distress has become so problematic in oncology that it has been recognized as the “sixth vital sign” implying that distress monitoring should occur as routinely as the monitoring of one’s temperature or blood pressure. The research reported herein investigated the impact of head and neck cancer on levels of distress, commonly reported problems, and perceptions of quality of life in individuals with head and neck cancer and their caregivers.

Method: Two distinct studies were conducted; the first explored the patient experience of distress and quality of life while the second assessed the caregiver experience of these same constructs. A …

Gsk-3Β Function In Bone Regulates Skeletal Development, Whole-Body Metabolism, And Male Life Span, J. R. Gillespie, J. R. Bush, G. I. Bell, L. A. Aubrey, H. Dupuis, F. Ferron, B. Kream, G. Dimattia, S. Patel, J. R. Woodgett, G. Karsenty, D. A. Hess, F. Beier

Paediatrics Publications

Glycogen synthase kinase 3 β (GSK-3β) is an essential negative regulator or “brake” on many anabolic-signaling pathways including Wnt and insulin. Global deletion of GSK-3β results in perinatal lethality and various skeletal defects. The goal of our research was to determine GSK-3β cell-autonomous effects and postnatal roles in the skeleton. We used the 3.6-kb Col1a1 promoter to inactivate the Gsk3b gene (Col1a1-Gsk3b knockout) in skeletal cells. Mutant mice exhibit decreased body fat and postnatal bone growth, as well as delayed development of several skeletal elements. Surprisingly, the mutant mice display decreased circulating glucose and insulin levels despite normal expression of …

Effect Of Fluid Loss Following Hemodialysis On Tibialis Anterior Muscle Strength In People With End-Stage Renal Disease, Anuradha Sawant

Electronic Thesis and Dissertation Repository

ABSTRACT

PURPOSE: The purpose of this study was to evaluate the effect of fluid loss following hemodialysis (HD) on tibialis anterior (TA) strength in participants with end-stage renal disease. Issues concerning measures of skeletal muscle hydration and efficacy of exercise as an anabolic intervention were also addressed.

METHODS: Data from published literature were combined in a meta-analysis to establish efficacy of exercise in participants on HD. Three clinical studies were undertaken using data acquired from healthy volunteers and participants on HD. Hydration of the calf muscles was estimated using bioelectrical impedance spectroscopy (BIS) [extracellular (ECF) and intracellular (ICF) fluid] …

Stress-Inducible Phosphoprotein 1 Has Unique Cochaperone Activity During Development And Regulates Cellular Response To Ischemia Via The Prion Protein., Flavio H Beraldo, Iaci N Soares, Daniela F Goncalves, Jue Fan, Anu A Thomas, Tiago G Santos, Amro H Mohammad, Martin Roffé, Michele D Calder, Simona Nikolova, Glaucia N Hajj, Andre L Guimaraes, Andre R Massensini, Ian Welch, Dean H Betts, Robert Gros, Maria Drangova, Andrew J Watson, Robert Bartha, Vania F Prado, Vilma R Martins, Marco A M Prado

Obstetrics & Gynaecology Publications

Stress-inducible phosphoprotein 1 (STI1) is part of the chaperone machinery, but it also functions as an extracellular ligand for the prion protein. However, the physiological relevance of these STI1 activities in vivo is unknown. Here, we show that in the absence of embryonic STI1, several Hsp90 client proteins are decreased by 50%, although Hsp90 levels are unaffected. Mutant STI1 mice showed increased caspase-3 activation and 50% impairment in cellular proliferation. Moreover, placental disruption and lack of cellular viability were linked to embryonic death by E10.5 in STI1-mutant mice. Rescue of embryonic lethality in these mutants, by transgenic expression of the …

Development Of Uv/Hplc Methods For Quantitative Analysis Of Benznidazole In Human Plasma And Urine For Application In Pediatric Clinical Studies, María Elena Marsón, Diego Dante Dana, Jaime Altcheh, Facundo García-Bournissen, Guido Mastrantonio

Paediatrics Publications

Objective: Chagas disease constitutes a major public health problem in Latin America. Correctly designed pharmacokinetic, safety, and bioequivalence studies are desirable in order to fill the knowledge gaps that presently exist on available drugs. It is necessary to develop accurate, simple, reproducible, and sensitive high-performance liquid chromatography (HPLC)/UV methods for the quantization of benznidazole (BNZ) in human plasma and urine for clinical applications, specially in pediatric patients. Methods: Quantization of BNZ in human plasma involved freeze-drying and re-suspension in organic solvent followed by reverse phase HPLC with UV detection. Analysis of BNZ in urine involved liquid/liquid extraction followed by reverse …

Endogenous Folate Accumulation In Oocytes And Preimplantation Embryos And Its Epigenetic Implications., Mellissa R W Mann, Andrew J Watson

Obstetrics & Gynaecology Publications

No abstract provided.

Development And Assessment Of An Impact Apparatus And High-Speed Camera Motion Tracking System To Quantify The Effect Of Static Muscle Loads On Fracture Threshold Measures In The Distal Radius, Jacob M. Reeves

Electronic Thesis and Dissertation Repository

Distal radius fractures are prevalent, debilitating, and costly. This thesis conducts an in vitro investigation of these injuries, examining the role of static muscle loading on fracture threshold measures (i.e., force, impulse, energy). Initially, an impact apparatus and custom LabVIEW colour-thresholding program were designed and assessed for repeatability and accuracy in quantifying fracture measures and impact kinematics. These tools were then used to test six pairs of cadaveric forearms, with static muscle loads simulated in one specimen from each pair. Distal radius fractures were achieved in 5 pairs, with perilunate dislocations in the remaining pair. None of the …

A Randomized Controlled Trial Comparing Arthroscopic Surgery To Conservative Management Of Femoroacetabular Impingement, Heather C. Klaus

Electronic Thesis and Dissertation Repository

OBJECTIVE: To determine whether patients with femoroacetabular impingement (FAI) who undergo arthroscopic hip surgery experience similar outcomes at two years post-operative with respect to physical function, pain, and health related quality of life, compared to similar patients who receive conservative management, including medication and physiotherapy. This thesis is an interim analysis of ten participants who are six-months post-randomization. METHODS: Participants were randomized to either operative treatment (6) or conservative treatment (4), and completed general and region specific quality of life questionnaires, including the Hip Outcome Score (HOS), Lower Extremity Functional Scale (LEFS), Modified Harris Hip Score (MHHS), Non-Arthritic Hip Score …

The Impact Of Lateral Electron Disequilibrium On Stereotactic Body Radiation Therapy Of Lung Cancer, Brandon Disher

Electronic Thesis and Dissertation Repository

Stereotactic Body Radiation Therapy (SBRT) is an effective treatment option for patients with inoperable early-stage lung cancer. SBRT uses online image-guidance technology [e.g. cone-beam CT (CBCT)] to focus small-fields of high energy x-rays onto a tumour to deliver ablative levels of radiation dose (e.g. 54 Gy) in a few treatment fractions (e.g. 3). For the combination of these treatment parameters and a low density lung, lateral electron disequilibrium (LED) can potentially occur, reducing lung and tumour doses. The goal of this thesis was to determine the impact of LED on stereotactic body radiation therapy for lung cancer.

The effect of …

Alignment, Mass And Orthoses In Medial Compartment Knee Osteoarthritis, Rebecca Moyer

Electronic Thesis and Dissertation Repository

Biomechanical factors during locomotion are important contributors to knee osteoarthritis (OA). A better understanding of their potential role in intervention strategies is required. The overall purpose of this thesis was to examine the interaction between lower limb alignment and body mass on dynamic knee joint loading, and to examine the effects of knee and foot orthoses, in patients with knee OA. The thesis included three studies. Chapter 2 was a cross-sectional study using three-dimensional gait analysis and full limb radiographs in 487 patients. Using sequential (hierarchical) linear regression, results indicated a statistical interaction between lower limb alignment and body mass …

Design And Development Of A Novel Expanding Pedicle Screw For Use In The Osteoporotic Lumbar Spine, Parham Rasoulinejad

Electronic Thesis and Dissertation Repository

Pedicle screws are commonly utilized in spinal surgery; however, traditional designs often do not provide adequate fixation in osteoporotic spines. The objective of this thesis was to develop a novel expanding screw for use in osteoporotic lumbar pedicles. Helical screws capable of expanding post insertion were built on a rapid prototype machine. A materials testing machine performed axial load to failure tests in both Sawbones and cadaveric specimens comparing the new design to traditional screws (rate = 10mm/min to 20 mm). Output parameters included yield load, ultimate load, stiffness, energy to failure and total energy. The expanding screw showed a …

A Model To Reduce The Proportion Of Inappropriate Referrals To Surgery For Patients With Osteoarthritis: A Pilot Study, Laura K. Churchill

Electronic Thesis and Dissertation Repository

A significant proportion of patients referred for total knee arthroplasty are inappropriate candidates for surgery, which warrants remediation of the referral process to reduce wait times for the initial consult. We conducted a prospective feasibility investigation involving 166 patients referred from their general practitioner for a consultation with an orthopaedic surgeon at a joint replacement clinic. The aim of this study was to improve the validity of data collection forms and to improve the feasibility of collecting data in a clinical setting. We also wanted to strengthen our estimate of the sample size to inform the timeline. We were able …

Complex Shoulder Instability: The Role Of The Latarjet Coracoid Transfer, Ryan Degen

Electronic Thesis and Dissertation Repository

Recurrent anterior shoulder instability is a common clinical entity often requiring surgical stabilization. Recurrence rates following soft-tissue stabilization procedures are moderately high and have been attributed to associated bony defects of either the glenoid or humeral head. Complex shoulder instability, defined as instability associated with bony defects around the shoulder, is a challenging clinical problem. The Latarjet coracoid transfer has been proposed as a treatment option and its resultant stabilizing effects have been explored in this biomechanical cadaver-based study.

For both glenoid and humeral head defects, the Latarjet coracoid transfer adequately stabilized the shoulder, outperforming other procedures often utilized for …

Optimization Of A Boundary Element Approach To Electromagnet Design With Application To A Host Of Current Problems In Magnetic Resonance Imaging, Chad T. Harris

Electronic Thesis and Dissertation Repository

Magnetic resonance imaging (MRI) has proven to be a valuable methodological approach in both basic research and clinical practice. However, significant hardware advances are still needed in order to further improve and extend the applications of the technique. The present dissertation predominantly addresses gradient and shim coil design (sub-systems of the MR system).

A design study to investigate gradient performance over a set of surface geometries ranging in curvature from planar to a full cylinder using the boundary element (BE) method is presented. The results of this study serve as a guide for future planar and pseudo-planar gradient systems for …

Patency And Complication Rates Of The Arteriovenous Fistula: A Systematic Review, Ahmed A. Al-Jaishi

Electronic Thesis and Dissertation Repository

Advantages of fistulas, which include long patency and low complication rates, were ascertained over two decades ago and may not apply to the contemporary dialysis population. We conducted a systematic review to summarize the patency and complication rates of fistulas from literature published after 1999. We screened 7,008 citations and 62 articles met our criteria. The risk of primary failure was 27% (95% confidence interval (CI): 23–32%). When primary failures were included, the primary and secondary patency rates were 59% (CI 53–64%) and 66% (CI 58–74%) at one year, respectively. The median rates of infection, ischemic steal syndrome, and thrombosis …

Secular Trends In Ischemic Stroke Subtypes, Chrysi Bogiatzi

Electronic Thesis and Dissertation Repository

Background: With an aging population and an increasing prevalence of therapy for atherosclerosis, it might be expected that stroke subtypes would be changing over time. Limited information exists on the ischemic stroke subtypes in adults in Canada.

Methods: Patients referred to the Urgent TIA Clinic, in London, Ontario, between 2002-2012 were included. Secular trends were analyzed using Poisson regression with spline trend function. Ischemic stroke subtype classification was validated.

Results: 3,445 consecutive patients (mean age + SD 64.8 + 14.9) were included. Cardioembolic strokes/TIAs increased from 21% in 2002 to 56% in 2012, whereas all other ischemic stroke subtypes …

Fetal And Neonatal Exposure To Nicotine Augments Hepatic Fatty Acid Synthesis In Rat Offspring Long-Term, Noelle L. Ma

Electronic Thesis and Dissertation Repository

While nicotine replacement therapy (NRT) is presumed to be a safer alternative to smoking in pregnancy, the long-term consequences in offspring are still largely unknown. Animal studies now suggest that maternal nicotine exposure during pregnancy and lactation (MNE-PL) leads to a wide variety of adverse outcomes for the offspring, including increased adiposity. The focus of this study was to investigate how MNE-PL in rats may lead to liver dysfunction long-term in offspring through alterations in gene expression and epigenetic modifications. Postnatal day 180 (PND180) offspring exposed to nicotine during pregnancy and lactation (1mg/kg/day) exhibited increased circulating and hepatic triglycerides concomitant …

Causes Of Post Stroke Falls Along The Care Continuum: Implications For Improving Patient Safety, Mona Madady

Electronic Thesis and Dissertation Repository

In Western countries stroke is responsible for 10-12% of all deaths. In 2000, strokes cost $3.6 billion for the Canadian healthcare system and lost productivity due to premature death and long-term disability. Falls are a frequent occurrence at all stages of post-stroke recovery and can have significant negative impacts. While information about the incidence and risk factors of falling among stroke survivors is available, considerably less is known about the specific factors contributing to falls and the circumstances surrounding these adverse events. The purpose of this project was to identify similarities between systemic factors of falls in stroke survivors across …

How Do Symbolic And Non-Symbolic Numerical Magnitude Processing Skills Relate To Individual Differences In Children's Mathematical Skills? A Review Of Evidence From Brain And Behavior, Bert De Smedt, Marie-Pascale Noël, Camilla Gilmore, Daniel Ansari

Paediatrics Publications

Many studies have tested the association between number magnitude processing and mathematics achievement. However, results appear to be quite different depending on the number format used. When using symbolic numbers (digits), data consistent and robust across studies and populations have been found, with weaker performance associated with weak math achievement and dyscalculia. However, when using non-symbolic format (dots), many conflicting findings are reported. These inconsistencies might be explained by methodological issues. Alternatively, it might be that the processes measured by non-symbolic tasks are not particularly critical for school-relevant mathematics. A few neuroimaging studies have also shown the brain signature of …

Β-Estradiol-Dependent Activation Of The Jak/Stat Pathway Requires P/Cip And Carm1, N. Coughlan, G. Thillainadesan, J. Andrews, M. Isovic, J. Torchia

Paediatrics Publications

The steroid receptor coactivator p/CIP, also known as SRC-3, is an oncogene commonly amplified in breast and ovarian cancers. p/CIP is known to associate with coactivator arginine methyltransferase 1 (CARM1) on select estrogen responsive genes. We have shown, using a ChIP-on-chip approach, that in response to stimulation with 17β-estradiol (E2), the p/CIP/CARM1 complex is recruited to 204 proximal promoters in MCF-7 cells. Many of the complex target genes have been previously implicated in signaling pathways related to oncogenesis. Jak2, a member of the Jak/Stat signaling cascade, is one of the direct E2-dependent targets of the p/CIP/CARM1 complex. Following E2-treatment, histone …

Maternal Taurine Supplementation In Rats Partially Prevents The Adverse Effects Of Early-Life Protein Deprivation On Β-Cell Function And Insulin Sensitivity, Christine Tang, Kelly Marchand, Loretta Lam, Victoria Lux-Lantos, Sandra M. Thyssen, June Guo, Adria Giacca, Edith Arany

Paediatrics Publications

Dietary protein restriction during pregnancy and lactation in rats impairs β-cell function and mass in neonates and leads to glucose intolerance in adult offspring. Maternal taurine (Tau) supplementation during pregnancy in rats restores β-cell function and mass in neonates, but its long-term effects are unclear. The prevention of postnatal catch-up growth has been suggested to improve glucose tolerance in adult offspring of low-protein (LP)-fed mothers. The objective of this study was to examine the relative contribution of β-cell dysfunction and insulin resistance to impaired glucose tolerance in 130-day-old rat offspring of LP-fed mothers and the effects of maternal Tau supplementation …

Narrative Medicine As A Means Of Training Medical Students Toward Residency Competencies, Shannon L. Arntfield, Kristen Slesar, Jennifer Dickson, Rita Charon

Paediatrics Publications

Objective: This study sought to explore the perceived influence of narrative medicine training on clinical skill development of fourth-year medical students, focusing on competencies mandated by ACGME and the RCPSC in areas of communication, collaboration, and professionalism. Methods: Using grounded-theory, three methods of data collection were used to query twelve medical students participating in a one-month narrative medicine elective regarding the process of training and the influence on clinical skills. Iterative thematic analysis and data triangulation occurred. Results: Response rate was 91% (survey), 50% (focus group) and 25% (follow-up). Five major findings emerged. Students perceive that they: develop and improve …

Expression Of Ski Can Act As A Negative Feedback Mechanism On Retinoic Acid Signaling, Meaghan A. Melling, Charlotte R.C. Friendship, Trevor G. Shepherd, Thomas A. Drysdale

Paediatrics Publications

Background: Retinoic acid signaling is essential for many aspects of early development in vertebrates. To control the levels of signaling, several retinoic acid target genes have been identified that act to suppress retinoic acid signaling in a negative feedback loop. The nuclear protein Ski has been extensively studied for its ability to suppress transforming growth factor-beta (TGF-β) signaling but has also been implicated in the repression of retinoic acid signaling. Results: We demonstrate that ski expression is up-regulated in response to retinoic acid in both early Xenopus embryos and in human cell lines. Blocking retinoic acid signaling using a retinoic …

Body Talk I: Habituation To Bodily Changes After Breast Surgery In Women, Jenny Slatman

Future Directions in Feminist Phenomenology

No abstract provided.

The Effect Of Selective Hypothermia On Stroke Volume, Thomas K. Mattingly

Electronic Thesis and Dissertation Repository

Hypothermia is a well-established neuroprotectant. Selective hypothermia to the ischemic area may eliminate side effects while improving induction time. We studied the effect of selective hypothermia on stroke volumes in adult domestic swine. Under general anesthesia, one MCA was occluded transcranially for 3 hours followed by 3 hours of reperfusion. In half the animals, hypothermia was induced during reperfusion via a dual-lumen balloon occlusion catheter placed in the carotid ipsilateral to the ischemic region. Following reperfusion, the animals were sacrificed. Brain MRI and histology were evaluated blinded to the intervention. In a series of animals, the mean temperature achieved was …

Adverse Drug Events And Renal Function, Matthew A. Weir

Electronic Thesis and Dissertation Repository

The objective of this thesis was to use health administrative data to investigate two important adverse drug reactions (ADRs) related to renal function. The first study examined the risk of hyperkalemia associated with the antibiotic trimethoprim-sulfamethoxazole (TMP-SMX) and its interaction with beta-adrenergic receptor blockers (“beta blockers”). The second study evaluated the effect of impaired kidney function on the risk of hypoglycemia conferred by the anti-diabetic drug glyburide. The simultaneous use of beta adrenergic receptor blockers (β-blockers) and trimethoprim-sulfamethoxazole (TMP-SMX) may confer a high risk of hyperkalemia. We conducted two nested case-control studies to examine the association between hospitalization for hyperkalemia …