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 …

Risk Of Kidney Stones In Living Kidney Donors: A Matched Cohort Study, Sonia Thomas

Electronic Thesis and Dissertation Repository

A kidney stone in a person with one kidney requires urgent attention which may result in surgical and/or hospital attention. We conducted a matched retrospective cohort study to determine if living kidney donors compared to healthy non-donors have a higher risk of: 1) kidney stones with surgical intervention, and 2) hospital encounters for kidney stones. We reviewed and linked information from pre-donation charts to Ontario healthcare databases. We selected healthy non-donors from the general population, matching ten non-donors to every donor, to generate a cohort of 2,019 donors and 20,190 non-donors. There was no difference in the rate of 1) …

Placed-Based Rural Public Health Policy, Angela M. Jurich

Electronic Thesis and Dissertation Repository

Abstract

Attention to place in public health policy development at the provincial level often overlooks the specific and unique needs of rural places. The principle aim of this research was to explore whether and how “place” was considered in the context of rural Ontario public health policy implementation for chronic disease prevention (CDP) programs. A secondary analysis of focus group and interview data along with the policy documents from three rural Ontario public health unit sites for the primary Renewal of Public Health Systems (RePHS) study was conducted. Based on a review of the literature on rural health policy and …

Mitigating Risk Factors For Disease Progression In Patients With Varus Gonarthrosis, Angelo Boulougouris

Electronic Thesis and Dissertation Repository

Knee osteoarthritis (OA) is a leading cause of disability worldwide. Its growing burden is related to an aging population, obesity and physical inactivity. The progression of knee OA involves both biomechanical and systemic mechanisms. Known risk factors that might be altered through interventions include lower limb alignment, the distribution of loads across the knee during walking, body composition and muscular strength. The overall purpose of this thesis was to evaluate the effects of multi-modal, rehabilitative and surgical interventions that target different risk factors for disease progression in patients with medial compartment knee OA and varus mal-alignment (varus gonarthrosis). The thesis …

How Age Friendly Is This City? Strategies For Assessing Age-Friendliness, Michelle Dellamora

Electronic Thesis and Dissertation Repository

The Age-Friendly Cities framework, created by the World Health Organization (WHO), has emerged as a community-based response to the challenges of demographic aging and increasing urbanization. In 2010, London, Ontario, became the first city in Canada to join the WHO Global Network of Age-Friendly Communities. Network milestones require the measurement of the baseline age-friendliness of the community. The objectives of this thesis are: 1. Determine the best available assessment tools for measuring the age-friendliness of a community, and 2. Establish the baseline age-friendliness of London, Ontario. A scoping review was utilized to collect and assess available surveys and questionnaires. A …

Exploring Accuracy In Journalism Stories Reporting On Neuroscience Research Findings: A Comparative Case Study, Andrea M. Campbell-Davison

Electronic Thesis and Dissertation Repository

Abstract

Neuroscience has seen explosive growth in research and public interest, but research findings are often reported inaccurately, impacting public understanding. Exploratory descriptive case study methods were used to analyze two peer reviewed research articles, one on brain imaging for patients in a Persistent Vegetative State (PVS), and another on Brain Training (BT), and all journalism stories regarding these two studies. Statistical and content analyses were used to analyze the accuracy of the translation of the research into journalism stories. PVS research received more media attention and this reporting was less accurate than for BT research; the information was also …

Effects Of A Power-Line Frequency Magnetic Field On Human Cognitive Processing, Michael Corbacio

Electronic Thesis and Dissertation Repository

Extremely low frequency (ELF, < 300 Hz) magnetic fields (MFs) have been reported to modulate human cognitive performance. However, little research has investigated MF exposures comparable to the highest levels experienced in some occupations. This research evaluated the impact of a 60 Hz, 3 mT MF on human cognitive performance. Ninety-nine participants completed the double-blind protocol performing a selection of psychometric tests under two consecutive MF exposure conditions (exposure vs. no exposure). A significant interaction effect on a working memory test (digit span forward - F=5.21, p

The Relation Between Finger Gnosis And Mathematical Ability: Why Redeployment Of Neural Circuits Best Explains The Finding, Marcie Penner-Wilger, Michael L. Anderson

Brain and Mind Institute Researchers' Publications

This paper elaborates a novel hypothesis regarding the observed predictive relation between finger gnosis and mathematical ability. In brief, we suggest that these two cognitive phenomena have overlapping neural substrates, as the result of the re-use ("redeployment") of part of the finger gnosis circuit for the purpose of representing numbers. We offer some background on the relation and current explanations for it; an outline of our alternate hypothesis; some evidence supporting redeployment over current views; and a plan for further research.

Examining The Shift In Occupational Identity After A Brain Injury, Mikelle Bryson-Campbell

Electronic Thesis and Dissertation Repository

Occupational identity is defined by Kielhofner (2002) as a sense of who we are as an occupational being, based on our past, current, and future occupational roles. When a life disruption occurs such as a brain injury (BI) and the disruption impacts the ability to conduct an occupation deemed meaningful an important process of transition occurs (Muenchberger, Kendall, & Neal, 2008). In turn occupational identity may shift to reflect the current health and economic status of the individual and what occupations are judged as meaningful.

The current study examined the shift in occupational identity in BI survivors in a two …

The Effects Of Pre- And Postnatal Administration Of Propionic Acid And Lipopolysaccharide On The Behaviour Of Adolescent Male And Female Rats, Kelly A. Foley

Electronic Thesis and Dissertation Repository

The gut microbiome plays an important role in immune functioning and neurodevelopment. Altered microbiome composition, leading to short chain fatty acid, and/or immune system dysfunction has been observed in children with autism spectrum disorders (ASD). This thesis describes the developmental influence of prenatal exposure to propionic acid (PPA), a metabolic fermentation product of enteric bacteria, or prenatal exposure to lipopolysaccharide (LPS), a bacterial mimetic and product of enteric bacteria, on a range of behaviours in male and female neonatal, adolescent and adult rats. Study one evaluated the effects of prenatal PPA and LPS, and postnatal PPA, on developmental milestones in …

Interprofessional Socialization And Dual Identity Development Amongst Cross-Disciplinary Students, Hossein Khalili

Electronic Thesis and Dissertation Repository

The purpose of this study was to develop and test an interprofessional socialization (IPS) framework through assessing the impact of an IPS-based interprofessional education program on interprofessional socialization and dual identity development among health professional students. Although health professional educational programs have been successful in equipping graduates with skills, knowledge and professionalism, the emphasis on specialization and profession-specific education has enhanced the development of a uniprofessional identity, which has been found to be a major barrier towards Interprofessional Person-Centered Collaborative Practice (IPCPCP). Despite the growing acknowledgment of IPS in the current IPE and collaborative practice literature, there is a lack …

One, Two And Three-Dimensional Ultrasound Measurements Of Carotid Atherosclerosis Before And After Cardiac Rehabilitation: Preliminary Results Of A Randomized Controlled Trial., Tamas J Lindenmaier, Daniel N Buchanan, Damien Pike, Tim Hartley, Robert D Reid, J David Spence, Richard Chan, Michael Sharma, Peter L Prior, Neville Suskin, Grace Parraga

Medical Biophysics Publications

BACKGROUND: It is still not known how patients who are post-transient ischemic attack (TIA) or post-stroke might benefit from prospectively planned comprehensive cardiac rehabilitation (CCR). In this pilot evaluation of a larger ongoing randomized-controlled-trial, we evaluated ultrasound (US) measurements of carotid atherosclerosis in subjects following TIA or mild non-disabling stroke and their relationship with risk factors before and after 6-months of CCR.

METHODS: Carotid ultrasound (US) measurements of one-dimensional intima-media-thickness (IMT), two-dimensional total-plaque-area (TPA), three-dimensional total-plaque-volume (TPV) and vessel-wall-volume (VWV) were acquired before and after 6-months CCR for 39 subjects who had previously experienced a TIA and provided written informed …

Re-Cognizing Power In The Culture Of Dementia Care Knowledge, Ryan T. Deforge

Electronic Thesis and Dissertation Repository

In light of increasing system demands, system regulations, and constrained resources, those living and working with dementia in the long-term care sector are vulnerable to oppressive care practices. This is true so long as our understanding of how social power affects the ways in which dementia care knowledge is created, shared, and enacted remains limited. Based on prolonged field observations and on informal and formal interviews with care recipients, family members, and staff, the aim of this critical qualitative research was to examine the culture of dementia care knowledge in two sites: a specialized dementia care unit in a long-term …

Bio-Identical Hormone Therapy: Understanding Women's Decision-Making Process And Family Physicians' Views, Lemmese Alwatban

Electronic Thesis and Dissertation Repository

This thesis explored women’s and family physicians’ experiences with Bio-identical Hormone Therapy (BHT). It aimed to develop a deeper understanding of women’s decision-making process in choosing this therapeutic modality, and the influence family physicians may have on this process. To capture the phenomenon under study, two complementary and sequential qualitative studies were conducted. The studies involved in-depth interviews with women using BHT and family physicians that care for this population. The collective findings of both studies demonstrated the complexity of menopause care. The findings illuminated the major factors involved in women’s BHT decision-making process. It also offered important information about …

Nurses’ Learning And Conceptualization Of Technology Used In Practice, Richard G. Booth

Electronic Thesis and Dissertation Repository

How nurses conceptualize and learn about health technology used in practice was examined in this qualitative, interpretive-descriptive study. Traditionally, conceptualizations of technology used in the nursing profession have been viewed from either socially- or technically- centric perspectives that have clouded the real nature of nurse-technology interactions. For instance, current perspectives examining nurses’ use of technology typically ignore or minimize socio-technical considerations impacting technology acceptance and adoption by nurses. A research approach that embraced the mingling of social and material (sociomaterial) actors was used to address the following research questions: (a) How do nurses conceptualize health technology used in practice?, and, …

Evaluation Of Ontario's Street Racers, Stunt And Aggressive Drivers Legislation, Aizhan Meirambayeva

Electronic Thesis and Dissertation Repository

The purpose of this thesis was to conduct a process and outcome evaluation of the deterrent effect of Ontario’s Street Racers, Stunt and Aggressive Drivers Legislation. The focus of this study was on police enforcement (implementation), a change in speeding on the provincial highways (intermediate outcome) as well as on a decrease in both extreme speeding convictions and casualties, measured as a sum of injuries and fatalities (criterion outcomes). The deterrent effect of the legislation on Ontario drivers was examined, using data obtained from the Ministry of Transportation of Ontario. Employing interrupted time series …

The Prion Protein Ligand, Stress-Inducible Phosphoprotein 1, Regulates Amyloid-Beta Oligomer Toxicity, Valeriy G. Ostapchenko, Flavio H. Beraldo, Amro H. Mohammad, Yu-Feng Xie, Pedro H. F. Hirata, Ana C. Magalhaes, Guillaume Lamour, Hongbin Li, Andrzej Maciejewski, Jillian C. Belrose, Bianca L. Teixeira, Margaret Fahnestock, Sergio T. Ferreira, Neil R. Cashman, Glaucia N. M. Hajj, Michael F. Jackson, Wing-Yiu Choy, John F. Macdonald, Vilma R. Martins, Vania F. Prado, Marco A. M. Prado

Anatomy and Cell Biology Publications

In Alzheimer's disease (AD), soluble amyloid-beta oligomers (A beta Os) trigger neurotoxic signaling, at least partially, via the cellular prion protein (PrPC). However, it is unknown whether other ligands of PrPC can regulate this potentially toxic interaction. Stress-inducible phosphoprotein 1 (STI1), an Hsp90 cochaperone secreted by astrocytes, binds to PrPC in the vicinity of the A beta O binding site to protect neurons against toxic stimuli. Here, we investigated a potential role of STI1 in A beta O toxicity. We confirmed the specific binding of A beta Os and STI1 to the PrP and showed that STI1 efficiently inhibited A …

Health Literacy Of Individuals Living With Parkinson's Disease, Nicole D. Leblanc

Electronic Thesis and Dissertation Repository

In the past two decades, there has been an increased interest in the development of self-management programs for people with chronic diseases. Fundamental to chronic disease management is adequate literacy and health literacy skills. Research on the health literacy skills of individuals managing Parkinson’s disease (PD) is seemingly absent from the research literature. The purpose of this study was to assess the health literacy skills of older adults managing PD and to examine the relationships of functional health literacy, self-efficacy, social support, and empowerment in this population. Using a cross-sectional design, this study surveyed 33 older adults living with PD …

The Relationship Between Quality Of Parks And Playgrounds And Park-Based Physical Activity In Children, Hammad Ali Qazi

Electronic Thesis and Dissertation Repository

Research on the quality of parks and playgrounds has been limited, particularly regarding how conditions and cleanliness of parks and playgrounds influence park-based physical activity in children. This thesis explored the relationship between the quality of parks and playgrounds and physical activity in children, through a scoping review and a mixed-methods study.

The scoping review used a systematic search to identify gaps in the literature and to disseminate research findings on the topic. A total of 10 articles were selected in accordance with the selection criteria. The review showed that the features, amenities, and safety of parks and playgrounds were …

Structure-Function Analysis Of Udp-Sugar: Polyisoprenyl Phosphate Sugar-1-Phosphate Transferases, Sarah E. Furlong

Electronic Thesis and Dissertation Repository

The synthesis of lipid-linked glycans is a conserved process in eukaryotes and prokaryotes that is initiated by two major enzyme families: the polyisoprenyl-phosphate hexose-1-phosphate transferases (PHPTs) and the polyisoprenyl-phosphate N-acetylaminosugar-1-phosphate transferases (PNPTs). These enzymes contain multiple membrane domains and transfer a sugar-1-phosphate from a nucleotide sugar precursor to a lipid carrier. The prototypic PNPT member used in this study is the E. coli WecA, which initiates the synthesis of O antigen and enterobacterial common antigen in Enterobacteriaceae by transferring N-acetylglucosamine-1-P to undecaprenyl phosphate (Und-P). We investigated the topology and function of the highly conserved VFMGD motif. Our results revealed that …

Forebrain Deletion Of The Vesicular Acetylcholine Transporter Results In Deficits In Executive Function, Metabolic, And Rna Splicing Abnormalities In The Prefrontal Cortex, Benjamin Kolisnyk, Mohammed A. Al-Onaizi, Pedro H. F. Hirata, Monica S. Guzman, Simona Nikolova, Shahar Barbash, Hermona Soreq, Robert Bartha, Marco A. M. Prado, Vania F. Prado

Anatomy and Cell Biology Publications

One of the key brain regions in cognitive processing and executive function is the prefrontal cortex (PFC), which receives cholinergic input from basal forebrain cholinergic neurons. We evaluated the contribution of synaptically released acetylcholine (ACh) to executive function by genetically targeting the vesicular acetylcholine transporter (VAChT) in the mouse forebrain. Executive function was assessed using a pairwise visual discrimination paradigm and the 5-choice serial reaction time task (5-CSRT). In the pairwise test, VAChT-deficient mice were able to learn, but were impaired in reversal learning, suggesting that these mice present cognitive inflexibility. Interestingly, VAChT-targeted mice took longer to reach criteria in …

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 …

The Effects Of Acute High- And Low-Intensity Exercise On Hsp70 And Hsp90 Accumulation In Rat Skeletal Myofibres And Vasculature, Hana Kowalchuk

Electronic Thesis and Dissertation Repository

Exercise induces cytoprotective stress proteins in blood vessels (BV) and skeletal myofibres. The localization and extent of induction with different exercise intensities is unclear. Rats (n=10 per group) were run at high (HIEX; 30m/min) versus low-intensity exercise (LOEX; 15m/min) for 1hr, sacrificed 24hr later. Sections of the white portion of the vastus were immunofluorescently stained for Hsp70 and Hsp90. It was hypothesized that: 1) a greater abundance of Hsp70 and Hsp90 would be observed in BVs following HIEX, 2) due to earlier recruitment, larger BVs would have a more robust response than small BVs, 3) more myofibres surrounding BVs expressing …

"Being Stuck": Understanding The Health-Related And Everyday Lived Experiences Of Young Mothers In Rexdale, Ontario Through A Social Determinants Framework, Jaspreet Kaur

Electronic Thesis and Dissertation Repository

The purpose of this study was to gain an understanding of the ways the health-related and everyday lived experiences of young mothers are shaped by various social determinants, and in the context of their neighbourhood. Using a critical qualitative methodology, five mothers between the ages of 17 to 19 were interviewed from Rexdale, a neighbourhood in the City of Toronto characterized by a number of social risk factors(e.g. high rates of visible minorities, unemployment, and teen mothers). In-depth thematic analysis led to the emergence of four themes: 1) Living in Rexdale: Representations and realities; 2) Leaving Rexdale and wanting something …

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 …

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 …

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 …

Prognosis And Movement Patterns In Patients After Rotator Cuff Repair, Jayaprakash Raman

Electronic Thesis and Dissertation Repository

Rotator cuff repairs are done in patients who failed to achieve functional improvement with conservative management for rotator cuff tears. This thesis focuses on prognostic factors that predict outcomes after rotator cuff repair (RCR) and change in functional range of motion (ROM) and muscle endurance before and after RCR. A meta-analysis was performed to statistically analyze all available evidence in the literature concerning prognostic factors that determine outcome after RCR. Based on this study, several factors were identified that had significant and moderate effects on outcomes after RCR. Two prospective studies were conducted to analyze change in functional ROM and …

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 …