Life Sciences Commons^™

Urologist Burnout: Frequency, Causes, And Potential Solutions To An Unspoken Entity, Julie Franc-Guimond, Brian Mcneil, Steven M. Schlossberg, Amanda C. North, Alp Sener

Anatomy and Cell Biology Publications

Physician burnout has been linked to decreased job performance, increased medical errors, interpersonal conflicts, and depression. Recent multispecialty studies suggest that urologists have higher rates (up to 63.6%) of burnout compared to physicians in other specialties; however, these reports were limited by low sample sizes.1 We aimed to evaluate the prevalence of urologist burnout, verify risk factors, and recommend preventative measures and solutions for colleagues at risk or suffering from burnout. Urologist burnout is a true entity that transcends level of training and nationality. Its roots appear to be deep-seated in our tireless efforts to strive for excellence in care …

Power Reserve Following Ramp-Incremental Cycling To Exhaustion: Implications For Muscle Fatigue And Function, Michael D. Hodgson

Electronic Thesis and Dissertation Repository

In ramp-incremental cycling exercise, some individuals are capable of producing power output (PO) in excess of that produced at their limit of tolerance (LoT) while others cannot. This study sought to describe the: 1) prevalence of a “power reserve” within a group of young men (n=21; mean ± SD: age 25±4 years; V̇O_2max45±8 ml•kg^-1•min^-1); and 2) muscle fatigue characteristics of those with and without a power reserve. Power reserve was determined as the difference between peak PO achieved during a ramp-incremental test to exhaustion and maximal, single-leg isokinetic dynamometer power. Pre- versus post-exercise changes …

Exploiting Fission Yeast Genetic Interaction Data To Identify Disease-Specific Drug Targets For Tuberous Sclerosis Complex, Ashyad Rayhan

Electronic Thesis and Dissertation Repository

Tuberous sclerosis complex (TSC) is an inherited genetic disorder caused by loss-of-function mutations in either TSC1 or TSC2. Their respective gene products regulate the mechanistic target of rapamycin (mTOR) signaling pathway, which serves as an activator of cellular proliferation, metabolism, and cell survival. Orthologs of the TSC1 and TSC2 genes exist in a wide range of organisms, including the commonly used and genetically tractable model eukaryote, Schizosaccharomyces pombe. To better understand the functional roles of S. pombe tsc1 and tsc2, I exploited recent advances in genetic interaction biology to identify and characterize genes that modulate the phenotypic …

The Feasibility Of Square-Stepping Exercise As A Universal Intervention For Older Adults With Chronic Disease To Improve Cognitive And Physical Function, Erin M. Shellington

Electronic Thesis and Dissertation Repository

Square-stepping exercise (SSE) is a cognitive training program with a physical component. An instructor demonstrates a stepping pattern across a gridded mat and participants are required to memorize and repeat the patterns on their own. In community-dwelling older adults, SSE has demonstrated some benefits on global cognitive functioning (GCF), balance, functional fitness, and social interaction.

Aims: to investigate the feasibility and efficacy of SSE in varied populations and settings to improve mobility and cognition. Populations included older adults with: knee osteoarthritis (OA), type 2 diabetes mellitus (T2DM) and self-reported cognitive complaints (sCC), and those living in long-term care (LTC) …

The Anatomy Of The Infrarenal Lumbar Splanchnic Nerves In Human Cadavers: Implications For Retroperitoneal Nerve-Sparing Surgery, Tyler Beveridge, Dale Fournier, Adam M.R. Groh, Marjorie Johnson, Nicolas E. Power, Brian L. Allman

Anatomy and Cell Biology Publications

Injury to the nerves of the aortic- and superior hypogastric plexuses during retroperitoneal surgery often results in significant post-operative complications, including retrograde ejaculation and/or loss of seminal emission in males. Although previous characterizations of these plexuses have done well to provide a basis for understanding the typical anatomy, additional research into the common variations of these plexuses could further optimize nerve-sparing techniques for retroperitoneal surgery. To achieve this, the present study aimed to document the prevalence and positional variability of the infrarenal lumbar splanchnic nerves (LSNs) through gross dissection of 26 human cadavers. In almost all cases, two LSNs were …

Multiparametric Mri Changes Persist Beyond Recovery In Concussed Adolescent Hockey Players, Kathryn Y. Manning Msc, Amy Achranz Bmsc, Robert Bartha Phd, Gregory A. Dekaban Phd, Christy Barreira Bsc, Arthur Brown Phd, Lisa Fischer Md, Kevin Asem Md, Timothy J. Doherty, Douglas D. Fraser Md Phd, Jeff Holmes Phd, Ravi S. Menon

Anatomy and Cell Biology Publications

Objective: To determine whether multiparametric MRI data can provide insight into the acute and long-lasting neuronal sequelae after a concussion in adolescent athletes.

Methods: Players were recruited from Bantam hockey leagues in which body checking is first introduced (male, age 11–14 years). Clinical measures, diffusion metrics, resting-state network and region-to-region functional connectivity patterns, and magnetic resonance spectroscopy absolute metabolite concentrations were analyzed from an independent, age-matched control group of hockey players (n 5 26) and longitudinally in concussed athletes within 24 to 72 hours (n 5 17) and 3 months (n 5 14) after a diagnosed concussion.

Results: …

Disruption Of Hippocampal Multisynaptic Networks By General Anesthetics., Min-Ching Kuo, L Stan Leung

Physiology and Pharmacology Publications

BACKGROUND: Previous studies showed that synaptic transmission is affected by general anesthetics, but an anesthetic dose response in freely moving animals has not been done. The hippocampus provides a neural network for the evaluation of isoflurane and pentobarbital on multisynaptic transmission that is relevant to memory function.

METHODS: Male Long-Evans rats were implanted with multichannel and single electrodes in the hippocampus. Spontaneous local field potentials and evoked field potentials were recorded in freely behaving rats before (baseline) and after various doses of isoflurane (0.25 to 1.5%) and sodium pentobarbital (10 mg/kg intraperitoneal).

RESULTS: Monosynaptic population excitatory postsynaptic potentials at the …

A Simulated Walk In Nature: Testing Predictions From The Attention Restoration Theory, Corey Crossan

Electronic Thesis and Dissertation Repository

Attention Restoration Theory (ART) predicts that top-down processing during everyday activities can cause attentional fatigue and that bottom-up processing that occurs when people experience nature will be restorative (Kaplan, 1995). The present study examined this prediction by exposing participants to three different conditions using a repeated measures design: a control condition during which participants walked on a typical treadmill, a nature/restorative condition during which participants walked on the same treadmill, experiencing a simulated nature walk, and a perturbation condition that included the same simulated nature scene but also required top-down processing during the walk. The findings supported ART predictions. As …

Behaviour Change Intervention Strategies To Prevent Excessive Gestational Weight Gain In Pregnant Women Using A Nutrition And Exercise Lifestyle Intervention Program (Nelip), Karishma Hosein

Electronic Thesis and Dissertation Repository

Maternal obesity and excessive gestational weight gain (EGWG) are associated with adverse maternal and fetal outcomes. To evaluate the effectiveness of different behaviour change intervention strategies, it was hypothesized that the introduction of a single behaviour change, followed by a second, would be more effective at preventing early and total EGWG in pregnant women compared to the early simultaneous introduction of both behaviour changes. Eighteen pregnant women were block randomized into one of 3 Nutrition and Exercise Lifestyle Intervention Program (NELIP) strategies (full NELIP, Nutrition followed by Exercise N+E, Exercise followed by Nutrition E+N) and were followed at weekly face-to-face …

Differential Functional Roles Of Aldh1a1 And Aldh1a3 In Mediating Metastatic Behavior And Therapy Resistance Of Human Breast Cancer Cells, Alysha K. Croker, Mauricio Rodriguez-Torres, Ying Xia, Hon Sing Leong, Siddika Pardhan, John D. Lewis, Alison L. Allan

Anatomy and Cell Biology Publications

Previous studies indicate that breast cancer cells with high aldehyde dehydrogenase (ALDH) activity and CD44 expression (ALDHhiCD44+ ) contribute to metastasis and therapy resistance, and that ALDH1 correlates with poor outcome in breast cancer patients. The current study hypothesized that ALDH1 functionally contributes to breast cancer metastatic behavior and therapy resistance. Expression of ALDH1A1 or ALDH1A3 was knocked down in MDA-MB-468 and SUM159 human breast cancer cells using siRNA. Resulting impacts on ALDH activity (Aldefluor® assay); metastatic behavior and therapy response in vitro (proliferation/adhesion/migration/colony formation/chemotherapy and radiation) and extravasation/metastasis in vivo (chick choroiallantoic membrane assay) was assessed. Knockdown of ALDH1A3 …

Spatial And Temporal Epithelial Ovarian Cancer Cell Heterogeneity Impacts Maraba Virus Oncolytic Potential, Jessica G. Tong, Yudith Ramos Valdes, Milani Sivapragasam, John W. Barrett, John C. Bell, David Stojdl, Gabriel E. Dimattia, Trevor G. Shepherd

Anatomy and Cell Biology Publications

Background: Epithelial ovarian cancer exhibits extensive interpatient and intratumoral heterogeneity, which can hinder successful treatment strategies. Herein, we investigated the efficacy of an emerging oncolytic, Maraba virus (MRBV), in an in vitro model of ovarian tumour heterogeneity. Methods: Four ovarian high-grade serous cancer (HGSC) cell lines were isolated and established from a single patient at four points during disease progression. Limiting-dilution subcloning generated seven additional subclone lines to assess intratumoral heterogeneity. MRBV entry and oncolytic efficacy were assessed among all 11 cell lines. Low-density receptor (LDLR) expression, conditioned media treatments and co-cultures were performed to determine factors impacting MRBV oncolysis. …

Amelioration Of Prenatal Alcohol Effects By Environmental Enrichment In A Mouse Model Of Fasd, Aniruddho Chokroborty-Hoque

Electronic Thesis and Dissertation Repository

Maternal alcohol consumption during pregnancy results in a spectrum of behavioural and cognitive deficits collectively known as Fetal Alcohol Spectrum Disorders (FASD). Currently, little is know about if and how the external environment may modulate these deficits. I have used C57BL/6 mice to study this interaction between prenatal alcohol exposure and the postnatal environment. Alcohol exposure during synaptogenesis produces high levels of anxiety-like traits and decreased memory performance. Alcohol-exposed mice (and matched unexposed controls) were put in 'environmentally-enriched' conditions of voluntary exercise, physical activities and cognitive stimulation to ascertain the effects of a positive postnatal environment. The results show that …

Contribution Of Activating Transcription Factor 3 To Development Of Acinar-To-Ductal Cell Metaplasia, Jelena Toma

Electronic Thesis and Dissertation Repository

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in North America. The highest risk factor for PDAC is recurrent pancreatitis. While the link between PDAC and pancreatitis is unknown, de-differentiation of acinar cells is common to both diseases. Our lab has shown that Activating Transcription Factor 3 (ATF3), a factor upregulated during pancreatic injury, contributes to the development of acinar-to-ductal cell metaplasia (ADM), a precursor phenotype of PDAC. The goal of this study was to identify how ATF3 contributes to ADM. I hypothesize that ATF3 regulates acinar gene expression promoting ADM. We observed decreased ADM development …

Accurate Cytogenetic Biodosimetry Through Automated Dicentric Chromosome Curation And Metaphase Cell Selection, Jin Liu, Yanxin Li, Ruth Wilkins, Canadian Nuclear Laboratories, Joan H. Knoll, Peter Rogan

Biochemistry Publications

Accurate digital image analysis of abnormal microscopic structures relies on high quality images and on minimizing the rates of false positive (FP) and negative objects in images. Cytogenetic biodosimetry detects dicentric chromosomes (DCs) that arise from exposure to ionizing radiation, and determines radiation dose received based on DC frequency. Improvements in automated DC recognition increase the accuracy of dose estimates by reclassifying FP DCs as monocentric chromosomes or chromosome fragments. We also present image segmentation methods to rank high quality digital metaphase images and eliminate suboptimal metaphase cells. A set of chromosome morphology segmentation methods selectively filtered out FP DCs …

A Diffusion Tensor Imaging Study Of Motor Fibre Path Integrity And Overt Responsiveness In Disorders Of Consciousness, Clara A. Stafford

Electronic Thesis and Dissertation Repository

This study investigated the relationship between motor thalamo-cortico-cerebellar fibre path integrity and overt responsiveness in patients with disorders of consciousness (DOC). Additionally, we investigated the potential of imaging these motor tracts at ultra-high fields. Study I and II aimed to map the white matter connections of motor execution fibres in DOC patients. Our results showed significant reductions in motor fibre path integrity across DOC diagnostic categories. Study III and IV aimed to develop a 7T MRI Diffusion Tensor Imaging (DTI) sequence. We optimized this sequence to image motor fibre paths in DOC patients. We concluded that, in healthy controls, probabilistic …

The Application Of Self-Administered Nutrition Screening Tools And Evaluations Of The Impact Of Malnutrition On Quality Of Life In Individuals With Head And Neck Cancer, Mark J. P. Lynch

Electronic Thesis and Dissertation Repository

Abstract

Background: Individuals with head and neck cancer (HNCa) are at an increased risk of malnutrition. Therefore, self-administered nutrition screens which attempt to address their nutritional concerns may yield benefits for treatment outcomes and quality of life (QOL).

Methods: 34 participants (26 men, 8 women) completed one demographic and two QOL surveys, two nutrition self-screening tools, a nutrition assessment and an ease-of-use questionnaire. Results of the screens were compared to those of the assessment, and relationships between QOL, nutrition status, and demographics were examined.

Results: 32.3% of participants were identified as nutritionally compromised. The sensitivity and specificity for the PG-SGA …

The Effects Of Moderate Intensity Strength Training Coupled With Blood Flow Restriction: A 12 Week Intervention, Kelly Barrett

Electronic Thesis and Dissertation Repository

Blood flow restriction training (BFRT) has been suggested to increase muscle size and strength in trained and untrained individuals when using light load intensities (30 percent 1-RM). However, there is little data to support its use when working with moderate load intensities, specifically, above 50 percent of an individual’s 1-RM. The purpose of this study was to evaluate the effects of moderate load intensity BFRT on muscle size and strength of the biceps brachii after a 12 week strength training intervention. Nine, previously strength trained, participants performed an elbow flexion exercise at 70 percent of their individualized 1-RM, twice per …

Developing A Plant Virus-Based Expression System For The Expression Of Vaccines Against Porcine Reproductive And Respiratory Syndrome Virus, Hong Hanh Tran

Electronic Thesis and Dissertation Repository

Virus-based expression systems have been widely exploited for the production of recombinant proteins in plants during the last three decades. Advances in technology have boosted scale-up manufacturing of plant-made pharmaceuticals to high levels, via the complementation of transient expression and viral vectors. This combination allows proteins of interest to be produced in plants within a matter of days and thus, is well suited for the development of plant-made vaccines or therapeutics against emerging infectious diseases and potential bioterrorism agents. Several plant-based products are currently in varying stages of clinical development. To investigate the viability of virus-based expression systems for plant-made …

Functional Characteristics Of Four Novel Lone Atrial Fibrillation-Linked Connexin40 Mutants, Mahmoud Noureldin

Electronic Thesis and Dissertation Repository

Atrial fibrillation (AF) is the most common form of cardiac arrhythmia. Recently, four novel heterozygous Cx40 mutations, K107R, L223M, Q236H, and I257L were identified in 4 of 310 unrelated AF patients. To study possible alterations associated with these mutants, we studied their localization and function using gap junction (GJ)-deficient model cells. Cell pairs expressing Q236H alone or together with wildtype Cx43 showed a significantly lower coupling conductance. Impaired GJ function and dominant negative action on Cx43 of this mutant are consistent with previous findings on the majority of AF-linked Cx40 mutants. The remaining three novel AF-linked mutants did not show …

Milder Alzheimer's Disease Pathology In Heart Failure And Atrial Fibrillation, Luciano A. Sposato, Estefania Ruiz Vargas, Patricia M. Riccio, Jon B. Toledo, John Q. Trojanowski, Walter A. Kukull, Lauren E. Cipriano, Antonia Nucera, Shawn N. Whitehead, Vladimir Hachinski

Anatomy and Cell Biology Publications

Introduction:Heart failure (HF) and atrial fibrillation (AF) have been associated with a higher risk of Alzheimer’s disease (AD). Whether HF and AF are related to AD by enhancing AD neuropathological changes is unknown.

Methods:We applied network analyses and multiple logistic regression models to assess the association between HF and AF with severity of AD neuropathology in patients from the National Alzheimer’s Coordinating Center database with primary neuropathological diagnosis of AD.

Results:We included 1593 patients, of whom 129 had HF and 250 had AF. HF and AF patients were older and had milder AD pathology. In the network …

Nutrition Screening In The Adult Stroke Population Using The Canadian Nutrition Screening Tool In Comparison With The Subjective Global Assessment, Tess Coutu

Electronic Thesis and Dissertation Repository

Although the Canadian Best Practice Recommendations for Stroke Care recommend all acute stroke patients be screened for malnutrition within 48 hours of admission to hospital using a valid screening tool, none have been validated for use in adult acute stroke patients. The Canadian Nutrition Screening Tool (CNST) tool has been validated within medicine and surgery patients. The purpose of this study is to estimate the level of agreement between the CNST and the Subjective Global Assessment (SGA), a nutrition assessment tool, in a cohort of 58 acute adult stroke patients at the Southwestern Ontario Regional Stroke Centre in London. In …

Spontaneous Low Frequency Bold Signal Variations From Resting-State Fmri Are Decreased In Alzheimer Disease, Samaneh Kazemifar, Kathryn Y. Manning, Nagalingam Rajakumar, Francisco A. Gomez, Michael J. Borrie, Ravi S. Menon, Robert Bartha, Alzheimer's Disease Neuroimaging Initiative

Anatomy and Cell Biology Publications

Previous studies have demonstrated altered brain activity in Alzheimer's disease using task based functional MRI (fMRI), network based resting-state fMRI, and glucose metabolism from 18 F fluorodeoxyglucose-PET (FDG-PET). Our goal was to define a novel indicator of neuronal activity based on a first-order textural feature of the resting state functional MRI (RS-fMRI) signal. Furthermore, we examined the association between this neuronal activity metric and glucose metabolism from F-18 FDG-PET. We studied 15 normal elderly controls (NEC) and 15 probable Alzheimer disease (AD) subjects from the AD Neuroimaging Initiative. An independent component analysis was applied to the RS-fMRI, followed by template …

The Effect Of Insulin Treatment And Exercise Modality On Skeletal Muscle Fiber Size In Streptozotocin-Induced Type 1 Diabetic Rats, John Z. Nickels

Electronic Thesis and Dissertation Repository

Severe Type 1 Diabetes Mellitus (T1DM) is known to have several negative effects on skeletal muscle mass, a condition known as diabetic myopathy. One of these effects is the atrophy of the glycolytic muscle fibers. However, the role of intensity of insulin treatment and exercise modality in attenuating this loss in fiber cross-sectional area (CSA) specifically has yet to be determined. The purpose of this investigation was to determine the effects of 12 weeks of differing intensity of insulin therapy and exercise modality on the CSA of plantaris muscle fibers, identified by myosin heavy chain (MHC) of STZ-induced T1DM rats. …

A National Perspective On Childhood Obesity Medical Education: Do Medical Students In Canada Perceive That They Are Prepared To Treat Children With Obesity?, Dr. Dalia Hasan

Electronic Thesis and Dissertation Repository

The purposes of this survey-based, mixed-methods study were to investigate medical students’ perceptions of: (1) the overall level of medical school training acquired in relation to childhood obesity treatment; (2) the medical school training acquired in relation to specific competencies associated with the treatment of children with obesity and their caregiver(s); and (3) additional training needed. Results showed that of the 507 students who provided complete data, approximately 60% (n = 303) disagreed or strongly disagreed that their medical training related to childhood obesity was adequate. With regard to specific competencies and additional training needed, quantitative and qualitative data revealed …

Soluble Bone-Derived Osteopontin Promotes Migration And Stem-Like Behavior Of Breast Cancer Cells, Graciella M. Pio, Ying Xia, Matthew M. Piaseczny, Jenny E. Chu, Alison L. Allan

Anatomy and Cell Biology Publications

Breast cancer is a leading cause of cancer death in women, with the majority of these deaths caused by metastasis to distant organs. The most common site of breast cancer metastasis is the bone, which has been shown to provide a rich microenvironment that supports the migration and growth of breast cancer cells. Additionally, growing evidence suggests that breast cancer cells that do successfully metastasize have a stem-like phenotype including high activity of aldehyde dehydrogenase (ALDH) and/or a CD44(+)CD24(-)phenotype. In the current study, we tested the hypothesis that these ALDH (hi) CD44 (+) CD24(-)breast cancer cells interact with factors in …

Therapeutic Strategies And Drug Development For Vascular Cognitive Impairment, Eric E. Smith, Alicja Cieslak, Philip Barber, Jerry Chen, Yu-Wei Chen, Ida Donnini, Jodi D. Edwards, Richard Frayne, Thalia S. Field, Janka Hegedus, Victoria Hanganu, Zahinoor Ismail, Jamila Kanji, Makoto Nakajima, Raza Noor, Stefano Peca, Demetrios Sahlas, Mukul Sharma, Luciano A. Sposato, Richard H. Swartz, Charlotte Zerna, Sandra E. Black, Vladimir Hachinski

Anatomy and Cell Biology Publications

No abstract provided.

Soluble Bone-Derived Osteopontin Promotes Migration And Stem-Like Behavior Of Breast Cancer Cells, Graciella Pio, Ying Xia, Matt M. Piaseczny, Jenny E. Chu, Alison Allan

Anatomy and Cell Biology Publications

Breast cancer is a leading cause of cancer death in women, with the majority of these deaths caused by metastasis to distant organs. The most common site of breast cancer metastasis is the bone, which has been shown to provide a rich microenvironment that supports the migration and growth of breast cancer cells. Additionally, growing evidence suggests that breast cancer cells that do successfully metastasize have a stem-like phenotype including high activity of aldehyde dehydrogenase (ALDH) and/or a CD44(+)CD24(-)phenotype. In the current study, we tested the hypothesis that these ALDH (hi) CD44 (+) CD24(-)breast cancer cells interact with factors in …

The Cdk-Resistant Prb-E2f1 Complex Recruits Chromatin-Organizing Proteins To Repetitive Dna Sequences, Charles A. Ishak

Electronic Thesis and Dissertation Repository

This thesis investigates mechanistic links between genome integrity and the recruitment of chromatin organizing proteins to repetitive DNA sequences mediated by the retinoblastoma tumor suppressor protein (pRB). I demonstrate that a CDK-resistant interaction between the pRB C-terminus and the E2F1 coiled-coil marked box domain establishes a scaffold that facilitates recruitment of multiple chromatin-organizing proteins to repetitive sequences across the genome throughout the cell cycle. Specifically, pRB recruits the enhancer-of-zeste-homologue 2 (EZH2) histone methyltransferase to establish repressive facultative heterochromatin at repetitive sequences, and the Condensin II complex to ensure proper DNA replication and mitotic progression. To disrupt the CDK-resistant pRB-E2F1 interaction …

Bk Channels Mediate Synaptic Plasticity Underlying Habituation In Rats, Tariq Zaman, Cleusa De Oliveira, Mahabba Smoka, Chakravarthi Narla, Michael O. Poulter, Susanne Schmid

Anatomy and Cell Biology Publications

Habituation is a basic form of implicit learning and represents a sensory filter that is disrupted in autism, schizophrenia, and several other mental disorders. Despite extensive research in the past decades on habituation of startle and other escape responses, the underlying neural mechanisms are still not fully understood. There is evidence from previous studies indicating that BK channels might play a critical role in habituation. We here used a wide array of approaches to test this hypothesis. We show that BK channel activation and subsequent phosphorylation of these channels are essential for synaptic depression presumably underlying startle habituation in rats, …

Cerebral Lactate Metabolism And Memory: Implications For Alzheimer's Disease, Richard Andrew Harris

Electronic Thesis and Dissertation Repository

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by amyloid plaques that are comprised of aggregated amyloid-beta peptides. These toxic proteins promote mitochondrial dysfunction and neuronal cell death. A shift in metabolism away from oxidative phosphorylation and toward aerobic glycolysis, with the concomitant production of lactate, affords neurons a survival advantage against amyloid-beta toxicity. Recent evidence now suggests that aerobic glycolysis in the brain plays a critical role in supporting synaptic plasticity, learning, and memory. However, the role of aerobic glycolysis and lactate metabolism in AD-mediated cognitive decline is unknown. My objective was to test the hypotheses that aerobic glycolysis …