Medicine and Health 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 …

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: …

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. …

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 …

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 …

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 …

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 …

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 …

Can Time-Resolved Nirs Provide The Sensitivity To Detect Brain Activity During Motor Imagery Consistently?, Androu Abdalmalak, Daniel Milej, Mamadou Diop, Mahsa Shokouhi, Lorina Naci, Adrian M. Owen, Keith St. Lawrence

Anatomy and Cell Biology Publications

Previous functional magnetic resonance imaging (fMRI) studies have shown that a subgroup of patients diagnosed as being in a vegetative state are aware and able to communicate by performing a motor imagery task in response to commands. Due to the fMRI's cost and accessibility, there is a need for exploring different imaging modalities that can be used at the bedside. A promising technique is functional near infrared spectroscopy (fNIRS) that has been successfully applied to measure brain oxygenation in humans. Due to the limited depth sensitivity of continuous-wave NIRS, time-resolved (TR) detection has been proposed as a way of enhancing …

Ang1 Treatment Reduces Muscle Pathology And Prevents A Decline In Perfusion In Dmd Mice, Kelly M. Gutpell, Nikola Tasevski, Boaz Wong, William Thomas Hrinivich, Feng Su, Lise Desjardins, Ting-Yim Lee, Lisa Marie Hoffman

Anatomy and Cell Biology Publications

Vascular endothelial growth factor (VEGF) and other pro-angiogenic growth factors have been investigated to enhance muscle tissue perfusion and repair in Duchenne muscular dystrophy (DMD). Current understanding is limited by a lack of functional data following in vivo delivery of these growth factors. We previously used dynamic contrast-enhanced computed tomography to monitor disease progression in murine models of DMD, but no study to date has utilized this imaging technique to assess vascular therapy in a preclinical model of DMD. In the current study, we locally delivered VEGF and ANG1 alone or in combination to dystrophic hind limb skeletal muscle. Using …

Cost-Effectiveness Of Cerebrospinal Biomarkers For The Diagnosis Of Alzheimer's Disease, Spencer A. W. Lee, Luciano A. Sposato, Vladimir Hachinski, Lauren E. Cipriano

Anatomy and Cell Biology Publications

Background: Accurate and timely diagnosis of Alzheimer's disease (AD) is important for prompt initiation of treatment in patients with AD and to avoid inappropriate treatment of patients with false-positive diagnoses. Methods: Using a Markov model, we estimated the lifetime costs and quality-adjusted life-years (QALYs) of cerebrospinal fluid biomarker analysis in a cohort of patients referred to a neurologist or memory clinic with suspected AD who remained without a definitive diagnosis of AD or another condition after neuroimaging. Parametric values were estimated from previous health economic models and the medical literature. Extensive deterministic and probabilistic sensitivity analyses were performed to evaluate …

P23. Elucidation Of The Signaling Pathway Of Mertk, Kyle Taruc

Western Research Forum

Background

Mer Tyrosine Kinase (MERTK) is a receptor which mediates efferocytosis – removal of apoptotic cells by phagocytes such as macrophages. MERTK plays a critical role in homeostasis, with mutations in MERTK associated with the development and progression of atherosclerosis, the buildup of cholesterol-laden plaque in the sub-arterial space. Indeed, one MERTK allele is associated with 66% (heterozygous) to 75% (homozygous) protection from atherosclerosis, while other alleles and SNP’s pre-dispose to atherosclerosis and autoimmunity. Complications resulting from atherosclerosis, including heart attack and stroke, are currently the second leading cause of mortality in Canada. Despite the importance of MERTK in atherosclerosis …

Pulmonary Surfactant Fortified With Cath-2 As A Novel Therapy For Bacterial Pneumonia, Brandon J. Baer

Western Research Forum

Background: Bacterial pneumonia is a leading cause of death worldwide, with high mortality rates persisting even after antibiotic treatment. Current treatments for pneumonia involve administration of antibiotics, however after the bacteria are killed they release toxic substances that induce inflammation and lung dysfunction. Host defense peptides represent a potential solution to this problem through their ability to down regulate inflammation. However, effective delivery to the lung is difficult because of the complex branching structure of the airways. My study addresses this delivery problem by using exogenous surfactant, a pulmonary delivery vehicle capable of improving spreading of these peptides throughout the …

A Method For Independent Component Graph Analysis Of Resting-State Fmri, Demetrius Ribeiro De Paula, Erik Ziegler, Pubuditha M. Abeyasinghe, Tushar K. Das

Anatomy and Cell Biology Publications

Introduction: Independent component analysis (ICA) has been extensively used for reducing task-free BOLD fMRI recordings into spatial maps and their associated time-courses. The spatially identified independent components can be considered as intrinsic connectivity networks (ICNs) of non-contiguous regions. To date, the spatial patterns of the networks have been analyzed with techniques developed for volumetric data. Objective: Here, we detail a graph building technique that allows these ICNs to be analyzed with graph theory. Methods: First, ICA was performed at the single-subject level in 15 healthy volunteers using a 3T MRI scanner. The identification of nine networks was performed by a …

Eligibility For Minimally Invasive Coronary Artery Bypass Examination Of Epicardial Adipose Tissue Using Computed Tomography, Kate E. M. Dillon, Marjorie Johnson, Bob Kiaii

Anatomy and Cell Biology Publications

Objective: A variable that necessitates conversion to a conventional full-sternotomy coronary artery bypass procedure from a robotic-assisted endoscopic single-vessel small thoracotomy is the inability to visualize the left anterior descending coronary artery within the surrounding epicardial adipose tissue using the endoscopic camera. The purpose of this study was to determine whether anatomical properties of the epicardial adipose tissue examined using preoperative computed tomography (CT) images are able to predict and thus reduce the need for intraoperative conversion based on effective preoperative exclusion criteria. Methods: Retrospective analysis of patient preoperative CT angiography scans from both converted (n = 17) and successful …

The Effects Of Acetylenic Tricyclic Bis-(Cyano Enone) On Cell Migration, Eddie Chan

Electronic Thesis and Dissertation Repository

Although cancer survival rates have significantly improved over the past few decades, the improvements are primarily due to early diagnosis and inhibiting cancer growth. Limited progress has been made in the treatment of cancer metastasis, which contributes to 90% of cancer related deaths, and therapeutic agents targeting the various aspects of metastasis are lacking. One potential approach is to utilize small pharmacological compounds to inhibit tumour cell motility, as a strategy against tumour cell migration, invasion, and metastasis. The acetylenic tricyclic bis-(cyano enone), TBE-31, has been shown to be a promising chemopreventative compound. However, its effects on cell migration are …

Mosaic Expression Of Atrx In The Mouse Central Nervous System Causes Memory Deficits, Renee J. Tamming, Jennifer R. Siu, Yan Jiang, Marco A. M. Prado, Frank Beier, Nathalie G. Berube

Anatomy and Cell Biology Publications

The rapid modulation of chromatin organization is thought to play a crucial role in cognitive processes such as memory consolidation. This is supported in part by the dysregulation of many chromatin-remodelling proteins in neurodevelopmental and psychiatric disorders. A key example is ATRX, an X-linked gene commonly mutated in individuals with syndromic and nonsyndromic intellectual disability. The consequences of Atrx inactivation for learning and memory have been difficult to evaluate because of the early lethality of hemizygous-null animals. In this study, we evaluated the outcome of brain-specific Atrx deletion in heterozygous female mice. These mice exhibit a mosaic pattern of ATRX …

Sleep Spindles And Intellectual Ability: Epiphenomenon Or Directly Related?, Zhuo Fang, Valya Sergeeva, Laura B. Ray, Adrian M. Owen, Stuart M. Fogel

Anatomy and Cell Biology Publications

Sleep spindlesshort, phasic, oscillatory bursts of activity that characterize non-rapid eye movement sleepare one of the only electrophysiological oscillations identified as a biological marker of human intelligence (e.g., cognitive abilities commonly assessed using intelligence quotient tests). However, spindles are also important for sleep maintenance and are modulated by circadian factors. Thus, the possibility remains that the relationship between spindles and intelligence quotient may be an epiphenomenon of a putative relationship between good quality sleep and cognitive ability or perhaps modulated by circadian factors such as morningness-eveningness tendencies. We sought to ascertain whether spindles are directly or indirectly related to cognitive …

Mt1-Mmp Mediates The Migratory And Tumourigenic Potential Of Breast Cancer Cells Via Non-Proteolytic Mechanisms, Mario Cepeda

Electronic Thesis and Dissertation Repository

Membrane Type-1 Matrix Metalloproteinase (MT1-MMP) is a multifunctional protease that affects cell function via proteolytic and non-proteolytic mechanisms such as promoting degradation of the extracellular matrix (ECM) or augmentation of cell migration and viability, respectively. MT1-MMP has been implicated in metastatic progression ostensibly due to its ability to degrade ECM components and to allow migration of cells through the basement membrane. Despite in vitro studies demonstrating this principle, this knowledge has not translated into the use of MMP inhibitors (MMPi) that inhibit substrate catalysis as effective cancer therapeutics, or been corroborated by evidence of in vivo ECM degradation mediated by …

Discovery Of Novel Diagnostic Biomarkers On Prostate Tumor Microparticles For Discriminating Between Low And High Risk Prostate Cancer And Improving Prostate Cancer Screening, Sabine Brett

Electronic Thesis and Dissertation Repository

There are few protein-based biomarkers to accurately distinguish between patients with low risk prostate cancer from those with high risk disease in a non-invasive manner. Prostate specific antigen (PSA) is used for clinical follow-up of prostate cancer; however, it is not effective as a screening tool. As a result, many men with non-life threatening disease having to undergo unnecessary and painful biopsies. Therefore, there is a dire need for minimally invasive platforms for monitoring patients with clinically significant prostate cancer. Prostate cell microparticles (PCMPs) released by prostate epithelial cells into plasma are a potential source of biomarkers specific for prostate …

Covert Narrative Capacity: Mental Life In Patients Thought To Lack Consciousness, Lorina Naci, Mackenzie Graham, Adrian M. Owen, Charles Weijer

Anatomy and Cell Biology Publications

Despite the apparent absence of external signs of consciousness, a significant proportion of behaviorally nonresponsive patients can respond to commands by willfully modulating their brain activity. However, little is known about the mental life of these patients. We discuss a recent innovative approach, which sheds light on the preserved cognitive capacities of these patients, including executive function, theory of mind, and the experience of affective states. This research represents a fundamental shift in our understanding of these patients, and has important implications for both their continued treatment and care. Moreover, this research marks out avenues for future inquiry into the …

Real-Time Interactive Tractography Analysis For Multimodal Brain Visualization Tool: Multixplore, Saeed M. Bakhshmand, Sandrine De Ribaupierre, Roy Eagleson

Anatomy and Cell Biology Publications

Most debilitating neurological disorders can have anatomical origins. Yet unlike other body organs, the anatomy alone cannot easily provide an understanding of brain functionality. In fact, addressing the challenge of linking structural and functional connectivity remains in the frontiers of neuroscience. Aggregating multimodal neuroimaging datasets may be critical for developing theories that span brain functionality, global neuroanatomy and internal microstructures. Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) are main such techniques that are employed to investigate the brain under normal and pathological conditions. FMRI records blood oxygenation level of the grey matter (GM), whereas DTI is able …

The Roles Of Insulin-Like Growth Factors In Mesenchymal Stem Cell Niche, Amer Youssef, Doaa Aboalola, Victor K. M. Han

Anatomy and Cell Biology Publications

Many tissues contain adult mesenchymal stem cells (MSCs), which may be used in tissue regeneration therapies. However, the MSC availability in most tissues is limited which demands expansion in vitro following isolation. Like many developing cells, the state of MSCs is affected by the surrounding microenvironment, and mimicking this natural microenvironment that supports multipotent or differentiated state in vivo is essential to understand for the successful use of MSC in regenerative therapies. Many researchers are, therefore, optimizing cell culture conditions in vitro by altering growth factors, extracellular matrices, chemicals, oxygen tension, and surrounding pH to enhance stem cells self-renewal or …