Medicine and Health Sciences Commons^™

Share Cannabidiol Exposure During Gestation Leads To Adverse Cardiac Outcomes Early In Postnatal Life In Male Rat Offspring., Daniel B. Hardy, Steven R. Laviolette, Kendrick Lee, David Rc Natale

Physiology and Pharmacology Publications

Introduction: Studies indicate that *7% of pregnant individuals in North America consume cannabis in pregnancy. Pre-clinical studies have established that maternal exposure to D9-tetrahydrocannabinol (THC; major psychoactive component in cannabis) leads to fetal growth restriction and impaired cardiac function in offspring. However, the effects of maternal exposure to cannabidiol (CBD; major non-euphoric constituent) on cardiac outcomes in offspring remain unknown. Therefore, our objective is to investigate the functional and underlying molecular impacts in the hearts of offspring exposed to CBD in pregnancy. Methods: Pregnant Wistar rats were exposed to either 3 or 30mg/kg CBD or vehicle control i.p. daily from …

The Impact Of Access To Oral Health Care On Inadequate Oral Health And Multimorbidity, Luis Limo

Electronic Thesis and Dissertation Repository

The connection between oral health and other non-communicable chronic conditions—commonly referred in the dental literature as the oral-systemic health connection—emphasizes the role of oral health care on both oral diseases and chronic conditions, particularly in vulnerable populations like the elderly. This thesis comprises 2 studies: the first is a systematic review on the impact of oral health care interventions, as an indicator of access to oral health care, on chronic conditions of which their co-existence would result in multimorbidity; the second study is a cross-sectional investigation of the associations between oral health, access to oral health care, and multimorbidity among …

Secretion Of Salivary Proteins And Their Interactions, Karla Tonelli Bicalho Crosara

Electronic Thesis and Dissertation Repository

Saliva’s clinical application for disease diagnosis and monitoring is limited by incomplete knowledge of salivary protein interactions, the effect of stimulation on the salivary proteome, and if these factors impact protein identification. This thesis expands knowledge of the salivary interactome and effects of stimulation intensity and duration on parotid saliva’s proteome. First, previous in vitro studies identified 43 proteins in the histatin 1-protein network and demonstrated histatin 1’s increased stability in whole saliva when interacting with amylase. We hypothesized that protein-protein-interaction databases could enlarge the histatin 1-protein network. A comprehensive histatin 1-protein network was created using STRING database, merging previous …

Anatomical And Functional Lung Imaging With Volumetric Computed Tomography In Non-Small Cell Lung Cancer, Heather Young

Electronic Thesis and Dissertation Repository

Non-small cell lung cancer (NSCLC) is one of the most diagnosed cancers in Canada, and the leading cause of cancer deaths. A significant challenge in treating NSCLC is balancing aggressive treatment with the potentially severe side effects. In radiation therapy, the management of respiratory motion and the risks of radiation-induced lung injury (RILI) pose significant challenges. 4-dimensional computed tomography (4D-CT) is an important part of motion management, but images often suffer from motion-induced artifacts. Volumetric CT scanners with wide axial field-of-view (aFOV) may reduce these artifacts and present an opportunity to advance CT-based functional lung imaging.

Chapter 2 presents a …

Cost-Effective Non-Destructive Testing Of Biomedical Components Fabricated Using Additive Manufacturing, Santiago Fabian Cobos

Electronic Thesis and Dissertation Repository

Biocompatible titanium-alloys can be used to fabricate patient-specific medical components using additive manufacturing (AM). These novel components have the potential to improve clinical outcomes in various medical scenarios. However, AM introduces stability and repeatability concerns, which are potential roadblocks for its widespread use in the medical sector. Micro-CT imaging for non-destructive testing (NDT) is an effective solution for post-manufacturing quality control of these components. Unfortunately, current micro-CT NDT scanners require expensive infrastructure and hardware, which translates into prohibitively expensive routine NDT. Furthermore, the limited dynamic-range of these scanners can cause severe image artifacts that may compromise the diagnostic value of …

Investigating Bone Cement Susceptibility Related Artifacts And Adhesion, Eric Kuindersma

Electronic Thesis and Dissertation Repository

Blood Oxygen Level Dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) utilizes pulse sequences sensitive to changes in concentration of deoxyhemoglobin to indirectly measure neural activity. Sequences used for BOLD are sensitive to magnetic susceptibility differences that may cause signal voids. Our lab has designed an awake marmoset head coil that eliminates confounds associated with imaging an animal under anesthesia. This design requires a head chamber attached to an animal’s skull with a cement that may cause a susceptibility artifact. Motivation behind this project was to find an MRI compatible cement that remains secure to the skull with minimal artifacts. Four …

Functional Organization Of Frontoparietal Cortex In The Marmoset Investigated With Awake Resting-State Fmri, Yuki Hori, Justine C. Cléry, David J. Schaeffer, Ravi S. Menon, Stefan Everling

Brain and Mind Institute Researchers' Publications

Frontoparietal networks contribute to complex cognitive functions in humans and macaques, such as working memory, attention, task-switching, response suppression, grasping, reaching, and eye movement control. However, there has been no comprehensive examination of the functional organization of frontoparietal networks using functional magnetic resonance imaging in the New World common marmoset monkey (Callithrix jacchus), which is now widely recognized as a powerful nonhuman primate experimental animal. In this study, we employed hierarchical clustering of interareal blood oxygen level-dependent signals to investigate the hypothesis that the organization of the frontoparietal cortex in the marmoset follows the organizational principles of the macaque frontoparietal …

Erythrokeratodermia Variabilis Et Progressiva (Ekvp) Linked Cx30.3 Mutants Can Be Selectively Rescued By Co-Expression Of Wildtype Keratinocyte Connexins, Rhett O. Figliuzzi

Electronic Thesis and Dissertation Repository

Connexin 30.3 (Cx30.3) is a β-connexin encoded by GJB4 that is key in epidermal homeostasis. Eleven mutations to the GJB4 are linked to an autosomal dominant skin disease called erythrokeratodermia variabilis et progressiva (EKVP). These mutations remain largely uncharacterized, limiting therapeutic options. In this study, we characterize the expression and functional status of three EKVP-linked Cx30.3 mutants, G12D, T85P and F189Y in rat epidermal keratinocytes. We found that EKVP-linked Cx30.3 mutants were not functional due to their retention in the endoplasmic reticulum (ER), but did not upregulate BiP, an indicator of ER stress. Sub-physiological incubation and chemical chaperones (such as …

The Antimicrobial Properties Of Exogenous Copper In Human Synovial Fluid Against Staphylococcus Aureus: An In-Vitro Study, Fernando Diaz Dilernia

Electronic Thesis and Dissertation Repository

We sought to analyse the antimicrobial properties of exogenous copper in human synovial fluid against Staphylococcus aureus. We performed several in-vitro growth and viability assays to determine the capability of multiple S. aureus strains to survive in synovial fluid under different growth conditions. S. aureus UAMS-1 significantly died at 24 hours (p=0.017), and S. aureus USA300 WT survived at 24 hours. We confirmed a high sensitivity to killing with the addition of exogenous copper on both strains at 4 (p=0.011), 12 (p=0.011), and 24 hours (p=0.011). Both WT and CopAZB-deficient USA300 strains significantly died in synovial fluid, evidencing a …

Disease-Related Cortical Thinning In Presymptomatic Granulin Mutation Carriers, Sergi Borrego-Écija, Roser Sala-Llonch, John Van Swieten, Barbara Borroni, Fermín Moreno, Mario Masellis, Carmela Tartaglia, Caroline Graff, Daniela Galimberti, Robert Laforce, James B. Rowe, Elizabeth Finger, Rik Vandenberghe, Fabrizio Tagliavini, Alexandre De Mendonça, Isabel Santana, Matthis Synofzik, Simon Ducharme, Johannes Levin, Adrian Danek, Alex Gerhard, Markus Otto, Chris Butler, Giovanni Frisoni, Sandro Sorbi, Carolin Heller, Martina Bocchetta, David M. Cash, Rhian S. Convery, Katrina M. Moore, Jonathan D. Rohrer, Raquel Sanchez-Valle

Medical Biophysics Publications

Mutations in the granulin gene (GRN) cause familial frontotemporal dementia. Understanding the structural brain changes in presymptomatic GRN carriers would enforce the use of neuroimaging biomarkers for early diagnosis and monitoring. We studied 100 presymptomatic GRN mutation carriers and 94 noncarriers from the Genetic Frontotemporal dementia initiative (GENFI), with MRI structural images. We analyzed 3T MRI structural images using the FreeSurfer pipeline to calculate the whole brain cortical thickness (CTh) for each subject. We also perform a vertex-wise general linear model to assess differences between groups in the relationship between CTh and diverse covariables as gender, age, the estimated years …

Cortico-Subcortical Functional Connectivity Profiles Of Resting-State Networks In Marmosets And Humans, Yuki Hori, David J. Schaeffer, Atsushi Yoshida, Justine C. Cléry, Lauren K. Hayrynen, Joseph S. Gati, Ravi S. Menon, Stefan Everling

Brain and Mind Institute Researchers' Publications

Copyright © 2020 the authors Understanding the similarity of cortico-subcortical networks topologies between humans and nonhuman primate species is critical to study the origin of network alternations underlying human neurologic and neuropsychiatric diseases. The New World common marmoset (Callithrix jacchus) has become popular as a nonhuman primate model for human brain function. Most marmoset connectomic research, however, has exclusively focused on cortical areas, with connectivity to subcortical networks less extensively explored. Here, we aimed to first isolate patterns of subcortical connectivity with cortical resting-state networks in awake marmosets using resting-state fMRI, then to compare these networks with those in humans …

A Clinically Representative Rat Model Of Hip Hemiarthroplasty, Adam Dm Paish

Electronic Thesis and Dissertation Repository

Joint replacement is an increasingly common surgery with over 130,000 procedures performed annually in Canada. Although joint replacement surgery is highly successful, implants do not last a lifetime, and often have to be replaced via costly revision surgeries. Before innovations aimed at extending the life of implants are applied to the clinic, testing must be performed in animal models. Clinically representative small-animal models of joint replacement would be ideal in the initial stages of research and development, due to ease of handling and low costs, but few such models have been established in the literature. Thus, we describe the development …

Machine Learning For Prostate Histopathology Assessment, Wenchao Han

Electronic Thesis and Dissertation Repository

Pathology reporting on radical prostatectomy (RP) specimens is essential to post-surgery patient care. However, current pathology interpretation of RP sections is typically qualitative and subject to intra- and inter-observer variability, which challenges quantitative and repeatable reporting of lesion grade, size, location, and spread. Therefore, we developed and validated a software platform that can automatically detect and grade cancerous regions on whole slide images (WSIs) of whole-mount RP sections to support quantitative and visual reporting. Our study used hæmatoxylin- and eosin-stained WSIs from 299 whole-mount RP sections from 71 patients, comprising 1.2 million 480μm×480μm regions-of-interest (ROIs) covering benign and cancerous tissues …

Functional Localization Of The Frontal Eye Fields In The Common Marmoset Using Microstimulation, Janahan Selvanayagam, Kevin D. Johnston, David J. Schaeffer, Lauren K. Hayrynen, Stefan Everling

Brain and Mind Institute Researchers' Publications

Copyright © 2019 the authors. The frontal eye field (FEF) is a critical region for the deployment of overt and covert spatial attention. Although investigations in the macaque continue to provide insight into the neural underpinnings of the FEF, due to its location within a sulcus, the macaque FEF is virtually inaccessible to electrophysiological techniques such as high-density and laminar recordings. With a largely lissencephalic cortex, the common marmoset (Callithrix jacchus) is a promising alternative primate model for studying FEF microcircuitry. Putative homologies have been established with the macaque FEF on the basis of cytoarchitecture and connectivity; however, physiological investigation …

Discovery Of Novel Mechanisms Regulating Cancer Extravasation In The Chorioallantoic Membrane Model, Yohan Kim

Electronic Thesis and Dissertation Repository

Cancer metastasis is a multistep process that begins with the invasion of tumour cells into the stroma and migration towards the blood vessels. Tumour cells that have entered the bloodstream must then survive and leave by a process known as extravasation. Finally, extravasated cells proliferate and establish the secondary site in the metastatic cascade. Although extravasation encompasses key events during cancer cell invasion to aid in the development of effective treatments, an in vivo model that rapidly, reproducibly and economically recapitulates cancer cell extravasation is needed. Therefore, the objectives of my research were to 1) establish and validate an in …

High Frequency Oscillations Are Phase-Amplitude Coupled In Stress Induced Seizures Following Traumatic Brain Injury, Paul Jung

Electronic Thesis and Dissertation Repository

Traumatic Brain Injury (TBI) often leads to the development of epilepsy, especially with the occurrence of stressful events. Stressors increase the levels of corticotropin-releasing factor (CRF) in the amygdala, which can be damaged by the secondary effects of TBI. It is hypothesized that the activity of CRF receptor type 1 (CRFR₁) in the amygdala is altered post-TBI and supports the generation of epileptiform waves, namely high-frequency oscillations (HFOs). Sprague-Dawley rats were given a moderate TBI and in vivo recordings of the amygdala were taken during the administration of an acute tail pinch stressor. The stressor increased broadband activity …

Piezo1: Proteins For Mechanotransduction And Integration Of Endothelial Shear Stress & Intravascular Pressure, Juan Garcia Robledo M.D.

Electronic Thesis and Dissertation Repository

Piezo proteins are transmembrane ion channels, specialized in detecting mechanosensitive stimuli and transduce mechanical forces into biochemical signals. Piezo proteins research has helped understand physiological mechanisms, but the integrative role that Piezo1 plays in the regulation of the microvasculature has remained unstudied. Our main objective was to characterize ex vivo microvascular responses to the blockade of Piezo1 mechanotransduction in male (n=29) and female (n=24) Sprague-Dawley (SD) rats. Gracilis arterioles (GA) and middle cerebral arterioles (MCA) were harvested for ex-vivo vessel preparations. After vessel viability confirmation, every vessel was submitted to myogenic and flow challenges under control conditions and after Grammostola …

Comorbid Metabolic Syndrome And Prodromal Alzheimer's Disease In A Rat Model, Nadezda Ivanova

Electronic Thesis and Dissertation Repository

Metabolic syndrome (MetS), the development of which is associated with high-caloric Western diet intake, represents a risk factor for mild cognitive impairment (MCI) and Alzheimer’s disease (AD) and appears to contribute to AD progression when MetS and AD are comorbid. The interaction between AD and MetS might be through white matter inflammation, since white matter abnormalities and inflammation are important early events in the etiopathogenesis of both diseases. In these investigations, the effect of a high-caloric diet (HCD), to induce metabolic disturbances, on white matter neuroinflammation and cognitive function was investigated in a transgenic (TG) rat model of prodromal AD …

Functional Magnetic Resonance Spectroscopy In First-Episode Schizophrenia: Measuring Glutamate And Glutathione Dynamics At 7-Tesla, Peter Jeon

Electronic Thesis and Dissertation Repository

Schizophrenia is a neuropsychiatric illness without known etiology or cure. Current efforts for symptom treatment still seem to leave a large portion of affected individuals without proper symptom management, with those experiencing symptom relief still having to wrestle with potential side-effects from medication trials. There has been growing evidence suggesting that glutamate and glutathione abnormalities hold major roles in development and manifestation of schizophrenia symptoms.

Magnetic resonance spectroscopy (MRS) provides a non-invasive means to observe in-vivo brain chemistry, including glutamate and glutathione. By adding a functional component to an MRS paradigm (fMRS), such as the color-word Stroop task, it is …

The Role Of The Tau N-Terminal Phosphatase-Activating Domain And Phosphorylation At Thr175 In The Formation Of Tau Cytoplasmic Inclusions, Matthew A. Hintermayer

Electronic Thesis and Dissertation Repository

Cytoplasmic inclusions and fibrils of the microtubule-associated protein tau (tau protein) are a key neuropathological hallmark in tauopathies, including Alzheimer’s disease, chronic traumatic encephalopathy, and amyotrophic lateral sclerosis with cognitive impairment. Previous research has demonstrated that the phosphorylation of tau protein at Thr¹⁷⁵ is sufficient for the initiation of fibril formation both in vitro and in vivo. Here we use mutated tau protein constructs to demonstrate that phosphorylation at Thr¹⁷⁵ results in the aberrant exposure of an N-terminal phosphatase-activating domain (PAD). The tau PAD interacts with protein phosphatase 1 (PP1) leading to the activation of glycogen synthase …

Δ9-Tetrahydrocannabinol Leads To Endoplasmic Reticulum Stress And Mitochondrial Dysfunction In Human Bewo Trophoblasts., Tina Lojpur, Zachary Easton, Sergio Raez-Villanueva, Steven Laviolette, Alison C Holloway, Daniel B Hardy

Physiology and Pharmacology Publications

While studies have demonstrated that the main psychoactive component of cannabis, Δ9-tetrahydrocannabinol (Δ9-THC) alone induces placental insufficiency and fetal growth restriction, the underlying mechanisms remain elusive. Given that both (i) endoplasmic reticulum (ER) stress in pregnancy and (ii) gestational exposure to Δ9-THC leads to placental deficiency, we hypothesized that Δ9-THC may directly induce placental ER stress, influencing trophoblast gene expression and mitochondrial function. BeWo human trophoblast cells treated with Δ9-THC (3-30 μM) led to a dose-dependent increase in all ER stress markers and CHOP; these effects could be blocked with CB1R/CB2R antagonists. Moreover, expression of ER stress-sensitive genes ERRγ, VEGFA, …

Towards On-Line Plan Adaptation Of Unified Intensity-Modulated Arc Therapy Using A Fast-Direct Aperture Optimization Algorithm, Michael Macfarlane

Electronic Thesis and Dissertation Repository

External beam radiotherapy (EBRT) plays a vital role in the treatment of cancer, with close to half of all cancer patients receiving EBRT at some point over their course of treatment. Although EBRT is a well-established form of treatment, there are a number of ways in which EBRT could still be improved in terms of quality and efficiency for treatment planning and radiation dose delivery. This thesis reports a series of improvements made to EBRT.

First, we developed and evaluated a new treatment planning technique called unified intensity-modulated arc therapy (UIMAT) which combines the optimization and delivery of rotational volumetric …

Potential Role Of Extracellular Atp Released By Bacteria In Bladder Infection And Contractility, Behnam Abbasian

Electronic Thesis and Dissertation Repository

Urgency urinary incontinence (UUI), the result of conditions such as overactive bladder (OAB), could potentially be influenced by both commensal and urinary tract infection-associated bacteria. The sensing of bladder filling involves interplay between various parts of the nervous system eventually resulting in contraction of the detrusor muscle during micturition. Here we model host responses to various urogenital bacteria, firstly by using urothelial bladder cell lines and then with myofibroblast contraction assays. To measure responses, we examined calcium influx, gene expression and alpha smooth muscle actin deposition assays. We found that organisms such as Escherichia coli IA2 and Gardnerella vaginalis ATCC …

Crf Mediates Stress-Induced Pathophysiological High-Frequency Oscillations In Traumatic Brain Injury, Chakravarthi Narla, Paul S. Jung, Francisco Bautista Cruz, Michelle Everest, Julio Martinez-Trujillo, Michael O. Poulter

Physiology and Pharmacology Publications

Copyright © 2019 Narla et al. It is not known why there is increased risk to have seizures with increased anxiety and stress after traumatic brain injury (TBI). Stressors cause the release of corticotropin-releasing factor (CRF) both from the hypothalamic pituitary adrenal (HPA) axis and from CNS neurons located in the central amygdala and GABAergic interneurons. We have previously shown that CRF signaling is plastic, becoming excitatory instead of inhibitory after the kindling model of epilepsy. Here, using Sprague Dawley rats we have found that CRF signaling increased excitability after TBI. Following TBI, CRF type 1 receptor (CRFR1)-mediated activity caused …

Applications Of Ct Perfusion-Based Triaging And Prognostication In Acute Ischemic Stroke, Eric A. Wright

Electronic Thesis and Dissertation Repository

CT Perfusion (CTP) is a minimally invasive imaging technique that aids acute ischemic stroke (AIS) triage and prognostication by determining tissue viability based on hemodynamic parameters. The goals of this research are to determine: 1) CTP thresholds for estimation of infarct and penumbra volume, 2) how CTP scan duration impacts infarct and penumbra volume estimates, and 3) reliability of CTP for predicting functional outcomes following intra-arterial therapy (IAT).

Chapter 2 introduced an experimental study for determining ischemia-time dependent thresholds for brain infarction using multimodal imaging in a porcine stroke model that is easier to implement than previous large animal stroke …

Assessment Of Interprofessional Team Collaboration Scale (Aitcs): Further Testing And Instrument Revision., Carole Orchard, Linda L Pederson, Emily Read, Cornelia Mahler, Heather Laschinger

Nursing Publications

INTRODUCTION: The need to be able to assess collaborative practice in health care teams has been recognized in response to the direction for team-based care in a number of policy documents. The purpose of this study is to report on further refinement of such a measurement instrument, the Assessment of Interprofessional Team Collaboration Scale (AITCS) first published in 2012. To support this refinement, two objectives were set: Objective 1: to determine whether the items from the data collected in 2016 load on the same factors as found for the 2012 version of the 37-item AITCS. Objective 2: to determine whether …

Medial Geniculate Projections To Auditory And Visual Cortex In Hearing And Deaf Cats, Benjamin Trachtenberg

Electronic Thesis and Dissertation Repository

Following early-onset deafness, studies have demonstrated crossmodal plasticity, throughout “deaf” auditory cortex. Crossmodally reorganized auditory cortex shows increased dendritic spine density, which suggests increased numbers of axon terminals. I examined projections from the medial geniculate body (MGB) of hearing and early-deaf cats in order to reveal the distribution of synaptic boutons in the cortex, originating from MGB neurons. Anterograde fluorescent dextran tracers were deposited bilaterally in the MGB in order to label cortical axon terminals. Deafness resulted in axon terminal increases in visual cortex, and conservation of auditory axon terminal distribution. Visual areas PLLS and area 18 received increased projections …

Multi-Scale Peripheral Vasculopathy With Metabolic Syndrome, Kent Lemaster

Electronic Thesis and Dissertation Repository

The combination of cardiovascular and metabolic risk factors including obesity, dyslipidemia, hypertension, and insulin resistance, in combination with a prothrombotic and proinflammatory state, is a condition termed Metabolic Syndrome (METS). Twenty percent of the adult population is afflicted with METS which increases the risk of type-2 diabetes mellitus and cardiovascular disease. Further, the presence of peripheral vascular disease (PVD) is tightly coupled with METS which is a perfusion-demand mismatch of blood supply to active skeletal muscle resulting in painful claudication and a late-stage potential for amputation. The underlying contributors of METS associated micro-vasculopathies in the skeletal muscle, their impact on …

Limbic System Involvement In Absence Seizures, Rukham Ajaz

Electronic Thesis and Dissertation Repository

Absence epilepsy is characterized by brief spells of absent stare and spike wave discharges (SWDs), generally believed to be generated by a thalamocortical network. Our lab showed that hippocampal neuronal firings were synchronous with SWDs in a gamma butyrolactone (GBL) model of absence epilepsy in rats (Arcaro et al., 2016). We hypothesize that, in a GBL model of absence seizures, 30-400 Hz oscillations in the spontaneous local field potentials (LFPs) in the hippocampus and other parts of limbic system (amygdala and nucleus accumbens) are phase modulated by SWDs, and this modulation is mediated through nucleus reuniens of midline thalamus (RE). …

Understanding The Impact Of Hiv-1 Genetic Diversity On The Function Of Nef And Its Role In Serinc5 Antagonism, Aaron Leslie Johnson

Electronic Thesis and Dissertation Repository

HIV-1 Nef is a key pathogenic protein, allowing HIV-1 to evade the host immune system by downregulating MHC-I and CD4. Furthermore, it was recently discovered that Nef counteracts the host factor SERINC5 to increase HIV-1 infectivity, but the mechanistic details of the Nef:SERINC5 interaction still need to be explored. Throughout this dissertation, I will explore the hypothesis that the genetic diversity that defines HIV-1 has a pronounced effect on the HIV-1 protein Nef, altering its function between and within group M subtypes. To address this hypothesis I investigated how MHC-I and CD4 downregulation differ among all non-recombinant group M subtypes. …