Medicine and Health Sciences Commons^™

The Role Of Cholinergic Signaling In Cardiac Function, Rachel Reingold

Electronic Thesis and Dissertation Repository

Cardiovascular disease is one of the leading causes of death in Canada. Treatment currently focuses on preventing the increase of sympathetic signaling seen in heart failure. However, it has recently been noted that cardiac function is dependent on parasympathetic tone. Previous studies have demonstrated the development of heart failure when cholinergic targets are knocked out in cardiomyocytes. Transgenic mouse models that have increased cholinergic transmission show protection against cardiovascular insults. We have shown that transgenic mice overexpressing vesicular acetylcholine transporter in cholinergic cells show cardiovascular protection in response to ex vivo insults. As well, this protection is seen when cholinergic …

Examining The Tissue-Level And Gross Phenotypic Effects Of The Connexin43i130t/+ Mutation On The Developing Mouse Skull, Sommer G.E. Jarvis

Electronic Thesis and Dissertation Repository

The purpose of this study was to investigate the effects of reduced Connexin43 function on the developing skull phenotype, osteoblast and chondrocyte proliferation and differentiation, and to determine if a correlation exists between cell processes and gross morphology. Using the Cx43^I130T/+mouse model, skull shape was analyzed using geometric morphometrics and cell proliferation and differentiation were assessed using immunohistochemistry at late embryonic and early post-natal stages. The largest shape changes between Cx43^I130T/+ and wildtype mice were observed in the cranial base and facial skeleton. Changes infacial morphology correspond to reduced osteoblast differentiation. However, no changes in chondrocyte proliferation …

The Effects Of Tracheal Occlusion On Wnt Signaling In A Rabbit Model Of Congenital Diaphragmatic Hernia, Martina M. Mudri

Electronic Thesis and Dissertation Repository

Purpose: Tracheal occlusion (TO) reverses pulmonary hypoplasia (PH) in congenital diaphragmatic hernia (CDH), but its effect on epithelial-mesenchymal transition (EMT) in lung development remains poorly understood. The purpose of this study was to a) confirm the CDH rabbit model produced PH which was reversed by TO and b) determine the effects of CDH +/- TO on EMT pathways.

Methods: CDH was created at 23 days, TO at 28 days and lung collection at 31 days gestation in fetal rabbits. Lung body weight ratio (LBWR), mean terminal bronchiole density (MTBD), and expression of mRNA and micro-RNA was determined.

Results: Fifteen CDH, …

Measurement And Protection Of Lung Health In Poultry Farmers Of Southwestern Ontario, Rose-Marie Doyon Dolinar

Electronic Thesis and Dissertation Repository

Chronic obstructive lung disease (COPD), develops gradually, and tends to be noticed by farmers only after there has been a significant loss of lung function. People with symptoms of COPD often present for health care in later stages of disease, because they accept cough or breathlessness as “normal”.

Measurement of lung health for those at risk of developing COPD provides an opportunity for early detection of lung disease, and deter the progression toward irreversible damage to the lungs. COPD is, however, under-diagnosed.

The importance of bringing primary care providers and farmers together, and acknowledging the high-risk nature of occupational exposures, …

Detecting A-Series Ganglioside Expression Profile Changes During Microglial Activation, Mona M. Alshaikh

Electronic Thesis and Dissertation Repository

With aging, our brains become more susceptible to disease and injury. Different regions of the brain have differing levels of vulnerability to stress and injury, and this brain region-dependent variability to vulnerability could be partly explained by the existence of glycosphingolipids within the cell’s plasma membrane called gangliosides. Gangliosides are expressed predominantly within the brain and play various roles within the central nervous system including neural repair, cell survival, and neurodegeneration. Our laboratory has demonstrated that gangliosides can shift their composition from GM1 back to GM2 and GM3 following stroke in mice and rats indicating a role for simple gangliosides …

Functional Anatomy Of Palmar Musculature, Colin W. Moore

Electronic Thesis and Dissertation Repository

The palmaris longus (PL) and palmaris brevis (PB) are upper limb muscles considered atavistic remnants of those found in animal species. Despite their use in surgical grafting and tendon transfer procedures, the functional role of the PL and PB have not been investigated comprehensively in vivo. Using a multi-modal experimental approach consisting of indwelling fine wire electromyography (EMG), ultrasonography and immunohistochemical muscle staining techniques, the function of the PL and PB in the hand was evaluated both in in vivo and in situ.

The purpose of Study 1 was to determine whether the PL provides synergistic contributions to …

Teaching Neuroanatomy Virtually: Integrating An Interactive 3d E-Learning Resource For Enhanced Neuroanatomy Education, Lauren Allen

Electronic Thesis and Dissertation Repository

An interactive 3D e-learning module was developed to complement neuroanatomy instruction in both an undergraduate medicine neuroanatomy laboratory course, and an undergraduate systemic human anatomy course. The 3D e-learning resource provided students the opportunity to manipulate a dynamic 3D model to view structures from any desired angle, view deep cortical structures at high magnification, and add interactive structural labels. The study utilized a cross-over design, to separate participants into two groups. Each group completed baseline anatomy knowledge and spatial ability knowledge assessments, followed by access to either the 3D e-learning module or conventional learning resources. Participants completed a post-module anatomy …

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 …

Examination And Assessment Of Commercial Anatomical E-Learning Tools: Software Usability, Dual-Task Paradigms And Learning, Sonya E. Van Nuland

Electronic Thesis and Dissertation Repository

Technological innovation is changing the landscape of higher education, and the competing interests and responsibilities of today’s learners have propelled the movement of post-secondary courses into the online environment. In the anatomical sciences, commercialized e-learning tools have become a critical component for teaching the intricacies of the human body when physical classroom space and cadaveric resources are limited. This dissertation comparatively assessed the impact of two commercial anatomical e-learning tools (1) a simple 2-dimensional e-learning tool (A.D.A.M. Interactive Anatomy) and (2) a complex tool that allows for a 3-dimensional perspective (Netter’s 3D Interactive Anatomy). The comparison was then extended to …

The Neuroprotective Effects Of Endurance Training On The Aging Brain, Katelyn Norton

Electronic Thesis and Dissertation Repository

Dysregulation of autonomic control often develops with advancing age, favoring a chronic state of heightened sympathetic outflow with parasympathetic withdrawal. However, the mechanisms of this age-related autonomic impairment are not known and may relate to alterations in brain structure (e.g. cortical atrophy) and/or altered neural function, particularly in regions related to the cortical autonomic network, namely, the medial prefrontal cortex (MPFC), insula cortex (IC), and hippocampus (HC). Exercise exerts beneficial effects on brain structure and, in the case of cognition, neurologic function; however, how exercise affects regions of the brain related to autonomic function are not known. This thesis tested …

Unravelling The Subfields Of The Hippocampal Head Using 7-Tesla Structural Mri, Jordan M. K. Dekraker

Electronic Thesis and Dissertation Repository

Probing the functions of human hippocampal subfields is a promising area of research in cognitive neuroscience. However, defining subfield borders in Magnetic Resonance Imaging (MRI) is challenging. Here, we present a user-guided, semi-automated protocol for segmenting hippocampal subfields on T2-weighted images obtained with 7-Tesla MRI. The protocol takes advantage of extant knowledge about regularities in hippocampal morphology and ontogeny that have not been systematically considered in prior related work. An image feature known as the hippocampal ‘dark band’ facilitates tracking of subfield continuities, allowing for unfolding and segmentation of convoluted hippocampal tissue. Initial results suggest that this protocol offers sufficient …

Markerless Radiostereogammetry Of The Shoulder Joint In Humans: Comparisons Of Scapulohumeral Kinematics Between Individuals With Healthy And Supraspinatus-Impaired Shoulders, Ashley N. Hannon

Electronic Thesis and Dissertation Repository

The purpose of this collection of studies was to further develop the knowledge of shoulder motion in order to better understand joint function through direct measurement of 3D scapulohumeral joint kinematics using a technique of high accuracy. Markerless, bi-planar fluoroscopic radiostereometric analysis using a generic shoulder model was developed in this thesis, reducing the amount of radiation exposure to subjects. The studies compared kinematic data of the scapulohumeral joint in six degrees of freedom with a precise, in-vivo measuring technique. Data were collected on young and older healthy individuals, individuals with a torn supraspinatus and post-surgical intervention.

Although this generic …

Pulmonary Imaging To Better Understand Asthma, Sarah Svenningsen

Electronic Thesis and Dissertation Repository

Asthma is characterized using the spirometry measurement of the forced expiratory volume in one second (FEV₁). Simple and inexpensive, FEV₁ provides a global estimate of lung function but this metric cannot regionally identify airways responsible for airflow limitation, asthma symptoms or control. Work that brought about an understanding that airway abnormalities are heterogeneously distributed within the lung in asthma patients has motivated the development of pulmonary imaging approaches, such as hyperpolarized helium-3 (³He) and xenon-129 (¹²⁹Xe) magnetic resonance imaging (MRI). These methods provide a way to visualize and quantify lung regions accessed by …

Evaluating The Pathological And Behavioural Consequences Of Injecting Amyloid Beta Oligomers In The Rat, Ryan S. Wong

Electronic Thesis and Dissertation Repository

Alzheimer’s disease (AD) is the most common form of dementia and is characterized by progressive neuronal loss and cognitive decline. Currently, no therapeutic treatments are available and our understanding of the disease progression is still unclear. Amyloid beta oligomers (AβO) are potent neurotoxic proteins and may be a potential initiator of the progression of AD. The purpose of this project was to identify the spatial and temporal consequences of injecting AβO into the rat brain by evaluating pathological and behavioural outcomes. We hypothesized that injecting AβO into the rat brain will result in microglial response as well as behavioural and …

Degrees Of Damage: Quantifying Male Vs. Female Exercise-Induced Muscle Damage Through Magnetization Transfer Ratios, Nicholai Michael Clausius Crawford

Electronic Thesis and Dissertation Repository

No direct, quantitative, and non-invasive markers presently exist to assess exercise-induced muscle damage (EIMD). However, magnetization transfer ratios (MTR), an emerging measurement quantified via magnetic resonance imagery, provide more direct indication of muscle integrity following EIMD. This study compares and correlates the temporal pattern of the MTR to alternative indirect markers of EIMD in male vs. female populations, and subsequently establishes whether there are sex differences in biochemical activity during recovery. The antioxidant properties of estrogen hypothetically minimize muscle trauma, maintain membrane stability, and limit swelling resulting in heightened tissue integrity and resilience to EIMD. Six males and three females …

The Ctcf Chromatin Organizer Is Required For Hindlimb Development, Katherine L. Rabicki

Electronic Thesis and Dissertation Repository

Mutations in chromatin organizer CTCF were identified in patients with intellectual disability and skeletal defects. Previous studies demonstrated that depletion of CTCF in murine limb mesenchyme results in apoptosis in the forelimb. The role of CTCF in the hindlimb, however, is unknown. My objective was to investigate effects of CTCF deletion on chondrogenesis and skeletal development in the hindlimb. In vitro wild-type micromass cultures demonstrate that chondrocyte gene expression is delayed in the hindlimb when compared to forelimbs. Embryonic Ctcf^Fl/Fl;Prx1Cre mice were investigated, and qRT-PCR and histology were performed on limb buds and long bones. Results show that …

Response Of Endothelial Cells To Quantified Hemodynamic Shear Stress, Hamed Avari

Electronic Thesis and Dissertation Repository

Cardiovascular diseases (CVDs) are the number one cause of death globally. Arterial endothelial cell (EC) dysfunction plays a key role in many of these CVDs, such as atherosclerosis. Blood flow-induced wall shear stress (WSS), among many other pathophysiological factors, is shown to significantly contribute to EC dysfunction.

The present dissertation is an in vitro investigation of quantified WSS on ECs to quantitatively analyze the EC morphometric parameters, as well as cytoskeletal remodeling.

A hemodynamic facility based on the parallel plate flow chamber (PPFC) concept. The Laser Doppler Velocimetry (LDV) method with a custom set-up was implemented to suit the needs …

Non-Invasive Quantification Of Alveolar Morphometry Measurements In Older Never-Smokers, Gregory A. Paulin

Electronic Thesis and Dissertation Repository

Diffusion-weighted noble gas pulmonary magnetic resonance imaging (MRI) provides in vivo images with a contrast uniquely sensitive to molecular displacement at cellular and sub-cellular length scales. We estimated the external airway radius (R) and internal airway radius (r) of the alveolar dimensions to evaluate potential differences in acinar duct morphometries in healthy older never-smokers and compared those with a group of ex-smokers. The acinar duct and alveolar MRI morphometry results were within the physiologically-valid range of parameters. Estimated values of internal (r) and external (R) airway radius as well as alveolar sheath (h) and …

The Antisaccade Task: Visual Distractors Elicit A Location-Independent Planning 'Cost', Jesse C. Desimone

Electronic Thesis and Dissertation Repository

Prosaccades are rapid eye movements with direct stimulus and response relations and are designed to bring the fovea onto a target or area of interest. In contrast, antisaccades require the inhibition of a prosaccade and the evocation of a saccade to a target’s mirror-symmetrical location. Previous work has shown that a remote (i.e., midline, contralateral) – but not proximal (i.e., ipsilateral) – task-irrelevant distractor relative to a visual target delays prosaccade reaction times (RT) (i.e., remote distractor effect: RDE). To my knowledge, however, no work has examined whether antisaccade RTs are similarly influenced by a RDE. Accordingly, I sought to …

Surgical Approach In Total Hip Arthroplasty: Patient Outcomes And Impact On Costs, Stephen M. Petis

Electronic Thesis and Dissertation Repository

Total hip arthroplasty is often renowned as one of the most important surgical advances of the past century. Orthopaedic surgeons must choose a surgical approach to gain access to the hip joint in order to perform the reconstruction. There is debate in the literature as to which surgical approach optimizes patient outcomes, minimizes complications, and reduces costs to hospitals as a high volume procedure.

In the current studies, patient reported outcomes were compared at short-term follow-up using a prospective study design across the anterior, posterior, and lateral approach. A micro-costing method was used to acquire costs related to each procedure, …

Functional Anatomy Of The Anconeus: Muscle Architecture And Motor Unit Number Estimation, Daniel E. Stevens

Electronic Thesis and Dissertation Repository

Exploring muscle architecture in vivo and estimating the number of MUs in the human anconeus muscle have important implications related to the neuromuscular function of this muscle as a model for study in health and disease. The two studies presented in this thesis investigate the functional anatomy of the anconeus in 10 healthy young men (25±3y).

Ultrasound imaging has facilitated the measure of the architectural variables, fascicle length (L_F) and pennation angle (PA), in many human skeletal muscles in vivo. However, the functional anatomy of the anconeus has been investigated mainly from cadavers exclusively. Thus, the purpose …

Extracting Vessel Structure From 3d Image Data, Yuchen Zhong

Electronic Thesis and Dissertation Repository

This thesis is focused on extracting the structure of vessels from 3D cardiac images. In many biomedical applications it is important to segment the vessels preserving their anatomically-correct topological structure. That is, the final result should form a tree. There are many technical challenges when solving this image analysis problem: noise, outliers, partial volume. In particular, standard segmentation methods are known to have problems with extracting thin structures and with enforcing topological constraints. All these issues explain why vessel segmentation remains an unsolved problem despite years of research.

Our new efforts combine recent advances in optimization-based methods for image analysis …

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

Electronic Thesis and Dissertation Repository

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

Effects Of Prenatal Testosterone On The Reproductive And Metabolic Neurons Of The Sheep Hypothalamus, Maria Cernea

Electronic Thesis and Dissertation Repository

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders affecting reproductively aged women. Women with PCOS and ewes prenatally exposed to testosterone (T) show similar reproductive and metabolic defects, including anovulatory dysfunctions stemming from abnormal gonadotropin releasing hormone (GnRH) secretion and insulin resistance. For this dissertation, I examined the effects of prenatal T treatment on androgen receptor (AR) and insulin receptor (IR) expression with the reproductive and metabolic neurons of the hypothalamus, the ARC KNDy (co-expressing kisspeptin, neurokinin B/dynorphin), AgRP (agouti-related peptide) and proopiomelanocortin (POMC) neurons, and the preoptic area (POA) kisspeptin neurons, and the GnRH neurons. …

The Role Of Kisspeptin And Kndy Cells In The Reproductive Neuroendocrine System, Christina M. Merkley

Electronic Thesis and Dissertation Repository

The gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus represent the final common output in the central control of reproduction. GnRH secretion is modulated indirectly by steroid feedback action of gonadal steroids on afferent interneurons. In recent years, the neuropeptide, kisspeptin, has emerged as a key mediator of steroid feedback onto GnRH neurons and the reproductive system. Kisspeptin neurons located in the preoptic area (POA) mediate estradiol (E2) positive feedback leading to the preovulatory surge, and kisspeptin cells in the arcuate nucleus (ARC) have been shown to mediate the negative feedback actions of E2 on pulsatile GnRH secretion. ARC kisspeptin neurons …

Biomechanical Modeling For Lung Tumor Motion Prediction During Brachytherapy And Radiotherapy, Zahra Shirzadi

Electronic Thesis and Dissertation Repository

A novel technique is proposed to develop a biomechanical model for estimating lung’s tumor position as a function of respiration cycle time. Continuous tumor motion is a major challenge in lung cancer treatment techniques where the tumor needs to be targeted; e.g. in external beam radiotherapy and brachytherapy. If not accounted for, this motion leads to areas of radiation over and/or under dosage for normal tissue and tumors. In this thesis, biomechanical models were developed for lung tumor motion predication in two distinct cases of lung brachytherapy and lung external beam radiotherapy. The lung and other relevant surrounding organs geometries, …

Anatomy: The Relationship Between Internal And External Visualizations, Ngan T. Nguyen

Electronic Thesis and Dissertation Repository

This dissertation explored the relationship between internal and external visualizations and the implications of this relationship for comprehending visuospatial anatomical information. External visualizations comprised different computer representations of anatomical structures, including: static, animated, non-interactive, interactive, non-stereoscopic, and stereoscopic visualizations. Internal visualizations involved examining participants’ ability to apprehend, encode, and manipulate mental representations (i.e., spatial visualization ability or Vz). Comprehension was measured with a novel spatial anatomy task that involved mental manipulation of anatomical structures in three-dimensions and two-dimensional cross-sections. It was hypothesized that performance on the spatial anatomy task would involve a trade-off between internal and external visualizations available to …

Hearts And Minds: Examining The Evolution Of The Egyptian Excerebration And Evisceration Traditions Through The Impact Mummy Database, Andrew D. Wade

Electronic Thesis and Dissertation Repository

Egyptian mummification and funerary rituals were a transformative process, making the deceased a pure being; free of disease, injury, and disfigurements, as well as ethical and moral impurities. Consequently, the features of mummification available to specific categories of individuals hold social and ideological significance. This study refutes long-held classical stereotypes, particularly dogmatic class associations; demonstrates the apocryphal nature of universal heart retention; and expands on the purposes of excerebration and evisceration implied by synthetic and radiological analyses.

Features of the embalming traditions, specifically the variable excerebration and evisceration traditions, represented the Egyptian view of death. Fine-grain analyses, through primary imaging …