Life Sciences Commons^™

Shedding Light On Hearing In Coma: Investigating The Applicability Of Functional Near-Infrared Spectroscopy For Assessing Auditory Function And Aiding Prognosis In Patients With Acute Disorders Of Consciousness, Reza Moulavi Ardakani

Electronic Thesis and Dissertation Repository

There is a critical need for a bedside neuroimaging tool to aid in the prediction of functional recovery outcomes for patients with acute disorders of consciousness (DoC) in the early days following severe brain injury. Current neurobehavioral examinations and prognosis tools have limitations in predicting good outcomes, leading to potential mistreatment or premature withdrawal of life support. Functional near-infrared spectroscopy (fNIRS) is a viable candidate for such purposes due to its portability and cost-effectiveness. Auditory processing, viewed as a multi-level and multifaceted brain function, could provide a sensitive and specific marker of residual cognitive function in unresponsive patients. This study …

Maturation Of Default Mode Network Functional Connectivity Strength In Utero And The Association With Subcortical Macrostructure: Mapping Brain Ontogeny Supporting Early Cognitive Processing, Susana Correa

Electronic Thesis and Dissertation Repository

The third trimester of gestation is scarcely studied despite this being a key window for the development of learning and memory systems. In a prospective cohort study, 30 pregnant women participated in one or two fetal MR imaging sessions between 28- and 39 weeks of gestational age. Activation time courses were extracted from the default mode (DMN), medial temporal lobe (MTL), and thalamocortical (TCN) networks of the fetal brain. Generalized estimating equations were used to examine the association between the DMN-MTL, DMN-TCV connectivity strength, and subcortical volumes. Increased functional connectivity strength between the DMN-MTL networks was negatively associated with smaller …

Vertebral Endplate Structural Defects: Measurement, Prevalence And Associated Factors, Aliyu Lawan

Electronic Thesis and Dissertation Repository

Objective: To synthesize current knowledge on the association of endplate structural defects (EPSD) with back pain (BP), improve EPSD measurement, and investigate EPSD prevalence, distribution, and association with age and body mass index (BMI).

Methods: In study 1, a systematic review was conducted on five databases for studies reporting on the association between EPSD and BP. Studies 2 and 3 used CTs and mCTs of 19 embalmed cadavers to examine the diagnostic accuracy of common EPSD assessment methods, and to develop and validate a novel method. Study 4 used the novel method on 200 adult males’ MRI to estimate EPSD …

Sarcopenia In Head And Neck Cancer: A Prognostic Analysis, Nedeljko Jovanovic

Electronic Thesis and Dissertation Repository

Introduction: In head and neck cancer (HNC), loss of skeletal muscle mass (SMM), or sarcopenia, is a strong prognostic factor for outcomes. However, inconsistencies in its assessment limit our understanding of the relationship between sarcopenia and nutrition-related outcomes. This project evaluated the significance of sarcopenia as described in the literature and as demonstrated in a cohort of HNC patients.

Methods: A scoping review was first conducted followed by a retrospective cohort study with data collected from 194 oropharyngeal carcinoma patients treated with definitive radiation/chemoradiation. Sarcopenia was assessed from computed tomography (CT) imaging at the third cervical vertebra (C3) and the …

The Clinical Value Of Oculomotor Assessments Across The Continuum Of Concussion, Dillon Richards

Electronic Thesis and Dissertation Repository

Concussions are complex conditions that are difficult to manage medically. Variations in symptom presentation, intricate neurophysiological processes, and the availability of a variety of possible assessment tools may contribute to this complexity. Clinicians must use a broad approach, employing both subjective symptom assessment and objective assessments to confirm a diagnosis and/or monitor progression and recovery. Oculomotor function after concussion may be an important indicator of injury, given the interconnectedness of oculomotor function, vestibulo-ocular and visual systems, and even cognition. Oculomotor function may be assessed objectively or indirectly using patient-reported symptom checklists as part of subjective assessments. One way of objectively …

Myeloarchitectonic Maps Of Cat Auditory Cortex, Austin Robertson

Electronic Thesis and Dissertation Repository

The cerebral cortex contains myriad cortical areas that differ in structure, function, and connectivity. Current methods of delineating cortical structures and their subregions are insufficient for in vivo applications, either being highly invasive or requiring a detailed knowledge of a region’s tuning properties. To address this, we seek to establish a structural biomarker capable of delineating the cortex that possesses a non-invasive correlate. We explore myelin as a potential candidate by evaluating its efficacy in parcellating the feline auditory cortex through the generation of depthwise myelin density profiles for each of the 13 auditory cortical subregions. Our analyses revealed significant …

The Role Of Coagulase-Negative Staphylococcal Secreted Products On Staphylococcus Aureus And Staphylococcus Lugdunensis Infections, Denny Chin

Electronic Thesis and Dissertation Repository

The Staphylococcus genus is comprised of over 40 bacterial species. The most well-studied species in this genus is the notorious human pathogen Staphylococcus aureus, a bacterium that produces coagulase among many other virulence factors. Since S. aureus is a major health burden and causes a plethora of diseases in humans, it has received significant attention and much research has been done to understand its biology to treat diseases caused by this pathogen. However, the coagulase-negative staphylococci (CoNS) make up most of the staphylococcal species and have received less attention since they are thought to have a lesser impact on …

Validation Of Arterial Spin Labeling For Longitudinal Monitoring And Differential Diagnosis Of Frontotemporal Dementia, Tracy Ssali

Electronic Thesis and Dissertation Repository

Frontotemporal dementia (FTD) is a devastating neurodegenerative disease characterized by a rapid decline in behavioural, language, and motor abilities. Advances in the understanding of FTD genetics and pathophysiology, and the subsequent development of novel disease modifying treatments have highlighted the need for tools to assess their efficacy. While structural magnetic resonance imaging (MRI) and functional imaging with ¹⁸F-flurodeoxyglucose (FDG) positron emission tomography (PET) are used for clinical diagnosis, structural changes are subtle at the early stages and PET imaging is expensive and access limited. Given the coupling of cerebral blood flow (CBF) to energy metabolism, an attractive alternative is …

Exogenous Surfactant As A Delivery Vehicle For Intrapulmonary Therapeutics, Brandon J. Baer

Electronic Thesis and Dissertation Repository

As an organ system, the lung has unique advantages and disadvantages for direct drug delivery. Its contact with the external environment allows for the airways to be easily accessible to intrapulmonary delivery. However, its complex structure, which divides into more narrow airways with each branch, can make direct delivery to the remote alveoli challenging. The objective of this thesis was to overcome this issue by using exogenous surfactant, a lipoprotein complex used to treat neonatal respiratory distress syndrome, as a carrier for pulmonary therapeutics. It was hypothesized that therapeutics administered with a surfactant vehicle would display enhanced delivery to the …

Maternal Lifelong Western Diet Consumption Impacts Placental And Brain Development In The Term Guinea Pig Fetus, Carlene H. Cihosky

Electronic Thesis and Dissertation Repository

Both metabolic and cognitive dysfunction can originate from fetal reprogramming precipitating from adverse conditions experienced in utero. Of note is the western diet (WD), which is associated with maternal energy imbalances that may hinder fetal development through altered placental function. Brain-derived neurotrophic factor (BDNF), a growth factor that supports the placenta and developing brain, is responsive to such energy imbalances. This study sought to investigate the impact of lifelong maternal WD consumption on fetoplacental development, focusing on relations between placental changes, and fetal growth and neurodevelopment in a guinea pig model. Maternal WD consumption resulting in a lean metabolically …

21°C Is The Emerging Ideal Temperature For Kidney Preservation In The Presence Of Hydrogen Sulfide, Smriti Juriasingani

Electronic Thesis and Dissertation Repository

Kidney transplantation is the treatment of choice for patients with end-stage kidney disease. However, the shortage of transplantable kidneys has led to ever-increasing waiting lists. As a result, kidneys obtained via donation after cardiac death (DCD) are being used more frequently for transplantation. However, they exhibit poorer outcomes due to ischemia-reperfusion injury (IRI) and cold preservation methods, such as static cold storage (SCS). Supplementing cold preservation solutions with hydrogen sulfide donors, such as AP39, has been shown to improve renal IRI and graft outcomes, but the injury associated with cold preservation remains. This thesis evaluates the effect of subnormothermic kidney …

Interplay Between Shift Work, Psychological Distress, Sleep Quality, And Cognitive Performance, Rea Therese Alonzo

Electronic Thesis and Dissertation Repository

Shift work schedules are designed to maintain a continuous operation of goods and services. However, engaging in shift work may impact cognitive functioning. This thesis assessed the relationship between shift work and cognitive performance. Using cross-sectional data from the Canadian Longitudinal Study on Aging, multiple linear regression models were used to investigate the association between shift work and cognitive performance, as well as the moderating effects of psychological distress and sleep quality. Differences by sex and retirement status were also investigated. Shift work was significantly associated with poor performance for executive functioning but not for declarative memory. Poorer cognitive performance …

Differential Effects Of Kim-1 In Subcutaneous And Orthotopic Renca Models Of Kidney Cancer, Demitra M. Yotis Dy

Electronic Thesis and Dissertation Repository

Renal Cell Carcinoma (RCC) is the most common and fatal type of kidney cancer. Over 30% of patients that are diagnosed with RCC exhibit metastases. Almost 88% of patients with distant metastases succumb to the disease within 5 years of diagnosis. Kidney Injury Molecule-1 (KIM-1) is a cell surface glycoprotein that is not expressed in a healthy kidney but becomes highly expressed on proximal tubular epithelial cells (PTECs) following injury. Data from the Cancer Genome Atlas (TCGA) reveals that >90% of RCC tumours express KIM-1 mRNA and that higher expression levels correlate with increased overall survival rates of patients. The …

Hiv-1 Drug Resistance To Integrase Strand Transfer Inhibitors In Hiv-1 Non-B Subtypes, Emmanuel Ndashimye

Electronic Thesis and Dissertation Repository

Human immunodeficiency syndrome (HIV-1) has infected over 75 million people and over 35 million have succumbed to virus related illnesses. Despite access to a variety of antiretroviral therapy (ART) options, ART programs have been disproportionally spread in the world with low-and middle-income countries (LMICs) facing challenges to access the most potent ART options. With less potent ART remaining in use in LMICs, HIV-1 drug resistance (HIVDR) presents a growing challenge in LMICs. Since approval of the first-generation integrase strand transfer inhibitor (INSTIs), Raltegravir (RAL) in 2007, INSTIs remain the best choice as a backbone of ART. Access to second generation …

Functional Role Of Dream And Dyrk1a In High-Grade Serous Ovarian Cancer Cell Dormancy, Pirunthan Perampalam

Electronic Thesis and Dissertation Repository

High-grade serous ovarian cancer (HGSOC) is the most common form of ovarian cancer. The majority of women are disproportionately diagnosed at an advanced stage (stage III-IV) of the disease when tumours have progressed beyond the ovaries or fallopian tubes and into the peritoneal cavity. Survival rates at late-stage are as low as 25% and chemoresistant disease recurrence is common, affecting up to 90% of patients. Multicellular clusters called spheroids contribute to dormancy, chemoresistance, and metastases and are a major challenge to treatment of HGSOC. Spheroid cells undergo reversible quiescence to evade chemotherapy in a process mediated by the mammalian DREAM …

Evaluating Anesthetic Protocols For Non-Human Primate Functional Neuroimaging, Megha Verma

Electronic Thesis and Dissertation Repository

Functional magnetic resonance imaging (fMRI) is a non-invasive technique that can be used to measure a proxy of neural activity in vivo with high spatial specificity. One subject can be followed for a long period of time to assess changes in functional brain organization. However, fMRI is extremely sensitive to motion. The challenges of training non-human primates to reduce motion in an MRI scanner motivate the study of anesthesia which is commonly used to substitute for this training. In this thesis, I compare three different commonly used anesthetic protocols: isoflurane, propofol-fentanyl in combination, and fentanyl alone, to test which of …

Pan-Cancer Analysis Of Telomerase Reverse Transcriptase (Tert) Isoforms, Mathushan Subasri

Electronic Thesis and Dissertation Repository

Reactivation of the multi-subunit ribonucleoprotein telomerase is the primary telomere maintenance mechanism in cancer, but it is rate-limited by the enzymatic component, telomerase reverse transcriptase (TERT). While regulatory in nature, TERT alternative splice variant/isoform regulation and functions are not fully elucidated and are further complicated by their highly diverse expression. In this thesis, I characterized TERT expression across normal and neoplastic tissues using TCGA and GTEx RNA-sequencing data. In doing so, I demonstrated the global overexpression and splicing shift towards full-length TERT in neoplastic tissue. Furthermore, my studies identified tumour subtype expression differences possibly regulated by subtype-specific characteristics, detailed heterogeneity …

Advanced Phenotyping Of Otosclerosis In An Ontario Population And Two Large Newfoundland Families, Matthew B. Lucas

Electronic Thesis and Dissertation Repository

Otosclerosis is a relatively common hearing loss disorder characterized by abnormal bone growth in the otic capsule leading to stapes fixation. In approximately half of cases, otosclerosis is inherited as an autosomal dominant trait. Typically, gene discovery efforts rely on surgical confirmation, audiometry and occasionally acoustic reflexes to identify affected cases of otosclerosis within families, requiring that the otosclerosis was at an advanced stage to be detected. This makes it difficult to identify individuals with early otosclerosis. The use of advanced phenotyping to identify cases of otosclerosis was tested in an Ontario otosclerotic population as well as in two large …

Neurodevelopmental Outcomes Of Infantile Hydrocephalus: An Fmri Case Study, Ikhlas Ahmed Hashi

Electronic Thesis and Dissertation Repository

Ventricle dilatation caused by infantile hydrocephalus may result in extensive damage of the posterior cortex (parietal and occipital lobes). We hypothesize that pathological changes in the development of the posterior cortex can be linked to non-verbal learning disabilities in children with previous infantile hydrocephalus. This case study will investigate the neurodevelopmental outcomes of 3 treated hydrocephalus patients, when compared to a group of healthy control children (n = 12). Within the hydrocephalus group, patients displayed differences in non-verbal test performance as well as parietal brain activation during an fMRI number comparison task. We associated these differences with clinical variables such …

Maternal Nicotine Exposure Induces Congenital Heart Defects In The Offspring Of Mice, Elizabeth Greco

Electronic Thesis and Dissertation Repository

Congenital heart defects are the most prevalent birth defect, and maternal cigarette smoking is a known risk factor. Nicotine replacement therapies are recommended to pregnant women who smoke to aid in smoking cessation, as this alternative is thought to be much safer compared to cigarette smoking. However, these products contain nicotine, and the safety of nicotine on the developing heart is not well known. In this thesis, a mouse model was used to test the hypothesis that maternal nicotine exposure (MNE) during pregnancy leads to congenital heart defects and coronary artery defects in the offspring of mice. MNE resulted in …

Ultra-High Field Magnetic Resonance Imaging For Stereotactic Neurosurgery, Jonathan Lau

Electronic Thesis and Dissertation Repository

Stereotactic neurosurgery is a subspecialty within neurosurgery concerned with accurate targeting of brain structures. Deep brain stimulation (DBS) is a specific type of stereotaxy in which electrodes are implanted in deep brain structures. It has proven therapeutic efficacy in Parkinson’s disease and Essential Tremor, but with an expanding number of indications under evaluation including Alzheimer’s disease, depression, epilepsy, and obesity, many more Canadians with chronic health conditions may benefit. Accurate surgical targeting is crucial with millimeter deviations resulting in unwanted side effects including muscle contractions, or worse, vessel injury. Lack of adequate visualization of surgical targets with conventional lower field …

Translational Control Of Stress Induced Breast Cancer Plasticity, Michael Jewer

Electronic Thesis and Dissertation Repository

Cancer cell plasticity, whereby stem-cell-like properties are acquired in response to stress, represents a major challenge in cancer treatment. Using cell line and patient-derived xenograft (PDX) models, we demonstrate that translational reprogramming occurs in response to stresses such as hypoxia and chemotherapy which elicits stem cell properties in breast cancer. Other stresses like chemotherapy demonstrate the translational inhibition that has been well characterized as an integral hypoxic cellular response. The inhibition of translation is primarily regulated at initiation by mTOR/4E-BP1 and PERK/eIF2α signalling. We identify previously undescribed 5’ untranslated regions (5’UTRs) of plasticity-associated genes like NANOG, SNAIL and NODAL. …

White Matter Inflammation And Executive Dysfunction: Implications For Alzheimer Disease And Vascular Cognitive Impairment, Alexander Levit

Electronic Thesis and Dissertation Repository

White matter integrity is crucial to healthy executive function, the cognitive domain that enables functional independence. However, in the ageing brain, white matter is highly vulnerable. White matter inflammation increases with age and Alzheimer disease (AD), which disrupts the normal function of white matter. This may contribute to executive dysfunction, but the relationship between white matter inflammation and executive function has not been directly evaluated in ageing nor AD. White matter is also particularly vulnerable to cerebrovascular disease, corresponding with the common presentation of executive dysfunction in vascular cognitive impairment (VCI). Thus, white matter may be an important substrate by …

Effects Of Maternal Protein Restriction On The Pulmonary Surfactant System During The Early Life And Adulthood, Reza Khazaee

Electronic Thesis and Dissertation Repository

Fetal growth restriction (FGR) is defined by low birth weight and contributes to a variety of adult-onset diseases with different severities between males and females. However, the effects of FGR on the pulmonary surfactant are not fully elucidated. In this thesis, first, we investigated the FGR effects on the lung function and the surfactant system at the early postnatal life. It was hypothesized that FGR contributes to alterations of lung mechanics and the surfactant system during the neonatal period. Second, we assessed the FGR effects on the surfactant system in response to sepsis in adulthood. It was hypothesized that FGR …

Impact Of Feeding Tube Status On Health Outcomes For Individuals With Oropharyngeal Cancer, Nedeljko Jovanovic

Electronic Thesis and Dissertation Repository

Abstract

This study investigated differences in outcomes related to health, swallowing, and quality of life (QoL) for individuals with oropharyngeal squamous cell carcinoma (OPSCC) receiving either radiotherapy (RT) alone, or concomitant chemoradiotherapy (CRT). Differences were assessed based on whether patients received a feeding tube (FT group) or not (NFT group). Measures including the Functional Oral Intake Scale (FOIS), Performance Status Scale for Head and Neck Cancer (PSS-HN), M.D. Anderson Dysphagia Inventory (MDADI), and weight were collected for 126 individuals at baseline, and at 3, 6, and 12 months post-treatment. Data were analyzed to identify potential prognostic differences between the groups, …

Working Memory And Falls Risk In Older Adults: An Event-Related Potential Study, Yee (Michelle) S. Wong

Electronic Thesis and Dissertation Repository

BACKGROUND: The aging population is rapidly increasing, where currently in North America, the population of older adults (ages 60+) outnumbers the population of children. Falls are a major concern for older adults and their quality of life. Cognitive impairment has been shown to be declined in older adults at-risk for falls, but working memory has not been thoroughly investigated within this population. PURPOSE: To examine differences in Non-Fallers, Moderate Risk for Falls, and Fallers in a working memory task using electroencephalography (EEG). METHODS: Older adults (n=44, female=27) aged 60 – 80 years (m=68.8, SD=4.7) completed two sessions. The first session …

Characterization Of Urinary Microbiome And Their Association With Health And Disease, Yige Bao

Electronic Thesis and Dissertation Repository

There has been a growing interest in human microbiome studies in the past decade, with the development of high-throughput sequencing techniques. These microorganisms interact and respond to the host as an entity, and are involved in various homeostatic functions including nutrition digestion, immune response, metabolism and endocrine regulation. The urinary microbiome, however, remains relatively under-investigated.

One of the technical challenges of urinary microbiome studies is the samples usually contain a large number of host cells and low microbial biomass. These samples with the high host, low microbial abundance (“high-low” samples) are associated with increased risk of compromised quality of …

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 …

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 …