Medicine and Health Sciences Commons^™

Identification Of Dna Methylation Episignatures For Classification And Phenotype/Genotype Correlation In Mendelian Neurodevelopmental Disorders, John Reilly

Electronic Thesis and Dissertation Repository

ABSTRACT: Diagnosis for neurodevelopmental disorders poses numerous challenges, related to the lack of specific findings and limited understanding of clinical impact of the majority of genetic variation. Epigenomics mechanisms involve chemical modifications in DNA that involve a range of cellular mechanisms. DNA methylation is an epigenetic mechanism involving addition and removal of methyl groups to cytosine residues. These methylation signals form episignatures; patterns of methylation that can be used as biomarkers capable of differentiating neurodevelopmental disorders. EpiSigns have enabled molecular diagnosis of a number of genetic conditions, classification of variants of unknown significance, and provided insights into the pathophysiology of …

Investigating The Pathogenesis Of Staphylococcus Aureus In Periprosthetic Joint Infections, Santiago L. Iglesias

Electronic Thesis and Dissertation Repository

The most challenging complication after total joint replacement is the periprosthetic joint infection (PJI). Staphylococcus aureus is a commensal bacterium and a human pathogen. It is responsible for more than half of the PJI. We demonstrated that synovial fluid has antimicrobial properties against S. aureus and the iron restriction is one of the mechanisms used for the host to prevent bacterial growth, and is even able to increase killing of S. aureus. We have shown a clear role of transferrin as a restrictive factor in synovial fluid that functions by iron starving the bacteria and sensitizing them to killing …

Kallikrein-Related Peptidases Are Dysregulated In Pleomorphic Adenoma, Matthew D. Morrison

Electronic Thesis and Dissertation Repository

Objectives: Pleomorphic adenoma (PA) is the most common benign salivary gland tumor. Kallikrein-related peptidases (KLKs) have been identified as biomarkers in many human tumors and may influence tumor behavior. We investigated KLK1-15 messenger ribonucleic acid (mRNA) and proteins in PA specimens to determine a KLK expression profile for this tumor.

Methods: Fresh frozen PA tissue specimens (n = 26) and matched controls were subjected to RT-qPCR to detect KLK1-15 mRNA. Expression of KLK1, KLK12, KLK13 and KLK8 proteins were then evaluated via immunostaining techniques. Statistical analyses were performed with the level of significance set at P < .05.

Results: We observed downregulation …

Determining The Detective Quantum Efficiency (Dqe) Of X-Ray Detectors In Clinical Environments, Terenz R. Escartin

Electronic Thesis and Dissertation Repository

According to Health Canada, dental and medical radiography accounts for more than 90% of total man-made radiation dose to the general population. Ensuring patients receive the health benefits of diagnostic x-ray imaging without use of higher radiation exposures requires knowledge and understanding of the detective quantum efficiency (DQE). Currently, the DQE is not measured in clinics because it requires specialized instrumentation and specific DQE-expertise to perform an accurate analysis. In this regard, the goals of this thesis were to: 1) address the limitations of measuring the DQE in clinical environments that affects the accuracy of the measurement; 2) develop and …

Developments In Pet-Mri For Radiotherapy Planning Applications, John Christian Patrick

Electronic Thesis and Dissertation Repository

The hybridization of magnetic resonance imaging (MRI) and positron emission tomography (PET) provides the benefit of soft-tissue contrast and specific molecular information in a simultaneous acquisition. The applications of PET-MRI in radiotherapy are only starting to be realised. However, quantitative accuracy of PET relies on accurate attenuation correction (AC) of, not only the patient anatomy but also MRI hardware and current methods, which are prone to artefacts caused by dense materials. Quantitative accuracy of PET also relies on full characterization of patient motion during the scan. The simultaneity of PET-MRI makes it especially suited for motion correction. However, quality assurance …

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 …

Hyperpolarized 129xe Magnetic Resonance Imaging Of Radiation-Induced Lung Injury, Ozkan Doganay

Electronic Thesis and Dissertation Repository

Lung cancer is the largest contributor to cancer-related mortality worldwide. Only 20% of stage III non-small cell lung cancer patients survive after 5-years post radiation therapy (RT). Although RT is an important treatment modality for lung cancer, it is limited by Radiation-Induced Lung Injury (RILI). RILI develops in two phases: (i) the early phase (days-weeks) referred to radiation pneumonitis (RP), and (ii) the late phase (months). There is a strong interest in early detection of RP using imaging to improve outcomes of RT for lung cancer. This thesis describes a promising approach based on ¹²⁹Xe gas as a contrast …

Interpretation Of Mutations, Expression, Copy Number In Somatic Breast Cancer: Implications For Metastasis And Chemotherapy, Stephanie Dorman

Electronic Thesis and Dissertation Repository

Breast cancer (BC) patient management has been transformed over the last two decades due to the development and application of genome-wide technologies. The vast amounts of data generated by these assays, however, create new challenges for accurate and comprehensive analysis and interpretation. This thesis describes novel methods for fluorescence in-situ hybridization (FISH), array comparative genomic hybridization (aCGH), and next generation DNA- and RNA-sequencing, to improve upon current approaches used for these technologies. An ab initio algorithm was implemented to identify genomic intervals of single copy and highly divergent repetitive sequences that were applied to FISH and aCGH probe design. FISH …

Analysis Of Invariant Natural Killer T Cells In Intra-Abdominal Sepsis, Ram Venkatesh Anantha

Electronic Thesis and Dissertation Repository

Sepsis is characterized by a severe systemic inflammatory response to infection that is associated with high morbidity and mortality despite optimal care. Invariant natural killer T (iNKT) cells are potent regulatory lymphocytes that can produce pro- and/or anti-inflammatory cytokines, thus shaping the course and nature of immune responses; however, little is known about their role in sepsis. We demonstrate here that patients with sepsis/severe sepsis have significantly elevated proportions of circulating iNKT cells in their peripheral blood, as compared to non-septic patients. We therefore investigated iNKT cells in mice with intra-abdominal sepsis (IAS). Our data show that iNKT cells are …

A Pilot Study To Investigate Concerns In Patients Undergoing Neck Dissection Surgery, Daniel Sundar Raj Arulananda Doss

Electronic Thesis and Dissertation Repository

Abstract:

This study investigates concerns in patients undergoing neck dissection surgery. Forty patients were recruited at Pre-surgery, Discharge and 1-month Post-surgery. The Patient Concerns Inventory - Level of Importance questionnaire (PCI-LOI), Shoulder Pain and Disability Index (SPADI), Neck Dissection Impairment Index (NDII) and the University of Washington - Quality of Life questionnaire (UWQOL) were used.

The study identified "Anxiety" at Pre-surgery and "Appearance" at Discharge and 1-month Post-surgery as the important patient concerns. Patients’ concerns were found to change over time. Support for cross-sectional convergent validity of the PCI-LOI was evidenced by significant correlations between the PCI-LOI and the UWQOL …

An Evaluation Of The Frankfort Mandibular Plane Angle Bisector (Fmab) Wits Appraisal In The Assessment Of Anteroposterior Jaw Relationships, Natalie Swoboda

Electronic Thesis and Dissertation Repository

An accurate anteroposterior measurement of jaw relationships is essential in orthodontic diagnosis and treatment planning. The purpose of this longitudinal study was to establish a new cephalometric Wits appraisal using a bisector of the mandibular plane angle, named the Frankfort Mandibular Plane Angle Bisector (FMAB). The FMAB was used to assess the sagittal jaw relationship in a sample of Class I individuals, and compare this measurement to the ANB angle and the Wits appraisal using the Maxillomandibular Bisector (MMB).

The data were collected from pre-treatment (T0), immediate post-treatment (T1) and two year post-retention (T2) lateral cephalograms of 61 male and …