Medicine and Health Sciences Commons^™

Investigation Of Novel Virulence Mechanisms In Candida Albicans, Elisa Marie Tafoya Vesely

Dissertations & Theses (Open Access)

Candida albicans is the most important fungal species associated with humans. Normally present in the human microbiome as a commensal colonizer, C. albicans is also the fourth most prevalent organism isolated from bloodstream infections in hospitals. Disseminated infections have an associated mortality rate of around 40%. The results of the work described in this dissertation cover the broad subject of C. albicans adaptation to the host and the mechanisms by which this organism is able to survive and cause infection through a variety of means. A key determinant in disease progression is interaction with innate immune cells, specifically macrophages and …

Behavioral Insights Into Nociceptor Function: A Systematic Approach To Understanding Postsurgical And Neuropathic Pain Mechanisms In Rats, Max Odem

Dissertations & Theses (Open Access)

Postsurgical and neuropathic pain are each clinically common, and often associated with ongoing pain. Ongoing pain has been linked to ongoing activity (OA) in human C-fiber nociceptors. Preclinical studies using rodent neuropathic models have concentrated on allodynia driven by OA generated in non-nociceptive Aβ fibers, but little attention has been paid to postsurgical pain in sham controls or to C-fiber nociceptor OA promoting ongoing pain.

Operant assays that reveal negative motivational and cognitive aspects of voluntary pain-related behavior may be particularly sensitive to pain-related alterations. In the mechanical conflict (MC) test, rodents can freely choose to escape from a brightly …

Targeting Ph Domain Proteins For Cancer Therapy, Zhi Tan

Dissertations & Theses (Open Access)

Targeted therapy has been one of the most promising treatment options for cancer during the past decade. Discoveries of potent and selective small molecule inhibitors are critical to new and promising targeted therapy. Pleckstrin Homology (PH) domain proteins are one of the biggest protein families in the human proteome. However, no drugs have been achieved to the late development stages, let alone getting to the market. Thus, a deeper understanding of this protein family is required and there is an urgent need to develop novel small molecule compounds targeting these proteins.

Studies of PH domains began around two decades ago …

Changes In The Testes Following Spinal Cord Injury And The Attenuating Effects Of Licofelone, Ryan Fortune

Dissertations & Theses (Open Access)

Spinal cord injury is a devastating disease that researchers have had very limited success in treating. In addition to interrupted innervation, spinal cord injury causes pathologic changes in a multitude of organ systems. Male infertility is one such complication that is particularly devastating because the patient population is predominantly young men. Our lab has previously shown that the blood testis barrier breaks down after spinal cord injury. This dissertation shows the local metabolomic and mRNA changes that spinal cord injury causes within the testes using a Sprague Dawley rat model, including the elevation in eicosanoids, increased oxidative stress, chronically elevated …

Simvastatin Does Not Sensitize Ibc3 Her2+ Inflammatory Breast Cancer Brain Metastases To Whole Brain Irradiation In An Immunocompromised Mouse Model, Swaminathan Kumar

Dissertations & Theses (Open Access)

Retrospective data analysis suggests that inflammatory breast cancer (IBC) patients who take statins have better locoregional control after radiotherapy than those who do not [23]. Our lab has previously demonstrated that simvastatin radiosensitizes IBC cells in vitro [23], and brain metastases have strong expression of cholesterol-regulation genes compared to lung metastases in vivo [unpublished]. Delaying whole-brain irradiation (WBI) beyond 21 days is insufficient to reduce the incidence of brain metastases (developed by injecting IBC3 cells through the tail vein) in our mouse model because even high rates of cell killing leave substantial cell volume in established metastases [unpublished].

With the …

Trichuris Muris Whey Acidic Protein Induces Type 2 Protective Immunity Against Whipworm, Neima Briggs

Dissertations & Theses (Open Access)

Human whipworm (Trichuris trichiura) infects approximately 1 in 15 people worldwide, representing the leading infectious cause of colitis and subsequent, inflammatory bowel disease (IBD). Current control measures focused on mass deworming have had limited success due to low drug efficacies. Vaccination would be an ideal, cost-effective strategy to induce protective immunity, leading to control of infection and transmission. Here we report the identification of whey acidic protein, a whipworm secretory protein, as a strong immunogen for inducing protective efficacy in a surrogate mouse T. muris infection model. The near full-length recombinant WAP protein (rTm-WAP49), as well …

Characteristics Of Individuals Undergoing Panel Genetic Testing For Primary Brain Tumors, Sarah Azam

Dissertations & Theses (Open Access)

Background. Currently, there are no genetic testing guidelines for patients with a primary brain tumor (PBT). This population is largely understudied in terms of the family history, tumor grade, pathology, and their relation to genetic contribution. Our aim was to describe patient-specific characteristics and family histories across mutation-positive, negative, and variant of uncertain significance (VUS) cohorts based on cancer-panel genetic test results among patients with a PBT.

Methods. Subjects were referred for multi-gene panel testing between March 2012 and June 2016. Clinical data were ascertained from test requisition forms. The incidence of pathogenic mutations (including likely pathogenic) and VUS’s were …

Psychiatric Impact Of Tuberous Sclerosis Complex And Utilization Of Mental Health Treatment, Kate Mowrey

Dissertations & Theses (Open Access)

Tuberous sclerosis complex (TSC) is a multi-system, neurocutaneous disorder with neuropsychiatric features known as TSC-associated neuropsychiatric disorders (TAND). While 90% of individuals with TSC have some TAND features, only 20% receive treatment, leading to a 70% treatment gap. This study evaluated perception of disease severity, presence of anxiety and depression, as well as the utilization and barriers towards mental health services among adults with TSC. Disease severity had a moderate and low-moderate association with anxiety and depression, respectively. Regardless of past utilization, respondents had a positive outlook towards the use of mental health services with the major barrier being cost.

Outcomes Of Genetic Testing In A Genitourinary Genetics Clinic, Annelise Pace

Dissertations & Theses (Open Access)

Several known hereditary cancer syndromes confer an increased risk for genitourinary (GU)related malignancies. Various guidelines indicate when to refer patients to genetic counseling for GU-related hereditary cancer syndromes but there is limited research on the clinical picture of these patients, including their cancerous and non-cancerous features, the genetic testing strategy for this population, and the probability of having a positive germline mutation if testing is performed. The purpose of this study is to determine the most common indications for ordering genetic testing in a GU Genetics Clinic and evaluate whether there is a relationship between the indication for genetic testing …