Medicine and Health Sciences Commons^™

Characterizing The Human Vaginal Microbiome Using High-Throughput Sequencing, Jean Megan E. Macklaim

Electronic Thesis and Dissertation Repository

The human vaginal microbiome undoubtedly has a significant role in reproductive health and for protection from infectious organisms. Recent efforts to characterize the bacterial species of the vagina using molecular techniques have uncovered an unexpected diversity. Using high-throughput sequencing I sought to describe the structure and function of the vaginal microbiome under different physiological states including healthy, bacterial vaginosis (BV), post-menopausal vaginal atrophy, and acute vulvovaginal candidiasis (VVC).

Partial 16S rRNA gene sequencing revealed that healthy, asymptomatic women most often have vaginal biotas dominated by Lactobacillus iners or L. crispatus. In contrast, BV is a heterogeneous, highly diversified condition …

Exploring The Structure And Biochemistry Of Oxidation-Mediated Inhibitation Of The Peptidyl-Prolyl Isomerase Pin1, Brendan T. Innes

Electronic Thesis and Dissertation Repository

Pin1 is a phosphorylation-dependent peptidyl-prolyl isomerase that has been shown to be neuroprotective in aging-related neurodegenerative diseases such as Alzheimer's disease (AD). However, it is not active in AD brain, and a recent proteomic screen of Mild Cognitive Impairment (MCI) brain samples revealed that Pin1 is oxidized in the brains of these pre-AD patients. This suggests that this oxidation may be the cause of the loss of the neuroprotective Pin1 function in AD. The Pin1 active site contains a functionally critical cysteine residue (Cys113) with a low predicted pKa, making it highly susceptible to oxidation. We hypothesize that Pin1 is …

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 …

Prenatal Programming Of Hepatic Glucose And Cholesterol Regulation In Male Rat Offspring By Chronic Intermittent Hypoxia, Waseem Iqbal

Electronic Thesis and Dissertation Repository

Obstructive sleep apnea (OSA) is a chronic disorder involving repetitive interruptions in breathing during sleep. Sufferers of OSA are exposed to chronic intermittent hypoxia (CIH), characterized by cyclical reductions in oxygen availability. A number of studies have established a link between OSA and various cardiovascular and metabolic comorbidities in adulthood, including hypertension, obesity, and type II diabetes. While the consequences of OSA in adults have been well described, the cross-generational impact of this condition and potential effects on fetal development are not known. Epidemiological and animal studies have demonstrated that physiological insults during pregnancy lead to diminished growth of offspring …

Tetraspanin Cd9: Contributions To Cancer Cell And Vascular Cell Phenotypes From The Sixth Man, Michael James Herr Ii

Theses and Dissertations (ETD)

Cancer and vascular disease are the two most predominant causes of mortality in the United States. Potential regulatory mechanisms for these two diseases have consumed research interests. Tetraspanins are cell surface proteins that organize the cell membrane. Cellular membrane organization is a prerequisite for cellular signaling to occur. Deregulation of cellular signaling often precedes the formation of cancer or vascular disease phenotypes. This insinuates the necessity to understand how tetraspanins contribute to membrane organization and subsequent downstream signaling. This work examines tetraspanin CD9 contributions in a model of cancer cell invasion and vascular cell contraction. The findings presented here demonstrate …

Development And Characterization Of A Recombinant Vesicular Stomatitis Virus (Rvsv) For The Treatment Of Glioblastoma, Erika A. Dillard

Theses and Dissertations (ETD)

Background: Over the past 30 years, little has changed in the treatment modalities and prognosis of patients suffering from Glioblastoma multiforme (GBM), the most common and by far the most devastating adult primary malignant brain tumor. Conventional therapies provide only a marginal increase in survival of GBM patients, post-diagnosis. Therefore, more novel means of treating GBM are needed to increase long-term survival and quality of life for those affected. Replication competent oncolytic viruses (OVs) have recently emerged as a possible option for treatment of high-grade gliomas. Particularly, recombinant vesicular stomatitis virus (rVSV), an enveloped, negative strand RNA virus, has shown …

The Staphylococcus Pseudintermedius Adhesin Spsd Contains A Central Fibronectin-Binding Domain, Andrea S. Bordt

Dissertations & Theses (Open Access)

Staphylococcus pseudintermedius is a Gram-positive bacterium significant because of its ability to cause costly and difficult to treat veterinary infections worldwide. It exhibits several similarities to Staphylococcus aureus, however, very little is known about its surface adhesins. Surface adhesins in S. aureus are significant contributors to pathogenesis. S. pseudintermedius encodes the surface protein SpsD, which contains characteristics of the microbial surface components recognizing adhesive matrix molecules family and confers attachment of the heterologous host Lactococcus lactis to fibronectin. This work has identified a centrally-located fibronectin binding domain in SpsD which binds the 30 kDa N-terminal domain of fibronectin with …

Sympathetic Nerve Modulation Of Joint Pathology In Adjuvant-Induced Arthritis, Carlo Anthony Wood

Loma Linda University Electronic Theses, Dissertations & Projects

Background: There is increasing data suggesting a net increase in sympathetic tone plays an important role in rheumatoid arthritis. Several studies have reported altered distribution and density of autonomic nerves in patients with rheumatoid arthritis and animal models for the disease. This provides anatomical evidence that supports a neurally-mediated drive in inflammation and joint destruction. Methods: Adult rats were injected with complete Freund’s adjuvant. At 12 days post immunization, animals were randomly placed into a drug treatment group (SH1293, which interacts with - and ß2-ARs), an adjuvant arthritic group, or a control group. These animals were sacrificed at 14, 21, …

In Vitro Analysis Of Short Chain Fatty Acids And Human Fecal Microbiota Stimulated By Pectin Sources, Byungjick Min

Graduate Theses and Dissertations

As interest increases for colonic health, various studies have been conducted to investigate functional ingredients for host health and prevention of chronic disease in humans such as colon cancer and Type 2 diabetes. In particular dietary fiber has been reported to have beneficial effects on colonic health. More recently, dietary fiber has been categorized based on its characteristics and numerous studies have been conducted to determine correlations with chronic diseases. Pectin is a naturally occurring biopolymer that has been used in various applications for purposes of pharmaceutical and biotechnology. Pectin is a soluble dietary fiber and can be entirely fermented …

The Partial Characterization Of The 142r Protein Of Tanapox Virus, Krystal N. Seibert

Dissertations

Due to the complex nature of cancer, a variety of strategies are being employed to treat patients. Among these are oncolytic viruses that conditionally replicate in tumor cells with specific cellular landscapes. Several viruses including Herpesviruses, Adenoviruses, and Poxviruses, predominantly vaccinia virus (VV), have been explored for their oncolytic potential. Most of these viruses can productively infect a variety of cell types and it is one goal to create conditionally lethal viruses that can only replicate in tumor cells. Due to the prevalence of p53 inactivating mutations in cancers viruses that are restricted to p53 null cells are desirable and …

Scanned Ion Beam Therapy For Thoracic Tumors, John Gordon Eley

Dissertations & Theses (Open Access)

Although frequently cured of Hodgkin lymphoma, adolescents and young adults can develop radiation induced second cancers. These patients could potentially benefit from scanned ion radiotherapy yet likely would require motion mitigation strategies. In theory, four-dimensional (4D) optimization of ion beam fields for individual motion states of respiration can enable superior sparing of healthy tissue near moving targets, compared to other motion mitigation strategies. Furthermore, carbon-ion therapy can sometimes provide greater relative biological effectiveness (RBE) for cell sterilization in a target but nearly equivalent RBE in tissue upstream of the target, compared to proton therapy. Thus, we expected that for some …

Phenotypic, Physiological And Growth Interactions Among Salmonella Serovars, Juliany Rivera Calo

Graduate Theses and Dissertations

This thesis consists of four research parts: a literature review that covers Salmonella spp., one of the more prominent foodborne pathogens that represents a major risk to humans (chapter 1). Understanding the growth of Salmonella serovars and strains is an important basis for more in depth research. In this case we studied a) the aerobic and anaerobic growth responses of multiple strains from six different serovars, b) how the spent media from different serovars, more importantly S. Heidelberg, affect the growth of S. Typhimurium, and c) determined whether or not two different serovars undergo competitive interactions when they were …

Effect Of Electrostatic Spraying Of Food-Grade Organic And Inorganic Acids, And Grape Seed Extract On Salmonella Typhimurium And Escherichia Coli O157:H7 On Spinach And Iceberg Lettuce, Vijayalakshmi Ganesh

Graduate Theses and Dissertations

The safety of fresh produce is often challenged by the sporadic incidences of outbreaks owing to Salmonella Typhimurium (S.T.) and Escherichia coli O157:H7 (E.c.). Washing and current disinfection strategies do not completely decontaminate leafy greens such as spinach and iceberg lettuce. Therefore, more effective treatments are essential to ensure the microbial safety of the produce at the selling point. Here, a multiple hurdle approach was applied: (1) Natural antimicrobials - organic acids (malic, lactic and tartaric acids; MA, LA, TA, respectively) and plant extract (grape seed extract, GSE) and (2) Application method - Electrostatic spraying, was …

Electrostatic Spray Application Of Food-Grade Organic Acids And Plant Extracts To Decrease Escherichia Coli O157:H7 And Salmonella Typhimurium On Select Produce, Leighanna Maeree Massey

Graduate Theses and Dissertations

Both consumers and suppliers have been negatively affected by an increase in foodborne pathogens contaminating fruits. Consequently, there is a need for the development of more efficient antimicrobials and application techniques to decrease contamination. Natural preservatives such as organic acids and plant extracts have demonstrated promising results in decontaminating produce. In addition, the effectiveness of such preservatives may be enhanced by the use of an electrostatic sprayer. The objective of this research was to determine the combinations and concentrations of organic acids and plant extract that were able to reduce Salmonella Typhimurium (ST) and Escherichia coli O157:H7 (EC) inoculated fruits …

A Novel Mechanism Of Enhanced Susceptibility To Bacterial Pneumonia In Influenza-Infected Hosts, Hazem Elsayed Ghoneim

Theses and Dissertations (ETD)

Viruses such as influenza suppress host immune function by a variety of methods. This may result in a significant morbidity through several pathways, including facilitation of secondary bacterial pneumonia from pathogens such as Streptococcus pneumoniae. Lungresident alveolar macrophages (AMs) act as the first line of innate cellular immunity against respiratory bacterial pathogens, including pneumococcus. Therefore, they represent an attractive target for study Before investigating the impact of influenza infection on resident AMs, we first characterized different subsets of lung-resident macrophages in naïve mice using a novel in vivo labeling approach in conjunction with multicolor flow cytometric analysis and confocal microscopic …

Erg11-Mediated Azole Resistance In Candida Albicans, Stephanie Ann Flowers

Theses and Dissertations (ETD)

Although many medically important Candida species are commensal to the gut or colonizers of the skin, these organisms have the propensity to cause disease in the event of a waning immune system. Clinical manifestations of infections with Candida species can range from superficial mucosal infections to deep organ involvement usually resulting from haematogenous spread of infection. Despite significant progress made in the management of patients with fungal infections, the emergence of antifungal resistant clinical isolates creates significant problem in regards to antifungal prophylaxis and empirical treatment strategies. Antifungal resistance is associated with high mortality rates and hefty medical costs. The …

A Comparison Of Prostatic Acid Phosphatase With Testosterone And Prostate Specific Antigen For The Serodiagnosis Of Prostate Cancer In Adult Males, Hannah R. Rice

Honors Theses

Cancer is a hyperplastic cellular malignancy that affected 1,436,000 people (newly diagnosed cases) in the United States last year. The top three most frequent forms of cancer were lung, prostate, and breast. Oncogenesis is associated with both genetic predisposition and environmental onslaught, with a mixture of the two being required for the malignancy to progress. Tumor markers, circulating serum factors, are used in the diagnosis of cancer. Prostate cancer is one of the most prevalent forms of this malignancy, affecting 230,110 men in 2004 alone. Diagnosis of prostate cancer is currently performed using results of an assay for prostate specific …

Attenuation Of Parenteral Nutritionassociated Liver Disease By Omega-3 Long-Chain Polyunsaturated Fatty Acids, Emma Monique Tillman

Theses and Dissertations (ETD)

No abstract provided.

Signal Transduction And Transcriptional Regulation Pathways Essential For Azole Resistance In Candida Albicans, Erin M. Vasicek

Theses and Dissertations (ETD)

Candida albicans is the most prevalent human fungal pathogen, found as a commensal organism in the mucosa, gastrointestinal, and urogenital tracts of humans. This pathogenic fungus causes a wide spectrum of diseases, including the mucosal infection oropharyngeal candidiasis (OPC) which frequently effects patients with human immunodeficiency virus (HIV). The azole antifungals (such as fluconazole) are the most widely used and important ergosterol biosynthesis inhibitors (EBIs) for the treatment of Candida infections, including OPC. However, the azoles are fungistatic against C. albicans and therefore have limited efficacy against this organism, especially for immunocompromised patients. In C. albicans, the transcription factor Upc2 …

Identification Of Novel Hif1a Target Genes That Regulate Tumor Progression And Metastasis, Danielle L. Peacock

Theses and Dissertations (ETD)

Hypoxia is a hallmark of most solid tumors. In response to hypoxic stress tumor cells adapt by regulating survival, metabolism and angiogenesis. The heterodimeric HypoxiaInducible Factor (HIF) transcription factors are the master regulators of this response. HIFs play key roles in many critical aspects of cancer biology including angiogenesis, stem cell maintenance, metabolic reprogramming, invasion, metastasis and resistance to radiation therapy and chemotherapy. Overexpression of HIF-1α and HIF-2α has been documented in multiple human cancers and HIF-1 protein is over-expressed in ~30% of primary breast tumors and ~70% of metastases, which independently correlates with poor prognosis and decreased survival in …

Nkg2d Ligands In Cancer, Neha Das Gupta

Theses and Dissertations (ETD)

NK cell transplantation has been increasingly used to treat cancers that are resistant to chemotherapy. However, not all cancers are susceptible to NK cell killing. The prevalence and mechanisms of NK cell resistance have not been well elucidated. Because NKG2D is a major activating receptor on NK cells, we sought to test the hypothesis that NKG2D is the primary pathway in tumor cell recognition. Herein, we comprehensively assessed 20 cancer cell lines representing a broad array of cancer types. In line with our primary hypothesis, no cancer cell lines that expressed low levels of NKG2D ligands were susceptible to NK …

Toll-Like Receptors 2 And 9 Are Important For Innate Immune Cell Activation And Recruitment In Hypersensitivity Pneumonitis, Kelly J. Andrews

Theses and Dissertations (ETD)

Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by repeated inhalation of environmental antigens. The disease is characterized by alveolitis and granuloma formation; however, some patients develop chronic HP (CHP), a restrictive lung disease characterized by fibrosis. Previous studies revealed that neutrophils are recruited into the lung via a MyD88- dependent pathway and regulate disease severity through cytokine production. Toll-like receptors (TLRs) 2 and 9 recognize conserved molecular patterns present in bacteria, and signal through the adaptor molecule MyD88. The goal of my project is to investigate the role of TLRs 2 and 9 in the pathogenesis of HP …

Radiosensitization Of Head & Neck Carcinoma Cells By Linifanib, A Receptor Tyrosine Kinase Inhibitor, Heng-Wei Hsu

Loma Linda University Electronic Theses, Dissertations & Projects

Tumor angiogenesis is a hallmark of advanced cancers and promotes invasion and metastasis. Over 90% of head and neck squamous cell carcinomas (HNSCC) express angiogenic factors such as vascular endothelial growth factor (VEGF). Since radiotherapy is one of the most commonly used treatments for HNSCC, it is imperative to identify the interactions between antiangiogenic therapy and radiotherapy, and to develop combination therapy to improve clinical outcome. The mechanisms between antiangiogenic agents and ionizing radiation are complicated and involve many interactions between the vasculature, tumor stroma and tumor cells. The proliferation and metastasis of tumor cells rely on angiogenesis/blood vessel formation. …

Identification Of Biomarkers Associated With Ascites Incidence In Broilers, Kaylee Rowland

Graduate Theses and Dissertations

Poultry is key in genetic research due to breeding feasibility, relatively short generation interval, and distinct phenotypes. It is estimated that 8% of broiler deaths annually can be attributed to ascites, an economically important disease that has been challenging the industry for the past 2 decades. Genetically selected ascites resistant (RES) and susceptible (SUS) chicken lines have been established and maintained by the University of Arkansas, Fayetteville. Intensive research efforts have been made to reveal physiological and biochemical characteristics for the incidence of ascites. Since the whole genome of the major ancestral chicken, the Red Jungle Fowl, has been sequenced, …

Measuring The Sixth Vital Sign: A Descriptive Analysis Of Distress In Individuals With Head And Neck Cancer And Their Caregivers, Catherine C. Bornbaum

Electronic Thesis and Dissertation Repository

Introduction: Distress has become so problematic in oncology that it has been recognized as the “sixth vital sign” implying that distress monitoring should occur as routinely as the monitoring of one’s temperature or blood pressure. The research reported herein investigated the impact of head and neck cancer on levels of distress, commonly reported problems, and perceptions of quality of life in individuals with head and neck cancer and their caregivers.

Method: Two distinct studies were conducted; the first explored the patient experience of distress and quality of life while the second assessed the caregiver experience of these same constructs. A …

Image Quality Of Energy-Dependent Approaches For X-Ray Angiography, Jesse Evan Tanguay

Electronic Thesis and Dissertation Repository

Digital subtraction angiography (DSA) is an x-ray-based imaging method widely used for diagnosis and treatment of patients with vascular disease. This technique uses subtraction of images acquired before and after injection of an iodinated contrast agent to generate iodine-specific images. While it is extremely successful at imaging structures that are near-stationary over a period of several seconds, motion artifacts can result in poor image quality with uncooperative patients and DSA is rarely used for coronary applications.

Alternative methods of generating iodine-specific images with reduced motion artifacts might exploit the energy-dependence of x-ray attenuation in a patient. This could be performed …

The Role Of Il-22 Produced By Th17 Cells In Type 1 Diabetes, Stacey M. Bellemore

Electronic Thesis and Dissertation Repository

Interleukin-22 (IL-22) is produced by T helper 17 (Th17) cells. Th17 cells have been shown to be pathogenic in autoimmune diseases, however their role in type 1 diabetes (T1D) remains controversial. We have shown that Th17-differentiation of naïve T cells can be driven by IL-23 + IL-6 to produce large amounts of IL-22 and induce T1D. Conversely, polarizing T cells using TGF-β + IL-6 led to nonpathogenic Th17 cells that produced lower IL-22 levels. We have shown that neutralizing IFN-γ during polarization leads to a drastic increase in IL-22. We have also found IL-22-producing cells in the pancreas of diabetic …

Vascular Stem Cells In Diabetic Complications, Emily C. Keats

Electronic Thesis and Dissertation Repository

Diabetes leads to a variety of secondary complications. At the heart of these complications lies endothelial cells (ECs) – cells that take up unregulated plasma glucose, experience various biochemical alterations, and provide the basis for whole organ vascular dysfunctions. With the purpose of generating new vascular networks for the treatment of these chronic complications, my initial work focused on vascular stem cells (VSCs). VSCs have the ability to differentiate into both endothelial (EPC) and mesenchymal (MPC) progenitor cells, both of which are necessary for the creation of stable and functional blood vessels. To establish whether these progenitor populations retain their …

Risk Factors For Diabetes Mellitus: A Comparative Analysis Of Subpopulation Differences In A Large Canadian Sample, Michael James Taylor

Electronic Thesis and Dissertation Repository

Objectives: Certain Canadian subpopulations observe numerous modifiable and non-modifiable risk factors for diabetes. This study compares immigrants and Aboriginals (First Nations, Inuit, and Métis) with Canada-born individuals at higher risks for diabetes, and deciphers the determinant differences between them.

Methods: Pooled Canadian Community Health Survey data (2001-2010) were used. Time trends for diabetes within each subsample were calculated using individual survey year prevalence rates; diabetes diagnoses were self-reported (N=33,565). Various risk factors were also examined using logistic regression.

Results: Diabetes prevalence rates significantly increased from 2001 to 2010 for each subpopulation, as well as the total sample: Canada-Born individuals (3.9% …

Evaluation Of Matricellular Proteins As Potential Therapeutics For The Treatment Of Human Chronic Skin Wounds, Christopher G. Elliott

Electronic Thesis and Dissertation Repository

There is currently an unmet need for treatments to enhance healing of human chronic skin wounds. Previously, therapy development has focused on growth factors and physical matrices, often resulting in disappointing clinical outcomes. In this thesis, we approached chronic skin wound treatment with a focus on fibrosis and matricellular proteins. Fibrosis is a pathological condition where tissue repair continues, unchecked, resulting in excess contraction, matrix accumulation and fibrogenic growth factor activity; features critically reduced in chronic skin wounds. Identifying factors that promote fibrosis may offer new therapeutic targets for use in chronic skin wounds. Two such factors are the matricellular …