Medicine and Health Sciences Commons^™

Micellular Electrokinetic Chromatography For Studying Amyloid Beta Oligomer Membrane Affinity, Andrew Bryson

Biomedical Engineering Undergraduate Honors Theses

Amyloid Beta (Aβ) was the major focus of this study. It is a peptide that is present in the brain with a high tendency to self-aggregate. When this protein aggregates, it forms oligomers and protofibrils which in turn are deposited as senile plaques in the brain. The reason for the concern with these plaques is their association with the neurological disorder Alzheimer’s disease. It has been found that the most dangerous oligomers are formed in a portion of the plasma membrane known as lipid rafts. The purpose of this study was to understand how micelles affect the aggregation properties of …

Exploring The Mechanisms Of Action Of Antifungal Peptides Using Saccharomyces Cerevisiae., Michelle L. Mason

Biological Sciences Undergraduate Honors Theses

Candida albicans is a normal inhabitant of the skin and mucosal membranes of humans, however, in individuals with depressed immune systems or disrupted cutaneous flora, Candida can overgrow and cause serious infection. Candida infection is the fourth leading cause of nosocomial infection in the United States. These infections are often associated with longer hospital stays and higher mortality. Current drug therapies for this infection are largely ineffective due to the increased drug resistance of Candida species, and for some therapeutics, high levels of drug toxicity to humans. Histatin 5 is a naturally occurring salivary peptide that has strong antifungal properties. …

The Effects Of Pulmonary Hypertension In Diabetic Zucker Rats On Pulmonary Vascular Contraction And Right Ventricular Size, Michael Franzetti

Biological Sciences Undergraduate Honors Theses

Pulmonary hypertension is a life-threatening disease that is identified by a resting mean pulmonary arterial pressure over 25 mmHg and established by right heart catheterization (Saglam et al., 2015). The symptoms commonly associated with pulmonary hypertension include fatigue, dyspnea, syncope, and chest pain, which severely limit quality of life in diagnosed patients (Saglam et al., 2015). According to recent studies in patients with pulmonary hypertension, the one, three and five year mortality rates are 8%, 25%, and 34%, respectively (Burudpakdee, Shah, Joish, Divers, & Yaldo, 2014). Although some advances have been made in therapies for pulmonary hypertension, the prognosis is …

The Effects Of Patient Education And Knowledge Of Chf Patients As Evaluated By The Paksac Survey, Nabil Tovar

The Eleanor Mann School of Nursing Undergraduate Honors Theses

After diagnosis, management of congestive heart failure (CHF) can pose quite a struggle to many patients, since it requires that lifestyle changes be implemented into their daily life. Patients require the sufficient knowledge and education in order to best manage symptoms and improve their quality of life after being diagnosed. Use of Patient Knowledge of Self-care activities in Congestive Heart Failure^© (PaKSAC) survey in transitional care programs could identify patient gaps in knowledge, as well as decreasing acute care service use. The purpose of this research study was to investigate the knowledge level of CHF patients at the time …

The Effect Of Increased Exposure Of Uvc Light On Human Skin Microbiota, T'Kylia S. Moss

Honors Theses

Many methods have been employed to prevent infections from opportunistic pathogens in immunocompromised individuals. Among these are the use of ultraviolet light (UV). In this study, UVC light, was found to have a deleterious effect on specific skin flora. Organisms tested included Acinetobacter baumanii, Candida albicans, Candida kefyr, Corynebacterium renale, Enterococcus faecalis, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus pyogenes. Nutrient agar was used to cultivate most organisms. Blood agar was used for the cultivation of Streptococcus pyogenes and Enterococcus faecalis. Bacterial suspensions were made and utilized to plate each organism onto a set of 7 nutrient agar or …

Microrna-186 And Metastatic Prostate Cancer., Dominique Zilpha Jones

Electronic Theses and Dissertations

MicroRNA (miR) dysregulation alters cancer-associated gene expression, which contributes to cancer pathogenesis. For example, miR-186 over expression lead to enhanced proliferation and migration in pancreatic cancer cell models. However, the role of miR-186 in prostate cancer (PCa) remains controversial. Previously, miR-186-5p was up-regulated in PCa patient serum (stage III/IV) compared to controls. Furthermore, miR-186-5p was up-regulated in metastatic PCa (PC-3, MDA PCa 2b, LNCaP) relative to normal prostate epithelial cells (RWPE1). We hypothesized miR-186 inhibition will reduce aggressive PCa using metastatic cell models. To test this, we evaluated whether miR-186-5p inhibition would reduce aggressive PCa behavior and overexpression induce malignant …

Stabilization Of Gp120 Outer Domain For Hiv-1-1 Vaccine Immunogen Design, Duoyi Hu

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

The sole envelope glycoprotein spike on the surface of Human Immunodeficiency Virus (HIV-1) is composed of two subunits: gp120 and gp41. The gp120 consists of three domains: the inner domain, outer domain and bridging sheet, to which the viral primary receptor CD4 binds and induces a conformational change in gp120 to expose the co-receptor binding site. Previous studies have found that the outer domain of gp120 is relatively more stable than the inner domain and bridging sheet. When superimposed, the co-crystal structures of CD4-gp120 complex and VRC01-gp120 complex revealed that the CD4-binding site (CD4-BS) antibody VRC01 actually mainly bound to …

Programming Heart Disease: Does Poor Maternal Nutrition Alter Expression Of Cardiac Markers Of Proliferation, Hypertrophy, And Fibrosis In Offspring?, Cathy Chun

Honors Scholar Theses

Maternal malnutrition can affect fetal organogenesis, metabolic processes, and factors involved in developmental regulation. Of the many physiological effects poor maternal nutrition can induce in offspring, one of the most important organs affected is the heart. Cardiovascular disease has been associated with poor maternal diet. It also been suggested that hypertension can originate during impaired intrauterine growth and development. Hypertension can trigger hypertensive heart disease and is associated with numerous heart complications. We hypothesized that poor maternal nutrition would alter critical growth factors associated with normal heart development, specifically, insulin-like growth factor (IGF)-1, IGF-2, transforming growth factor (TGF)β, and connective …

Harnessing Teams And Technology To Improve Outcomes In Infants With Single Ventricle., Girish S. Shirali, Lori A. Erickson, Johnathan Apperson, Kathy Goggin, David D. Williams, Kimberly J. Reid, Andrea Bradley-Ewing, Dawn Tucker, Michael Bingler, John Spertus, Leslie Rabbitt, Richard Stroup

Manuscripts, Articles, Book Chapters and Other Papers

Infants with single ventricle require staged cardiac surgery, with stage I typically performed shortly after birth, stage II at 4 to 6 months of age, and stage III at 3 to 5 years of age. There is a high risk of interstage mortality and morbidity after infants are discharged from the hospital between stages I and II. Traditional home monitoring requires caregivers to record measurements of weight and oxygen saturation into a binder and requires families to assume a surveillance role. We have developed a tablet PC-based solution that provides secure and nearly instantaneous transfer of patient information to a …

Poly (Adp) Ribose Polymerase Inhibitors For The Treatment Of Malignant Peripheral Nerve Sheath Tumor, Christine M. Kivlin

Dissertations and Theses (Open Access)

Malignant peripheral nerve sheath tumor (MPNST) is a rare subtype of soft tissue sarcoma. Surgical excision has remained the standard of care for this highly aggressive malignancy for over a decade. Conventional chemotherapy and radiotherapy have shown limited efficacy in MPNST; therefore, it is imperative that targeted treatment be identified to improve the outcome for MPNST patients. Poly (ADP) ribose polymerase (PARP) inhibitors were first reported over a decade ago to have substantial anti-tumorigenic effects in malignancies with defective DNA repair, specifically those with BRCA1/2 (breast cancer, early onset 1/2) mutations. Further evaluation of these inhibitors has shown multiple mechanisms …

The Roles Of Malt1 In Nf-Κb Activation And Solid Tumor Progression, Deng Pan

Dissertations and Theses (Open Access)

The transcription factor NF-κB plays a central role in many aspects of biological processes and diseases, such as inflammation and cancer. Although it has been suggested thatNF-κB is critical in tumorigenesis and tumor progression, the molecular mechanism by which NF-κB is activated in solid tumor remains largely unknown. In the current work, we focus on growth factor receptor-induced NF-κB activation and tumor progression, including epidermal growth factor receptor (EGFR)-induced NF-κB in lung cancer and heregulin receptor (HER2)-induced NF-κB in breast cancer. We found that Mucosa-associated lymphoma translocation protein 1 (MALT1), also known as paracaspase, is required for EGFR-induced NF-κB activation …

Cll Metabolism Is Regulated By Prognostic Factors, Modulated By Stroma And Abrogated By Pi3k Inhibition, Hima Vangapandu

Dissertations and Theses (Open Access)

Metabolism of chronic lymphocytic leukemia (CLL), a disease characterized by the relentless accumulation of mature B cells has been little explored. Bone marrow stromal cells provide a survival benefit to CLL cells, in part through PI3K/AKT pathway. Compared with proliferative B-cell lines, metabolic fluxes of oxygen and lactate were low in quiescent malignant B lymphocytes from CLL patients. Glycolysis (extracellular acidification rate, ECAR) was consistently low in CLL samples, but oxygen consumption (OCR) varied considerably. Higher OCR was associated with poor prognostic factors such as ZAP 70 positivity, unmutated IgVH, high β2M levels, and higher Rai stage. Co-culture with the …

Clinical And Demographic Variables Associated With Cognitive Deficits, Symptom Severity, And Duration After Concussive Injury In Adolescents: A Retrospective Study, Seema S. Aggarwal

Dissertations and Theses (Open Access)

Background: Concussions in adolescents are a public health concern with the growing popularity of high school sports. Recent legislation mandates that athletes who are suspected of a concussion be cleared to return-to-play by a clinician. More research is needed to develop a concussion predictive model to identify populations at risk for more severe and prolonged symptoms and long-term neurologic deficits.

Aims: The aims of this study were to (1) examine the effect of race and gender on neurocognitive and symptom scores and (2) determine which clinical (e.g., number of concussions, migraine history, learning disabilities/ attention deficit disorders) and demographic factors …

Epidemiological Characteristics Of Clinically-Confirmed Cases Of Chikungunya In Teculutan, Guatemala, Annaly Aldana

Senior Honors Projects

As no vaccine currently exists for the Chikungunya virus (CHKV), mosquito control and efficient public health campaigns are crucial for the prevention of disease propagation. The purpose of this research project is to identify populations particularly at-risk for acquiring Chikungunya, and to explore the role that cultural attitudes may play in impacting mosquito-borne disease. Due to its geographical structure and climate, Guatemala is an ideal territory for the spread of emerging and re-emerging mosquito-borne diseases. This project was developed by collaborating with the public governmental health clinic in the municipal town of Teculután, in the department of Zacapa in Guatemala. …

Diffusion Modeling And Device Development For Peritoneal Membrane Oxygenation, Liana Hatoum

Department of Mechanical and Materials Engineering: Dissertations, Theses, and Student Research

Acute respiratory distress syndrome (ARDS) is a pulmonary disease that causes hypoxemia and respiratory failure. The mortality rate for ARDS ranges between 27% and 45%. Current treatments including mechanical ventilation and extracorporeal membrane oxygenation (ECMO) are often associated with high risk complications including barotrauma, infection, thrombosis, and hemorrhage. Alternative pulmonary support techniques are needed to improve the survival rate of patients suffering from ARDS. Previous studies introducing pure O₂ gas, perfluorocarbons and red blood cells into the intraperitoneal (IP) cavity have reported no effect or only a mild increase in oxygenation. Here we report peritoneal membrane oxygenation (PMO) using …

Facilitators And Barriers To Ncd Prevention In Pakistanis-Invincibility Or Inevitability: A Qualitative Research Study., Ambreen Gowani, Hafiz Imtiaz Ahmed, Wardah Khalid, Abdul Muqeet, Saad Abdullah, Shariq Khoja, Ayeesha Kamran Kamal

Department of Medicine

Background: Non-communicable diseases (NCD) are the leading causes of death globally. In Pakistan, they are among the top ten causes of mortality, especially in the productive age group (30–69 years). Evidence suggests that health perceptions and beliefs strongly influence the health behavior of an individual. We performed focus group interviews to delineate the same so as to design the user interface of a non-invasive stroke risk monitoring device.

Methods: It was a qualitative study, designed to explore how health perceptions and beliefs influence behavior for NCD prevention. Four focus group discussions (FGD) were conducted with 30 stable participants who had …

Lesion Identification And The Effect Of Lesion On Motor Mapping After Stroke, Ruixi Zhou

McKelvey School of Engineering Graduate Student Theses & Dissertations

Stroke is the most common cause of long-term severe disability and the motor system that is most commonly affected in stroke. One of the mechanisms that underlies recovery of motor deficits is reorganization or remapping of functional representations around the motor cortex. This mechanism has been shown in monkeys, but results in human subjects have been variable. In this thesis, I used a database that includes longitudinal behavioral and multimodal imaging data in both stroke patients and healthy controls for two research projects. Firstly, I improved an automatic lesion segmentation method to aid in the identification of the location and …

Novel Oncogenic Drivers In Pediatric Gliomagenesis, Alexander K. Diaz

Theses and Dissertations (ETD)

Pediatric high-grade gliomas (pHGGs), with a two-year survival rate of less than 20%, are some of the most aggressive human cancers. This dissertation begins with our analysis of 127 pHGGs, including brainstem (BS) and non-brainstem (NBS) tumors, from 118 patients using next-generation sequencing technologies. Nearly one-third of BS-HGGs, also known as diffuse intrinsic pontine gliomas (DIPGs), harbored somatic heterozygous missense mutations in ACVR1, coding for a receptor serine-threonine kinase involved in bone morphogenetic protein (BMP) signaling. These alterations led to gain-of-function as evidenced by increased phosphorylation of downstream targets in primary astrocytes and zebrafish embryo ventralization. Whole-genome sequencing and …

The Role Of Drak2 In T Cell Function And Autoimmunity, Tarsha L. Harris

Theses and Dissertations (ETD)

The immune system utilizes many regulatory mechanisms to limit immune responses and ensure that immune cells target foreign pathogens and not healthy cells of the body. However, some immune cells can escape these checkpoints and attack the body’s healthy cells, leading to tissue destruction and devastating autoimmune disorders. For example, multiple sclerosis (MS) occurs when immune cells attack the myelin sheath surrounding neurons of the central nervous system (CNS). Likewise, the destruction of pancreatic islet cells by dysregulated immune cells leads to type 1 diabetes (T1D). Remarkably, there are more than 80 types of autoimmune diseases. An estimated 50 million …

Antibodies To Heterogenous Nuclear Ribonucleoprotein A1 Penetrate Neurons Leading To Multiple Downstream Effects Resulting In Neurodegeneration, Joshua Nathan Douglas

Theses and Dissertations (ETD)

Multiple sclerosis (MS) is the most common demyelinating disorder of the central nervous system. MS is believed to occur in genetically susceptible individuals due to an unknown environmental stimulus. MS patients produce autoantibodies to heterogenous nuclear ribonuclearprotein A1 (hnRNP A1), an RNA binding protein (RBP) highly expressed in neurons. hnRNP A1 functions in pre-mRNA splicing, mRNA trafficking, and translation. Furthermore, the anti-hnRNP A1 antibodies are specific to a N-terminal region termed ‘M9’ which serves as a nuclear export sequence/nuclear localization sequence (NES/NLS) responsible for nuclear/cytoplasmic transport of the protein. In this manuscript we will provide data revealing that anti-hnRNP A1 …

Hit Identification For Pkcζ Inhibitors: Structure-Based Optimization, Virtual Screening, And Biological Evaluation, Xiaoxin Wu

Theses and Dissertations (ETD)

Protein kinase C ζ (PKCζ) is believed to be a promising target for the treatment of some diseases, including inflammatory diseases, obesity and diabetes. Hit identification of PKCζ inhibitors was conducted by structure-based modification, virtual screening and biological evaluation. Among all the compounds selected and synthesized, compound JW-1-60A showed moderate activity against PKCζ at 30 μM and 100 μM. The molecular modeling studies showed that the binding mode of JW-1-61A was very close to the binding mode of JP-3-149, a reported PKCζ inhibitor with very potent activity, which might partially explain the moderate activity of JW-1-61A. Based on the structure …

Assessment Of The Zoonotic Potential Of A Novel Bovine Influenza Virus, Laura Evelyn Eckard

Theses and Dissertations (ETD)

A novel orthomyxovirus was recently identified from pigs, with subsequent work suggesting the natural reservoir being bovine populations. The virus had genome characteristics most similar to influenza C viruses (ICV) but, due to the extent of sequence divergence, was proposed as a new genus, influenza D virus (IDV). Current literature on IDV has largely focused on the agricultural significance of the virus and provided evidence for the agricultural impact via observation of widespread prevalence and pathology in laboratory infected cattle. However, only one study, which identified 1.3% seroprevalence in a small cohort, has addressed the zoonotic potential of IDV to …

Pten Signaling In Regulatory T Cells And Inflammatory Disease, Sharad Krishna Shrestha

Theses and Dissertations (ETD)

Regulatory T (Treg) cells suppress CD4+ T cell responses during homeostasis and inflammation to prevent autoimmunity and other immune disorders. Although the transcriptional and epigenetic programs impacting Treg cell function have been extensively studied, the signaling and metabolic pathways underlying Treg stability and function are not fully understood. In this study, we determined the role of the phosphatase PTEN in Treg cells. We found that specific depletion of PTEN in Treg cells results in excessive TH1 and T follicular helper cells (TFH) responses, associated with elevated germinal center (GC) B cells and spontaneous development of autoimmune and lymphoproliferative disease in …

A Molecular Approach To Understanding The Effects Of Original-Xpc On The Modulation Of The Cecal Microbiota And The Survival Of Salmonella In The Poultry Host, Stephanie Roto

Graduate Theses and Dissertations

Salmonella is a foodborne pathogen commonly associated with poultry products; the economic burden to the U.S. is estimated to be approximately $693 million (without factoring in contaminated eggs). Recently, there has been pressure to withdraw sub-therapeutic levels of antibiotics (also known as antibiotic growth promoters; AGP) from poultry due to concern over antibiotic-resistant bacteria spreading to the human population. Therefore, various feed additives have been researched for their ability in providing protection against harmful pathogens and their potential growth promoting effects, both of which were attributes of poultry treated with AGP. This thesis consists of a comprehensive literature review that …

Effect Of Passive Heating On Males And Females With Elevated Arterial Stiffness, Forrest Blake Robinson

Graduate Theses and Dissertations

Context: Cardiovascular disease (CVD) is one of the leading causes of mortality in the United States, accounting for about 1 in every 4 deaths annually. Studies have shown that passive heating does have some degree of effect on arterial stiffness, but not much is known about populations with higher stiffness. Objective: To examine the independent effect of core temperature increase during passive heating on arterial stiffness. Methods: Participants visited the lab three times; one familiarization and two experimental trials. The experimental trials consisted of subjects being passively heated in an environment of 40°C / 40% relative humidity (HEAT) or normal …

Association Of Ecological Factors With Rift Valley Fever Occurrence And Mapping Of Risk Zones In Kenya, Gladys Mosomtai, Magnus Evander, Per Sandström, Clas Ahlm, Rosemary Sang, Osama Ahmed Hassan, Hippolyte Affognon, Tobias Landmann

All Peer-Reviewed Publications

Objective: Rift Valley fever (RVF) is a mosquito-borne infection with great impact on animal and human health. The objectives of this study were to identify ecological factors that explain the risk of RVF outbreaks in eastern and central Kenya and to produce a spatially explicit risk map. Methods: The sensitivity of seven selected ecological variables to RVF occurrence was assessed by generalized linear modelling (GLM). Vegetation seasonality variables (from normalized difference vegetation index (NDVI) data) and 'evapotranspiration' (ET) (metrics) were obtained from 0.25-1 km MODIS satellite data observations; 'livestock density' (N/km2), 'elevation' (m), and 'soil ratio' (fraction of all significant …

Health Behaviors And Their Correlates Among Participants In The Continuing To Confront Copd International Patient Survey, Hana Müllerová, Sarah H. Landis, Zaurbek Aisanov, Kourtney J. Davis, Masakazu Ichinose, David M. Mannino, Joe Maskell, Ana M. Menezes, Thys Van Der Molen, Yeon-Mok Oh, Maggie Tabberer, Meilan K. Han

Preventive Medicine and Environmental Health Faculty Publications

Background and aims: We used data from the Continuing to Confront COPD International Patient Survey to test the hypothesis that patients with COPD who report less engagement with their disease management are also more likely to report greater impact of the disease.

Methods: This was a population-based, cross-sectional survey of 4,343 subjects aged ≥ 40 years from 12 countries, fulfilling a case definition of COPD based on self-reported physician diagnosis or symptomatology. The impact of COPD was measured with COPD Assessment Test, modified Medical Research Council Dyspnea Scale, and hospital admissions and emergency department visits for COPD in the prior …

The Emergence Of The Zika, Chikungunya, And Dengue Viruses In Brazil, The Dominican Republic, And Puerto Rico, Nelson Xavier Del Pilar

Honors Scholar Theses

The Zika, Chikungunya, and Dengue viruses are three emerging viral infections of the 21st century. Outbreaks have occurred in twenty countries, including areas of South America, and territories in the Caribbean. These viral diseases are mosquito-borne infections transmitted primarily by Aedes aegypti and Aedes albopictus mosquitoes. The origins of the diseases, viral morphology, and vector transmission will be described in this review as well as symptoms that humans experience, medical testing procedures, and preventative measures. This study will focus on three locations: Brazil, the Dominican Republic, and Puerto Rico. There are many similarities between the three viruses to emphasize, but …

Virus-Host Co-Evolution: Determining The Origin Of Human Cytomegalovirus Us27 And Us28, Jessica A. Scarborough, Juliet Spencer, John Paul

Creative Activity and Research Day - CARD

G protein-coupled receptors (GPCR) are the largest family of cell surface proteins, found in organisms from yeast to humans. Human cytomegalovirus (HCMV) is a widespread pathogen that is particularly skilled at evading immune detection and defense mechanisms, largely due to extensive co-evolution with its host’s immune system. One aspect of this co-evolution involves the acquisition of four virally encoded GPCR homologs: US27, US28, UL33 and UL78. In this research, phylogenetic analysis was used to investigate the origins of the US27 and US28 genes, which are adjacent in the viral genome. The results indicate that both US27 and US28 share the …

Torn Between Two Diseases: Changes In Tgfβ Signaling Prevents Diabetes But Promotes Neuropathy, Vasalya Panchumarthi

Creative Activity and Research Day - CARD

Type 1 diabetes (T1D) is an autoimmune disease that affects millions of children and adults worldwide. In this disease, white blood cells (Leukocytes) invade, attack, and destroy the Islets of Langerhans in the pancreas, resulting in increased blood glucose levels. Patients with T1D must use exogenous insulin injections, which can lead to many side effects over the lifespan of the person. Therefore, understanding the pathogenesis of this disease is crucial to develop new treatments for patients. The non-obese diabetic (NOD) mouse is a rodent model of T1D as well as other autoimmune diseases such as Sjogren’s syndrome, where immune cells …