Medicine and Health Sciences Commons^™

The Effect Of Standard Dose Multivitamin Supplementation On Disease Progression In Hiv-Infected Adults Initiating Haart: A Randomized Double Blind Placebo-Controlled Trial In Uganda., David Guwatudde, Molin Wang, Amara E. Ezeamama, Danstan Bagenda, Rachel Kyeyune, Henry Wamani, Yukari C. Manabe, Wafaie W. Fawzi

Journal Articles: Epidemiology

BACKGROUND: Efficacy trials investigating the effect of multivitamin (MV) supplementations among patients on Highly Active Antiretroviral Therapy (HAART) have so far been inconclusive. We conducted a randomized, double blind, placebo controlled trial to determine the effect of one recommended daily allowance (RDA) of MV supplementation on disease progression in patients initiating HAART.

METHODS: Eligible subjects were randomized to receive placebo or MV supplementation including vitamins B-complex, C and E. Participants were followed for up to 18 months. Primary endpoints were: change in CD4 cell count, weight and quality of life (QoL). Secondary endpoints were: i) development of a new or …

Effect Of Chemical Pocket Disinfection As An Adjunct To Non-Surgical Maintenance Therapy Of Inflamed Periodontal Pockets, Chad Riggs

Theses & Dissertations

Purpose: Scaling and root planing with adjunctive chemical pocket disinfection (SRP+C) utilizing sodium hypochlorite solution has been used to treat inflamed pockets of periodontal maintenance patients for many years, without evidence of its benefits. The primary objective was to determine if SRP+C is more effective than scaling and root planing alone (SRP) in improving clinical outcomes. The secondary objective was to compare the effect of SRP+C and SRP on pro-inflammatory IL-1β, anti-inflammatory IL-1ra, and anti-inflammatory index (IL-1ra/IL-1β ratio) found in gingival crevicular fluid (GCF).

Materials and Methods: Pockets (≥ 5 mm and BOP) of 31 maintenance patients were included. Test …

Use Of Smartphones To Capture Measures Of Functional Status In Frail And Non-Frail Community Dwelling Older Adults, Cassia R. Hanton

Theses & Dissertations

Numerous important health outcomes directly relate to one's ability to maintain normal gait speed. The purpose of this study is to employ ubiquitous smartphone technology, using algorithms developed and validated by our lab in a controlled setting, to continuously and noninvasively measure aspects of subject health status, including step counts, gait speed, and activity level, in a naturalistic community setting. A total of 33 ambulatory, independently dwelling older adults were recruited from Nebraska Medicine, including 22 healthy control and 11 frail individuals. Clinical performance measurements of frailty (4MW, TUG, F8W) and validated survey responses (LLFDI, SAFFE, PROMIS) were compared to …

Development Of Hypoxia Trapping Enhanced Bb2r-Targeted Radiopharmaceutics For Prostate Cancer, Zhengyuan Zhou

Theses & Dissertations

The Gastrin-Releasing Peptide Receptor (BB2r) has been investigated as a diagnostic and therapeutic target for prostate and other cancers due to the high expression level on neoplastic relative to normal tissues. A variety of BB2r-targeted agents have been developed utilizing the bombesin(BBN) peptide, which has shown nanomolar binding affinity to human BB2r. However, as with most of the low-molecular weight, receptor-targeted drugs, a major challenge to clinical translation of BB2r-targeted agents is the low retention at the tumor site due to intrinsically high diffusion and efflux rates. Our laboratory seeks to address this deficiency by developing synthetic approaches to selectively …

Targeted Magnetite Tissue Delivery For Antiretroviral Pharmacokinetics, Tianyuzi Li

Theses & Dissertations

Pharmacokinetics and pharmacodynamics studies are required for bench to bedside translation of any new drug, formulation or device. Multifunctional magnetite nanocarriers enable magnetic resonance imaging tracking of nanomaterial encased antiretroviral drugs serving to improve the effectiveness of formulation developments. Targeting ligands used to deliver nanoparticles to HIV harboring cells can be tested using multifunctional magnetite nanocarriers. To this end, two types of magnetite nanocarriers were developed. These included small magnetite antiretroviral therapy particles. The second were ALN-PEG coated magnetite particles for testing macrophages targeting ligands. Overall, these works should serve to speed the development of long acting nanoformulated ART to …

Improving Antibiotic Resistant Infection Transmission Situational Awareness In Enclosed Facilities With A Novel Graphical User Interface For Tactical Biosurveillance, Valeriya V. Kettelhut

Theses & Dissertations

Serious challenges associated with antibiotic resistant infections (ABRIs) force healthcare practitioners (HCP) to seek innovative approaches that will slow the emergence of new ABRIs and prevent their spread. It was realized that traditional approaches to infection prevention based on education, retrospective reports, and biosurveillance often fail to ensure reliable compliance with infection prevention guidelines and real-time problem solving. The objective of this original research was to develop and test the conceptual design of a situational awareness (SA)-oriented information system for coping with healthcare-associated infection transmission.

Constantly changing patterns in spatial distribution of patients, prevalence of infectious cases, clustering of contacts, …

The Role Of Glutaminase 1 In Hiv-1 Associated Neurocognitive Disorders And In Brain Development, Yi Wang

Theses & Dissertations

Glutaminase is the enzyme that converts glutamine into glutamate, which serves as a key excitatory neurotransmitter and one of the energy providers for cellular metabolism. Glutamate is essential for proper brain functioning but at excess levels, it is neurotoxic and has a key role in the pathogenesis of various neurodegenerative diseases, including HIV-1 associated neurocognitive disorders (HAND). However, the detailed mechanism of glutamate-mediated neurotoxicity remains unclear. In part I, we identified the regulation of glutaminase 1 (GLS1) in the central nervous system (CNS) of HAND animal models including HIV-Tat transgenic (Tg) mouse and HIVE-SCID mouse, since GLS1 is the dominant …

Polymeric Nanocarriers For Treatment Of Melanoma And Genetically Modified Mesenchymal Stem Cells To Improve Outcome Of Islet Transplantation, Vaibhav Mundra

Theses & Dissertations

Melanoma is a lethal malignancy with limited treatment options for advanced metastatic stages. New targeted therapeutic options with discovery of BRAF and MEK inhibitors have shown significant survival benefit. Despite the recent progress, inefficient tumor accumulation and dose limiting systemic toxicity remains pressing challenges for treating metastatic melanoma and there is a need for drug delivery approach to improve therapeutic index of chemotherapeutics. Nanoparticle based drug delivery represents promising approach to enhance efficacy and reduce the dose limiting systemic toxicity. Nanoparticles can be formulated either by physical encapsulation of drugs or by covalent conjugation of drugs to the polymeric backbone. …

Ccr5 And The Blood Brain Barrier During Hiv-1 Infection And Cell-Cell Communications, Shawna M. Woollard

Theses & Dissertations

Human Immunodeficiency Virus (HIV-1) infection often results in blood-brain barrier (BBB) dysfunction and central nervous system (CNS) impairment. Since most viral strains that cross the BBB and enter the CNS are macrophage-tropic and use the C-C chemokine receptor type-5 (CCR5) to enter and infect target cells, we hypothesized that CCR5 plays a major role in monocytes-endothelial interactions and HIV-induced BBB dysfunction. Because the cytoskeleton is responsible for cellular morphology and motility, we further hypothesized that HIV-induced monocyte-endothelial interactions and transendothelial migration involve cytoskeletal changes and that CCR5 blockers would also affect these changes. To this end we used two small …

Prevention Of Experimental Periodontitis In Rats With A Simvastatin Prodrug, Aaron Bradley

Theses & Dissertations

Introduction: Simvastatin (SIM) is a hypolipidemic drug that has been shown to have anti-inflammatory and bone anabolic properties. The aim of this study was to examine the effects of novel locally-applied SIM conjugated with methoxypolyethylene glycol to form micelles (SIM/SIM-mPEG) in an experimental periodontitis model in rats using micro-computed tomography (µ-CT) and histologic evaluation.

Methods: Experimental periodontitis was induced using silk ligatures around the maxillary right second molar (M2) in 40 Sprague-Dawley rats. Rats were divided into five groups using SIM/SIM-mPEG at 0.5, 1.0, or 1.5 mg SIM doses, mPEG-alone or no drug (ligature-alone) injected into the palatal M1-M2 gingiva …

Electronic Health Record Optimization For Cardiac Care, Lisa A. Grabenbauer

Theses & Dissertations

Electronic health record (EHR) systems have been studied for over 30 years, and despite the benefits of information technology in other knowledge domains, progress has been slow in healthcare. A growing body of evidence suggests that dissatisfaction with EHR systems was not simply due to resistance to adoption of new technology but also due to real concerns about the adverse impact of EHRs on the delivery of patient care. Solutions for EHR improvement require an approach that combines an understanding of technology adoption with the complexity of the social and technical elements of the US healthcare system. Several studies are …

Psychiatric Comorbidities And Bmi: An Exploratory Analysis, Nicholas Guenzel

Theses & Dissertations

Background: Individuals with most forms of mental illness have higher rates of obesity than members of the general public putting them at an increased risk for many physical health problems that reduce both quality of life and life expectancy. The presence of multiple comorbid psychiatric disorders has been associated with poorer clinical outcomes in other mental health measures such as disability and sobriety and is proposed as a risk factor for elevated BMI (body mass index) in this study.

Objective: Determine if multiple psychiatric comorbidities are associated with elevated BMI and, if so, which combinations are linked with the greatest …

Physical Activity Behaviors Of Prehypertensive And Stage I Hypertensive African American Women, Hope Jackson

Theses & Dissertations

The purpose of this study was to describe the physical activity (PA) behaviors and PA biomarkers of prehypertensive and stage I hypertensive African American women (AAW) and to examine the relationships between PA and personal factors and selected behavior-specific influences (perceived barriers to and interpersonal support for PA). Pender’s Health Promotion Model was the conceptual framework for the study.

A cross sectional design and convenience sample were used. Personal factors examined were: systolic and diastolic blood pressure [BP], body mass index [BMI], and waist circumference. Other variables measured were: International Physical Activity Questionnaire, 400 meter walk test, Borg perceived exertion …

Risk Factors For Agricultural Injury: An Evaluation Using Systematic Review And Injury Surveillance, Rohan Mahadeo Jadhav

Theses & Dissertations

Purpose- Agriculture is the most hazardous industry in the United States. The effectiveness of intervention programs for injury prevention can be improved by acquiring knowledge of risk factors for occupational injury in agricultural operators. The landscape of agriculture is changing in the U.S. Agricultural populations, environments and risk factors are changing as well with the changes in the structure of farms and ranches. The objective of this study was to identify significant risk factors for agricultural injury based on the literature and three years of injury surveillance data covering seven U.S. states. Methods- We conducted a systematic review of reported …

School Design To Promote Physical Activity, Jeri Brittin

Theses & Dissertations

Increasing children’s physical activity (PA) at school is a national focus to address childhood obesity. Research has demonstrated associations between school built environments and students’ PA, but has lacked a comprehensive synthesis of evidence. Chapter 1 presents new evidence-, theory-, and practice-informed school design guidelines, including evidence substantiality ratings, to promote PA in school communities. These guidelines delineate strategies for school designers, planners, and educators to create K-12 school environments conducive to PA. They also engage public health scientists in needed transdisciplinary perspectives.

There have been few longitudinal studies to verify causal relationships between the school built environment and PA. …

Association Between Socioeconomic Status And Bmi Among People With Schizophrenia And Bipolar Disorder, Nicholas Guenzel

Theses & Dissertations

Background: Many health disparities among individuals with schizophrenia and bipolar disorder are due to obesity-associated diseases. Several causes of obesity have been discovered, but few risk factors are known. In the general public, low socioeconomic status (SES) is associated with obesity.

Objective: Examine the relationship between SES and body mass index (BMI) among people with schizophrenia and bipolar disorder.

Design: A secondary analysis of the Collaborative Psychiatric Epidemiology Surveys dataset. The psychiatric group (N=480) included individuals with symptoms of schizophrenia or bipolar disorder. Those reporting no symptoms were controls (N=5,161). Childhood SES variables included mother and father education and profession, …

Investigation Of Behavioral And Cellular Changes In The Maternal Immune Activation Model Of Autism Spectrum Disorders, Shreya Roy

Theses & Dissertations

Maternal infection during pregnancy, which leads to maternal immune activation (MIA), is an environmental risk factor for autism spectrum disorders (ASD). MIA can be induced in mice and their offspring exhibit behaviors that model the core symptoms of ASD. One of the core behavioral symptoms in ASD patients is presence of increased repetitive behavior, which is modeled by an increase in marble burying in MIA mice. It has been shown that the deficits seen in MIA mice are associated with the dysregulation of cytokine levels in the developing brain, specifically an increase in pro-inflammatory cytokines. In this thesis, I tested …

The Impact Of Gasoline Prices On Medical Care And Costs Of Motor Vehicle Injuries, He Zhu

Theses & Dissertations

Background Traffic safety has placed a tremendous economic and social burden on individuals and nations. Gasoline prices have been linked to traffic safety in the recent studies. Higher gasoline price may prompt people to reduce expenses by changing travel distance and frequency, transportation mode, or driving behaviors.

Objective This study aims to examine the relationship of gasoline prices to hospital utilization and cost for motorcycle and non-motorcycle motor vehicle injuries in the United States.

Methods Data on inpatient hospitalization for motor vehicle injuries were obtained from the 2001-2010 Nationwide Inpatient Sample, which is part of the Healthcare Costs and Utilization …

Role Of Macrophages In Muscle Transfection With Pdna/Pluronic Formulation, Vivek Mahajan

Theses & Dissertations

Non-ionic amphiphilic block copolymers of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), Pluronics, arranged in a tri-block structure PEO-PPO-PEO, have raised a considerable interest in skeletal muscle Gene Therapy. Previous studies have demonstrated that co-administration of Pluronics with naked plasmid DNA (pDNA) by direct i.m. injection enhanced transgene expression not only in muscle but also in distal lymphoid organs (spleen and lymph nodes) and this response was strain-dependent; not observed in athymic (BALB/c nu/nu) mouse; suggesting a role of immune cells in gene transfer to skeletal muscles. Therefore, we first evaluated the role of inflammation and inflammatory cells, on muscle …

Determinants Of Patient Activation In Hospitalized Multimorbid Patients, Myra S. Schmaderer

Theses & Dissertations

Post-hospitalization care transition is a vulnerable time for multimorbid patients. Self-management challenges happen due to acute symptoms and complex new treatment plans. Literature suggests higher activated patients have better outcomes; however, there is little research that identifies determinants that predict patient activation in the multimorbid hospitalized patient. Understanding predictive factors will facilitate planning interventions that promote self-management of multimorbid conditions. The purpose of this dissertation was to identify determinants that predict patient activation in patients with multimorbidity at discharge from the hospital.

A descriptive, predictive research study was conducted with 200 hospitalized multimorbid patients discharged to home. Their mean age …

Understanding Access To Health Information: The Role And Measurement Of Social Location, Megan S. Kelley

Theses & Dissertations

The purpose of this research is to explore how application of social location theory may improve data collection on health information access in order to better inform and improve the effectiveness of health communication and messaging. This dissertation proposes a framework to understand how people obtain health information based on the idea of social location, Ritzer and Bell’s (1981) levels of social reality, and Dahlberg & Krug’s (2002) social ecological model. This research addressed the extent to which three studies of health information access support the use of such a framework, and if so, how its application could improve our …

Association Between Adverse Events In Childhood And Bmi Among People With Schizophrenia And Bipolar Disorder, Nicholas Guenzel

Theses & Dissertations

Background: People with schizophrenia and bipolar disorder die significantly earlier than members of the general public (16-18 years and 12-13 years, respectively). Diseases associated with obesity such as diabetes, heart disease, and stroke account for much of this discrepancy. People with mental illness often have difficulty losing weight despite intensive interventions. As a result, nurses caring for patients with mental illness need to monitor their weight diligently and implement individualized interventions to promote achieving or maintaining a healthy weight. Because intensive interventions come with some risk and expense, programs must target individuals with the most potential to develop obesity. In …

Roles Of Serum Lycopene In The Prevalence And Mortality Of Metabolic Syndrome In The Adult Population, Guang-Ming Han

Theses & Dissertations

Metabolic syndrome (MetS) is a cluster of metabolic disorders, including increased fasting glucose, blood pressure, plasma triglyceride, reduced high-density lipoprotein cholesterol and abdominal obesity. It leads to an increased risk of cardiovascular disease and diabetes. The growing prevalence of MetS is strongly related to the increasing prevalence of overweight/obesity. As an antioxidant, lycopene can reduce the risk of MetS. However, it is unclear whether lycopene has similar effects among overweight/obese individuals and whether lycopene can reduce the risk of mortality among individuals with MetS. The purpose of this study was to explore the roles of lycopene in the prevalence and …

Role Of Redox-Sensitive Calcium/Calmodulin-Dependent Protein Kinase Lla In Angiotensin Ii Intra-Neuronal Signaling And Angiotensin Ll-Mediated Hypertension, Urmi Basu

Theses & Dissertations

Activation of renin-angiotensin system and elevated levels of circulating and brain angiotensin II (AngII) has been implicated in the pathogenesis of neuro-cardiovascular diseases, such as hypertension and heart failure. In central neurons AngII increases generation of reactive oxygen species (ROS), which in turn regulates neuronal ion channels. Previous studies have demonstrated that ion channels can also be regulated by protein kinases, such as calcium /calmodulin-dependent protein kinase II (CaMKII) as a downstream mediator of AngII signaling. In the heart, CaMKIIδ undergoes oxidation upon AngII stimulation and increased pro-oxidant conditions. However, the exact mechanism by which AngII and ROS regulate CaMKIIα, …

Ca2+ Diffusion Through Endoplasmic Reticulum Supports Elevated Intraterminal Ca2+ Levels Needed To Sustain Synaptic Release From Rods In Darkness., Minghui Chen, Matthew J. Van Hook, Wallace B. Thoreson

Journal Articles: Ophthalmology

UNLABELLED: In addition to vesicle release at synaptic ribbons, rod photoreceptors are capable of substantial slow release at non-ribbon release sites triggered by Ca(2+)-induced Ca(2+) release (CICR) from intracellular stores. To maintain CICR as rods remain depolarized in darkness, we hypothesized that Ca(2+) released into the cytoplasm from terminal endoplasmic reticulum (ER) can be replenished continuously by ions diffusing within the ER from the soma. We measured [Ca(2+)] changes in cytoplasm and ER of rods from Ambystoma tigrinum retina using various dyes. ER [Ca(2+)] changes were measured by loading ER with fluo-5N and then washing dye from the cytoplasm with …

Confident Difference Criterion: A New Bayesian Differentially Expressed Gene Selection Algorithm With Applications., Fang Yu, Ming-Hui Chen, Lynn Kuo, Heather Talbott, John S. Davis

Journal Articles: Obstetrics & Gynecology

BACKGROUND: Recently, the Bayesian method becomes more popular for analyzing high dimensional gene expression data as it allows us to borrow information across different genes and provides powerful estimators for evaluating gene expression levels. It is crucial to develop a simple but efficient gene selection algorithm for detecting differentially expressed (DE) genes based on the Bayesian estimators.

RESULTS: In this paper, by extending the two-criterion idea of Chen et al. (Chen M-H, Ibrahim JG, Chi Y-Y. A new class of mixture models for differential gene expression in DNA microarray data. J Stat Plan Inference. 2008;138:387-404), we propose two new gene …

Muc16-Mediated Activation Of Mtor And C-Myc Reprograms Pancreatic Cancer Metabolism., Surendra K. Shukla, Venugopal Gunda, Jaime Abrego, Dhanya Haridas, Anusha Mishra, Joshua J. Souchek, Nina V. Chaika, Fang Yu, Aaron R. Sasson, A Lazenby, Surinder K. Batra, Pankaj K. Singh

Journal Articles: Eppley Institute

MUC16, a transmembrane mucin, facilitates pancreatic adenocarcinoma progression and metastasis. In the current studies, we observed that MUC16 knockdown pancreatic cancer cells exhibit reduced glucose uptake and lactate secretion along with reduced migration and invasion potential, which can be restored by supplementing the culture media with lactate, an end product of aerobic glycolysis. MUC16 knockdown leads to inhibition of mTOR activity and reduced expression of its downstream target c-MYC, a key player in cellular growth, proliferation and metabolism. Ectopic expression of c-MYC in MUC16 knockdown pancreatic cancer cells restores the altered cellular physiology. Our LC-MS/MS based metabolomics studies indicate global …

Microrna-587 Antagonizes 5-Fu-Induced Apoptosis And Confers Drug Resistance By Regulating Ppp2r1b Expression In Colorectal Cancer., Yinbo Zhang, Geoffrey Talmon, Jing Wang

Journal Articles: Eppley Institute

Drug resistance is one of the major hurdles for cancer treatment. However, the underlying mechanisms are still largely unknown and therapeutic options remain limited. In this study, we show that microRNA (miR)-587 confers resistance to 5-fluorouracil (5-FU)-induced apoptosis in vitro and reduces the potency of 5-FU in the inhibition of tumor growth in a mouse xenograft model in vivo. Further studies indicate that miR-587 modulates drug resistance through downregulation of expression of PPP2R1B, a regulatory subunit of the PP2A complex, which negatively regulates AKT activation. Knockdown of PPP2R1B expression increases AKT phosphorylation, which leads to elevated XIAP expression and enhanced …

Crispr/Cas9-Based Generation Of Knockdown Mice By Intronic Insertion Of Artificial Microrna Using Longer Single-Stranded Dna., Hiromi Miura, Channabasavaiah B. Gurumurthy, Takehito Sato, Masahiro Sato, Masato Ohtsuka

Journal Articles: Genetics, Cell Biology & Anatomy

Knockdown mouse models, where gene dosages can be modulated, provide valuable insights into gene function. Typically, such models are generated by embryonic stem (ES) cell-based targeted insertion, or pronuclear injection, of the knockdown expression cassette. However, these methods are associated with laborious and time-consuming steps, such as the generation of large constructs with elements needed for expression of a functional RNAi-cassette, ES-cell handling, or screening for mice with the desired knockdown effect. Here, we demonstrate that reliable knockdown models can be generated by targeted insertion of artificial microRNA (amiRNA) sequences into a specific locus in the genome [such as intronic …

Pharmacodynamics Of Folic Acid Receptor Targeted Antiretroviral Nanotherapy In Hiv-1-Infected Humanized Mice., Pavan Puligujja, Mariluz Araínga, Prasanta Dash, Diana L. Palandri, R. Lee Mosley, Santhi Gorantla, Larisa Y Poluektova, Joellyn Mcmillan, Howard Gendelman

Journal Articles: Pharmacology & Experimental Neuroscience

Long-acting nanoformulated antiretroviral therapy (nanoART) can sustain plasma drug levels and improve its biodistribution. Cell targeted-nanoART can achieve this and bring drug efficiently to viral reservoirs. However, whether such improvements affect antiretroviral responses remains unknown. To these ends, we tested folic acid (FA)-linked poloxamer407-coated ritonavir-boosted atazanavir (FA-nanoATV/r) nanoparticles for their ability to affect chronic HIV-1 infection in humanized mice. Following three, 100mg/kg FA-nanoATV/r intramuscular injections administered every other week to infected animals, viral RNA was at or below the detection limit, cell-associated HIV-1p24 reduced and CD4+ T cell counts protected. The dosing regimen improved treatment outcomes more than two fold …