Medicine and Health Sciences Commons^™

Long-Acting Nanoformulated Small Molecule Inhibitor Prodrugs For Antiviral Treatment And Prevention, Nathan Smith

Theses & Dissertations

Over 30 years of antiretroviral therapy (ART) has transformed human immunodeficiency virus type one (HIV-1) outcomes from certain death to a nearly complete and normal life. Though disease growth has slowed, the virus still creates substantial co-morbid diseases as well as social and economic burdens worldwide. Lack of success with curative efforts combined with shortcomings in global treatment remain to be properly addressed. The requirement for daily use of combination antiretroviral drugs (ARVs) in low to middle income countries - where the majority of the HIV-1 positive population resides - can lead to breaks in regimen adherence due to a …

Synthesis And Characterization Of A Long-Acting Emtricitabine Prodrug Nanoformulation, Ibrahim M. Ibrahim

Theses & Dissertations

The introduction of highly active antiretroviral therapy led to a paradigm shift in the management of HIV/AIDS changing a disease considered “a death sentence” to “a manageable chronic disease”. Nevertheless, challenges exist for successful treatment of HIV, including patient adherence to the complex daily regimens and the inability of current formulations to target viral sanctuaries. Introduction of nanoformulated antiretroviral therapy (ART) is a promising alternative to tackle these challenges. Our laboratory has been focusing on developing long-acting (LA) nanoformulated antiretrovirals and has succeeded in developing LA integrase inhibitors. However, challenges for this approach extend to a range of short-acting hydrophilic …

Development Of Local Drug Delivery Systems For Periodontal Disease, Yosif Hassan Almoshari

Theses & Dissertations

Periodontitis is an inflammatory disease induced by complex interactions between the host immune system and pathogens that affect the integrity of teeth-supporting tissues. To prevent disease progression and thus preserve the alveolar bone structure, simultaneous anti-inflammatory and osteogenic intervention is essential. Hence, simvastatin (SIM) and a glycogen synthase kinase 3 beta inhibitor (BIO) were selected as anti-inflammatory and osteogenic agents.

First, SIM is a HMG-CoA reductase inhibitor widely prescribed for hypercholesterolemia. It has been reported to ameliorate inflammation and promote osteogenesis. Its clinical applications on these potential secondary indications, however, have been hampered by its lack of osteotropicity and poor …

The Effect Of Enamel Matrix Derivative/Papilla Reflection Surgery On The Clinical And Alveolar Bone Outcomes In Periodontal Maintenance Patients, Erica E. Jasa

Theses & Dissertations

The purpose of this study was to determine if local application of enamel matrix derivative (Emdogain; EMD), combined with minimally invasive papilla reflection/root preparation (PR/RP), is effective in improving probe depth (PD), clinical attachment level (CAL), and interproximal bone height (IBH) in persistent 6-9 mm periodontal pockets in patients on periodontal maintenance therapy (PMT). Fifty periodontal maintenance patients with advanced chronic periodontitis presenting with a 6-9 mm interproximal PD were included in study. Experimental (PR/RP+EMD; n=24) and control (PR/RP+S; n=26) therapies were randomly allocated. Roots were treated with reflection of interproximal papillae, root planing assisted with endoscope evaluation, and acid …

A Beginner's Guide To Research Using Electronic Health Record Data, Jenenne A. Geske

Theses & Dissertations

Since the passage of the American Recovery and Reinvestment Act in 2009, the use of Electronic Health Records (EHRs) in the healthcare system has increased substantially. Accompanying this surge in EHR usage is a surge in healthcare data and increased opportunities to improve our understanding of health care through research using these data. The use of EHR data for research has many benefits, limitations and considerations. Using data that was originally intended to facilitate billing, insurance, and maintenance of clinical records for research can be fraught with challenges, but they can also be a rich source of information. This paper …

Exploring The Relationships Between Moral Distress, Moral Courage, And Moral Resilience In Undergraduate Nursing Students, Erin Gibson

Nursing Theses and Dissertations

The pervasiveness of moral distress in nursing can no longer be ignored. Moral distress can have devastating effects on a nurse and lead to burnout and/or cause the nurse to leave the profession. To mitigate these effects, strategies to decrease moral distress should be implemented as early as nursing school. Related concepts such as moral courage and moral resilience show favorable effects as strategies to combat moral distress. However, little evidence is known as to how these three moral concepts are related with one another.

Chapter 2, “Student Courage: An Essential for Today’s Health Education” provides a concept analysis of …

Evaluation Of The Role Of Microvascular Pathology On Peripheral Artery Disease, Constance Mietus

Theses & Dissertations

Background: Peripheral Artery Disease (PAD) begins with atherosclerotic narrowing of arteries, including those that supply the legs. Individuals with PAD experience pain during walking, which becomes increasingly limiting. Studies from our group and others have shown that a myopathy is present in the skeletal muscle of PAD patients, and is characterized by myofiber degeneration, fibrosis, and remodeling of vessels ranging from 50 – 150 mm in diameter. However, microvascular pathology, particularly of the smallest microvessels (5 – 15 mm in diameter) remains poorly characterized. Furthermore, little is known about the relationships between microvascular architecture, microperfusion, and patient walking performance. We …

Development Of A Long-Acting Nanoformulation Of Dolutegravir For Prevention And Treatment Of Hiv-1 Infection, Brady Sillman

Theses & Dissertations

Dolutegravir (DTG) is a potent human immunodeficiency virus type 1 (HIV-1) integrase strand-transfer inhibitor (INSTI) with a high barrier to viral drug resistance. However, opportunities to improve its profile abound. These include extending the drug’s apparent half-life, increasing penetrance to “putative” viral reservoirs, and reducing inherent toxicities. These highlight, in part, the need for long-acting, slow effective release antiretroviral therapy (LASER ART) delivery schemes. A long-acting (LA) DTG was made by synthesizing a hydrophobic and lipophilic prodrug encased with poloxamer (P407) surfactant. This modified DTG (MDTG) reduced systemic metabolism and polarity, increased lipophilicity and membrane permeability, improved encapsulation, and formed …

The Effect Of Emdogain Periodontal Regenerative Material On Inflammation In Periodontal Maintenance Patients, Jessica M. Gradoville

Theses & Dissertations

The purpose of this double-blinded, randomized, controlled clinical trial was to determine if local application of enamel matrix protein derivative (Emdogain:EMD), combined with minimally-invasive papilla reflection is effective in reducing inflammation in periodontal pockets in patients on periodontal maintenance therapy (PMT).Fifty patients diagnosed with advanced chronic periodontitis presenting with a 6-9mm interproximal probing depth were included in the trial. Experimental (EMD; n=24) and control (saline, n=26) therapies were randomly allocated. Roots were treated with mini-flaps and root planing assisted with endoscope evaluation before EMD or saline application. Inflammation was assessed by bleeding on probing (BOP) at baseline, 6-, and 12-months …

Relationship Between Binge Eating Disorder And Circadian Chronotype, Leon B. Jons

Theses & Dissertations

Binge eating disorder (BED) is a common condition in the general population and is more common in individuals with obesity. The later timing of food intake has been associated with an increase incidence of obesity. The purpose of this study was to evaluate the relationship between circadian chronotype and BED in a population of individuals with obesity. The sample consists of a retrospective review of 170 subjects presenting to an obesity medicine clinic who had been clinically evaluated for BED and chronotype.

No significant correlation was found between BED and a late chronotype in this population. In a secondary analysis …

Monocyte Anti-Inflammatory Activity Is Dictated By Metabolic Status During Staphylococcus Aureus Biofilm Infection, Kelsey J. Yamada

Theses & Dissertations

Staphylococcus aureus biofilms represent a significant cause of morbidity and economic burden and are often associated with nosocomial infections, including medically implanted devices. In particular, prosthetic joint infections (PJIs) are a growing concern due to the continued increase in orthopedic procedures. Staphylococcal species cause >50% of all PJIs, while S. aureus represents the most invasive and associated with the most morbidity. S. aureus-associated biofilm infections are recalcitrant to antibiotic therapy, due to both the acquisition of genetic elements and metabolic dormancy. Furthermore, S. aureus biofilm infections remain chronic because they cannot be cleared by the immune system. Recent studies …

Potentially Reduced Exposure Products, Occupational Variations In Smoking, And Hardcore Smokers: Examining Important Elements In The Tobacco Use Spectrum, Raees A. Shaikh

Theses & Dissertations

The purpose of this research was to examine three important aspects of the smoking phenomenon that are, and will remain, important for the future of tobacco control research and policy. First and currently one of the most debated and researched topics in the tobacco research field relates to the group of products regarded by some as the potentially reduced exposure products (PREPs). We studied determinants of use of these products. Second aspect was to examine the socioeconomic subgroup of smokers based on their occupations who might potentially benefit from the use of PREPs and the third stage involved studying the …

Development Of Macromolecular Prodrug Conjugates For The Treatment Of Inflammatory Diseases, Gang Zhao

Theses & Dissertations

Inflammation is the complex biological response to the stimuli triggered by various factors like pathogens, damaged cells, or irritants. Constant uncontrolled acute inflammation may become chronic conditions, leading to significant tissue damage, contributing to a series of chronic inflammatory diseases. Our lab has been working on the different types of inflammatory diseases and has developed multiple macromolecular prodrug conjugates for the better therapeutic efficacy and reduced toxicity. The general approach we have taken is to incorporate small molecules containing monomers into water-soluble and biocompatible polymers, such as N-(2-Hydroxypropyl) methacrylamide (HPMA) copolymers. The superior and the sustained efficacy of those macromolecular …

The Role Of Ros In The Progression And Treatment Of Castration-Resistant Prostate Cancer, Dannah R. Miller

Theses & Dissertations

Prostate cancer is the second leading cause of cancer-related deaths in U.S. men, primarily due to the development of castration-resistant (CR) prostate cancer (PCa), of which there are no effective treatment options. Reactive oxygen species (ROS) plays a critical role in prostate carcinogenesis, including the progression of the CR PCa phenotype. ROS regulates both cell proliferation and apoptosis; a moderate increase in ROS can promote proliferation; however, a substantial rise in ROS levels will result in apoptosis. Oxidase p66Shc is elevated in clinical PCa cells and has been associated with a metastatic phenotype of CR PCa cells, promoting PCa cell …

Prostaglandins And Kidney Function: A Comparison Between The Cortical And Inner Medullary Collecting Duct On Prostaglandin Production, Dane N. Wilson

Theses & Dissertations

Prostaglandins are paracrine and autocrine signaling molecules that play important roles through various physiological and pathophysiological functions in the human body including the inflammatory response, control of blood pressure, and water and salt homeostasis in the kidney. Prostaglandins have been shown to have great influence on kidney function. In particular, prostaglandin E₂ influences the function of the collecting duct, primarily decreasing vasopressin-stimulated collecting duct water permeability. The aim of this study was to see how various treatments to cells, as well as different growth times, impacted prostaglandin production between two different collecting duct cell lines, one arising from the …

Human Immunodeficiency Virus Theranostics, Christopher J. Woldstad

Theses & Dissertations

RATIONALE: Long-acting slow effective release antiretroviral therapy (LASER ART) was developed to improve patient regimen adherence, prevent new infections, and facilitate drug delivery to human immunodeficiency virus cell and tissue reservoirs. However, maintenance of sustained plasma drug levels, for weeks or months, after a single high-level dosing, could improve regimen adherence but, at the same time, affect systemic toxicities. Of these, the most troubling are those that affect the central nervous system (CNS) In an effort to facilitate LASER ART development, “multimodal imaging theranostic nanoprobes” were created. These allow combined bioimaging, drug pharmacokinetics and tissue biodistribution tests in animal …

Impact Of Healthcare Delivery And Policies On Children's Outcomes After The Affordable Care Act Of 2010, Shreya Roy

Theses & Dissertations

The Patient Protection and Affordable Care Act (ACA) of 2010 introduced programs to promote integrated pediatric healthcare delivery and to expand public health insurance (Medicaid) eligibility for adults from low-income families in the United States. This dissertation examined whether progress was made towards integration of healthcare delivery for children with developmental disabilities after the implementation of ACA, and also whether expansion of Medicaid for adults impacted the preventive care utilization and school absenteeism of children from low-income families. A cross-sectional study design was used to examine whether integration of pediatric healthcare delivery was accomplished and a quasi-experimental difference-in-differences approach was …

Neurological Balance Assessment To Screen Fall Risk: A Methodological Study, Yiwen Xia

Theses & Dissertations

According to the World Health Organization, falls are the second leading cause of accidental or unintentional injury deaths worldwide. The medical cost on fall related injuries becomes a huge financial burden. In order to prevent falls and fall related injuries, fall risk assessment becomes a routine practice for healthcare providers. In most clinics, practitioners conduct a quick neurological balance assessment in the room or along the hallway to determine abnormal gait pattern, indicating increased risk of falls. However, the validity of such subjective assessment is questionable. The purpose of this study was to identify a single feasible neurological balance task …

Common Areas For Improvement From After Action Reports (Aars) Generated After Exercises Or Actual Disasters, As Reported By A National Sample Of U.S. Hospitals, Abdoulaye Abdoulaziz

Theses & Dissertations

Many hospitals conduct exercises every year, and they conclude the process with an After-Action Report and Improvement Plan. Therefore, there are thousands of AAR/IP’s across the country with limited opportunity to compare them or to learn from them collectively. Our project has gathered Improvement Plans (IP’s) and conducted a qualitative analysis which determined whether the “lessons learned” can be categorized into common themes.

Examining Depressive Symptoms Over Time In Women With Coronary Heart Disease, Sydney A. Buckland

Theses & Dissertations

Coronary heart disease (CHD) is the number one killer of women in the US. Women also experience roughly twice as much depression as men, and depression in CHD is associated with increased morbidity and mortality. Despite these facts, women continue to be under-represented in CHD research, and results by gender are not routinely reported.

Screening for depression in this population is problematic due to inconsistent inclusion of somatic symptoms on screening instruments and disagreement about appropriate cutoff scores.

This body of work clarifies the concept of depression in women with CHD, presents a systematic review of the longitudinal literature on …

The Correlation Between Undergraduate Students Who Attend The University Recreation Center And Students Exhibiting Symptoms Of An Eating Disorder, Olivia Daniels

Senior Honors Projects, 2010-2019

Background: The prevalence of eating disorders on college campuses indicates an important issue in contemporary society. As students experience a heightened level of freedom, they have the option to explore multiple forms of weight- management, including compulsive exercise.

Methodology: An online survey was distributed to female undergraduate students(n=206) at James Madison University.

Results: A significant relationship was found between eating disorder symptomology and where participants decided to spend their time at the University Recreation Center (UREC), as well as what type of physical activity they chose to perform. A significant inverse relationship between increasing muscle mass and burning calories was …

Increasing Food Security: Developing And Testing A Nutrition Education Curriculum For A Mobile Food Pantry, Alexandra Lepecha, Kathleen M. Kraft

Senior Honors Projects, 2010-2019

Background: The Neighborhood Produce Market (NPM) is a food distribution model similar to a mobile food pantry. NPM stakeholders observed a lack of community engagement and familiarity with produce offered.

Project Description: The objective was to develop a nutrition education curriculum for NPM volunteers to better engage families and community members by providing food samples, recipes, and nutrition education. A stakeholder steering committee guided the needs assessment, curriculum development, volunteer training, and pilot test. The curriculum consisted of food safety, cultural considerations, and nutritional information for nine produce items and food tasting procedures and recipes. Seven student volunteers were trained …

An Examination Of Factors Associated With Body Appreciation, Sociocultural Attitudes Of Appearance, And Ratings Of Diverse Performing Artists, Stephanie Rathjen

Senior Honors Projects, 2010-2019

Introduction: Multiple studies have found that performing artists have low body image which may be associated with the media’s portrayal of performers. Low body image can cause negative health effects including depression and eating disorders. This study explores body attitudes among performing and non-performing arts students and the possible media influences on those attitudes.

Methods: Undergraduate students (n=522) were asked to participate in an anonymous online survey regarding their perceptions of their individual body perception. During the survey, they were randomized to watch a video depicting either slim mostly Caucasian performers (video A) or performers of different ethnicities …

The Reproducibility Crisis In Scientific Research, Sarah Eline

Senior Honors Projects, 2010-2019

Following the push for evidence based practice, came a huge proliferation of research journals and journal articles. With this increase in quantity came an increased concern about the quality of these articles being published, which led to a multifield investigation regarding the reproducibility of scientific research. With studies in the fields of psychology and biomedicine only reaching approximately a 30% reproducibility rate, a conversation has been sparked that spans across every field of research. Upon further investigation, various causes for this reproducibility crisis have surfaced which include, lack of data sharing/ transparency, statistical errors, funding corruption, and the culture surrounding …

Understanding Awareness And Completion Of Advanced Care Directives: An Exploratory Study, Katherine Anna Chiu, Katherine Grace Topf

Senior Honors Projects, 2010-2019

Background: Advance Care Directives (ACDs) are forms that are beneficial for expressing end-of-life wishes during Advance Care Planning (ACP); however, few studies have focused on awareness and completion among college-aged populations. Completion of ACDs are more common among populations forced to think about potential of death, such as the elderly and chronically ill.

Methodology: This research is comprised of two parts in order to explore the availability of resources on four-year public institutions’ official websites (institutional level), and college-aged students’ beliefs and values. The institutional level took inventory of information available on the official websites of four-year public institutions (n=1,642). …

Overcoming Degradation: A Novel Synthetic Strategy For Antisense Oligonucleotide Analogs, Annie Lin

Senior Honors Projects, 2010-2019

Antisense oligonucleotides (ASO) are single-stranded deoxyribonucleic acids that bind to mRNA to inhibit the synthesis of proteins that have been associated with the central mechanisms of disease development. Due to their gene silencing capabilities, the potential for ASOs as therapeutic agents is wide, but many toxicological challenges such as poor membrane permeability, low solubility, and rapid degradation by exonucleases must be overcome before ASO medications can be reliably utilized. In order to negate these challenges, the natural sugar- phosphate backbone of ASO’s, which is responsible for its rapid degradation, will be replaced by one that is hydrolytically stable. To do …

Levels Of Human Tear Lacritin Isoforms In Healthy Adults, Brooke Justis

Senior Honors Projects, 2010-2019

Current diagnostics of dry eye disease are unable to identify the multiple complex causes of dry eye, thereby limiting the proper treatments of the disease. The tear glycoprotein lacritin has been reported to be decreased in dry eye patients, specifically those with Sjӧgren’s syndrome associated dry eye. Therefore, the use of lacritin in a diagnostic test for dry eye could improve the current diagnostics available. Western blot assays have revealed the presence of an active lacritin monomer as well as an inactive tissue transglutaminase cross-linked polymer in human tears. A third isoform of lacritin, the splice variant lacritin-c, has also …

Recent Veterans’ Self-Management Of Health During Military To Civilian Life Transition: A Grounded Theory Study, Narda A. Ligotti

Theses & Dissertations

United States Veterans of combat within Iraq and/or Afghanistan return home to face an array of somatic and psychological health concerns. Little was known about how they manage their health after military discharge. The research question for this study was “how do OIF/OEF/OND combat Veterans and their primary support persons manage Veterans’ health at home?” There is little information about these Veterans’ perspective of self-management of health in the home. This study was designed to provide a theoretical understanding of self-management and family support in this population. The Family Management Style Framework (Knafl, Deatrick & Havill, 2012) was used as …

Role Of Rac1-Pak Pathway In Aggressive B-Cell Lymphoma, Tian Tian

Theses & Dissertations

Aggressive B-cell lymphomas are diverse group of neoplasms that arise at different stages of B-cell development and by various mechanisms of neoplastic transformation. Aggressive B-cell lymphomas include many types, subtypes and variants of diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), mantle cell lymphoma (MCL) and B lymphoblastic lymphoma. The treatment of patients with aggressive B-cell lymphomas remains a clinical challenge. Conventional chemotherapeutic regimens, mainly based on the CHOP (cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone) combination, obtain a relatively high number of complete or partial clinical responses (20-80%), but the tumor relapses in most patients, who will die of the disease. …

Examining The Effects Of Approaches On Reducing Hospital Utilization: The Patient-Centered Medical Home, Continuity Of Care, And The Inpatient Palliative Consultation At The End-Of-Life, Xiaoting Sun

Theses & Dissertations

Background: It has become a national priority to reduce the high health care expenditure in the United States while improving the quality of care. Hospital care is taking up one-third of the healthcare spending, and services offered in hospitals are costly compared to others. Only one-twentieth of the patients with high-needs account for about half of the health care spending. They consuming a high level of hospital services if their conditions are not well-managed in the outpatient settings. Therefore, it is important to examine the effectiveness of the approaches that have the potentials to reduce costly care utilization through improvements …