Digital Commons Network^™

Subcutaneous Delivery Of Albumin, Vy Nguyen

Electronic Theses and Dissertations

An increasing number of protein drugs are used in the clinic to treat a broad range of diseases. However, because of their large molecular sizes and high hydrophilicity, protein drugs are not orally bioavailable, which commonly require intravenous, intramuscular or subcutaneous injection. Thermosensitive polymers have been widely investigated as in situ depots for sustained drug release delivered through subcutaneous route.Albumin is the most abundant proteins in bloodstream. It has long half-life (19 days in human) and plays important roles such as acting as carrier for fatty acids, amino acids, waste products and medical compounds. Albumin has been studied for decades …

Applications Of Fluoronitroalkenes In 1,3-Dipolar Cycloaddition And 1,4-Conjugate Addition, Hamdan Eid Alrefaei

Electronic Theses and Dissertations

Fluorinated compounds have been routinely synthesized in the pharmaceutical and agricultural industries. Approximately, 45% of drugs approved by the U.S. Food and Drug Administration in 2018−2019, and 52% of agricultural products between 2010 and 2017 were fluorinated compounds. In comparison to their non-fluorinated counterparts, fluorinated drugs have different pharmacokinetics and pharmacodynamics profiles. Bond strength and electronegativity of the fluorine atom can affect the compound's pKa, dipole moment, and metabolic stability. Therefore, methods to access fluorinated compounds are highly pursued in organic synthesis. Various fluorinating agents (nucleophilic and electrophilic) have been developed over the last few decades and are widely employed …

Metal-Organic Frameworks As Bacteria Mimicking Delivery Systems For Tuberculosis, Ailin Guo

Electronic Theses and Dissertations

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (M.tb), with an estimated 1.5 million deaths and 10 million infections each year. Although TB can be effectively treated with antibiotics, because of the complications and length of treatment, many people fail to complete the treatment which exacerbates the emergence of drug-resistant M. tb strains. The goal of this work is to develop biomimetic particles as host-directed therapy to target the infected macrophages. Two types of metal-organic frameworks (MOFs), MIL-100(Fe) and MIL-88A(Fe) were developed for bacteriamimicking particles. As a proof-of-concept, Mannose was selected as a ligand to target macrophages because …

An Exploration Of The Effects Of An Early Postpartum Intravenous Infusion With Carnosic Acid On Physiological Responses Of Transition Dairy Cows, Tainara Michelotti

Electronic Theses and Dissertations

The transition period is commonly defined as the last 3 wk before parturition to 3 wk after parturition. It is the most critical stage of the lactation cycle of high-producing dairy cows. The period consists of a complex interplay of metabolic and hormonal adaptations, inflammation, and immune activation. During the transition period, dairy cows commonly face oxidative stress, an underlying factor for dysfunctional immune response and enhanced inflammation, which can further increase the susceptibility of dairy cattle to health disorders and decrease productivity. In the last few decades, there has been an increased interest in studying alternative natural compounds with …

Antiparasitic Peptide From The Ocean: Discovery, Synthesis And Structure-Activity Relationship Study, Kh Tanvir Ahmed

Electronic Theses and Dissertations

Millions of people die every year because of infectious diseases, and malaria is among the top five of the deadliest infectious disease. In 2018, malaria took more than four hundred thousand lives, and more than half of them are children under five years of age. Most malaria-affected parts of the world are also the home of the most underprivileged people. Seemingly, antimalarial drug discovery never achieved the attraction that it requires. Like malaria, another infectious disease that is not extensively explored by drug discovery campaigns is American trypanosomiasis or Chagas disease. More than a hundred years have passed since discovering …

Rna Structure And Function: Biological Relevance In Neurodegenerative And Infectious Disease Pathogenesis, Joshua Imperatore

Electronic Theses and Dissertations

The studies outlined in this dissertation encompass a broad focus, relating to the pathogenesis of neurological disorders such as Alzheimer’s disease, fragile X syndrome, and amyotrophic lateral sclerosis, as well as a novel infectious disease, COVID-19. However, all four studies detailed within this dissertation contain similar elements, namely, the coordinated role of RNA structure and function in essential molecular mechanisms. The results of these investigations allow us to speculate on various disease- related mechanisms, including dysregulated microRNA processing pathways, nucleocytoplasmic shuttling via distinct RNA-protein interactions, and fine-tuned molecular switches controlling genomic dimerization and viral hijacking of host cellular microRNAs. Taken …

The Contribution Of A Global Ethics Approach To Health And The Environment In The Niger Delta Region, Augustine Wayii

Electronic Theses and Dissertations

ABSTRACT

THE CONTRIBUTION OF A GLOBAL ETHICS APPROACH TO HEALTH AND THE

ENVIRONMENT IN THE NIGER DELTA REGION

By

Augustine Lezorgia Wayii, M. ED, M.A.

May 2020

Dissertation supervised by Gerard Magill, PhD

The dissertation presents a global ethics approach that connects health and the environment in the context of the Niger Delta Region. The people of the Niger Delta region in Nigeria are experiencing major catastrophes that connect health and the environment. In the bid to ameliorate these pivotal problems, this dissertation undertakes an ethical analysis that connects health and the environment. Insofar as these problems can be characteristic …

Epidemics, Politics And Public Health: Ludwig Rajchman, Md, The League Of Nations Health Organization And The Creation Of A Transnational Health Institution, Paul J. Weinbaum

Electronic Theses and Dissertations

Traditional scholarship on the League of Nations labels the organization as a failure because it did not prevent the outbreak of the World War II. Recent research examines League activities in a more comprehensive manner and concludes that the organization should be credited with important and enduring achievements. Perhaps the most successful work was carried out by the Health Section led by Dr. Ludwick Rajchman. Using primary sources from the League archives in Geneva, documents from organizations such as the Rockefeller Foundation, articles from medical journals and other relevant secondary sources, I argue that the Health Section, became the world’s …

Malaria, Microbes, And Mice: The Role Of The Gut Microbiota On The Immune Response To Plasmodium Infection And The Treatment Potential Of Microbiota Modulation., Morgan L. Waide

Electronic Theses and Dissertations

Plasmodium infection leads to over 200 million cases of malaria and 400,000 deaths worldwide each year. These deaths are largely in children under the age of five and pregnant women [1]. Caused by transmission of Plasmodium parasites by the female Anopheles mosquito, malaria poses a risk for over 40 percent of the world’s population [1]. Despite worldwide efforts to eradicate malaria leading to a decrease in malaria-associated mortalities in the early 2000s [2], growing resistance to the available antimalarials and the lack of an effective, long-lasting vaccine has caused this decrease to plateau in recent years [1, 3-6]. Furthermore, malaria …

The Use Of Nanoparticles And Electrospun Fibers For Intravaginal Delivery To Treat Viral And Bacterial Infections And Electrophysiological Measurements Of Synthetic Chloride Channels., Farnaz Minooei

Electronic Theses and Dissertations

Female reproductive viral and bacterial infections affect millions of women worldwide. Given the diversity and magnitude of these unmet reproductive health challenges, topical administration of antiretrovirals (ARVs) and antibiotics have emerged as promising approaches to maintain and restore reproductive health. However, currently available intravaginal dosage forms often suffer from low user adherence and the need for frequent, daily administration to achieve therapeutic effect. To address these challenges, the broad goal of this research was to focus on the development of new localized nanoparticle (NP) and electrospun fiber dosage forms to prolong the delivery and enhance the efficacy of active agents …

Assessing Nurse Practitioners' Knowledge And Clinical Practice With Regard To The Oral-Systemic Link, Angela Haynes

Electronic Theses and Dissertations

Nurse Practitioners (NPs) comprise a significant portion of the U.S. primary care workforce and play an essential role in patients' health awareness, prevention strategies, disease management, and in providing appropriate provider referrals. Nurse Practitioners receive education on the oral-systemic connection, yet there have been limited studies on the clinical practice of NPs assessing the oral cavity to evaluate the condition of the teeth and the oral tissues. The purpose of this study was to explore the nurse practitioners’ knowledge and practice habits of assessing the oral cavity for diseases or abnormalities in the mouth that can, in turn, affect overall …

Immune Activation Induces Telomeric Dna Damage, Reduces Memory Precursors, And Promotes Short-Lived Effector T Cell Differentiation In Chronic Hcv Infection, Lam Nguyen

Electronic Theses and Dissertations

Chronic hepatitis C virus (HCV) infection exhibits persistent high viral load, inducing T cells differentiation and dysfunction in chronically infected individuals. Recent longitude studies in both HCV specific- and bulk T cells reveal that chronic immune stimulation is the driving force for the impaired T cell functions, however, the underlying mechanisms remain elusive. Here, we show that peripheral CD4⁺ T cells from chronically HCV-infected patients exhibit lymphopenia with the reduction of naïve population and expansion of effector memory T cells. CD4⁺ T cells from HCV patient also display elevated activation markers. including HLA-DR, GLUT1, Granzyme B, and short-lived …

“Fetch M’Dear”: Healers, Midwives, Witches, And Conjuring Women In Select Ya And Toni Morrison Novels, Diane Mallett-Birkitt

Electronic Theses and Dissertations

Accusations and persecution of witchcraft have been embedded in global culture for centuries. For as long as these persecutions have occurred, women have found themselves accused most frequently. Older women with herbal knowledge were often called on to assist with childbirth or termination of pregnancies and this “secret knowledge” often led them to be suspected of supernatural abilities, often of a satanic nature. Intrigued by these wise women who appeared to have mysterious powers and a penchant for arousing the ire of men in the legal, medical, and religious communities, I began to notice their frequent appearance in novels. Does …

Privacy In Multigenerational Homes Before And Amidst Covid-19, Jennifer Luque

Electronic Theses and Dissertations

Multigenerational households in the United States are more prevalent now than they have been in the last forty years. In part, aging, illness, job loss, saving money, and even tradition are factors that contribute to the idea of multiple generations living together in one home. Given the health of the individuals, size of the home, and number of dedicated bedrooms and bathrooms, living multigenerational can have both positive and adverse effects. Many family groups fall into the category of multigenerational living. However, this study investigates the relationships between adults and senior family members in terms of privacy in the home. …

Tissue-Resident Myeloid-Derived Suppressor Cells Modulate Immune Homeostasis In Healthy Adipose., Katlin Brooke Stivers

Electronic Theses and Dissertations

Our goal with this study was to gain insight into the homeostatic immune cell network in healthy adipose tissue. Specifically, we sought to determine if the immature myeloid cells found in healthy and inflamed adipose were, in fact, tissue-resident myeloid-derived suppressor cells (MDSCs). Using various in vitro and in vivo methods, we have uncovered a population of CD11b^Hi Ly6C^Hi Ly6G^- MDSCs resident in healthy adipose tissue. To the best of our knowledge this is the first time that these cells have been investigated and described in healthy adipose tissue. Systemic MDSC depletion lead to the accumulation of …

Plasmodium Impairs Antibacterial Innate Immunity To Systemic Infections In Part Through Hemozoin-Bound Bioactive Molecules., Christopher Lynn Harding

Electronic Theses and Dissertations

Despite efforts to decrease the global health burden of malaria, infections with Plasmodium species continue to cause over 200 million episodes of malaria each year which resulted in 405,000 deaths in 2018 [1]. One complication of malaria is increased susceptibility to invasive bacterial infections. Plasmodium infections impair host immunity to non-Typhoid Salmonella (NTS) through activities of heme oxygenase I (HO-I) )-induced release of immature granulocytes and myeloid cell-derived IL-10. Yet, it is not known if these mechanisms are specific to NTS. We show here, that Plasmodium yoelii 17XNL (Py) infected mice had impaired clearance of systemic Listeria monocytogenes (Lm) during …

Identification And Structural Characterization Functional Motifs In The Porphyromonas Gingivalis Mfa1 Short Fimbria., Mohammad K. Roky

Electronic Theses and Dissertations

Porphyromonas gingivalis is a causative agent of periodontal disease, initially colonizes the oral cavity by adhering to commensal streptococci. Adherence requires the interaction of the minor fimbrial protein (Mfa1) of P. gingivalis with streptococcal antigen I/II (Ag I/II). A peptide derived from Ag I/II peptide has been well characterized and shown to significantly reduce P. gingivalis colonization and bone loss in vivo, suggesting that this interaction represents a potential target for therapeutic intervention. However, the functional motifs of Mfa1 involved in the interaction with Ag I/II remain uncharacterized. A series of N- and C-terminal peptide fragments of Mfa1 were …

Incarceration Experiences Of Older African American Adults Living With Hiv - A Constructivist Grounded Theory Study., Verena Schmidt

Electronic Theses and Dissertations

Two epidemics disproportionally impact older (50 years and over) African Americans compared to the general U.S. population: Incarceration and HIV/AIDS. Those aged 50 and older constitute the fastest growing age group of persons who are incarcerated in the United States. It is estimated that by the year 2030 about one third of the incarcerated population in the U.S. will be aged 55 years and older. While areas of “Incarceration, racial disparities and HIV” as well as “Aging and HIV” have been well studied and discussed in the literature, little is known about the lived incarceration experiences of African American persons …

Development, Expansion And Role Of Myeloid-Derived Suppressor Cells In Post-Sepsis Immune Suppression, Tuqa Alkhateeb

Electronic Theses and Dissertations

Myeloid-derived suppressor cells (MDSCs) numbers increase significantly in sepsis and are associated with high mortality rates. These myeloid cell precursors promote immunosuppression, especially in the late (post sepsis) stage. However, the mechanisms that underlie MDSC expansion and programming are not completely understood. To investigate these mechanisms, we used a cecal-ligation and puncture (CLP) mouse model of polymicrobial sepsis that progresses from an early/acute proinflammatory phase to a late/chronic immunosuppressive phase. Previous studies in our laboratory showed that microRNA (miR)-21 and miR-181b elevate levels of the transcription factor nuclear factor 1 (NFI-A) that promotes MDSC expansion. We report here that miR-21 …

Investigation Of Factors Affecting The Hiv Continuum Of Care In Tennessee, Elaine Loudermilk

Electronic Theses and Dissertations

Introduction: Factors contributing to the HIV continuum of care (HCC) for adults in Tennessee (TN) have not been studied in depth with known predictors for HIV risk, specifically adverse childhood experiences (ACEs), among low annual income or sexual minority groups [lesbian, gay, bisexual, or transgender (LGBT)].

Methods: A mixed methods study design was used to assess factors related to the HCC. Quantitative analysis used the TN Behavioral Risk Factor Surveillance System data to examine at risk and ever tested for HIV, to (1) investigate ACEs among adults with low-income (<$25,000 annually) in 2016-2017 and (2) among LGBT in 2018. Descriptive statistics and multiple logistic regression (MLR) analysis stratified by TN grand division were performed. Qualitative analysis included 11 interviews with persons living with HIV (PLWH) receiving care at a local clinic to evaluate surveillance questions related to ACEs and the HCC to develop a culturally appropriate survey.

Results: Quantitative results found that among LGBT (N=262) and low-income …

Roles Of Endothelial Cell Heat Shock Protein A12b And Β-Glucan, A Reagent For Trained Immunity In The Regulation Of Inflammation In Sepsis, Fei Tu

Electronic Theses and Dissertations

Sepsis is dysregulated host immune response to infection causing life-threatening organ dysfunction. Endothelial cell dysfunction and uncontrolled inflammatory responses are two contributors for sepsis-induced mortality. The crosstalk between endothelial and immune cells plays a critical role in the pathophysiology of sepsis. Therefore, understanding the mechanism of interaction between endothelial and immune cells will provide novel information to develop therapeutic strategies for sepsis.

Pathogen associated moleculear patterns (PAMPs) and/or damage associated molecular patterns (DAMPs) produced during sepsis, activate endothelial cells to increase the expression of adhesion molecules, attracting immune cell infiltration into the tissues. Uncontrolled inflammatory responses during the early phase …

A School-Based Sexual Health Education Program, Tracy L. Kendall

Electronic Theses and Dissertations

A small rural community has high incidence rates of chlamydia (4,751 per 100,000) and gonorrhea (970 per 100,000) in females 15–24 years old. Data obtained from Texas Health and Human Services showed that incidence rates of chlamydia and gonorrhea in females 15–24 years old were higher in Navarro County, Texas, than the state of Texas. Texas schools do not mandate sex health education. There is a gap in school-based sexual health education available to 18- and 19-year-old females residing in this rural community in Texas. The purpose of this research study was to evaluate the impact of school-based sexual health …

An Analysis Of The Role Of Reality Television In The Representation Of Immigrants On Tlc's Show, 90 Day Fiancé., Morohunfolu Jimade Seton

Electronic Theses and Dissertations

A larger number of people reside outside their country of birth today than in any other time in history, and these levels are expected to continue to rise in the future (International Organization for Migration, 2011). The United States is currently the most popular immigrant destination in the world, with more immigrants than any other country. Immigrants statistics indicate that the immigrant population in the United States reached a record of 44.4 million in 2017 (Pew Research Centre, 2019). Correspondingly, the percentage of immigrants who were admitted into the U.S. as spouses of citizens has increased over of the last …

Louisville's Dark Tourist: Liminality, Legend, And The Macabre., Montgomery Quaid Adams

Electronic Theses and Dissertations

This thesis is a historical and theoretical analysis of touristic motivations behind visiting dark tourist attractions that uses two Louisville, Kentucky attractions as case-studies. It begins by providing an overview of concepts relevant to the analysis of these motivations including liminality, dark tourism, and legend studies, thereby drawing connections between these concepts to develop a framework for the analysis of these liminal spaces and the legends that surround them. It uses these theories to build a framework that argues for the inclusion of legend studies in the conversation of dark tourism and providing a new lens for viewing touristic motivation …

Development Of Rationally Designed Live Attenuated Vaccines For Lassa Fever And Venezuelan Equine Encephalitis., Dylan Macgregor Johnson

Electronic Theses and Dissertations

Lassa Virus (LASV) and Venezuelan Equine Encephalitis Virus (VEEV) are two single stranded RNA viruses belonging to the Arenavirus and Alphavirus families, respectively. Both are emerging pathogens without approved vaccines or treatments. VEEV is an important biothreat pathogen because it has been weaponized and is extremely infectious as an aerosol. VEEV causes biphasic febrile illness that can progress to a viral encephalitis with low mortality, but high morbidity. LASV causes a viral hemorrhagic fever, Lassa Fever (LF), which is endemic in West Africa, and responsible for between 100-500k annual infections with a 1-2% overall mortality rate. ML29 and VEEV TC-83 …

Dual Role Of Antimicrobial Peptide Cathelicidin In Alcohol-Associated Liver Disease., Fengyuan Li

Electronic Theses and Dissertations

Patients with alcohol-associated liver disease (ALD) have high morbidity and mortality in its severe forms. One of the major features in different forms of ALD is the altered gut microbiota. Antimicrobial peptides (AMPs) play a crucial role in maintaining gut microbiota homeostasis. LL-37 (known as CRAMP in mouse) is the sole member of the human cathelicidin family and has piqued great research interest for its dual role in modulating microbiota and the immune response in metabolic diseases. Inflammasome activation is an important component of the liver pathophysiology in ALD and requires two signals for its full activation to induce the …

The Emerging Oral Pathogen, Filifactor Alocis, Disrupts Neutrophil Functions To Enhance Survival And Dysregulate Inflammation., Irina Miralda Molina

Electronic Theses and Dissertations

Periodontitis is an irreversible, chronic inflammatory disease where pathogenic microbial communities accumulate in the gingival crevice. Advances in culture-independent techniques have facilitated the identification of new bacterial species in periodontal lesions, such as the Gram-positive anaerobe, Filifactor alocis. Neutrophils are a major component of the innate host response, and the outcome of their interaction with F. alocis may be a determinant of oral health status. While neutrophil functions typically protect the host against periodontal disease, oral pathogens have adapted to evade or disarm neutrophil microbicidal functions while promoting mechanisms that drive inflammation, which also provides a source of nutrients …

Tobacco Smoke Exposures And Fertility-Related Outcomes Among Females Seeking Fertility Care, And The Interaction With N-Acetyltransferase 2 (Nat2).., T'Shura S. A. Ali

Electronic Theses and Dissertations

Cigarette smoke contains thousands of harmful substances and is one of the leading preventable causes of mortality and morbidity in the United States. Past studies examining tobacco smoke exposures on fecundability and pregnancy outcomes are inconsistent. NAT2 is an important enzyme in the metabolism of xenobiotic substances found within tobacco smoke. This preconception cohort study examines associations between active smoking and secondhand smoke exposure (SHSe) on fecundability and spontaneous abortion (SA), and explores a possible interaction with NAT2 acetylator status. A total of 223 women seeking fertility care were followed for up to 2.3 years. Preconception tobacco smoke exposures were …

Functionalizing Nanoparticles With Cafa Protein To Target Bar Peptide For Oral Delivery Applications., Hetal Desai

Electronic Theses and Dissertations

Background: Porphyromonas gingivalis adherence to Streptococcus gordonii may be important for P. gingivalis colonization in the oral cavity. Nanoparticles encapsulating synthetic peptide BAR (BAR-NPs) inhibit P. gingivalis adherence more potently than free BAR. However, BAR-NPs would exhibit low retention in an open flow environment. Hypothesis: Targeting BAR-NPs to the streptococcal surface using CafA protein will enhance their efficacy. Methods: CafA-modified NPs encapsulating BAR were synthesized using double emulsion approach. Surface binding and retention, and release kinetics of BAR from CafA-modified NPs was assessed. Functional inhibition assays were performed using dual a species biofilm. Results: CafA-modified NPs demonstrated specificity of adhesion, …

Tobacco Enhances Bacterial-Induced Periodontal Bone Loss In Mice., Mina Iskander

Electronic Theses and Dissertations

Background: Tobacco smoking is the leading environmental risk factor for periodontal diseases. Delineation of the mechanisms underlying tobacco-induced or exacerbated periodontitis is hampered by the lack of an appropriate and reliable animal model. Hypothesis: We hypothesized that Porphyromonas-gingivalis-infected, cigarette smoke-exposed mice would represent reproducible models of acute (ligature model) and chronic (oral gavage model) tobacco-enhanced periodontitis that reflect multiple aspects of the disease noted in human smokers. Methods: In a chronic oral gavage disease model, Balb/c mice (6-8 weeks, 4 groups of n = 6 per group) were exposed to smoke produced by a Teague-10 smoking machine from 1R6F research …