Medicine and Health Sciences Commons^™

Effectiveness Of Antibiotic Stewardship For Healthcare Providers At Urgent Care Clinics, Helen T. Adewole

Electronic Theses and Dissertations

Antibiotics have revolutionized modern medicine; however, the overuse in urgent care and primary care significantly contributes to the global burden of infections resistant to available antimicrobial medicines. Approximately 30% of the antimicrobials prescribed in acute care settings are unnecessary. Patient demand for antibiotics has seemingly skyrocketed following the recent COVID-19 pandemic. Practitioners must be knowledgeable about antibiotic stewardship initiatives, such as the wait-and-see approach, to reduce antibiotic overuse and improve the trajectory of antibiotic resistance and patient health outcomes. The gap in practice was the limited awareness of scientific evidence-based tools to partner with patients and improve antibiotic prescription patterns. …

Isolation And Total Synthesis Of Sigma-2 Ligands From Marine Cyanobacteria, Andrea Hough

Electronic Theses and Dissertations

Cyanobacteria have been studied for over 50 years as a source of new antibiotics, antiviral, and anticancer drugs. The research described in this dissertation investigates marine cyanobacteria as a source of natural products with activity within the central nervous system and with cytotoxicity against breast cancer cells. Barbamide (1) is a known cyanobacterial metabolite that has been re-isolated from a variety of species and collection sites suggesting broad utility as a signaling molecule. Utilizing the psychoactive drug screening program, we screened barbamide for CNS activity and found that barbamide exhibited affinity for the kappa opioid receptor (KOR) and …

Exploring The Experiences Of Underrepresented Students Pursuing Health-Related Graduate Or Professional Programs, Alison Williams

Electronic Theses and Dissertations

For many years graduate and professional education programs for the health professions have sought to increase the diversity of their student body to include students from a wider variety of backgrounds. Increasing the diversity of healthcare providers is an essential component of addressing inequities in healthcare. However, despite initiatives to increase racial and ethnic diversity in the health professions, these professions remain largely White and female. Previous researchers have sought to identify the reasons that racial and ethnic minorities are underrepresented in healthcare, and the barriers to persistence and success. Little research exists explaining why men are underrepresented in the …

The Association Of Long Working Hours And The Use Of Prescription Sedatives Among U.S. Workers., Emmanuel Ezekekwu

Electronic Theses and Dissertations

BACKGROUND: Meeting the needs of a round-the-clock and globalized society has led to an increase in long working hours. This trend has been accompanied by a corresponding rise in sleep disorders and subsequent use of sedating medications. Overtime hours have been associated with adverse health outcomes such as cardiovascular diseases, symptoms of psychological distress, and health behaviors, including risky intake of alcohol and smoking. Hence, the main objectives of this three-paper dissertation were to examine the multi-faceted relationship between working hours, the use of prescription sleep aids, the onset of psychological distress, and the use of health care services. METHODS: …

Hgf-Mediated C-Met Signaling In Human Corneal Epithelial Cells., Kate Tarvestad

Electronic Theses and Dissertations

Vision is often regarded as the primary sense of humans. The cornea is the main refractive tissue that permits light through to the retina, allowing a clear image. When the cornea sustains damage, it opens a pathway for infection and blindness through fibrotic processes. Healing the corneal tissue is critical for vision restoration and pain alleviation. Growth factors and their cognate receptors are currently under investigation as tools to restore proper corneal physiology. We hypothesize that manipulating the hepatocyte growth factor (HGF)/ c-Met signaling pathway is one route to promote quality corneal healing. This thesis investigates the signaling, trafficking, and …

Quality By Design Based Optimization Of Anti-Inflammatory Nanoemulgels For Local Treatment Of Burn Wounds, Leah Dickey

Electronic Theses and Dissertations

Burns are some of the most traumatizing and damaging skin injuries, with the potential of causing extensive internal damage that increases the risk of chronic wound development. Oral and topical analgesics in combination with antibiotics can provide temporary relief and improve wound healing progress for both mild and severe burns. However, recurrent systemic exposure to pain relievers and antibiotics has been associated with adverse side effects including nausea, drowsiness, abdominal pain, etc., and increased risk of new infections or even ulcers. Local and targeted drug delivery systems, such as nanomedicine, have gained attention as potentially more effective alternatives to improve …

Prevalence And Predictors Of Polypharmacy In Adolescents Who Have Engaged In Sexually Abusive Behaviors, Rebecca Gilley

Electronic Theses and Dissertations

Polypharmacy, or the concurrent use of multiple medications, is associated with detrimental outcomes for patients and has gathered increasing attention within the scientific clinical literature. Pediatric populations warrant special consideration for the practice of polypharmacy, as medication effects are more pronounced in youth and adverse effects may have a lasting impact on development. This dissertation study examined psychotropic prescribing practices in a sample of adolescents who have engaged in sexually abusive behaviors, a subset of justice-involved youth who are at risk for polypharmacy. General prescribing trends were examined, and a principle components analysis involving variables associated with risk of polypharmacy …

Development Of Anti-Inflammatory Theranostic Nanocolloids Using Quality By Design Approaches, Michele Herneisey

Electronic Theses and Dissertations

Nanocolloids are attractive delivery vehicles for drugs with poor aqueous solubility. Despite this, relatively few nanocolloid products exist on the market. Currently, there is a lack of standardization in the pre-clinical, academic setting regarding nanocolloid development and quality control testing. Adaptation of quality by design (QbD) methods used in the pharmaceutical industry to nanocolloid development is a desirable approach that can improve nanocolloid product and process understanding, resulting in an increased number of marketable products.

The central hypothesis of this work is that QbD approaches can be utilized to optimize theranostic (therapeutic and diagnostic) nanocolloid stability, drug loading, and imaging …

Effect Of Chemical And Physical Enhancers On The Skin Permeation Of Cromolyn Sodium, Miranda Holman

Electronic Theses and Dissertations

Cromolyn sodium (CS) has clinically shown to be an effective topical remedy for atopic dermatitis, however its physiochemical properties prevent efficient passive drug delivery beyond the outermost skin layer. This project aimed to optimize CS gel formulations and applications to improve drug delivery to the dermis of skin by examining various topical enhancement strategies. Oleic acid, salcaprozate sodium, and microneedles were investigated as enhancers for their effect on skin permeation of CS. In vitro permeation studies across dermatomed porcine ear skin tested CS gels to determine 24-hour drug permeation profiles and skin layer distribution of drug. Further, extraction method efficiency, …

35ci Solid-State Nmr Characterization Of Polymorphs And Cocrystals Of Xylazine Hci, Louae M. Abdulla

Electronic Theses and Dissertations

Xylazine HCl (X), a common veterinary analgesic, has four reported polymorphs that are stable under ambient conditions, Form A (Xa), Form X (Xx), Form Z (Xz), and Form M (Xm), and one monohydrate (Xh). A commercial sample of X was found to contain mixtures of polymorphs and previous synthetic approaches proved unreliable and/or unsuccessful for the production of pure phases in high yields. Herein, we report methods for the reliable preparation and interconversion of polymorphs of X (including mechanochemical synthetic pathways), the discovery of a novel polymorph (Xy), and synthesis of three novel cocrystals with coformers containing amide and carboxylic …

Polymeric Nanovaccine Delivery System For Influenza Vaccine, Chaitanya K. Valiveti

Electronic Theses and Dissertations

Vaccines are the most efficient and cost-effective method for preventing illnesses caused by infectious pathogens. Even though the great success of vaccines over decades, the development of safe and robust vaccines is still essential for emerging new pathogens, re-evolving old pathogens, and improving the insufficient protection given by existing vaccines. One of the most critical strategies for developing effective new vaccines is selecting and using a suitable adjuvant or immune stimulant. Immunologic adjuvants are essential for improving vaccine potency by enhancing the immune response of vaccine antigens. The amount of antigen could be spared with improved potency, especially during mass …

Immune-Related Adverse Events Of Immune Checkpoint Inhibitors: Incidence, Risk Factors, Clinical Outcomes, And Economic Burden In Older Adults With Non-Small Cell Lung Cancer, Yiran Rong

Electronic Theses and Dissertations

To fill the gap in existing literature related to immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC), this dissertation focused on: 1) assessing the incidence, spectrum and risk factors for the development of irAEs; 2) assessing the clinical impact of irAE occurrence on survival and treatment discontinuation; 3) analyzing and estimating the incremental economic burden of irAEs among an older population in the United States (US). A retrospective cohort study was conducted using the SEER-Medicare 2020 linkage database in order to evaluate the three study objectives. The dissertation included 8,175 patients diagnosed …

Design And Synthesis Of Fused Pyrimidines As Single Agents With Combination Chemotherapy Potential, As Tubulin Polymerization And One-Carbon Metabolism Inhibitors For Cancer, Tasdique Quadery

Electronic Theses and Dissertations

This dissertation describes the design, synthesis, and biological evaluation of bicyclic fused pyrimidines as single agents with combination chemotherapy potential with both antiangiogenic and cytotoxic effects. The dissertation also discusses one-carbon metabolism inhibitors and tumor targeting proteolysis targeting chimeras (PROTACs).

In cancer chemotherapy, the two major limitations are the dose-limiting toxicities of clinically used agents and the development of resistance to the treatment. Combination chemotherapy with antiangiogenic agents and microtubule targeting agents has shown an advantage against both these drawbacks. Single agents with both antiangiogenic activity and cytotoxicity would afford a therapy that circumvents pharmacokinetic problems of multiple agents, avoid …

Decreasing Unintentional Pregnancies For Tennesseans, Paula M. Todd

Electronic Theses and Dissertations

In 2018, 49% of all pregnancies in the United States were unintended, with women with a lower- income status being five times more likely to experience an unplanned pregnancy. Tennessee has a high rate of unintended pregnancies, particularly among the uninsured, low-income, and rural teen populations; some 22% of these unintended pregnancies end in abortion. Oral or transdermal contraceptives that are affordable and accessible for women of childbearing age can reduce unintentional pregnancies. The addressed gap in clinical practice was that contraceptives are not currently available over the counter in Tennessee pharmacies without a prescription, which necessitates a costly medical …

Development Of A Combined Feedforward-Feedback Quality Control System For Extended-Release Granules Using A Quality By Design Approach, Yuxiang Zhao

Electronic Theses and Dissertations

Objectives

For a fluid bed film coating process to consistently deliver quality products, its control system needs to be robust against the variability of input materials and environmental disturbances. Presently, limited studies have been reported to understand the effects and interactions of the material attributes, environmental variables, and process parameters on the product in vitro drug dissolution. A control system can be developed with a proper understanding of the coating process, by adjusting the process parameters in feedback and feedforward manners to compensate for the undesired effect caused by disturbances, and ensure consistent product quality.

Methods

The control system was …

Towards A "Universal Chemical Biology Toolbox" For Tackling Human Diseases, Christopher Swank

Electronic Theses and Dissertations

A lack of new drug targets and drug mechanisms, coupled with drug-pipeline attrition, represent significant problems in oncology drug discovery. Towards addressing this challenge, “fully-functionalized small-molecule probes” (FFSMPs) have been established, which are compounds that can be immediately used as “bait” to capture their protein targets under the same assay conditions used for oncology-based phenotypic screening. Specifically, each FFSMP library member contains one or more structural-diversity elements to promote interactions of the probe with different protein targets in living cells, an electrophile or photoreactive functional group for covalent attachment of the probe to interacting proteins via affinity or photoaffinity labeling, …

The Role Of Mek1/2 And Mek5 In Melatonin-Mediated Actions On Osteoblasts And Osteoclasts Differentiation, Bone Formation, Bone Microarchitecture, And Bone Biomechanics, Fahima Akter Munmun

Electronic Theses and Dissertations

Melatonin, the main endogenous hormone to entrain the circadian system, is not limited to its role in regulating the sleep-wake cycle; rather, it affects a wide variety of systems involving antioxidant, anti-inflammation, blood pressure regulation, seasonal reproduction, ovarian physiology, and immune function. Driven by the diversity of its action, melatonin for a long time has also been studied in the field of bone and mineral research both clinically and pre-clinically. Exogenous administration of melatonin in clinical trials in perimenopausal women (MOPS; NCT01152580); or postmenopausal women with osteopenia (MelaOST; NCT01690000 and MOTS; NCT01870115) confirmed improvement of bone mineral density (BMD) (MelaOST; …

Histone Deacetylases In Alcohol Associated Liver Disease., Srineil Bodduluri

Electronic Theses and Dissertations

Alcohol abuse is endemic worldwide and there is no FDA approved treatment for Alcohol-Associated Liver Disease (ALD). Many scholars have posited that targeting Histone Deacetylases (HDAC) may be therapeutic in ALD intervention. In this study, the changes in hepatic gene expression and immune phenotyping of mice undergoing chronic plus binge alcohol exposure was examined. The characterization of relative mRNA levels for all 18 HDAC were performed. Results showed decreased expression of the genes HDAC 1,7,9,10,11 and Sirtuin enzymes (SIRT) 3,4,5,7. Other pathways related to lipid metabolism as well as systemic inflammation and hepatic injury also exhibited significant changes. These altered …

Clinical Pharmacy Services And Medication Utilization In Hospice Care, Aishwarya Kulkarni

Electronic Theses and Dissertations

Background: As discussed within the guidelines from the American Society of Health-System Pharmacists (ASHP), pharmacists are an integral part of the hospice multidisciplinary team involved in optimizing the treatments. Methadone, a long-active opioid, is particularly useful in this population but may be clinically underutilized. Additionally, the cost share of medication utilization in hospice and palliative care is shifting towards hospice providers. The assessment of medication utilization and methadone use in this setting can help develop overall cost/clinical optimization strategies. Thus, there is a need to understand the use and expenditure of various medications and pharmacists' role in providing methadone …

The Role Of Src In Nsclc Cell And Lung Fibroblast Migration On 3d Cell-Derived Matrix., Austin M Krueger

Electronic Theses and Dissertations

Lung cancer is responsible for the most cancer deaths between males and females, with a 6% five-year survival rate. Cancer metastasis is one of the leading causes of lung cancer lethality. Our lab has developed a method to culture cells on cell-derived matrix (CDM) and study cell-ECM interactions. This study utilized multiple cell migration methods to investigate the migration of NSCLC cells and IMR90 lung fibroblasts, both together and independently, on 2D plastic and 3D CDM. Our results showed that inhibiting Src, a significant influencer of cell migration and member of integrin activation, blocked cancer cell migration on 2D and …

Pde4 Inhibition: A Novel Therapeutic Strategy In Liver Fibrosis., Mohamed Elnagdy

Electronic Theses and Dissertations

Background: Liver fibrosis is accumulation of extracellular matrix (ECM) proteins due to chronic liver injury. Chronic hepatic damage can occur due to multiple causes including, alcohol, non-alcoholic steatohepatitis and chronic viral hepatitis. Liver fibrosis is a critical problem worldwide due to the extremely high incidence of alcohol associated liver damage and chronic viral hepatitis. Moreover, there is no FDA approved therapy for liver fibrosis. Activation and transdifferentiation of quiecent hepatic stellate cells (HSCs) to myofibroblasts (MFBs) is the main event contributing to liver fibrosis. This process involves two phases, the initiation and the perpetuation phases. Hepatocyte injury and inflammatory response …

The Place And Role Of Pharmacy Benefit Management (Pbm) Companies In Us Healthcare System, George Mattis Ii

Electronic Theses and Dissertations

On average, prescription drugs cost US consumers more than any other developed country in the world. US drug makers claim that intermediaries in the prescription drug supply chain, companies called pharmacy benefit managers (PBM), are forcing them to increase their drug prices. PBMs counter that the discounts they receive from drug makers are channeled to insurers. This thesis will examine the role that PBMs play in the prescription drug supply chain and determine what effect they have on drug prices. This thesis will utilize a comparative static model, Structure, Conduct, Performance (SCP) framework to analyze the pharmaceutical manufacturing and the …

Nmr-Based Characterization Of A Glucan Isolated From Ganoderma Lucidum, Alysia Gonzales

Electronic Theses and Dissertations

Ganoderma lucidum is a polypore fungus commonly known as Lingzhi, Youngji or Reishi mushroom in East Asia. It is frequently marketed as an herbal supplement and often utilized as traditional Chinese medicine. Our research comprises the structural investigation of the principal polysaccharide from this fungus. After proper purification, the fungal glucan was subjected to multiple experiments of NMR spectroscopy, including 1D 1H and 13C, 2D; 1H-1H COSY, 1H-1H TOCSY, 1H-1H NOESY, 1H-13C HSQC, 1H-1H Phase Sensitive-TOCSY, and 1H-13C TOCSY-HSQC NMR spectra. Data has confirmed that this fungal polysaccharide contains residues of glucose (91.31%) as major, galactose (4.99%), and mannose (3.69%) …

Influence Of Rage Signaling On Cellular Communication In Diabetes-Mediated Vascular Calcification, Amber Michelle Kennon

Electronic Theses and Dissertations

Chronic hyperglycemia is one of the main characteristics of type 2 diabetes mellitus (T2DM). With the increased prevalence of T2DM, the risk of cardiovascular complications, including heart attack or stroke, is increased. Complications linked to the vasculature are increased vascular calcification (VC) or mineral deposition within the medial layer of conducting arteries. Under calcification conditions, vascular smooth muscle cells (VSMCs) undergo an osteogenic switch to an osteoblast-like cell and begin producing bone proteins. Chronic hyperglycemia can also result in increased extracellular matrix (ECM) synthesis, accumulation, and crosslinking. One of the cell types responsible for increased ECM synthesis are ‘activated’ fibroblasts …

Hot-Melt Extrusion Based Fused Deposition Modeling 3d Printing Of Atorvastatin Calcium Tablets: Impact Of Shape And Infill Density On Printability And Performance, Preethi Mandati

Electronic Theses and Dissertations

The main objective of the current research is to investigate the effect of shapes (heart and round shape tablets) and infill densities (50% and 100%) on drug release profiles of tablets prepared by hot melt extrusion (HME) coupled fused deposition modeling (FDM) technique. Two different commercial FDM 3D printers with different filament feeding mechanisms were evaluated for suitability of printing. Drug-loaded filaments of 1.5 mm and 2.5 mm diameters were extruded using Process 11 mm HME, using atorvastatin as a model drug and Kollicoat® IR, Kollidon® VA64, Kollidon®12PF, and Kolliphor® P407 as hydrophilic polymers. Filaments of Kollicoat® IR in combination …

Responses Of Predatory Myxobacteria To Prey Signaling Molecules & Features Of A Pseudomonas Prey Avoiding Predation, Shukria Akbar

Electronic Theses and Dissertations

Gram-negative unicellular myxobacteria, along with their multicellular lifestyle andbiologically active specialized metabolites, are known for the predatory interactions with Gram-negative/ Gram-positive bacteria and fungi. Although myxobacterial predation range have been exploited extensively, little is known about the prey associated molecules contributing to myxobacterial predator-prey dynamics. By employing transcriptomics and untargeted metabolomics approaches, we demonstrate two structurally distinct classes of signaling molecules from Gram-negative bacterial prey elicit significant omics responses from myxobacteria, Myxococcus xanthus and Cystobacter ferrugineus. An overlapping and general response to acylhomoserine lactones, whereas a distinctive response to a quinolone signaling molecule is observed from both myxobacteria. Similarly, by …

Rap1a Overlaps The Age/Rage Signaling Cascade In Type 2 Diabetes Mellitus, Stephanie Burr

Electronic Theses and Dissertations

Diabetic individuals have an increased risk for developing cardiovascular disease due to stiffening of the left ventricle, which is thought to occur, in part, by increased AGE/RAGE signaling. Advanced glycation end products (AGEs) accumulate within the body over time, and under hyperglycemic conditions, the formation and accumulation of AGEs is accelerated. AGEs exert their effect by binding to their receptor (RAGE) and can induce myofibroblast differentiation, oxidative stress, cell-extracellular matrix contraction, and cell migration. Previous findings from our lab have demonstrated that preventing the production of Rap1a, a Ras-like GTPase signaling protein, in cardiac fibroblasts will decrease type 2 diabetes …

Abuse Deterrent Formulation Using Hot Melt Extrusion Technology, Vishvesh Raje

Electronic Theses and Dissertations

The purpose of the current study was to formulate hot melt extruded (HME) abuse deterrent pellets of acetaminophen(APAP), a model drug with the aid of high molecular weight hydroxypropyl methylcellulose (HPMC 4M ) and gelling agents (starch, pectin and carbopol). The formulated HME pellets were assessed for their abuse-deterrence (AD) potential using Category- 1 laboratory in-vitro evaluation standards. The pellets were examined for the particle size reduction (PSR), extraction in small volume, syringeability, thermal manipulation and dissolution for evaluating the resilience of the AD properties. Though, most of the formulation showed complete particle size reduction after grinding, grounded pellets were …

Applications Of Hot-Melt Extrusion (Hme) Technology And Investigation Of A Screening Tool For Hme, Gauri Deepak Shadambikar

Electronic Theses and Dissertations

Hot-melt extrusion (HME), an adaptable technology, has established its position in manufacturing operations like amorphous solid dispersions, immediate and controlled oral formulations, implants and taste masked products. In recent years the industrial focus has shifted towards continuous manufacturing, thus HME is being explored for new applications. The aim of this research was to investigate the novel applications of HME by carrying out an in-depth study to understand the interaction between the process and product and to investigate a screening tool for its small-scale formulation and development.As HME consumes large amount of samples during the developmental phase, we investigated a screening …

Design And Synthesis Of Salvinorin-Based Compounds For The Opioid Receptors., Nicholas S. Akins

Electronic Theses and Dissertations

Opioid receptors (OR) are expressed throughout both the peripheral and central nervous system and play crucial roles in the modulation of antinociception, addiction, anxiety, and depression. Salvinorin A, the main isolate of the hallucinogenic plant Salvia divinorum, is one of the most potent naturally occurring kappa opioid receptor agonists. Salvinorin A possesses beneficial effects as a therapeutic in a variety of CNS disorders, but due to its strong hallucinating, anxiogenic effects, and short half-life(t1/2), it has never advanced to clinical trials. Instead, salvinorin A has been used as an important prototype for the development of related drug candidates. Our initial …