Medicine and Health Sciences Commons^™

Peromyscus Maniculatus Bairdii And Peromyscus Maniculatus Sonoriensis Polymorphisms, Matthew Dixon Lucius

Theses and Dissertations

Sequencing technology has advanced greatly over the past couple of decades. This has led to many studies developing hypotheses based on genomic data. This requires many genomic studies to have up-to-date information on the species’ or subject’s genome being investigated. If a study does not have accurate or up-to-date background information, then they cannot fully develop their theories that are being established. In this study, I utilize outbred Peromyscus maniculatus, deer mice that are genetically diverse, to record the polymorphisms that are found throughout the Peromyscus maniculatus genome. I first explore the differences between the polymorphisms found in Peromyscus …

Genomic Analysis Workflows To Identify Mutational Signatures And Structural Variations In Ovcar8 Cells And Rad51d-Deficient Mouse Embryonic Fibroblasts, Manli Yang

Theses and Dissertations

Specific genomic profiles associated with exposure to DNA damaging agents have been identified in cancer related genes, revealing that mutational patterns can be carcinogen- specific. However, there have been limited efforts to demonstrate similar clear relationships for endogenous mutational processes. One endogenous source of mutations is contamination of the deoxynucleotide pool with damaged bases that, if incorporated into DNA, cause mutations.

The Catalog of Somatic Mutations In Cancer (COSMIC) represents an international effort to characterize mutations in cancer. A mutational signature is the pattern of mutations generated by a mutational process. Each mutational process contains two parts: DNA damage and …

Medication Therapy Management Implementation In Conjunction With A Rural Health Clinic In Minnesota: A Cqi Impact On Diabetes Metrics, Abigail Sirek Pharmd

Theses and Dissertations

The purpose of this continuous quality improvement project was to implement a pharmacist-led Medication Therapy Management (MTM) clinic in rural, central Minnesota and assess the impact on patients’ healthcare over a six-month period. Patients were identified through the clinic’s diabetes registry, which included patients 18 through 75 years old with a diagnosis of diabetes not meeting all five D5 goals, as recommended by the Minnesota Community Measurements, independently referred by the provider, or be identified by their insurance company as a patient that would benefit from an MTM visit. The D5 focuses on blood pressure and blood sugar control, appropriate …

Discovery And Mechanistic Study Of Novel Pbd-Targeted Inhibitors Of Plk1 For Prostate Cancer Treatment, Danda Pani Chapagai

Theses and Dissertations

Polo-like kinase 1 (PLK1) is a central player in regulating entry into and progression through mitosis. Inhibition of sub-cellular localization and kinase activity of PLK1 through the Polo-box domain (PBD) is emerging as a viable alternative to ATP binding site directed drugs for which the development of resistant mutants and inhibition of closely related members of the PLK family (tumor suppressor roles) are primary concerns. I describe related novel non-peptidic PBD binding inhibitors, termed abbapolins, identified through successful application of the REPLACE strategy and demonstrate their potent antiproliferative activity in prostate tumors and other cell lines. Furthermore, the abbapolins show …

Selective Small Molecule Targeting Of Mcl-1 In Multiple Myeloma, Omar S. Al Odat

Theses and Dissertations

Multiple Myeloma (MM) is a deadly blood malignancy, characterized by the uncontrolled proliferation of aberrantly differentiated plasma cells. MM is challenging to diagnose and treat, accounting for approximately 12% of hematologic malignancies. The overexpression of anti-apoptotic group of Bcl-2 family proteins, particularly Myeloid cell leukemia 1 (Mcl-1), play a critical role in the pathogenesis of MM. The overexpression of Mcl-1 is associated with drug resistance and overall poor prognosis. Thus, inhibition of the Mcl-1 protein is an attractive therapeutic strategy against myeloma cells. Over the last decade, the development of selective Mcl-1 inhibitors has seen remarkable advancement. In this project, …

Protein Structure And Interaction: The Role Of Aromatic Residues In Protein Structure And Interactions Between Pyridoxine 5'-Phosphate Oxidase/Dopa Decarboxylase, Mohammed H. Al Mughram

Theses and Dissertations

Naturally developed proteins are capable of carrying out a wide variety of molecular functions due to their highly precise three-dimensional structures, which are determined by their genetically encoded sequences of amino acids. A thorough knowledge of protein structures and interactions at the atomic level will enable researchers to get a deep foundational understanding of the molecular interactions and enzymatic processes required for cells, resulting in more effective therapeutic interventions. This dissertation intends to use structural knowledge from solved protein structures for two distinct objectives.

In the first project, we conducted a bioinformatics structural analysis of experimental protein structures using our …

Examining Ayahuasca Constituents At 5-Ht2a Receptors In Search Of Antidepressant Action, Jeremy D. Rolquin

Theses and Dissertations

Recently, it has been reported that ligands of the 5-HT_2A receptor can have drastic and fast-acting efficacy towards a number of different mental health disorders, such as depression and anxiety. A mixture of Amazonian plants calledayahuasca contains multiple compounds which have been shown to interact with the serotonergic system, and the 5-HT_2Areceptor in particular.

The structurally similar compounds (DMT, harmine, harmaline, and tetrahydroharmine) found in ayahuasca were examined for differences in their physiochemical properties that might contribute to their binding affinity for the 5-HT_2Areceptor. 3D Molecular modeling and docking studies of these compounds were …

Pharmacists' Role In Opioid Use Disorder And Overdose Prevention And Treatment And Their Attitudes And Perceptions Towards Distributing Naloxone Under A Standing Order, Stephen C. Ijioma

Theses and Dissertations

Background: Opioids are a class of drugs that bind to opioid receptors (mu, delta, and kappa), located in the central and peripheral nervous systems, to exert responses such as analgesia, respiratory depression, euphoria, and miosis. The opioid epidemic is characterized in large part by an increase in opioid overdose deaths. Community pharmacists are one of the most accessible healthcare professionals who frequently interact with patients and can implement OUD and opioid overdose prevention strategies. Treatment for opioid overdose and OUD include naloxone for overdose deaths as well as medication-assisted treatment for OUD.

Objective: The specific aims of this thesis include …

Budget Impact Analysis Of Upadacitinib For The Management Of Moderate-To-Severe Atopic Dermatitis In Patients Treated With Systemic Therapies In The United States, Haya O. Alobaid

Theses and Dissertations

Objective: This study evaluated the budget impact of introducing upadacitinib for patients with uncontrolled moderate-to-severe atopic dermatitis (AD) from a United States (U.S.) private payer perspective.

Methods: The model estimated costs before and after the adoption of upadacitinib for a hypothetical one million covered lives over 3 years. The model included immunosuppressant agents and dupilumab. Market uptake was assumed to be 2% per year. Treatments incur a cost for drug acquisition, and the costs associated with drug administration, laboratory testing, and clinic visits. The model calculated the impact on the budget in 2022 U.S. dollars. Various assumptions on market …

Trajectories Of Medication Non-Adherence With Time-Varying Predictors And Association With Health Outcomes: A Comparison Of Classical Statistical Methods With Machine Learning Algorithms, Vasco Pontinha

Theses and Dissertations

Background: Medication adherence is a major obstacle to improving health care outcomes in long-term therapies for chronic diseases. According to the World Health Organization, interventions for improving medication adherence can have a higher impact on the health of the population than any other advance in medical treatments. Approximately 125,000 individuals die every year in the U.S. because of non-adherence to medication, representing societal costs of $100-289 billion. Previous research has successfully used group-based trajectories methods to identify similar longitudinal medication adherence trajectories. However, medication adherence is not an isolated behavior and is influenced by many factors that current interventions fail …

Structure-Based Drug Discovery And Development Of Protein Structure Prediction Tools Using An Empirical Force Field, Noah B. Herrington

Theses and Dissertations

Traditional drug discovery has rapidly accelerated thanks to development of computational molecular modeling. The crucial component that these computational studies hinge upon is having a well-defined, and energetically favorable structure. Structures of proteins and ligands that meet these criteria are important for accurately simulating models used to study drug binding. To demonstrate the role of accurate structure simulation in the study of these events, this thesis presents, first, a story examining the problem of accurate structure modeling of ionizable residues within protein structures, specifically aspartic acid, glutamic acid, and histidine. I present our method, which uses the HINT force field …

The Economic Value Of Pharmacist-Physician Collaborative Care Models In Hypertension Management, Jessica S. Jay

Theses and Dissertations

Background: Hypertension is highly prevalent in the United States, affecting nearly half of all adults (43%). Studies have shown that pharmacy-physician collaborative care models (PPCCM) for hypertension management significantly improve blood pressure (BP) control rates and provide consistent control of BP. Time in target range (TTR) for systolic BP is a novel measure of BP control consistency that is independently associated with decreased cardiovascular (CV) risk. There is no evidence observed improvement in TTR for systolic BP with PPCCM is cost effective.

Objective: This study aimed to compare the cost-effectiveness of PPCCM with usual care for the management of hypertension …

Development And Optimization Of A Low Volume Air-Jet Dry Powder Inhaler (Dpi) Platform For The Delivery Of High Dose Aerosolized Powder To Infants, Connor Howe

Theses and Dissertations

The goal of this research project was to develop an infant air-jet dry powder inhaler (DPI) platform for high-efficiency nose-to-lung (N2L) aerosol administration to infants through optimization of individual system components followed by expansion of the system to higher doses and different formulations using a new approach. Primary challenges associated with aerosol delivery to infants using the N2L route include the extremely narrow extrathoracic airways, short inspiratory times (~0.2 sec), low safe airway pressure (H₂O), and very low volumes of air (~10 mL) available to form the aerosol. The infant air-jet DPI system was comprised of three main …