Pharmacy and Pharmaceutical Sciences Commons^™

Positive Allosteric Modulation Of Glun1/Glun3 Nmda Receptors, Mia Ruth Johns

Graduate Student Theses, Dissertations, & Professional Papers

N-methyl-D-aspartate (NMDA) receptors are ionotropic glutamate receptors that mediate excitatory neurotransmission in the central nervous system (CNS) where they play critical roles in normal and pathological brain functions and neurodevelopment. While the glutamate/glycineactivated GluN2-containing NMDA receptors (GluN1/GluN2) have been extensively studied, the physiological roles and pharmacology of glycine-activated GluN3-containing receptors (GluN1/GluN3) remain less understood. Although GluN1/GluN3 receptors exhibit unique functional properties and play distinct roles in neuronal development and synapse maturation, studies of their precise roles in neurophysiology and circuit function are impeded by limited availability of GluN3-selective pharmacological tools. This study describes UCM-A86, a novel GluN3-selective positive allosteric …

The Effects Of Ph And Oncometabolites On Dna Repair Mediated By Alkb Family Enzymes, Quentin Mylie

Open Access Dissertations

Modifications of DNA and RNA, in particular methylations - such as N⁶-methyladenine (m6A), 5-methylcytosine (m5C), 1-methyladenine (m1A), and 3-methylcytosine (m3C) are crucial for gene regulation, genome integrity, and cellular adaptation. This dissertation investigates the role of the ALKB family of alpha-ketoglutarate (αKG) and iron-dependent dioxygenases in modulating these modifications, with a focus on how their activity is influenced by pH and metabolic factors, underscoring the connection between environmental conditions and epigenetic and genetic stability.

Chapter 1 provides a comprehensive literature review on the epigenetic and genetic regulation of DNA and RNA modifications, with a particular focus on methylation …

Real-World Clinical And Cost Effectiveness Of Osteoporotic Treatments In Men, Yu Ren

Open Access Dissertations

Osteoporosis is a condition characterized by the loss of bone mass, which increases the risk of fractures. In 2017-2018, the age-adjusted prevalence of osteoporosis among adults aged 50 and over was 12.6%, with 19.6% in women and 4.4% in men. Untreated osteoporosis can lead to a cycle of recurrent fractures that severely impact quality of life and place significant emotional, physical, and financial strain on patients, families, and healthcare resources. Approximately 50% of women and 20% of men will experience at least one fracture in their lifetime. In the United States, an estimated 1.5 million osteoporotic fractures occur each year, …

Analysis Of The Utilization Of Vegfinhibitors In Rhode Island And In Medicare Part B Nationally, Kevin Izzio

Open Access Master's Theses

Statement of the Problem: Age-related macular degeneration (AMD) and diabetic retinopathy (DR) are leading causes of blindness and low vision in the United States. In 2019, approximately 19.8 million Americans were living with AMD, which is classified into dry (non-neovascular) and wet (neovascular) forms, with the latter being more severe. DR, a complication of diabetes, affected an estimated 9.6 million Americans in 2021, with progression leading to proliferative DR (PDR) and diabetic macular edema (DME), both of which can cause vision loss. Vascular endothelial growth factor (VEGF) inhibitors are the standard treatment for these retinal diseases, targeting abnormal angiogenesis …

On! Original Flavor Oral Nicotine Pouch Characterization: Biorelevant In Vitro Nicotine Release Apparatus Assessment, Jason C. Funderburk, Melissa Morgan, Maria Lasaosa Garcia, Andreas S. L. Mendez, Matthew S. Halquist

Graduate Research Posters

Background: Oral nicotine pouch (ONP) use is rising. The sales of ONPs in 2019 were 126 million units, increasing to 808 million units in 2022. Understanding ONP in vitro release is critical for assessing exposure to ONP products.

Methods: The commercial brand ON! ONPs with nicotine label claims of 2, 4, and 8 mg, were evaluated in vitro for cumulative nicotine release using the bidirectional transmucosal apparatus (BTA) for 90 minutes. Nicotine quantification was performed by HPLC-PDA. For pH determination, ONP samples were prepared in water or artificial saliva (pH 6.8) with measurements for 30 minutes. BTA results were compared …

Flipped Classroom Versus Lecture: A Quasi-Experimental Study Evaluating The Performance Of Dental Students.”, Manal Elhijazi, Ihsane Benyahya

Health Sciences

Background: The flipped classroom is an active pedagogical modality that improves learning, autonomy and critical thinking. This work aims to evaluate the impact of the flipped classroom on student performance compared to the lecture in a biomaterials course.

Material and methods:Second-year dental students were invited to participate voluntarily in this quasi-experimental study .Thus, they were divided into two groups: one group benefited́ from the flipped classroom while the control group attended the lecture. At the end of a formative evaluation for both groups, their average grades were compared using Student's test (significance threshold set at p

Results : …

College-Specific Policies And Procedures: Barry And Judy Silverman College Of Pharmacy, Nova Southeastern University

Health Professions Divisions Course Catalogs and Course Descriptions

No abstract provided.

Optimization And Efficacy Of Car T Cells Derived From Newly Generated Anti-Cd22 Monoclonal Antibody For Blood Cancer Treatment, Wipawadee Ruengdej

Chulalongkorn University Theses and Dissertations (Chula ETD)

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of B-cell malignancies. Nevertheless, relapse due to loss of CD19 expression remains a major clinical challenge. CD22 serves as an alternative target because of its consistent expression on malignant B cells, even in CD19-negative disease. Optimization of CD22-directed CAR design is therefore critical to enhance antitumor potency and persistence. Two novel anti-CD22 CAR constructs were generated from monoclonal antibody clones 24A7G6 and 29H9C8, each incorporating either a 4-1BB or CD28 costimulatory domain. The resulting CAR T cells were evaluated for proliferation, phenotype, and cytotoxicity against CD22-positive (Raji, Nalm-6) and CD22-negative …

Transcriptional Regulation Of Mouse Line-1 Subfamilies, Karabi Saha

Electronic Theses and Dissertations

No abstract provided.

Development Of Novel Carbohydrate-Based Nanoparticles For Precision Drug Delivery, Krystal Ann Hughes

Graduate Theses, Dissertations, and Problem Reports (ETD)

Nanoparticle-based drug delivery has made tremendous advancements in the last decade. However, several critical factors, including precision drug delivery at the site of interest, long-term storage stability, and controlling release profiles of drugs in the systemic circulation, need to be addressed for successful clinical translation of nanomedicine. This dissertation presents novel carbohydrate-based nanoparticles that achieve precise intracellular delivery and therapeutic release at the disease site. We present the formulation and optimization of polymeric and polymer-lipid hybrid nanoparticles that enable precision intracellular delivery and passive accumulation of therapeutics in the bone marrow. Intracellular delivery is highly impactful and sought after. One …

Protein Marker-Dependent Drug Discovery Targeting Breast Cancer Stem Cells, Ashley V. Huang, Yali Kong, Kan Wang, Milton L. Brown, David Mu

Department of Biomedical and Translational Sciences Faculty Publications

Breast cancer is one of the most common cancers globally. Unfortunately, many patients with breast cancer develop resistance to chemotherapy and tumor recurrence, which is primarily driven by breast cancer stem cells (BCSCs). BCSCs behave like stem cells and can self-renew and differentiate into mature tumor cells, enabling the cancer to regrow and metastasize. Key markers like CD44 and aldehyde dehydrogenase-1 (ALDH1), along with pathways like Wingless-related integration site (Wnt), Notch, and Hedgehog, are critical to regulating this stem-like behavior of BCSCs and, thus, are being investigated as targets for various new therapies. This review summarizes marker-dependent strategies for targeting …

Benefit-Risk Assessment Of Rivaroxaban In Older Patients With Nonvalvular Atrial Fibrillation Or Venous Thromboembolism, Paul P. Dobesh, Albert A. Volkl, Ákos Ferenc Pap, C V Damaraju, Bennett Levitan, Zhong Yuan, Alpesh N. Amin

Journal Articles: Pharmacy Practice

BACKGROUND: Both bleeding and adverse ischemic events increase with age, compounding the benefit-risk balance of anticoagulants in older patients. We present analyses using benefit-risk methods to better understand the age-dependence of the benefit-risk profile of rivaroxaban in patients with nonvalvular atrial fibrillation (NVAF) or venous thromboembolism (VTE).

METHODS: Randomized controlled trial data from the ROCKET-AF (NVAF) and EINSTEIN DVT, EINSTEIN PE, EINSTEIN-Extension, and EINSTEIN CHOICE in (VTE) were used. For ROCKET-AF, benefits and risks were assessed with incidence rates for key thrombotic and bleeding endpoints and a net clinical benefit (NCB) measure. Cumulative incidences (estimated by the Kaplan-Meier method) were …

High-Throughput Drug Screening For Disease-Modifying Arthritis Therapy, Janapriya Vijayakumar

Honors Undergraduate Theses

Current therapy for arthritis predominantly focuses on the symptoms rather than the underlying causes of disease progression. Thus, it is necessary to identify novel drugs which target the underlying molecular basis of such diseases. Using high-throughput cell-based drug screening, we screened 458 different compounds, narrowed down from 811 starting compounds from the NIH Mechanistic Set. We selected drugs from the Mechanistic Set following Lipinski's Rule of 5 to ensure optimal pharmacokinetic properties. The study used modified primary human chondrocytes (IIAM-PRG4Luc), which secrete a lubricin promoter-driven luciferase reporter. We use this luciferase expression as a proxy to measure lubricin, a compound …

Investigation Of Lubricin-Stimulating Fda-Approved Compounds For A Disease-Modifying Osteoarthritic Drug, Swathi S. Menon

Honors Undergraduate Theses

Osteoarthritis (OA) is a degenerative disease that affects many people worldwide. Current methods of treatment are palliative, and no treatment exists to fully reverse or cure OA once it begins to progress. The discovery of a disease-modifying osteoarthritic drug (DMOAD) would increase the quality of life for millions and reduce the need for invasive procedures. Screening FDA-approved drugs ensures more promise due to their known safety profile and potential for faster translation to the clinic. The goal of this project was to conduct dose-response assays with FDA-approved drugs that have been shown to stimulate lubricin production in cells that mimic …

Changes In Cardiovascular Risk Factors And Health Care Expenditures Among Patients Prescribed Semaglutide, Yuan Lu, Yuntian Lu, Tedi Totojani, Chungsoo Kim, Rohan Khera, Hua Xu, John E. Brush Jr., Harlan M. Krumholtz, Jason Abaluck

Department of Medicine Faculty Publications

Importance Semaglutide, a glucagon-like peptide-1 receptor agonist, has demonstrated substantial weight reduction and cardiovascular benefits in clinical trials. However, its association with clinical outcomes and health care expenditures remains underexplored.

Objective To evaluate changes in cardiovascular risk factors and health care expenditures among patients prescribed semaglutide across multicenter cohorts.

Design, Setting, and Participants This retrospective cohort study included 23 522 adults (≥18 years) who received an initial semaglutide prescription between January 1, 2018, and January 1, 2025, at Sentara Healthcare and between January 1, 2018, and May 1, 2025, at Yale New Haven Health System.

Exposure The first prescription of …

Rational Design Of Small Molecules Targeting Mitochondrial Redox Proteins, Matheus Barbosa Belchior

Graduate Theses, Dissertations, and Problem Reports (ETD)

Reactive oxygen species play a crucial role in many cellular processes. Despite being a natural byproduct of cellular metabolism, overexpression of these species causes damage to the cell, leading to cell dysfunction. Central to the regulation of these highly reactive molecule is the mitochondria. Impairment in its function has been associated with oxidative stress within the cell. Herein, a ligand-based and structure-based approach to design new small molecules to inhibit mitochondrial redox proteins associated with oxidative stress and reactive oxygen species. In the first project two molecules were synthesized and characterized as potential monoamine oxidase B inhibitors. Results showed two …

Synthesis Of Tu100 Analogs And Biological Assays, Feyisope Tonye Oladapo

College of Graduate Studies: Theses & Dissertations

TU100 (14-methyl-5H-5,12-epiminobenzo[4,5]cyclohepta[1,2-b]naphthalene-6,11,13(12H)-trione) exhibits exceptional chemotherapeutic properties. It operates via a distinct mechanism that triggers cell death to create cytotoxic effects while concurrently inhibiting topoisomerase I and II. Its efficacy rivals that of well-known chemotherapeutic drugs like Daunorubicin. The distinctive characteristics of TU100 have led to initiatives aimed at creating structurally similar compounds to discover even more effective bioactive alternatives.

The analog synthesis incorporated quinoxaline or its derivatives (diphenyl quinoxaline, dipyridinyl quinoxaline, and dibenzophenazine-10,13-dione) that have been shown to have promising chemotherapeutic effects. Synthesizing the hetero naphthoquinones required a multi-step synthetic process, so quinoxaline/ derivatives intermediates are first prepared, then the …

Immersive Medical Practice And Clinical Training: Virtual And Mixed Reality In Pharmacy And Orthopedic Surgery, Silas Semprini De Toledo Contaifer

Theses and Dissertations

Extended‑reality (XR) technologies including virtual reality (VR) and mixed reality (MR) offer new ways to improve training and surgical precision. This thesis evaluates their educational and clinical impact through two complementary studies.

Specific Aim 1 compared an immersive 360° video VR module with conventional training for teaching USP < 797> sterile‑compounding skills to second‑year PharmD students (N = 36). VR trainees raised their knowledge from 6.14 ± 1.55 to 8.69 ± 1.07, yet the overall post‑test advantage versus control was not statistically significant (U = 71.50, p = 0.21). Item‑level McNemar testing showed significant VR‑exclusive gains on three critical questions (K5, K6, …

Utilizing Probiotics To Reduce Diet Induced Dysbiosis And Inflammation In Myelodysplastic Syndromes Susceptible Mice, Tejaswee Bolloju

Theses, Dissertations and Capstones

Human gut microbiota is helpful in digestion by helping in breaking complex carbohydrates, proteins, fats and fibers and many other physiological functions. The Western diet which is high in fat and carbo hydrate percentage alters gut microbiota and leads to growth of pathogenic bacteria and altered gut flora referred to as dysbiosis, which in turn cause gut inflammation and increased permeability of gut and it causes translocation of Lipopolysaccharides (LPS) which causes low grade systemic inflammation. Disturbance in gut microbiota correlated with metabolic conditions like obesity and leads to progression of hematologic diseases like Myelodysplastic Syndromes (MDS). Myelodysplastic syndromes are …

Optimization Of Chitosan Nanoemulsion And Its Application In Delivering 5-Fluorouracil And Quercus Infectoria For Wound Healing, Kalkedan Ameha

Theses, Dissertations and Capstones

BACKGROUND: Chitosan-based nanoemulsions are increasingly recognized for their potential in enhancing drug delivery for wound healing applications. The integration of Quercus infectoria (Qi) extract, known for its antibacterial and anti-inflammatory effects, with 5- fluorouracil (5-FU), a chemotherapeutic agent that regulates abnormal cell proliferation, presents a synergistic approach for treating chronic and non-healing wounds. Ensuring long-term physicochemical stability of these nanoemulsions is critical for their therapeutic viability.

OBJECTIVE: To optimize and characterize a chitosan-based nanoemulsion for the codelivery of 5-FU and Quercus infectoria extract, with emphasis on physicochemical properties including particle size, polydispersity index (PDI), and zeta potential. The …