Pharmacy and Pharmaceutical Sciences Commons^™

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 …

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 …

Levetiracetam-Induced Acute Kidney Injury In A Pediatric Patient, Makaila A. Geese Pharmd Candidate, Norm Fenn Bcps, Bcpps

Parkview Pharmacy Department

Presented at PPA Meeting.

Objective: To describe a case of acute kidney injury following levetiracetam administration in an adolescent patient.

Key takeaways:

Acute kidney injury (AKI) following levetiracetam is rare, especially in pediatric patients

Kidney injury was not correlated with supratherapeutic levetiracetam concentrations

Morganella Morganii Meningitis In A Neonate: A Case Report, Madelin Vessels Pharmd Candiadate, Cassie Rough Pharmd Candidate, Robyn Schmucker Md, Mph, Norm Fenn Bcps, Bcpps

Parkview Pharmacy Department

Presented at Midyear Clinical Meeting

Objective: To summarize the interventions that took place to add to the limited data that exists in the world surrounding the treatment and outcomes of M. morganii infections.

Key takeaways: 

• M. morganii meningitis is highly rare in neonates
• There are no defined treatment guidelines or outcomes available to date
• Cefepime sufficiently treated M. morganii meningitis, bacteremia, and concurrent E. coli urinary tract infection

Comparison Of Isoflurane To Sevoflurane In A Pediatric Patient With Refractory Status Asthmaticus: A Case Report, Janella Rianna N. Benitez Mba, Pharmd, Norm Fenn Bcps, Bcpps, Fashp

Parkview Pharmacy Department

Presented at Midyear Clinical Meeting.

Objective: To describe the use of inhaled anesthetics in a pediatric patient with severe, refractory status asthmaticus unresponsive to conventional therapies.

Implementation Of An Updated Intravenous Iron Order Panel In The Acute Care Setting: A Pre/Post Study, Robert D. Beckett

Parkview Pharmacy Department

Presented at Midyear Clinical Meeting

Implementation of the revised order panel led to reduced utilization including a reduction in the proportion of patients receiving IV iron, number of total doses, proportion of patients receiving more than one dose, and proportion of patients receiving more than 200 mg.

One Bolus, Many Benefits: Implementing Tenecteplase For Acute Ischemic Stroke, Robert D. Beckett Pharmd

Parkview Pharmacy Department

Presented at the Midyear Clinical Meeting.

Overall, no statistically significant differences in door-to-needle time or secondary outcomes between alteplase and tenecteplase groups was identified. This could relate to time in imaging and patient evaluation. Patients treated with tenecteplase showed greater bleeding risk versus alteplase, though these results were not statistically significant when accounting for baseline age in an exploratory regression. Patients who received tenecteplase were slightly older, on average.

Evaluation Of Terlipressin Use At A Community Health System, Robert D. Beckett Pharmd

Parkview Pharmacy Department

Presented at the Midyear Clinical Meeting.

Findings of this evaluation suggest opportunities to improve terlipressin utilization by sharing results back to Nephrology and GI and

reviewing P&T-approved criteria for use, implementing EMR alerts to reinforce dosing

protocols every 24-48 hours for dose adjustments

or discontinuation based on Scr trends (day 4 and

beyond), and supporting daily monitoring of fluid

and respiratory status.

Findings of this evaluation suggest opportunities to improve terlipressin utilization by sharing results back to Nephrology and GI and

reviewing P&T-approved criteria for use, implementing EMR alerts to reinforce dosing

protocols every 24-48 hours for dose adjustments

or …

Formulation And Immunogenicity Of L1 Orf1 Mrna Vaccine In Mice, Raj Nandani

Electronic Theses and Dissertations

This dissertation presents the design, formulation, and immunogenicity evaluation of a novel mRNA vaccine targeting the L1 ORF1p protein, a tumor-associated antigen. The vaccine was synthesized using in vitro transcription and encapsulated in lipid nanoparticles (LNPs), with both unmodified uridine and N1-methylpseudouridine variants tested. Physicochemical characterization confirmed optimal particle size (160–220 nm), acceptable zeta potential, and encapsulation efficiency ranging from 74% to 92%, with preserved RNA integrity post-formulation. These results validate the robustness of the formulation workflow and its suitability for antigen delivery. Immunogenicity studies in C57BL/6 mice revealed modest but promising immune responses. While early activation markers (CD69) and …

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 …

A Potentially Cat-Astrophic Missed Diagnosis: Systemic Autoimmune Disease Or Something More Sinister, Cameron Smith, Do, Mph, Amy Dechet

Books, Presentations, Posters, Etc.

Introduction: Disseminated bartonella infection has a mortality rate approaching 10%. Clinical presentation of bartonellosis can mimic systemic autoimmune disease. Traditional testing may not identify the organism, so a high degree of suspicion is warranted in patients with risk factors. Case Presentation: 32M with history of Tetralogy of Fallot with prosthetic pulmonary valve presented with fatigue x3 months. Reported severe splenomegaly, pancytopenia requiring transfusions, and renal failure requiring hemodialysis. Given concern for lupus-like syndrome, treated with steroids + cyclophosphamide. Persistent fevers despite broad antibiotics. Second opinion of renal biopsy: Postinfectious GN. Immunostains ruled out lupus-like disorder. Negative blood cultures, TEE, and …

A Scoping Review Of Randomised Controlled Trials Of Vaccines That Recruited Care Home Residents: Lessons For Future Trials, Selvarani Selvarani Subbarayan, Imogen Smith-Dodd, Gabriel Nicolson, Jennifer Kirsty Burton, Janet T. Scott, Seshadri S. Vasan, Susan D. Shenkin, Roy L. Soiza

Research outputs 2022 to 2026

Introduction: Older care home (CH) residents are particularly vulnerable to infections and often experience adverse outcomes. Despite this group being frequently prioritised for vaccinations, trials of vaccines rarely recruit CH residents. Given that the social and biological characteristics of CH residents may influence vaccine effectiveness, it is crucial to test vaccines in this population.

Methods: The Widening Access to Trials in Care Homes project was established to develop best practice guidance on designing and conducting vaccine trials in the CH population. As part of this project, a scoping review following Joanna Briggs Institute methodology was conducted to identify vaccine trials …

Association Of Prenatal Exposure To Phthalates And Phenols With Adverse Pregnancy Outcomes, Misa Hayasaka, Diana Aboukhater, George Saade, Tetsuya Kawakita

Department of Obstetrics & Gynecology Faculty Publications

OBJECTIVE:

To evaluate the association between prenatal exposures to phthalates and phenols and adverse pregnancy outcomes, including preterm birth (PTB), small-for-gestational-age (SGA) birth weight, and gestational diabetes mellitus (GDM).

METHODS:

This study analyzed data from the Environmental Influences on Child Health Outcomes consortium, which harmonized longitudinal data on more than 30,000 pregnancies and 57,000 children from 69 cohorts across the United States and Puerto Rico. Pregnancy outcomes included PTB, SGA, and GDM, identified from medical records or self-reports. Generalized estimating equations models with Poisson distribution and robust variance were used to estimate relative risks (RRs) and 95% CIs per interquartile …

Drug-Induced Leukocytoclastic Vasculitis From An Unreported Source: Daptomycin, Jennifer K. Priessnitz, Timothy Kuzel, Lindsay Ackerman, Nelson Nicolasora

Department of Medicine Faculty Publications

Leukocytoclastic vasculitis (LCV) is a rare small-vessel vasculitis caused by immune-complex-mediated deposition on endothelial cells of dermal capillaries. Common triggers include medications, infections, autoimmune disorders, and malignancies. We present a case of a 58-year-old male who developed daptomycin-induced LCV after being treated for Methicillin-resistant Staphylococcus aureus (MRSA) endocarditis. The patient experienced painful palpable purpura on his lower extremities, which was diagnosed as LCV by skin biopsy. At the time of the biopsy, warfarin and daptomycin were discontinued, and the patient was transitioned to heparin and ceftaroline. MRSA-induced LCV was ruled out, due to negative blood cultures and adequate source control …

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 …

A Novel D-Peptide Modulates Dclk1 Gelsolin Interactions, Reducing Pdac Tumor Growth, Landon L. Moore, Dongfeng Qu, Parthasarathy Chandrekesan, Kamille Pitts, Randal May, Byron E. Anderson, Milton L. Brown, Courtney W. Houchen

Department of Medicine Faculty Publications

What drives inflammation-associated tumorigenesis and progression in pancreatic ductal adenocarcinoma (PDAC)? Doublecortin-like kinase 1 (DCLK1) is a central driver of inflammation-associated tumorigenesis, with elevated expression linked to worse clinical outcomes. Two isoforms of DCLK1 possess a unique extracellular domain (ECD). DCLK1 isoform 2 contains two microtubule-binding domains, while isoform 4, lacks the microtubule-binding domains but, plays a pivotal role in tumor progression. We identified novel D-peptides that selectively target this ECD, significantly suppressing PDAC cell proliferation in vitro and tumor growth in xenograft models without inducing cell death. In silico modeling and binding assays revealed DCLK1 isoform 4 interacts with …

A Case Displaying The Importance Of Jak1 And Jak2 Gene Transcription In Antifungal Defense Against Coccidioidomycosis, Jennifer K. Priessnitz, Taylor Colore, Nelson Nicolasora

Department of Medicine Faculty Publications

This case report explores the consequences of ruxolitinib via inhibition janus kinase 1 (JAK1) and JAK2 pathways in the context of fungal defense in a patient diagnosed with pulmonary coccidioidomycosis during ruxolitinib therapy for polycythemia vera. The patient experienced a relapse of pulmonary coccidioidomycosis after antifungal treatment was discontinued while continuing ruxolitinib use. This case illustrates the heightened risk of discontinuing antifungal therapy in endemic regions, emphasizing the critical need for continued monitoring. Furthermore, this case underscores the vital role of the JAK1 and JAK2 signaling cascade, particularly the interferon-gamma (INF-γ)-JAK1 and JAK2-signal transducer and activator of transcription 1 (STAT) …

Automating The Amino Acid Identification In Elliptical Dichroism Spectrometer With Machine Learning, Ridhanya Sree Balamurugan, Yusuf Asad, Tommy Gao, Dharmakeerthi Nawarathna, Umamaheswara Rao Tida, Dali Sun

Electrical & Computer Engineering Faculty Publications

Amino acid identification is crucial across various scientific disciplines, including biochemistry, pharmaceutical research, and medical diagnostics. However, traditional methods such as mass spectrometry require extensive sample preparation and are time-consuming, complex and costly. Therefore, this study presents a pioneering Machine Learning (ML) approach for automatic amino acid identification by utilizing the unique absorption profiles from an Elliptical Dichroism (ED) spectrometer. Advanced data preprocessing techniques and ML algorithms to learn patterns from the absorption profiles that distinguish different amino acids were investigated to prove the feasibility of this approach. The results show that ML can potentially revolutionize the amino acid analysis …

Targeting Bone In Cancer Therapy: Advances And Challenges Of Bisphosphonate-Based Drug Delivery Systems, Fariba Ganji, Mohammadmahdi Eshaghi, Hossein Shaki, Lobat Tayebi

Electrical & Computer Engineering Faculty Publications

Background and Purpose: Bisphosphonates (BPs) are well-known for their strong affinity toward bone mineral matrices and are widely used to inhibit excessive osteoclast activity associated with various bone disorders. Beyond their clinical use, their unique bone-targeting capability has positioned them as promising ligands for drug delivery systems aimed at treating bone-related cancers. Approach: The review analyses published studies on BP-functionalized drug delivery systems, including direct drug conjugates, calcium-based nanomaterials, carbon-based nanostructures, and self-assembling systems such as micelles and liposomes. In vitro assays (e.g. hydroxyapatite binding, cell viability) and in vivo biodistribution studies are discussed to evaluate targeting efficiency and …

Novel Micro-And Nanoformulations Of Paclitaxel For Targeting Metastatic Breast, Non-Small Cell Lung, And Pancreatic Cancers, Lobat Tayebi, Mehran Alavi

Electrical & Computer Engineering Faculty Publications

Nonlinear pharmacokinetics resulting from high lipophilic and low oral bioavailability, and hypersensitivity reactions and hyperlipidemia caused by formulation by Cremophor EL have limited clinical effectiveness of paclitaxel (Taxol). In this way, there is the critical necessity of innovative drug delivery systems (DDSs) to mitigate severe side effects and overcome clinical limitations of paclitaxel. In recent years, various micro- and nanoformulations, specifically polymeric nanoparticles (NPs) and lipid NPs, have been presented and approved by the Food and Drug Administration (FDA). In addition, other nanoformulations, such as polymeric nanoparticles (NPs), micelles, liposomes, and mesoporous silica nanoparticles, have shown promising results in vitro …