Medicine and Health Sciences Commons^™

Growth And Feeding In The Sponge Agelas Tubulata From Shallow To Mesophotic Depths On Grand Cayman Island, Keir J. Macartney, Amelia Clayshulte Abraham, Marc Slattery, Michael P. Lesser

Faculty and Student Publications

On Caribbean coral reefs, sponges are important members of the benthic community and play multiple roles in ecosystem structure and function. They have an important role in benthic-pelagic coupling, consuming particulate organic matter (POM) and dissolved organic matter (DOM) and in turn providing food in the form of sponge biomass or the release of detritus for a variety of coral reef organisms. Throughout the Caribbean, sponges show consistent increases in their abundance and growth rates as depth increases into the mesophotic zone (30–150 m). This has been hypothesized to be driven by bottom-up forces, particularly the increased supply of nitrogen-rich …

Targeted Downregulation Of Myc Through G-Quadruplex Stabilization By Dnai, Alexandra Maria Psaras, Katarina T. Chang, Taisen Hao, Tracy A. Brooks

Faculty and Student Publications

Modulating the expression or function of the enigmatic MYC protein has demonstrated efficacy in an array of cancer types and a marked potential therapeutic index and safety profile. Despite its high therapeutic value, specific and selective inhibitors or downregulating therapeutics have proven difficult to develop. In the current study, we expanded our work on a MYC promoter G-quadruplex (G4) stabilizing DNA clamp to develop an oligonucleotide interfering DNA (DNAi) therapeutic. We explored six DNAi for G4-stabilization through EMSA, DMS footprinting, and thermal stability studies, focusing on the DNAi 5T as the lead therapeutic. 5T, but not its scramble control 5Tscr, …

Tissue-Specific Regulation Of Hnk-1 Biosynthesis By Bisecting Glcnac, Haruka Kawade, Jyoji Morise, Sushil K. Mishra, Shuta Tsujioka

Faculty and Student Publications

Human natural killer—1 (HNK-1) is a sulfated glyco-epitope regulating cell adhesion and synaptic functions. HNK-1 and its non-sulfated forms, which are specifically expressed in the brain and the kidney, respectively, are distinctly biosynthesized by two homologous glycosyltransferases: GlcAT-P in the brain and GlcAT-S in the kidney. However, it is largely unclear how the activity of these isozymes is regulated in vivo. We recently found that bisecting GlcNAc, a branching sugar in N-glycan, suppresses both GlcAT-P activity and HNK-1 expression in the brain. Here, we observed that the expression of non-sulfated HNK-1 in the kidney is unexpectedly unaltered in mutant mice …

Law Helps Ensure Safety Of The Supply Chain, Kenneth Maxik, Craig Kimble, Alberto Coustasse

Management Faculty Research

The Drug Quality and Security Act was signed into law on November 27, 2013, and included the Title 2 Drug Supply Chain and Security Act (DSCSA). This legislation was introduced to enact a federal prescription drug safety standard to decrease contamination, counterfeiting, diversion, and otherwise harmful illicit activities. It also improves the detection and elimination of potentially unsafe drugs from the drug supply chain to protect US consumers.

Improving Skin And Soft Tissue Antibiotic Duration Concordance With National Guidelines In Pediatric Urgent Care Clinics, Megan Hamner, Amanda Nedved, Holly Austin, Donna Wyly, Alaina N. Burns, Diana King, Brian Lee, Rana El Feghaly

Posters

Introduction: Skin and soft tissue infections (SSTIs) are the second most common diagnosis leading to pediatric antibiotic prescriptions in the outpatient setting after respiratory diagnoses. Children with SSTIs often receive >7 days of antibiotics, although current guidelines recommend 5-7 days for most diagnoses. At CMH urgent care clinics (UCCs), only 58% patients received the recommended 5-7 days of antibiotics. We aimed to increase the percentage of patients receiving 5-7 days of oral antibiotics for SSTIs from 58% to 75% by December 31st, 2021. Methods: We formed a multidisciplinary team in April 2020. A provider survey assessed factors influencing prescribing habits. …

Endophytes Of Brazilian Medicinal Plants With Activity Against Phytopathogens, Jucélia Iantas, Daiani Cristina Savi, Renata Da Silva Schibelbein, Sandriele Aparecida Noriler, Beatriz Marques Assad, Guilherme Dilarri, Henrique Ferreira, Jürgen Rohr, Jon S. Thorson, Khaled A. Shaaban, Chirlei Glienke

Pharmaceutical Sciences Faculty Publications

Plant diseases caused by phytopathogens are responsible for significant crop losses worldwide. Resistance induction and biological control have been exploited in agriculture due to their enormous potential. In this study, we investigated the antimicrobial potential of endophytic fungi of leaves and petioles of medicinal plants Vochysia divergens and Stryphnodendron adstringens located in two regions of high diversity in Brazil, Pantanal, and Cerrado, respectively. We recovered 1,304 fungal isolates and based on the characteristics of the culture, were assigned to 159 phenotypes. One isolate was selected as representative of each phenotype and studied for antimicrobial activity against phytopathogens. Isolates with better …

A Baker's Dozen Of Top Antimicrobial Stewardship Intervention Publications In 2020, Sarah B. Green, Kayla R. Stover, Katie Barber, Jeannette L. Bouchard, Matthew L. Brown, Connor R. Deri, Bailey J. Francis, Timothy P. Gauthier, Jillian E. Hayes, Ashley H. Marx, Edoabasi U. Mcgee, Krutika Mediwala, Rachel J. Musgrove, Douglas Slain, Stefanie A. Stramel, Christopher M. Bland, P Brandon Bookstaver

Faculty Publications

The number of articles related to antimicrobial stewardship published each year has increased significantly over the last decade. Keeping up with the literature, particularly the most innovative, well-designed, or applicable to one's own practice area, can be challenging. The Southeastern Research Group Endeavor (SERGE-45) network reviewed antimicrobial stewardship-related, peer-reviewed literature from 2020 that detailed actionable interventions. The top 13 publications were summarized following identification using a modified Delphi technique. This article highlights the selected interventions and may serve as a key resource for teaching and training, and to identify novel or optimized stewardship opportunities within one's institution.

Valproic Acid Autoinduction: A Case-Based Review, Sean Bennett, Mujeeb U. Shad

School of Medicine Faculty Research

Although valproic acid (VPA) induces the metabolism of multiple other drugs, the clinical reports of VPA autoinduction are rare. A comprehensive literature search yielded only one published case series, which provided the rationale to conduct a review of the published cases along with a new case of VPA autoinduction. Although there may be myriad of reasons for lack of published cases of VPA autoinduction, potential underreporting may be one of the core reasons. Lack of understanding into the highly complex metabolism of VPA may also make it difficult to recognize and report VPA autoinduction. However, it is important to mention …

Global Trends In Cancer Nanotechnology: A Qualitative Scientific Mapping Using Content-Based And Bibliometric Features For Machine Learning Text Classification, Nuwan Gedara, Xuan Xu, Robert Delong, Santosh Aryal, Majid Jaberi-Douraki

Pharmacy Faculty Publications and Presentations

This study presents a new way to investigate comprehensive trends in cancer nanotechnology research in different countries, institutions, and journals providing critical insights to prevention, diagnosis, and therapy. This paper applied the qualitative method of bibliometric analysis on cancer nanotechnology using the PubMed database during the years 2000-2021. Inspired by hybrid medical models and content-based and bibliometric features for machine learning models, our results show cancer nanotechnology studies have expanded exponentially since 2010. The highest production of articles in cancer nanotechnology is mainly from US institutions, with several countries, notably the USA, China, the UK, India, and Iran as concentrated …

Opioid Abuse: Are Doctors Creating The Problem?, Nguyen Tran

Symposium of Student Scholars

Opioid abuse and overdose are serious health problems in the United States. Current research has concentrated on the treatment and prevention of opioid abuse. Using data from the Controlled Substance Utilization Review and Evaluation System (CURES) for California zip codes, my research focuses on the causes of opioid overdose by considering the relationships between the following variables within each zip code: population size, average number of prescriptions per doctor, percentage of people who receive opioid prescriptions, percentage of people receiving the same prescription drug from 3 or more doctors, average number of opioid pills per prescription and number of people …

The Role Of The Pharmacist In The Treatment Of Infantile Botulism, Rachel E. Huntsman, Abigail Schauble

HCA Healthcare Journal of Medicine

Infantile botulism is a potentially devastating disease caused by ingestion of Clostridium botulinum spores through food products or dust particles. The toxin produced by the spores can lead to descending paralysis requiring hospitalization for supportive care which sometimes includes mechanical ventilation. Human Botulism Immune Globulin-Intravenous (BIG-IV or BabyBIG) from the Infant Botulism Treatment and Prevention Program (IBTPP) has been shown to greatly improve outcomes. A previously healthy 5-month-old infant was admitted to her regional hospital for poor feeding and lethargy. When the weakness progressed and she had trouble with protecting her airway, she was intubated and transferred to our institution. …

Value Of Systematic Approach To Assess Health-System Pharmacy Services, Sonnia Zambrano, Radha Patel, L. Hayley Burgess, Kimberly Heath

HCA Healthcare Journal of Medicine

Health-system pharmacy leaders are tasked with determining key staffing decisions based on evolving patient care needs and present-day staffing capacity. A systematic approach to evaluate patient care needs, current model and potential gaps enables leaders to allocate resources in patient care need expansions or sudden fluctuations of patient volumes. Resource management, preparedness and ongoing maintenance form principles used by pharmacy leaders to create an optimal operational environment and elevate clinical pharmacy services. Use of this approach for multiple sites of care across a large network of health systems resulted in identification and improvement in pharmacist coverage and retention of clinical …

Towards Quality By Design (Qbd) Of Pharmaceutical Oral Films Loaded With Poorly Watersoluble Drugs, Eylul Cetindag

Dissertations

Oral films are an emerging drug delivery dosage form with numerous advantages such as ease of handling, the possibility to circumvent the first-pass metabolism, better patient compliance, capability for continuous manufacturing, and as a platform for personalized medicine. As films are different from other final dosages by their dimensions and their matrix form, further research is required to better understand the impact of excipient and drug on product performance to assure a consistent and good quality product. Therefore, this dissertation aims to contribute towards the processability and manufacturability of films by examining the impact of the materials and processes. First, …

Exploring Fused Deposition Modeling (Fdm) Three-Dimensional Printing Tablet Design Options For Pharmaceutical Dosage Forms, Guluzar Gorkem Buyukgoz

Dissertations

This dissertation examines the use of Fused Deposition Modeling (FDM) based three-dimensional (3D) printing approach for developing patient-specific dosage forms and addressing related technical challenges in such drug delivery systems. The first main objective is to explore pharmaceutical tablet design options using novel FDM 3D printing technology as the drug delivery platform such that drug form and tablet properties are tailored by considering patient age-specific formulations and dissolution control. Of the five different design options, two proposed options meet the main objective of providing similar drug release, whereas the popular option of fixed drug concentration but differing tablet size could …

Subtype-Selective Positive Modulation Of KCa 2 Channels Depends On The Ha/Hb Helices, Young-Woo Nam, Meng Cui, Naglaa Salem, Razan Orfali, Misa Nguyen, Grace Yang, Mohammad Asikur Rahman, Judy Lee, Miao Zhang

Pharmacy Faculty Articles and Research

Background and Purpose

In the activated state of small-conductance Ca2+-activated potassium (KCa 2) channels, calmodulin interacts with the HA/HB helices and the S4-S5 linker. CyPPA potentiates KCa 2.2a and KCa 2.3 channel activity but not the KCa 2.1 and KCa 3.1 subtypes.

Experimental Approach

Site-directed mutagenesis, patch-clamp recordings and in silico modeling were utilized to explore the structural determinants for the subtype-selective modulation of KCa 2 channels by CyPPA.

Key Results

Mutating residues in the HA (V420) and HB (K467) helices of KCa 2.2a channels to their equivalent residues in KCa 3.1 channels diminished the potency of CyPPA. CyPPA elicited …

Chemical Properties, Biological Activities And Poisoning Treatment Of Novichok: A Review, Tesia Aisyah Rahmania, Bantari Wisynu Kusuma Wardhani, Editha Renesteen, Yahdiana Harahap

Pharmaceutical Sciences and Research

Novichok is an organophosphate compound found as a nerve agent chemical weapon. However, the information about its chemical properties, biological activities, and molecular interactions in the body are still protected under the “top secret” security clearance. Novichok, with the codes A230, A232 and A234, is a compound whose structure has been successfully determined. The compound is synthesized from a precursor through a nucleophilic substitution reaction. Novichok agents are considered more potent than VX gas and can be applied in unitary and binary forms. This compound has ability for the binding with acetylcholinesterase (AChE) due to inability of acetylcholine metabolism. AChE …

Validation Method For Simultaneous Analysis Of Betamethasone Dipropionate And Retinoic Acid In Cream Formulation By Ultra High-Performance Liquid Chromatography, Supandi Supandi, Umar Mansyur, Annisa Ananda Ranie, Linda Mazroatul Ulya

Pharmaceutical Sciences and Research

A simple, precise and rapid reverse phase UHPLC-PDA method has been developed and validated for the simultaneous analysis of betamethasone dipropionate (BTM) and retinoic acid (REA) in whitening cream dosage form. The mixture of betamethasone dipropionate (BTM) and retinoic acid (REA) was separated on Phenomenex Bonclone 10 C18 (150 mm x 3.9 mm) column. All separations were performed with a Dionex 3000 Photodiode Array (PDA) detector on 240 nm and 340 nm wavelength, column temperature at 40oC, and flow rate at 1.0 ml/min. The mobile phase was methanol-acetic acid 0.1% (85:15) with pH 5. The retention times of BTM and …

The Effect Of Ethanol Extract Of Punica Granatum Linn. Leaves On Lipid Profiles Of Dyslipidemic Rat, Neng Fisheri Kurniati, Afrillia Nuryanti Garmana, Lia Nurul Sakinah

Pharmaceutical Sciences and Research

It has been reported that peel of Punica granatum has antidyslipidemic activity. The aim of this research was to investigate the antidyslipidemic activity of Punica granatum leaf. The dried Punica granatum leaves were extracted with 96% ethanol. Rats were divided into several groups, which were normal, positive control, simvastatin at a dose of 10 mg/kg bw as reference group, and Punica granatum extract at a dose of 100 mg/kg. Before treatment, male Wistar rats were fed with high cholesterol chow for 3 months, and then plant extract was given for 4 weeks. Blood samples were collected at week 0, 12, …

Insights Into Molecular Interaction Of Flavonoid Compounds In Citrus Peel Bound To Collagenase And Elastase Enzymes: A Computational Study, Sani Ega Priani, Taufik Muhammad Fakih

Pharmaceutical Sciences and Research

Citrus peels contain various phytochemical active compounds such as flavonoids that are useful for antiaging cosmetic products. This study was conducted to identify the anti-collagenase and anti-elastase activities of flavonoid compounds in citrus peel and to determine the molecular interaction mechanism using the molecular docking method. The study was carried out through several stages, including preparation of enzyme macromolecules, preparation of flavonoid compound molecules, validation of molecular docking, identification of binding-free energy, visualization of interaction conformations, and predictions of molecular skin toxicity. The result showed that the flavonoid compounds in citrus peel (hesperidin, naringin, nobiletin, and tangeretin) could bind to …

Sex-Specific Impacts Of Exercise On Cardiovascular Remodeling, Rifat A. Islam, Siri Sham S. Khalsa, Arpita K. Vyas, Roshanak Rahimian

School of Pharmacy Faculty Articles

Cardiovascular diseases (CVD) remain the leading cause of death in men and women. Biological sex plays a major role in cardiovascular physiology and pathological cardiovascular remodeling. Traditionally, pathological remodeling of cardiovascular system refers to the molecular, cellular, and morphological changes that result from insults, such as myocardial infarction or hypertension. Regular exercise training is known to induce physiological cardiovascular remodeling and beneficial functional adaptation of the cardiovascular apparatus. However, impact of exercise-induced cardiovascular remodeling and functional adaptation varies between males and females. This review aims to compare and contrast sex-specific manifestations of exercise-induced cardiovascular remodeling and functional adaptation. Specifically, we …

Genomic Data From Nsclc Tumors Reveals Correlation Between Shp-2 Activity And Pd-L1 Expression And Suggests Synergy In Combining Shp-2 And Pd-1/Pd-L1 Inhibitors, Keller J. Toral, Mark A. Wuenschel, Esther P. Black

Pharmaceutical Sciences Faculty Publications

The identification of novel therapies, new strategies for combination of therapies, and repurposing of drugs approved for other indications are all important for continued progress in the fight against lung cancers. Antibodies that target immune checkpoints can unmask an immunologically hot tumor from the immune system of a patient. However, despite accounts of significant tumor regression resulting from these medications, most patients do not respond. In this study, we sought to use protein expression and RNA sequencing data from The Cancer Genome Atlas and two smaller studies deposited onto the Gene Expression Omnibus (GEO) to advance our hypothesis that inhibition …

Endeavors Toward Novel Synthetic Roadmaps In The Synthesis Of Pertinent Pharmacological Molecular Scaffold Moieties, Justin David Horgan

Theses and Dissertations

One of the main goals in the GML lab group is the development of novel, economical, and environmentally friendly organic methods for the synthesis of pharmacologically relevant molecular moieties. The most salient pieces of data to the GML lab group members, reading dependable organic journals, are finding organic moieties that are largely unexplored, finding organic moieties which various research groups are having difficulty synthesizing, and finding complex organic procedures to key organic structures that can be easily reduced, or reconstructed, into novel methods that are more economical and environmentally friendly. By looking at these unexplored molecules, as well as hard …

Adapting Decarbonylation Chemistry For The Development Of Prodrugs Capable Ofin Vivodelivery Of Carbon Monoxide Utilizing Sweeteners As Carrier Molecules, Ladie Kimberly De La Cruz, Xiaoxiao Yang, Anna Menshikh, Maya Brewer

Faculty and Student Publications

Carbon monoxide as an endogenous signaling molecule exhibits pharmacological efficacy in various animal models of organ injury. To address the difficulty in using CO gas as a therapeutic agent for widespread applications, we are interested in developing CO prodrugs through bioreversible caging of CO in an organic compound. Specifically, we have explored the decarboxylation-decarbonylation chemistry of 1,2-dicarbonyl compounds. Examination and optimization of factors favorable for maximal CO release under physiological conditions led to organic CO prodrugs using non-calorific sweeteners as leaving groups attached to the 1,2-dicarbonyl core. Attaching a leaving group with appropriate properties promotes the desired hydrolysis-decarboxylation-decarbonylation sequence of …

Knowledge Assessment Of Anti-Snake Venom Among Healthcare Practitioners In Northern Nigeria, Auwal A. Bala, Abubakar Jatau, Ismaeel Yunusa Ph.D., Mustapha Mohammed, Al-Kassim H. Mohammed, Abubakar M. Isa, Abubakar S. Wada, Kabiru A. Gulma, Inuwa Bello, Sani Malami

Faculty Publications

Introduction: Anti-snake venom (ASV) is the standard therapy for the management of snakebite envenoming (SBE). Therefore, the knowledge of ASV among healthcare practitioners (HCPs) is essential for achieving optimal clinical outcomes in snakebite management. This study aimed to assess knowledge of ASV among the HCPs in northern Nigeria.

Methods: We conducted a cross-sectional study involving eligible HCPs from different healthcare settings in northern Nigeria. The participants were recruited into the study using a combination of online (via Google Form) and face-to-face paper-based survey methods. The ASV knowledge of the respondents was measured using a validated anti-snake venom knowledge assessment tool …

Evaluating A1c Reduction In Patients With Diabetes Receiving Pharmacy Intervention, Christopher R. Evans, Kirsten Held, Stephanie Thomas, Jeanne Spencer

Advances in Clinical Medical Research and Healthcare Delivery

Introduction: Diabetes affects 34 million Americans and is the 7th leading cause of death in the United States. According to the American Diabetes Association (ADA) the A1c goal for most patients is less than 7%; however, in patients at risk for hypoglycemia or with complications that goal can be increased up to less than 8%. Management of diabetes with diet and exercise is essential, but insufficient for most patients and pharmacologic intervention is necessary to achieve therapeutic goals. Reducing A1c is associated with lower cardiovascular risk and a reduction in diabetes-associated complications. Previous studies have shown that pharmacist management of …

Utilizing Patient-Derived Epithelial Ovarian Cancer Tumor Organoids To Predict Carboplatin Resistance, Justin W. Gorski, Zhuwei Zhang, J. Robert Mccorkle, Jodi M. Dejohn, Chi Wang, Rachel W. Miller, Holly H. Gallion, Charles S. Dietrich Iii, Frederick R. Ueland, Jill M. Kolesar

Obstetrics and Gynecology Faculty Publications

The development of patient-derived tumor organoids (TOs) from an epithelial ovarian cancer tumor obtained at the time of primary or interval debulking surgery has the potential to play an important role in precision medicine. Here, we utilized TOs to test front-line chemotherapy sensitivity and to investigate genomic drivers of carboplatin resistance. We developed six high-grade, serous epithelial ovarian cancer tumor organoid lines from tissue obtained during debulking surgery (two neoadjuvant-carboplatin-exposed and four chemo-naïve). Each organoid line was screened for sensitivity to carboplatin at four different doses (100, 10, 1, and 0.1 µM). Cell viability curves and resultant EC₅₀ values …

Nanoparticle T Cell Engagers As A Modular Platform For Cancer Immunotherapy, Kinan Alhallak

McKelvey School of Engineering Graduate Student Theses & Dissertations

Immunotherapy has advanced significantly in recent years due to its promising clinical outcomes in a variety of malignancies and holds great promise in becoming the “cure” for cancer. Cancer immunotherapy is the treatment that stimulates a person’s own immune system to recognize, target, and eliminate cancer cells. As the field progresses with emerging and novel strategies, the ability to manipulate the immune system while mitigating toxicities is the goal for clinical translation. To control for both efficacy and safety, biomaterials have been incorporated into immunotherapies to achieve tissue- and/or cell-specific immunomodulation, overcome immunosuppression, and address tumor microenvironment heterogeneity.T cell-based immunotherapy, …

Serum Renin And Major Adverse Kidney Events In Critically Ill Patients: A Multicenter Prospective Study, Alexander H. Flannery, Victor M. Ortiz-Soriano, Xilong Li, Fabiola G. Gianella, Robert D. Toto, Orson W. Moe, Prasad Devarajan, Stuart L. Goldstein, Javier A. Neyra

Pharmacy Practice and Science Faculty Publications

BACKGROUND: Preliminary studies have suggested that the renin-angiotensin system is activated in critical illness and associated with mortality and kidney outcomes. We sought to assess in a larger, multicenter study the relationship between serum renin and Major Adverse Kidney Events (MAKE) in intensive care unit (ICU) patients.

METHODS: Prospective, multicenter study at two institutions of patients with and without acute kidney injury (AKI). Blood samples were collected for renin measurement a median of 2 days into the index ICU admission and 5-7 days later. The primary outcome was MAKE at hospital discharge, a composite of mortality, kidney replacement therapy, or …

Structural And Inhibitory Studies Of Enzymes Essential For Cell Wall And Ergothioniene Biosynthesis In Mycobacterium Tuberculosis, Thanuja D. Sudasinghe

Theses & Dissertations

Tuberculosis (TB) is one of the world’s oldest contagious diseases caused by Mycobacterium tuberculosis (M. tb). With the emergence and spread of drug-resistant M. tb strains, there is an urgent need to discover novel drugs and drug targets specifically against drug-resistant strains and dormant bacteria. This dissertation focuses on M. tbenzymes essential for the M. tb cell wall and ergothioneine biosynthesis. The M. tb cell wall acts as a protective barrier due to the presence of unique lipids and mycolic acids. Among these lipids, trehalose-dimycolate and mycolylarabinogalactan play a major role in constructing and maintaining the outer …

Development Of Once-A-Year Injectable Formulation Of Cabotegravir For Prevention And Treatment Of Hiv Infection, Tanmay Abhay Kulkarni

Theses & Dissertations

Long-acting cabotegravir (CAB) extends antiretroviral drug (ARV) dosing to monthly for maintenance of human immunodeficiency virus type one (HIV-1) suppression and to every other month for prevention of viral transmission. However, injection dose volumes, site reactions, and clinical oversights that are required remain obstacles towards broad usage. To meet these needs, surfactant coated hydrophobic and lipophilic CAB prodrugs were created with controlled prodrug dissolution, hydrolysis and drug tissue penetration. To such ends, fatty acid ester CAB nanocrystal prodrugs with 14, 18, and 22 added carbon chains were synthesized then nanoformulated as NMCAB, NM2CAB, and NM3CAB. These nanocrystal formulations were tested …