Pharmacy and Pharmaceutical Sciences Commons^™

Scaffolds With Spatiotemporally Controlled Growth Factor Delivery And Cyclodextrin-Enabled Antagonism Of Growth Factor Receptor Sequestration Promote Cutaneous Wound Healing, Jelena Marjanovic, Veronica Jurczuk, Lilian Valadares Tose, Yarixa Cintron Diaz, Francisco Fernandez Lima, Beatriz Abdo Abujamra, Sara Danker, Sinan Jabori, Devinder Singh, Jamie L. Burgess, Joshua Tam, Mohamadmahdi Samandari, Rivka C. Stone, Stephen C. Davis, Robert S. Kirsner, Marjana Tomic-Canic, Fotis M. Andreopoulos, Ivan Jozic

Mechanical & Aerospace Engineering Faculty Publications

Chronic wounds present a major burden to patients, health care professionals, and health care systems worldwide, yet treatment options remain limited and often ineffective. Although initially promising, growth factor-based therapies displayed limited and underwhelming effectiveness largely due to poor bioavailabilbioity and impaired receptor function within the chronic wound microenvironment. Here we demonstrate that chronic wounds exhibit elevated cholesterol synthesis, which disrupts growth factor signaling by sequestering receptors within lipid rafts. To address this, we developed a novel therapy combining growth factors with cyclodextrin in an ECM-mimetic scaffold, enabling localized cholesterol modulation and improved receptor accessibility. We demonstrate that this approach …

Antibiotic Alternatives And Next-Generation Therapeutics For Salmonella Control: A One Health Approach To Combating Antimicrobial Resistance, Mohamed Saleh, Ashutosh Verma, Khaled A. Shaaban, Yosra A. Helmy

Veterinary Science Faculty Publications

The growing prevalence of antimicrobial resistance has significantly compromised the efficacy of conventional antibiotic-based interventions in controlling Salmonella infections across human and veterinary settings. This growing challenge necessitates a strategic rethinking of pathogen control, prompting the integration of next-generation therapeutics capable of disrupting Salmonella pathogenesis through novel, antibiotic-sparing mechanisms. In this context, a diverse array of emerging alternatives, including bacteriophages, antimicrobial peptides, probiotics, prebiotics, short-chain fatty acids, nanoparticles, and host-directed immunomodulators, have gained prominence as a promising frontier in non-antibiotic therapeutics. These modalities offer targeted approaches to inhibit Salmonella colonization, virulence expression, and persistence, while minimizing collateral damage to the …

Burnout At University: Cross-Sectional Study Among Dental Students, Manal Elhijazi, Hajar Nafia, Ihsane Benyahya

Health Sciences

Context: The university constitutes a demanding and competitive learning environment which can impact the well-being of students. The objective of this survey is to assess the burnout of students at the faculty of dentistry.

Materials and methods: A cross-sectional study was conducted via an anonymous questionnaire with 3 sections: socio-demographic data, lifestyle and habit, and burnout through the Maslach burnout inventory-student survey (MBI-SS) . Continuous variables were presented as means and standard deviations,categorical variables as numbers and percentages. The variables were tested in univariate analysis to assess predictive factors related to burnout using the Khi-2 test. The significance level was …

Undergraduate Nursing Students' Perceptions Of A Screen-Based Virtual Simulation And Self-Debriefing: A Qualitative Study., Fatima Zahra Mahou, Guillaume Decormeille, Asmae Khattabi

Health Sciences

The integration of virtual simulation and self-debriefing in nursing education offers promising approaches for enhancing students' competency in medication administration and dosage calculation. This study aims to explore undergraduate nursing students' perceptions and experiences with virtual simulation and self-debriefing, building on findings from a previously published RCT that demonstrated improved learning outcomes through these approaches. In the first phase (self-debriefing), 153 students answered five open-ended questions, followed by a focus group with six students in the second phase.The data were analyzed using qualitative content analysis by two independent coders to ensure consistency and credibility. The study highlights the benefits of …

Crystal Structures And Low-Affinity Complex Formation Of Halogenase Ctcp And Fad Reductase Ctcq From The Chlortetracycline Biosynthetic Pathway, Caixia Hou, Sylvie Garneau-Tsodikova, Oleg V. Tsodikov

Pharmaceutical Sciences Faculty Publications

Enzymatic halogenation in natural products has been intensely investigated due to its potential utility as a tool to improve pharmacological and pharmaceutical properties of drug leads. Chlortetracycline (CTC), the first tetracycline (TC) antibiotic discovered nearly eight decades ago, contains a chlorine group. This chlorine is installed enzymatically by the flavin adenine dinucleotide (FAD)-dependent halogenase CtcP. CtcP and the FAD reductase CtcQ, which is also encoded in the CTC biosynthetic gene cluster, function as a two-component system. Structural information on CtcP and CtcQ has been lacking. In this study, we determined crystal structures of CtcP from Kitasatospora aureofaciens in a complex …

The Landscape Of Cyclin‑Dependent Kinase 4/6 Inhibitors In Solid Malignancies: Emphasis On Immunotherapy Combinatorial Strategies, Maha R.A. Abdollah, Sara A. Hussein, Ahmed H. Saadawy, Eman Badr, Neamtullah Wael, Rasha M. Allam, Ahmed M. Al‑Abd, Ana Maria Roncero Sanchez, Mai Tolba

Pharmacy

Given the pivotal role of CDK4/6 deregulation in the pathogenesis of various malignancies, CDK4/6 inhibitors have been incorporated into cancer treatment protocols. Beyond their antiproliferative effects, these inhibitors exhibit prominent immunomodulatory properties. Preclinical data indicated that CDK4/6 inhibitors enhance the tumor cell antigen presentation capacity and restrict the proliferation of immunosuppressive regulatory T-cells. Furthermore, studies showed that CDK4/6 inhibitors could enhance the development of memory T-cell in vivo in melanoma mouse models and in the clinical setting in breast cancer (BC) patients. In silico analysis identified 225 protein targets for CDK4/6 inhibitors involved in 57 immune-related pathways which further supported …

Corchorus Olitorius Exhibits Antiproliferative Potential Supported By Metabolic Profiling And Integrative Biological Analyses, Maha R.A. Abdollah, Salma Sameh, Ahmed Elissawy, Eman Al-Sayed, Rola Labib, Lan Ye, Fang-Rong Chang, Abdel Nasser B. Singab

Pharmacy

Herbal nutraceuticals could be employed as alternative or complementary routes for alleviating cancer. Corchorus olitorius (Malvaceae) was employed traditionally in the management of tumors. The study aimed to investigate the antiproliferative activity of C. olitorius leaves. In vitro cytotoxic and anti-angiogenic activities of C. olitorius were estimated. The bioactive fraction was subjected to in vivo study on BALB/ c female mice using Ehrlich Ascites Carcinoma model. UPLC-ESI-MS/MS analysis was done to determine the phytometabolites followed by in silico studies on the major identified compounds. The bioactive fraction possessed potent in vitro activity against A549 cells with IC50 = 7.8 µg/mL …

Comparison Of Hypertension Outcomes In Pharmacist Managed Patients Versus Cardiology Provider-Only Care Models, Alexis Clarke Pharmd

Pharmacy Residency

Presented at Midyear Clinical Meeting.

In this study, pharmacist-managed patients achieved BP goal 80 days faster than provider-only patients. Integrating pharmacists into care teams helps patients achieve their BP goal faster through increased visits and closer follow-up. Pharmacist managed groups had less therapeutic inertia regarding drug class changes.

No Cap! Evaluation Of Empiric Antibiotic Duration For Community Acquired Pneumonia, Bailey Castato Pharmd

Pharmacy Residency

Presented at the Midyear Clinical Meeting.

This evaluation found that patients hospitalized for CAP (including severe) without culture data or with negative respiratory cultures met clinical stability criteria early in admission. The maximum time to clinical stability was approximately 5 days. However, total median antibiotic duration was 7 days (IQR 6.0- 8.7), resulting in 2 days (IQR 1.5-3.9) of excess antibiotics.

Evaluation Of A Pharmacist-Driven Electrolyte Replacement Protocol In A Community Health System, Corey Uetrecht Pharmd Candidate

Pharmacy Residency

This evaluation found a higher rate of pharmacist consults for electrolyte management, though these were not always indicated. Repletion via oral route was not optimized and there were opportunities for improvement in protocol alignment.

Presented at Great Lakes PRC

Implementation Of An Evidence Based Skin And Soft Tissue Infection Algorithm At A Large Community Health System, Jennifer Mccarthy Pharmd, Ms

Pharmacy Residency

This study found a continued need for an updated skin and soft tissue infection algorithm. Ongoing reliance on IV antibiotics suggests underutilization of oral options. Promoting oral antibiotic use may reduce inpatient admissions and length of stay.

Presented at OHIO PRC

Evaluating The Impact Of A Pharmacist-Led Wellness And Weight Management (Wwm) Service In The Primary Care Setting, Nicholas Buttermore Pharmd

Pharmacy Residency

This evaluation found superior weight loss from baseline with pharmacist management, along with comparable GLP-1 and non-GLP-1 use and considerable financial benefits.

Aluminum In Beverages And Foods: A Comprehensive Compilation Of Regulations; Concentrations In Raw, Prepared, And Stored Beverages And Foods; And Intake, Robert Yokel

Pharmaceutical Sciences Faculty Publications

The history and controversy concerning aluminum use in beverage and food preparation and storage are reviewed. This review on aluminum in drinking water, foods, and beverages updates and exceeds prior reviews. Country and international organization regulations that permit incorporation of aluminum containing food additives, their use limit, and purposes are presented. The aluminum concentration in beverages and foods consumed worldwide was gleaned from approximately 2100 sources available to the author. The approximately 17700 values are compiled in 175 tables by beverage or food category that include the analytical method used, sample source, and reference. The tables are posted on the …

A Cocaine Hydrolase Engineered From Human Butyrylcholinesterase As A Medical Countermeasure For Aldicarb Poisoning, Johnathan E. Lesaint, Nellore Bhanu Chandar, Annet Kyomuhangi, Huimei Wei, Fang Zheng, Chang-Guo Zhan

Pharmaceutical Sciences Faculty Publications

Aldicarb is known to be the most toxic carbamate pesticide and could be used easily by terrorists to cause a mass casualty incident. It is highly desired to discover a medical countermeasure for aldicarb poisoning. Based on structural insights from molecular modeling and in vitro experimental validation, CocH3-Fc(M3), a potent cocaine hydrolase engineered from human butyrylcholinesterase (BChE), has a ~4-fold improved binding affinity with aldicarb compared to wild-type human acetylcholinesterase (AChE) and BChE and a 9-28-fold improved bimolecular rate constant for the carbamylation with aldicarb compared to AChE. CocH3-Fc(M3) also has significant catalytic activity for aldicarb hydrolysis and, hence, is …

Development Of A Ghrelin Deacylase To Attenuate Drug Reward And Associated Effects Of Methamphetamine, Madeline J. Stewart, Huimei Wei, Nellore Bhanu Chandar, Fang Zheng, Chang-Guo Zhan

Pharmaceutical Sciences Faculty Publications

All addictive substances directly or indirectly interact with the dopamine reward system to alter the brain’s dopamine receptor activities. It is essential for a truly effective addiction medication to attenuate substance reward and normalize the brain’s physiological functions. Conventional pharmacological intervention approaches to the treatment of substance addiction usually aim to develop and deliver a potential therapeutic agent to the brain to directly block or decrease actions of the substance or its therapeutic target in the brain. However, it is a grand challenge to attenuate the substance reward without affecting the normal physiological functions of brain receptors or transporters. Here, …

Effects Of Biased Analogues Of The Kappa Opioid Receptor Agonist, U50,488, In Preclinical Models Of Pain And Side Effects, Ross Van De Wetering, Loan Y. Vu, Lindsay D. Kornberger, Dan Luo, Brittany Scouller, Sheein Hong, Kelly F. Paton, Thomas E. Prisinzano, Bronwyn M. Kivell

Pharmaceutical Sciences Faculty Publications

Kappa opioid receptor (KOR) agonists have well-established antinociceptive effects. However, many KOR agonists have negative side effects, which limit their therapeutic potential. Some researchers have suggested that the development of biased agonists that preferentially stimulate KOR G-protein pathways over β-arrestin pathways may yield drugs with fewer adverse side effects. This was investigated in the current study. We describe the synthesis and characterization of three U50,488 analogues, 1, 2, and 3. We evaluated the acute and chronic antinociceptive effects of these compounds in mice using the warm-water tail flick assay and in a paclitaxel-induced neuropathic pain model. Side …

Effects Of Fentanyl-Adulterated Methamphetamine On Circulating Ghrelin In Rats, Huimei Wei, Elise C. Maul, Shawn Park, Kaniz Fatema, Daniel J. Peter, Chang-Guo Zhan, Fang Zheng

Pharmaceutical Sciences Faculty Publications

The appetite hormone ghrelin influences biological processes that are responsible for substance use disorder, which is related to alcohol and most abused drugs including cocaine, methamphetamine, nicotine, etc. In general, upregulation of the ghrelin system enhances drug cravings and substance use. Studies reported in the literature consistently demonstrated that the ghrelin system is associated with stimulants. However, research on opioids in combination with methamphetamine has not been reported. In this study, we examined the relationship of circulating ghrelin with the polydrug use of fentanyl and methamphetamine in male Sprague-Dawley rats, demonstrating for the first time that concurrent use of fentanyl …

Effects Of Fentanyl-Laced Cocaine On Circulating Ghrelin, Insulin, And Glucose Levels In Rats, Huimei Wei, Elise C. Maul, Annet Kyomuhangi, Shawn Park, Maddilynn L. Mutchler, Chang-Guo Zhan, Fang Zheng

Pharmaceutical Sciences Faculty Publications

Opioid mixed with cocaine has been increasingly implicated in overdose deaths, including both intentional co-use of opioid and cocaine and fentanyl-adulterated drug supply. As ghrelin plays an important role in drug reward and can also influence insulin, this study aimed to assess responses of the circulating ghrelin, insulin, and glucose levels to the combined use of fentanyl and cocaine (a polydrug) in rats by performing combined animal behavioral experiments and biochemical analysis. The experimental data consistently revealed that the fentanyl and cocaine co-use can significantly elevate both the acyl-ghrelin and desacyl-ghrelin levels and significantly decrease the insulin level without significant …

Fluorescence-Guided Resection Of Gl261 Red-Fluc And Trp-Mcherry-Fluc Mouse Glioblastoma Tumors, Louis T. Rodgers, Bryan J. Maloney, Anika M. S. Hartz, Björn Bauer

Pharmaceutical Sciences Faculty Publications

Background: Most preclinical studies on glioblastoma (GBM) fail to provide translational utility in the clinic. Fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) improves tumor resection, disease prognosis, and, thus, patient outcomes. Given the critical role of surgery in managing recurrent GBM, it is essential to incorporate surgical elements into preclinical models to accurately reflect clinical scenarios and enhance translational success. However, existing protocols for 5-ALA-guided resection in preclinical models are limited and often lack clinical relevance.

Methods: To address this gap, we developed a novel protocol for the 5-ALA-guided resection in two mouse GBM models: TRP-mCherry-FLuc and GL261 Red-FLuc.

Results: The …

Development Of Zafirlukast Analogues For Improved Antithrombotic Activity Through Thiol Isomerase Inhibition, Justine A. Keovilay, Kaitlind C. Howard, Kirk A. Taylor, Sabeeya Khan, Sienna E. Wurl, Melanie K. Szahaj, Tanya Sage, Nishad Thamban Chandrika, Caixia Hou, Oleg V. Tsodikov, Jonathan M. Gibbins, Sylvie Garneau-Tsodikova, Daniel R. Kennedy

Pharmaceutical Sciences Faculty Publications

Background:   Thiol isomerases play essential and nonredundant roles in platelet activation, aggregation, and thrombus formation. Thiol isomerase inhibitors have the potential to overcome the 2 major drawbacks of current antithrombotic therapies, as they target both arterial and venous thrombosis without enhancing bleeding risks. Recently, a Food and Drug Administration–approved drug, zafirlukast (ZAF), was shown to be a promising pan-thiol isomerase inhibitor. The objective of this study is to develop analogues of ZAF with optimized thiol isomerase inhibition and antithrombotic activity.   Methods:   Thirty-five ZAF analogues were tested in an insulin turbidometric assay for thiol isomerase inhibition. Analogues were tested for platelet …

Functional And Structural Studies On The Esperamicin Thioesterase And Progress Toward Understanding Enediyne Core Biosynthesis, Erome D. Hankore, Mitchell D. Miller, Abigael J. Kosgei, Weijun Xu, Kemin Tan, Michael Endres, Minakshi Bhardwaj, Grazyna Joachimiak, Andrzej Joachimiak, George N. Phillips Jr., Jon S. Thorson, Steven G. Van Lanen

Pharmaceutical Sciences Faculty Publications

Enediynes are among the most potent antitumor and antibacterial natural products. Studies on their biosynthetic pathways have identified a shared, linear polyene precursor generated from an iterative type I polyketide synthase (PKSE) as the source of the enediyne warhead. A key step is the release of this polyene from the PKSE by a discrete thioesterase (TE). Here, we used X-ray crystallography, site-directed mutagenesis, and heterologous coexpression of PKSEs and TEs to elucidate how enediyne TEs mediate the production of the polyene. We solved the structure of wild-type EspE7 from esperamicin producer Actinomodura verrucosospora. The substrate binding pocket was also …

Hypertensive Hijinks: Implementation Of An Emergency Department Hypertensive Emergency Order Panel, Caleb Hoppe Pharmd Candidate

Pharmacy Residency

This evaluation found that the order panel was effective in promoting rapid blood pressure attainment and appropriate antihypertensive dosing.

This was presented at the OHIO PRC.

Daratumumab Monotherapy: Reconsidering Relapsed And Refractory Multiple Myeloma Maintenance Therapy, Gabrielle O. Carreon Pharmd, Ms

Pharmacy Residency

Results from this study support the continued use of daratumumab monotherapy in carefully selected patients who may not be candidates for more intensive combination therapies due to age, comorbidities, or prior toxicities. However, further research is needed to confirm these early observations.

Presented at Great Lakes PRC

Silent Pressure: Outcomes Of As-Needed Antihypertensives In Hospitalized Adults*, Corey Uetrecht Pharmd Candidate

Pharmacy Residency

Presented at ACCP

This study found that PRN antihypertensives are frequently used for AEBP in hospitalized patients, despite limited benefit and potential risk of hypotension-related adverse events.

Development And Implementation Of An Analgesia, Sedation, And Paralysis Order Panel For Mechanically Ventilated Pediatric Patients At A Large Community Health System, Kristin Lytal Pharmd, Mspgx

Pharmacy Residency

This project describes best practices and steps taken in development of a protocol for analgesia, sedation, and paralysis in pediatric patients.

This was presented at OHIO PRC.

The Chemical Straightjacket: Institutional Over-Use Of Psychotropic Drugs On Children In Lieu Of Therapeutic Community Mental Health Services, Marisa Leib-Neri

Indiana Journal of Law and Social Equality

This Article argues that the abysmal state of children’s mental health in America is in part due to an overreliance on and over prescription of psychotropic drugs inside psychiatric residential institutions in lieu of community based mental health services. This overreliance on residential institutions and psychotropic drugs has allowed a new form of chemical restraint to flourish—the chemical straitjacket. This Article uses the medication lists of twelve children in seven different North Carolina psychiatric residential treatment facilities to demonstrate how the chemical straitjacket operates: the prescription of drugs not approved for pediatric populations, counter to evidence-based practices for particular diagnoses, …

Medical-Grade Honey And Standard Dressings In Burn Wound Care: Evaluating Effectiveness, Cost, And Patient Outcomes, Chloe Shin, Andrew Golonka

Nursing | Student Research Posters

Background: Burn injuries burden the healthcare system globally as silver sulfadiazine (SSD) is the standard treatment even though it delays healing and is highly costly. Medical-grade honey (MGH) demonstrates superior antimicrobial and anti-inflammatory properties, however, there are still evidence gaps when comparing effectiveness, cost efficiency, and patient centered outcomes. Purpose: This study aims to compare MGH and SSD amongst these gaps to inform evidence based burn care. Methods: A randomized controlled trial will enroll 100 people between 25-50 years of age with first and second degree burns, < 20% total body surface area within two hospital burn units. Participants will be assigned to either MGH or SSD treatment. The study will be a single blind design where dermatologists evaluating the wound photographs will not know the treatment given. Primary outcomes include wound healing time, infection rates, and patient reported pain scores. Secondary outcomes will focus on cost effectiveness analyses and patient quality of life. Standardized protocols will be implemented for data collection, wound assessment, and safety monitoring. Results: We anticipate that MGH will have lower infection rates, promote faster wound healing, improved outcomes from patient reports, and better cost effectiveness through shorter hospital stays and reduced medical treatments compared to SSD. Conclusion: This study will provide evidence comparing MGH and SSD across economic, clinical, and patient centered outcomes. If our hypothesis aligns with the results, MGH could be a new evidence based standard in burn care as it offers many advantages over SSD in patient comfort, healing efficiency, and medical costs. The findings will provide areas for future research, especially long term outcome and a bigger patient population.

Optimizing Endogenous Glp-1 Holistically: A Nursing Led Approach To Sustainable Weight Loss Without Glp-1 Agonist Use, Taylee A. Carscadden

Nursing | Senior Theses

The increase in off-label Glucagon-like peptide-1 (GLP-1) receptor agonist drugs, such as semaglutide (Ozempic), for weight loss has sparked concern in regards to the not fully understood drug outcomes and safety. GLP-1 agonists were originally developed to manage Type 2 Diabetes Mellitus, but have been widely prescribed for obesity management despite minimal research on prolonged use in non-diabetic patients. This study explores how off-label use of GLP-1 agonist drugs exacerbate various adverse health outcomes, highlighting gastrointestinal complications, and the very possible dependency on drugs for weight management. It will also examine the efficacy of nursing-led education on the implementation of …

Medical-Grade Honey And Standard Dressings In Burn Wound Care: Evaluating Effectiveness, Cost, And Patient Outcomes, Andrew Golonka, Chloe Shin

Nursing | Senior Theses

Background: Burn injuries burden the healthcare system globally as silver sulfadiazine (SSD) is the standard treatment even though it delays healing and is highly costly. Medical-grade honey (MGH) demonstrates superior antimicrobial and anti-inflammatory properties, however, there are still evidence gaps when comparing effectiveness, cost efficiency, and patient centered outcomes. Purpose: This study aims to compare MGH and SSD amongst these gaps to inform evidence based burn care. Methods:A randomized controlled trial will enroll 100 people between 25-50 years of age with first and second degree burns, < 20% total body surface area within two hospital burn units. Participants will be assigned to either MGH or SSD treatment. The study will be a single blind design where dermatologists evaluating the wound photographs will not know the treatment given. Primary outcomes include wound healing time, infection rates, and patient reported pain scores. Secondary outcomes will focus on cost effectiveness analyses and patient quality of life. Standardized protocols will be implemented for data collection, wound assessment, and safety monitoring. Results: We anticipate that MGH will have lower infection rates, promote faster wound …

Gramseq-Dta: A Grammar-Based Drug-Target Affinity Prediction Approach Fusing Gene Expression Information, Kasul Debnath, Pratip Rana, Preetam Ghosh

Computer Science Faculty Publications

Drug–target affinity (DTA) prediction is a critical aspect of drug discovery. The meaningful representation of drugs and targets is crucial for accurate prediction. Using 1D string-based representations for drugs and targets is a common approach that has demonstrated good results in drug–target affinity prediction. However, these approach lacks information on the relative position of the atoms and bonds. To address this limitation, graph-based representations have been used to some extent. However, solely considering the structural aspect of drugs and targets may be insufficient for accurate DTA prediction. Integrating the functional aspect of these drugs at the genetic level can enhance …