Medicine and Health Sciences Commons^™

Perturbation Modeling For Molecular Design Of Protein Tyrosine Kinase Inhibitors Using Unsupervised Machine Learning, Keerthi Krishnan

Computational and Data Sciences (MS) Theses

The field of computational drug discovery and development has grown, with the aid of new computational tools for novel molecule discovery. In specific, generative deep learning models have excelled as tools to aid in navigating the large space of known molecules and in the creation of new molecules. These models are fed various representations of molecules as inputs and learn to perform a variety of things, such as the optimization of these molecules towards a targeted property. Ultimately, these generative learning models allow us to build bridges between chemical and continuous spaces to understand the compromise between invoking small incremental …

Polymer Coated Polymeric (Pcp) Microneedles For Sampling Of Drugs And Biomarkers From Tissues, Deeksha Jakka, A. V. Matadh, H. N. Shivakumar, Howard Maibach

Faculty and Student Publications

The Polymer Coated Polymeric (PCP) microneedles were fabricated using PVP K30 in the core and ethyl cellulose in the coating. The PCP microneedles do not disintegrate in the tissue upon insertion and rather stays intact and allows diffusion of drugs and analytes across the membrane both inward and outward. In this project the potential use of PCP microneedles for sampling analytes from the dermal tissue was explored. The amount of analyte sampled depended on the concentration in the tissue, physicochemical properties of the analyte and duration of insertion of the array in the tissue. Further, an advanced type of PCP …

Comparative Single Dose Pharmacokinetics And Metabolism Of Racemic Primaquine And Its Enantiomers In Human Volunteers, Washim Khan, Yan Hong Wang, Narayan D. Chaurasiya, Np Dhammika Nanayakkara

Faculty and Student Publications

Primaquine (PQ) is a racemic drug used in treatment of malaria for six decades. Recent studies suggest that the two enantiomers of PQ are differentially metabolized in animals, and this results in different pharmacological and toxicological profiles. The current study characterizes the pharmacokinetic (PK) properties, metabolism and tolerability of the individual enantiomers of PQ in healthy human volunteers with normal glucose-6-phosphate dehydrogenase (G6PD) activity. Two cohorts (at two dose levels), each with 18 subjects, participated in three study arms in a crossover fashion: a single dose of the (−)-R enantiomer (RPQ), a single dose of the (+)-S enantiomer (SPQ), and …

An Exploration Of Ambulatory Visits And Medications Prescribed For Patients Diagnosed With Lupus Erythematosus In The United States, Salena Marie Preciado

Pharmaceutical Sciences (PhD) Dissertations

This dissertation sought to understand the management and treatment of patients diagnosed with lupus erythematosus. To accomplish the objectives of this research, three studies were conducted. First, a systematic literature review was done to assess the current landscape of available clinical guidelines for disease treatment. This research then used the National Ambulatory Medical Care Survey data from 2006-2016 to explore real-world trends in medications prescribed, comorbidities and chronic conditions associated with lupus. Data is weighted to be nationally representative of the U.S. The third study explored sociological influences or nonclinical factors on the prescribing of medications for patients with lupus. …

Approvals And Prices Of Systemic Antibiotics In Saudi Arabia And The United States, Saad Alharthi

Pharmaceutical Sciences (MS) Theses

Introduction

Antibiotics is one of the therapeutic classes with the highest level of consumption in the world. Despite the global diffusion of antibiotics, their availability and prices vary by country. This study assessed differences in the availability and prices of systemic antibiotics marketed in the United States (US) and Saudi Arabia and evaluated the factors associated with the differences in prices of systemic antibiotics marketed in both countries.

Material and Methods

We collected regulatory data from the US Food and Drug Administration (FDA) and the Saudi Food and Drug Authority (SFDA), the National Average Drug Acquisition Cost (NADAC) and the …

Effects Of Nnos Inhibitors On Melanoma-Induced Immunosuppression, Kate Alison Lozada

Pharmaceutical Sciences (MS) Theses

The incidence of cutaneous melanoma (CM) rises despite advances in immunotherapy and targeted therapy. Studies have shown that interferon-gamma (IFN-γ), a pro-tumorigenic cytokine in CM, induces the expression of programmed death-ligand 1 (PD-L1), leading to the escape of melanoma cells from immunosurveillance. Our previous study suggests that neuronal nitric oxide synthase (nNOS)-mediated nitric oxide (NO) signaling is crucial for melanoma progression and forms a mechanistic rationale behind nNOS inhibition as a novel treatment strategy for CM. An additional study demonstrated that IFN-γ interacts with nNOS signaling in melanoma and novel nNOS inhibitors (nNOSi) effectively diminished the induction of PD-L1 post …

Cyclic And Linear Cell-Penetarating Peptides Composed Of Tryptophan (Ww) And Arginine (Rr) Residues As Molecular Transporters, Lois Kim

Pharmaceutical Sciences (MS) Theses

The cell membrane has polar and negative charged characteristics and separates the inside of cells from the outside environment, and only allows small molecules to go into the cell to protect them from toxic substances. However, cell membrane characteristics make it difficult for polar and negatively-charged molecules to interact and penetrate the membrane. The delivery of cell impermeable compounds, such as phosphopeptides and siRNA, across the cell membrane remains a challenge. Previous studies in Dr. Parang’s laboratory have shown that cyclic peptides composed of tryptophan (W) and arginine (R) amino acids [WR]₅ have higher cellular uptake than the corresponding …

Identifying A Glucocorticoid-Activated Gpcr That Rapidly And Non-Genomically Increases Camp Levels In Mammalian Cells, Francisco Nunez

Pharmaceutical Sciences (PhD) Dissertations

Glucocorticoids (GCs) are steroid hormones that regulate diverse physiological processes. Synthetic versions of GCs are commonly used to treat inflammatory diseases such as asthma by modulating gene expression to suppressing several inflammatory activities. However, it is estimated that 5-10% of asthmatics are unresponsive to GCs, which may be explained by receptor desensitization and/or the presence of a neutrophilic endotype. One understudied phenomenon of GCs is their ability to induce rapid, non-genomic actions. For example, GCs can acutely modulate calcium concentrations levels, induce smooth muscle relaxation and modulate nitric oxide synthase activity, within minutes and sometimes seconds, which is too rapid …

Gaps In Patient Education On Safe Handling And Disposal Of Oral Chemotherapy Drugs: A Pilot Prospective Cohort Survey Study, Sun Yang, Priya Patel, Alexandra Corcoran, Eric Dobberpuhl, Samantha Isidro, Dustin Le, Analise Klassen, Jay Rho, David Tran, Richard Beuttler, Neda Noori Nassr, Katherine Gruenberg, Siu-Fun Wong

Pharmacy Faculty Articles and Research

Background

Oral anticancer chemotherapy (OC) has been misperceived as being safer than intravenous chemotherapy, leading to its increased risk of improper handling and disposal. This survey study assessed the knowledge, practices and attitudes of pharmacists and patients regarding OC handling and disposal, gaps in knowledge and barriers to patient education. Methods

Surveys were developed based on literature review and pilot study validation results. Patients completed a 33-item paper or electronic survey whereas pharmacists completed a 38-item electronic survey. Descriptive statistics and Fisher’s exact test computed using the R Project were used for analyses. Results

Pharmacist group (16/25, 62.5%) and patient …

Orphan Drugs: Designations, Approvals, And Prices In The Us, Hana Althobaiti

Pharmaceutical Sciences (PhD) Dissertations

Introduction. Rare disease drug approvals have accelerated significantly in recent years. Even with these advances, patients continue to face challenges in receiving treatment, with most rare diseases lacking any approved treatments. Moreover, even when a treatment is available, it does not always reach the patients who benefit from it.

Objectives. This dissertation assessed the characteristics of orphan drug designations and approvals and the factors associated with the time lag between orphan designation and approval in the US from 1983 to 2021. It also evaluated the treatment cost of orphan and non-orphan drugs and factors explaining the treatment cost of new …

Prevalence And Predictors Of Polypharmacy In Adolescents Who Have Engaged In Sexually Abusive Behaviors, Rebecca Gilley

Electronic Theses and Dissertations

Polypharmacy, or the concurrent use of multiple medications, is associated with detrimental outcomes for patients and has gathered increasing attention within the scientific clinical literature. Pediatric populations warrant special consideration for the practice of polypharmacy, as medication effects are more pronounced in youth and adverse effects may have a lasting impact on development. This dissertation study examined psychotropic prescribing practices in a sample of adolescents who have engaged in sexually abusive behaviors, a subset of justice-involved youth who are at risk for polypharmacy. General prescribing trends were examined, and a principle components analysis involving variables associated with risk of polypharmacy …

Adolescent Transport And Unintentional Injuries: A Systematic Analysis Using The Global Burden Of Disease Study 2019, Amy E. Peden, Patricia Cullen, Kate Louise Francis, Holger Moeller, Margaret M. Peden, Ismaeel Yunusa Ph. D., Et Al.

Faculty Publications

Background Globally, transport and unintentional injuries persist as leading preventable causes of mortality and morbidity for adolescents. We sought to report comprehensive trends in injury-related mortality and morbidity for adolescents aged 10–24 years during the past three decades.

Methods Using the Global Burden of Disease, Injuries, and Risk Factors 2019 Study, we analysed mortality and disability-adjusted life-years (DALYs) attributed to transport and unintentional injuries for adolescents in 204 countries. Burden is reported in absolute numbers and age-standardised rates per 100000 population by sex, age group (10–14, 15–19, and 20–24 years), and sociodemographic index (SDI) with 95% uncertainty intervals (UIs). We …

Preclinical Development Of Novel Chemotherapeutic Agent Ac1lpszg: Formulation Optimization, In Vitro Characterization, And In Vivo Pharmacokinetics, Ritu Gupta

Dissertations (2016-Present)

Preclinical development of novel chemotherapeutic agent AC1LPSZG, a mammalian target of rapamycin (mTOR) inhibitor, involved development of sensitive reverse-phase ultra-performance liquid chromatography (UPLC) and LC-MS/MS methods for quantification of AC1LPSZG in in vitro study samples and rat plasma, respectively. Pharmacokinetic studies were done in SD rats after intravenous injection of cosolvent formulations. The resulting pharmacokinetic parameters were analyzed using non-compartmental analysis (NCA) and two-compartmental modeling. Poly (D, L-lactic-co-glycolic acid) (PLGA) is most used biodegradable synthetic polymer for nano drug delivery due to its non-toxic and biodegradable nature, and tunable release properties. PLGA nanoparticles (NPs) were prepared by ‘nanoprecipitation’ technique using …

Prevention Of Deep Vein Thrombosis In Obese Trauma Patients, Sarah Autry

University Honors Theses

Deep vein thrombosis (DVT) is a frequent occurrence in trauma patients secondary to traumatic injury due to immobilization, reparative surgeries, and procedures, if no/minimal prophylaxis is utilized. Obesity has been shown to increase the risk of venous thromboembolism (VTE) by 2 to 3 times. The current DVT data may not discriminate between patient demographics that affect venous thromboembolisms (VTE) and chemoprophylaxis, such as weight or body mass index (BMI). A retrospective data analysis was performed using data collected from Oregon Health & Science University’s Trauma Registry that includes trauma patients admitted between January 2017 and December 2020, ≥17 years of …

Increasing Rosella Farmers Capacity By Double Diamond Design Thinking Approach, Florence Pribadi, Muliasari Kartikawati, Juli Karijati Njoto, Nurul Illahi Kusuma Sari, Farah Shania Nur

ASEAN Journal of Community Engagement

Rosella (Hibiscus sabdariffa Linn) is a well-known family medicinal plant (Toga). Spoilage due to the weather, and the consequent low revenue gained from selling dried rosella are two of the main challenges currently being encountered by rosella farmers. Regardless of previously practicing community engagement including regular training from local authorities, farmers are still encountering difficulties to implement the training materials, consequently experiencing loss. Method incorporated in this community engagement is the double diamond design thinking that ensures putting the farmers first in all stages. Method chosen for drying rosella was a mixed solar dryer equipped with heating lamps …

Treatment Of Tardive Dyskinesia With High Dose Vitamin B6 Associated With Depression, Marjorie Mccoy, Adam Schindzielorz, Suzanne Holroyd

Marshall Journal of Medicine

Tardive dyskinesia (TD) is a movement disorder associated with dopamine receptor blocking medications. Recommended treatments for TD include discontinuing the causative agent, adding vesicular monoamine transporter 2 (VMAT2) inhibitors, or adding vitamin B6. We present a 66-year-old Caucasian male with bipolar I disorder who developed TD while on lithium and quetiapine having been euthymic on this regimen for three years. He was initially treated with 1200 mg B6 daily. This failed to improve his TD and was associated with a depressive episode. He switched to valbenazine 40 mg daily which improved his TD and concurrently his mood, but months later …

Cardiovascular Adverse Events In Oncology Trials: Understanding And Appreciating The Differences Between Clinical Trial Data And Real-World Reports, Michael S Ewer, Jay Herson

Duncan NRI Faculty and Staff Publications

Reports of cardiac adverse events from oncology clinical trials often are at variance with reports derived from clinical observations or data-base reviews. These differences may lead to confusion, as different levels of risks abound in the literature, and the true cardiac risk of using some agents is uncertain. Additionally, such discrepancies may lead to the creation of over-cautious surveillance algorithms. Reasons for these reported differences are complex and often reflect subtleties in the criteria for individual patient evaluation. Both clinical trial data and real-world data have potential flaws that make reconciliation problematic. Importantly, however, both provide crucial information regarding the …

Abstracts From The 2022 Health Care Systems Research Network (Hcsrn) Annual Conference

Journal of Patient-Centered Research and Reviews

The Health Care Systems Research Network (HCSRN) is comprised of 20 health systems with embedded research units. The network’s annual conference serves as a forum for research teams from member institutions to disseminate scientific findings, explore new collaborations, and share insights about conducting research in real-world care delivery settings. Abstracts accepted for presentation at HCSRN 2022 are published in this supplement of Journal of Patient-Centered Research and Reviews, the official journal of HCSRN’s annual conference proceedings.

Partnering To Advance Health Equity And A Welcome Opportunity To Gather: Proceedings From The 28th Annual Conference Of The Health Care Systems Research Network, Robert T. Greenlee

Journal of Patient-Centered Research and Reviews

In April 2022, the Health Care Systems Research Network (HCSRN) — a consortium of 20 research institutions affiliated with large health systems spread across the United States (and one in Israel) — held its 28th annual conference in Pasadena, California, with 275 researchers, health care colleagues, and external academic partners in attendance. With a conference theme of “Promoting Collaboration and Partnerships to Advance Health Equity,” the scientific program was assembled by a multisite planning committee with input from representatives of informal local host Kaiser Permanente Southern California. Objectives of the annual conference are to showcase scientific findings from HCSRN projects …

Retrospective Cohort Evaluating The Comparative Effectiveness Of Ceftaroline And Daptomycin As First-Line Therapies For Inpatient Treatment Of Diabetic Foot Infection In The United States Veterans Health Care System, Alyssa C. Eaves, Chengwen Teng Pharm.D., Ph.D., Kirk E. Evoy, Christopher R. Frei

Faculty Publications

Background Both ceftaroline and daptomycin are possible therapeutic options for diabetic foot infection (DFI) and both are active against methicillin-resistant Staphylococcus aureus (MRSA) infection; however, no previous studies have evaluated their efectiveness head-to-head.

Objective This study compared hospital readmission and mortality proportions among patients receiving ceftaroline fosamil or daptomycin for DFI.

Patients and Methods This was a retrospective cohort, comparative efectiveness study of adults (aged ≥ 18 years) admitted to United States Veterans Health Care System hospitals with a diagnosis code for DFI between 1 October 2010 and 30 September 2014 with an electronic order for ceftaroline or daptomycin as …

Pharmacists Role In Preventing Drug Abuse, Renae L. Wilson

College of Pharmacy Student Research

In 2019, there were approximately 332,000 pharmacists active in the US workforce, Data USA, 2019. A survey of 1,700 American adults, discovered, that 34% of Americans still rely on healthcare providers such as pharmacists, for information in relation their health, KRC Research, 2018. Pharmacists are one of the three most trusted health care professions and were found to be the second most trusted source for health information by Americans in 2005. Blendon et al., 2006 found, that information from pharmacist was trusted by 67%, of participants in their survey. One of the oaths pledged by pharmacist is, ‘ …

Synthesis And Evaluation Of Anti-Hiv Activity Of Mono- And Di-Substituted Phosphonamidate Conjugates Of Tenofovir, Aaminat Qureshi, Louise A. Ouattara, Naglaa Salem El-Sayed, Amita Verma, Gustavo F. Doncel, Muhammad Iqbal Choudhary, Hina Siddiqui, Keykavous Parang

Pharmacy Faculty Articles and Research

The activity of nucleoside and nucleotide analogs as antiviral agents requires phosphorylation by endogenous enzymes. Phosphate-substituted analogs have low bioavailability due to the presence of ionizable negatively-charged groups. To circumvent these limitations, several prodrug approaches have been proposed. Herein, we hypothesized that the conjugation or combination of the lipophilic amide bond with nucleotide-based tenofovir (TFV) (1) could improve the anti-HIV activity. During the current study, the hydroxyl group of phosphonates in TFV was conjugated with the amino group of L-alanine, L-leucine, L-valine, and glycine amino acids and other long fatty ester hydrocarbon chains to synthesize 43 derivatives. Several …

Evaluation Of Residual Antibacterial Effects On Canine Skin Surface And Hairs Following Treatment With Five Commercial Mousse Products Against Staphylococcus Pseudintermedius In Vitro, Chi-Yen Wu

LSU Master's Theses

Topical products are essential treatments for canine superficial bacterial folliculitis. However, studies for commercial products typically evaluate antibacterial effects on hairs rather than the skin surface. In addition, the interference from the hair length has not been evaluated in these studies. Therefore, the study objective for this study was to evaluate the residual antibacterial effects of five mousse products, (1) 2% chlorhexidine and 2% miconazole, (2) 0.05% phytosphingosine, (3) 2% salicylic acid and 10% ethyl lactate, (4) 3% chlorhexidine and 0.5% climbazole, and (5) 2% chlorhexidine and 1% ketoconazole on both the skin surface and hairs in both short- and …

Oral Anticoagulant Underutilization Among Elderly Patients With Atrial Fibrillation: Insights From The United States Medicare Database, Muhammad Bilal Munir, Patrick Hlavacek, Allison V. Keshishian, Jennifer D. Guo, Rajesh Mallampati, Mauricio Ferri, Cristina Russ, Birol Emir, Matthew Cato, Huseyin Yuce, Jonathan C. Hsu

Publications and Research

Background

Oral anticoagulants (OACs) mitigate stroke risk in patients with atrial fibrillation (AF). The study aim was to analyze prevalence and predictors of OAC underutilization.

Methods

Newly diagnosed AF patients with a CHA2DS2-VASc score ≥ 2 were identified from the US CMS Database (January 1, 2013–December 31, 2017). Patients were stratified based on having an OAC prescription versus not and the OAC prescription group was stratified by direct OAC (DOACs) versus warfarin. Multivariable logistic regression models were used to examine predictors of OAC underutilization.

Results

Among 1,204,507 identified AF patients, 617,611 patients (51.3%) were not prescribed an OAC during follow-up …

Genetic Diversity Of Cladosporium Species Isolated From Air Of Cairo, Egypt Using Microsatellite Primed Pcr (Mp-Pcr) And Universally Primed Pcr (Up-Pcr) Techniques, Mohammed Salah Abdulrahman, Hamido M. Hefny, Moselhy S. Mansy, Amal A. I. Mekawey

Bulletin of Faculty of Pharmacy Cairo University

The samples were then identified by macroscopic and microscopical methods, Molecular fingerprinting, of Cladosporium strains populations depending on MP-PCR using Primers (AGG) 5 , (CAG) 5 , (GACA) 4 , and (AG) 8 C. In addition, we have applied the UP-PCR technique using L21 and Fok1 Genotyping patterns extracted by MP-PCR showed good discrimination with amplification of (AGG) 5 , (AG) 8 C and (CAG) 5 over (GACA) 4. In addition, L21 primer revealed variability over FOK1 primer. current work indicate that MP-PCR and UP-PCR fingerprinting method are appropriate for characterization of large groups of Cladosporium due to its simplicity

Phytochemicals, Acute Toxicity And Genotoxicity Of Chewing Sticks From Zanthoxylum Zanthoxyloides Root And Distemonanthus Benthamianus Stem, Chinwe S. Alaribe, Akolade R. Oladipupo, Anjola T. Adebesin, Omolayomi Kaska, Emuejevoke T. Toye

Bulletin of Faculty of Pharmacy Cairo University

Dental caries has been reported to touch almost half of the world’s population, making it one of the most prevalent disease conditions in the world. Studies have shown that chewing sticks could be useful in cleaning of teeth and could offer protection against dental conditions, including caries. Given the increasing usage of chewing sticks and their unstandardized nature, in this study we investigated the acute toxicity, genotoxic effects on liver and kidney, and phytochemical constituents of chewing sticks from Zanthoxylum zanthoxyloides root and Distemonanthus benthamianus stem, widely used in West Africa. Chemical tests showed the presence of saponins, alkaloids, flavonoids, …

Radiological Appearance Of Appendicular Osteosarcoma: A Case Report, Dr. Bathreenathh B, Dr. Vikram Patil, Dr. Anupama C

Radiology Teaching Files

A 42yr old male patient with complaints of on and off pain of right shoulder and arm since 3months. No e/o weight loss and loss of appetite. No e/o fever. No e/o discharging sinus/ superficial swelling over the right arm.

Implementation Of Pharmacy Access To Hormonal Contraception, Lindsay E. Dale

Biomedical Sciences ETDs

Women report significant barriers to obtaining hormonal contraception prescriptions, including difficulty scheduling clinician appointments, inconvenient clinic hours and desire to avoid pelvic examinations. To increase contraceptive access, states throughout the United States have and continue to pass legislation authorizing pharmacists to prescribe hormonal contraception, allowing women to initiate contraception directly at the pharmacy without involvement of a physician. Despite patient and pharmacist interest in direct pharmacy access to contraception, many pharmacists report challenges to prescribing contraception. Few studies have assessed the uptake of pharmacy-prescribed contraception in states with expanded pharmacist prescriptive authority, but no prior studies have evaluated the implementation …

Natural Products Inhibitors Of Monoamine Oxidases—Potential New Drug Leads For Neuroprotection, Neurological Disorders, And Neuroblastoma, Narayan D. Chaurasiya, Francisco León Ph.D., Ilias Muhammad, Babu L. Tekwani

Faculty Publications

Monoamine oxidase inhibitors (MAOIs) are an important class of drugs prescribed for treatment of depression and other neurological disorders. Evidence has suggested that patients with atypical depression preferentially respond to natural product MAOIs. This review presents a comprehensive survey of the natural products, predominantly from plant sources, as potential new MAOI drug leads. The psychoactive properties of several traditionally used plants and herbal formulations were attributed to their MAOI constituents. MAO inhibitory constituents may also be responsible for neuroprotective effects of natural products. Different classes of MAOIs were identified from the natural product sources with non-selective as well as selective …

Chemical Authentication And Speciation Of Salvia Botanicals: An Investigation Utilizing Gc/Q-Tof And Chemometrics, Joseph Lee, Mei Wang, Jianping Zhao, Bharathi Avula

Faculty and Student Publications

Members of the genus Salvia are used as culinary herbs and are prized for their purported medicinal attributes. Since physiological effects can vary widely between species of Salvia, it is of great importance to accurately identify botanical material to ensure safety for consumers. In the present study, an in-depth chemical investigation is performed utilizing GC/Q-ToF combined with chemometrics. Twenty-four authentic plant samples representing five commonly used Salvia species, viz. S. apiana, S. divinorum, S. mellifera, S. miltiorrhiza, and S. officinalis, are analyzed using a GC/Q-ToF technique. High-resolution spectral data are employed to construct a sample class prediction (SCP) model followed …