Chemicals and Drugs Commons^™

Vaginal Pra1 Identifies Clinically Relevant Candida Albicans Vaginitis And Excludes Asymptomatic Colonization: An Exploratory Study, Elena Roselletti, Barbara Kozma, David Ratonyi, Alexandra Kunkli, Bence Kozma, Peter Takacs, Duncan Wilson

Department of Obstetrics & Gynecology Faculty Publications

Background

Accurate interpretation of Candida detection in women with vulvovaginal symptoms remains difficult, because organism recovery may reflect either clinically relevant infection or nonpathogenic colonization. We have recently demonstrated that the secreted fungal zinc-binding protein, Pra1 is responsible for driving the inflammatory immunopathology of VVC. We therefore reasoned that PRA1 expression by Candida albicans in the vagina may act as a diagnostic tool to discriminate between commensal colonisation and active disease.

Methods

We conducted a 12-week prospective, single-center exploratory biomarker analysis nested within a registered parent clinical trial. Nine women with vulvovaginal symptoms provided cervicovaginal lavage samples and clinical data …

Trends In Glp-1 Based Therapy Use Before And After Pregnancy, Nansi S. Boghossain, Lauren Mcabee, Antonio F. Saad, Maged M. Costantine, Marwan Ma'ayeh, Joseph A. Ewing

Department of Obstetrics & Gynecology Faculty Publications

[Introduction] Glucagon-like peptide-1 (GLP-1)-based therapies are increasingly prescribed for the treatment of type 2 diabetes and obesity, with rapid uptake of newer agents such as semaglutide and tirzepatide [1, 2]. These medications improve glycemic control and promote weight loss and are now widely used among reproductive-aged individuals [2, 3]. However, GLP-1-based therapies are typically discontinued prior to pregnancy because of limited safety data and potential fetal risks, and current guidance recommends avoiding use during pregnancy [3]. As prescribing expands, a growing number of individuals entering pregnancy may have recent exposure to GLP-1-based …

Antibody-Drug Conjugates Beyond Her2 In Non-Small Cell Lung Cancer (Nsclc): Mechanisms, Emerging Targets, And Future Directions, Ahmed Ismail, Akash Desai, George R. Simon, Yanis Boumber

Department of Medicine Faculty Publications

Antibody–drug conjugates (ADCs) are a rapidly evolving class of oncology therapeutics that enable precise delivery of potent cytotoxic agents to tumor cells while minimizing systemic toxicity. While HER2-targeted ADCs such as trastuzumab deruxtecan (T-DXd) in HER2-mutant, Datopotamab deruxtecan (Dato-Dxd) in EGFR-mutant, and telisotumumab vedotin (Teliso-V) in MET IHC 3+ expressing lung cancer have already established a clinical role in non-small cell lung cancer (NSCLC), multiple ADCs targeting alternative antigens, including additional TROP2 ADCs, HER3, MET, CEACAM5, B7-H3, Nectin-4, and others, are now in advanced clinical development. This review synthesizes the current evidence for non-HER2 ADCs in NSCLC, highlighting mechanisms of …

The Impact Of A Vancomycin Intervention On Vancomycin-Associated Nephrotoxicity In Children: A Quality Improvement Initiative, Megan R. Nettleton, Hwi Eun Mary Shim, Joanne Abbotsford, Zoy Goff, Briony Hazelton, Matthew O'Brien, Tenielle Porter, Thomas Snelling, Daniel K. Yeoh, Asha C. Bowen, Christopher C. Blyth, Anita J. Campbell

Research outputs 2022 to 2026

Background: Vancomycin is first-line treatment for methicillin-resistant Staphylococcus aureus (MRSA) infections. However, despite guideline recommendations, there is no evidence that targeting vancomycin trough concentrations of ≥15 mg/L in children confers clinical benefit and is associated with vancomycin-associated nephrotoxicity (VAN). Aim: This study aimed to evaluate the impact of a vancomycin safety bundle on VAN and vancomycin utilisation in hospitalised paediatric inpatients. Method: A pre–post-intervention study was conducted in a tertiary paediatric hospital comparing January–December 2018 (pre-intervention) to May 2019–April 2020 (post-intervention). Hospitalised children, aged 30 days to <18 years, that received intravenous vancomycin with at least one trough concentration were included. The intervention bundle comprised: (1) lowered empiric vancomycin trough targets (5–15 mg/L), (2) enhanced creatinine monitoring (concomitant serum creatinine with vancomycin trough), (3) guideline modification (reduced pre-authorised indications for empiric vancomycin use), and (4) prescriber education initiatives. Ethical approval was granted by the WA Child and Adolescent Health Service Research Ethics Committee, Governance Evidence Knowledge Outcomes Program (Reference no: 41830) and the study conforms with the National Health and Medical Research Council's Ethical considerations in quality assistance and evaluation activities. Results: A total of 314 vancomycin prescriptions were analysed (n = 204 pre-intervention; n = 110 post-intervention). Post-intervention, VAN incidence decreased almost twofold from 0.46 to 0.25 episodes per 1000 patient bed days (p ≤ 0.01), and vancomycin prescription days decreased by 19%. Total hospital drug costs for vancomycin decreased by AUD $16 033. Overall, and for paediatric invasive MRSA, no significant difference in clinical outcomes or 30-day mortality was observed between study periods. Conclusion: This study demonstrated the implementation of a vancomycin safety bundle significantly reduced paediatric VAN and vancomycin utilisation without compromising clinical outcomes. These data support antimicrobial stewardship interventions to improve medication safety for children.

Intravenous Infusion Of Nicotinamide Adenine Dinucleotide (Nad+) Versus Nicotinamide Riboside (Nr): A Retrospective Tolerability Pilot Study In A Real-World Setting, Kirsten Reyna, Greer Heinzen, Nikita Patel, Marie Ritter, Alexandra Siojo, Henry Legere, Rachele Pojednic

Research outputs 2022 to 2026

Background: Nicotinamide adenine dinucleotide (NAD⁺) is a cofactor for NAD⁺-dependent enzymes that regulate DNA repair, cellular metabolism, and immune function. Supplementation with NAD⁺ and its precursors is commonly used to prevent age-related disease and extend healthspan. Commercial clinical and wellness settings increasingly provide intravenous (IV) NAD⁺ and nicotinamide riboside (NR) despite limited evaluation of safety and effectiveness. These considerations are important, as NAD⁺ and its precursors differ in reported side effects, cellular uptake, and metabolism. This study sought to compare commercially administered NAD⁺ IV and NR IV in humans by evaluating infusion …

A Comparison Of F/Taf And F/Tdf As Hiv Pre-Exposure Prophylaxis In A Predominantly Cisgender Women Population In East And South Africa: A Randomised, Factorial, Non-Inferiority Trial, Sheena Mccormack, David Dunn, Sylvia Kusemererwa, Patricia Munseri, Nishanta Singh, Wiston William, Gertrude Mutonyi, Henry Bern, Lauriane Goldwirt, Cherry Kingsley, Arne Kkroidl, Christian Holm Hansen, Song Ding, Rachel Kawuma, Mary Amondi, Ubaldo Bahemuka, Deus Buma, Daniel Clutterbuck, Zakir Gaffoor, Angus Jennings, Agricola Joachim, Ayoub Kakande, Berna Kalanzi, Abisai Kisinda, Mabela Matsoso, Thomas Miller, Neetha Mmedsci Morar, Jacqueline Musau, Jane Nabbuto, Ayanda Nzuza, Doreen Pamba, Simona Salomone, Thandiwe Sithole, Edith Tarimo, Kubashni Woeber, Kundai Chinyenze, Glenda Gray, Eligius Lyamuya, Muhammad Bakari, Said Aboud, Lucas Maganga, Gustavo Doncel, Janet Seeley, Jonathan Weber, Pontiano Kaleebu, Julie Fox, Eugene Ruzagira, On Behalf Of The Prepvacc Study Group

CONRAD Publications

Background:

F/TAF was shown to be non-inferior to F/TDF as pre-exposure prophylaxis (PrEP) in men, but approval was not extended to cisgender women. We report the results of PrEPVacc, in which a predominantly female population was randomly allocated to receive daily oral F/TDF or F/TAF for ∼6 months within a HIV-1 prophylactic vaccine trial.

Setting:

Five study sites in three African countries (Uganda, Tanzania, South Africa).

Methods:

The two regimens were compared by the averted infections ratio (AIR) - the proportion of infections averted by F/TAF relative to F/TDF. The counterfactual HIV incidence, an essential component of this metric, was …

Partial Post-Exposure Protection By Topical Inserts Containing Tenofovir Alafenamide Fumarate/Elvitegravir In A Macaque Model Of Rectal Simian Hiv (Shiv) Infection, Natalia Makarova, Tyana Singletary, M. Melissa Peet, Kristen Kelley, Ryan Johnson, Vivek Agrahari, Maria Mendoza, Yi Pan, Walid Heneine, Meredith R. Clark, J. Gerardo García Lerma, Gustavo F. Doncel, James W. Smith

CONRAD Publications

On-demand topical inserts for HIV prevention may be a good option for people who have a low frequency of sexual activity. We recently demonstrated in a preclinical macaque model that rectal application of inserts containing tenofovir alafenamide fumarate (TAF) and elvitegravir (EVG) conferred protection against SHIV infection (93% efficacy) when applied as pre-exposure prophylaxis 4 hours before SHIV exposure. Here, we show that the same inserts provide significant postexposure protection (82.9% efficacy) when applied 4 hours after SHIV exposure. Our findings further support the ongoing clinical development of TAF/EVG inserts for on-demand HIV prevention.

Repurposing Of Fda-Approved Drugs Identifies Glipizide As A Potent Hmg-Coa Reductase Inhibitor: A High-Throughput Virtual Screening And Molecular Dynamics Approach For Targeting Hypercholesterolemia, Parvej Ahmad, Eswara N. Hanuma Kumar Ghali, Sahir S. Alvi

School of Medicine Publications

Purpose:

Atherosclerotic cardiovascular disease (ASCVD) is one of the leading causes of mortality worldwide. Several inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-R), the key hepatic cholesterogenic enzyme, are prescribed to treat hypercholesterolemia and ASCVD. Statins, the established HMG-R inhibitors, exhibit promising cholesterol-lowering effects; however, their long-term use has prompted significant concerns, necessitating the search for additional therapeutic candidates with strong HMG-R inhibitory activity. Therefore, this study aims to find potential HMG-R inhibitor/s that may help reduce excess cholesterol levels via targeting HMG-R activity.

Methods: In this study, 1285 FDA-approved small molecules were assessed for their HMG-R inhibitory potential using …

Prenatal Exposure To Nicotine And Postpartum Depression: A Systematic Review And Meta-Analysis, Reem Sharaf-Alddin, May Salama, Denise Mckinney, George Saade, Qi Zhang

Health Behavior, Policy & Management Faculty Publications

Purpose: Postpartum Depression (PPD) is the most common mental health complication of childbirth, and has short-term and long-term consequences for mother, child, and the entire family. PPD is a function of several factors. Prenatal exposure to nicotine (PEN) by Active Tobacco Smoking (ATS), Secondhand Smoking (SHS), or Electronic Nicotine Products (ENPs) is a major potential risk factor. This systematic review and meta-analysis aim to summarize and evaluate all evidence regarding the association between PEN and PPD.

Methods: We searched the following databases, PubMed, Medline, Cochrane, EMBASE, and CINHAL, for studies published between Jan.1st ,2000&Sep.19th ,2024, with the outcome PPD. Studies …

The Weight Of Stigma, Rebekah A. King, Michael S. Sinha

All Faculty Scholarship

Many health care providers, both implicitly and explicitly, perpetuate stigma in their treatment of patients classified as obese. While medical professionals understand that a one-size-fits-all approach to treatment is ineffective, patients classified as obese are frequently offered limited treatment options that fail to account for their unique needs. Access to a range of effective treatment options has historically been limited, but new GLP-1 receptor agonist medicines like Wegovy (semaglutide) and Zepbound (tirzepatide), have shown incredible promise in addressing the obesity crisis. Unfortunately, these transformative drugs are costly, in high demand, and not widely covered by insurance, rendering them inaccessible for …

Attention-Based Multi-Omics Fusion For Drug Synergy Prediction, Kusal Debnath, Pratip Rana, Preetam Ghosh

Computer Science Faculty Publications

Drug combination therapy in disease management gained popularity in the last few decades. Computational modeling of such combinations is an active area of research in the drug discovery domain. While earlier approaches solely emphasized on the structural features of participating drugs for designing synergistic models, they lack other crucial factors directly linked with drug administration - omics expressions. As differential omics expression is a downstream consequence of the administered drug combinations, utilizing such expressions while designing synergistic models promises robust and dynamic modeling. In this work, we propose SynergyLM that fuses multi-omics features with drug embeddings to build an omics-aware …

Will They Be More Honest With An (External) Proctor? Evaluating Ufc Match Performance Before And After The Adoption Of The Usada Doping Program, Moonsup Hyun, Wonsok (Frank) Jee, Sehwon Kang, Yohan Lee

Human Movement Studies & Special Education Faculty Publications

Over the eight years from 2015 to 2023, the Ultimate Fighting Championship (UFC) partnered with the United States Anti-Doping Agency (USADA) to institute comprehensive external oversight of doping controls. This study investigates the effects of transitioning from internally administered anti-doping protocols to exclusive external governance by comparing UFC performance metrics before and during the USADA partnership. Using a Difference-in-Differences (DiD) approach with data from 2012 to 2018, we find that match duration significantly increased, while the likelihood of extreme outcomes, knockouts (KO), technical knockouts (TKO), and submissions, decreased during the USADA period. These results suggest that performance-enhancing drugs (PEDs) could …

Photo And Spatial Control Of Rna Structures And Functions: Exploring Positional Effects And Photo-Responsiveness Of Azobenzene Modified Nucleotides, Jinxi Du

Electronic Theses & Dissertations (2024 - present)

RNA molecules perform many important biological functions by forming complex three-dimensional structures stabilized by base pairing, tertiary interactions, and metal ion coordination. Because RNA function depends strongly on its structure, methods that allow reversible control of RNA conformation and activity are important for understanding RNA behavior and for potential therapeutic applications. However, achieving reversible and site-specific control of RNA structure, especially at the single-nucleotide level, remains challenging. In this dissertation, I developed and applied azobenzene-modified nucleotides as a chemical tool to enable optical and spatial control of RNA structure and function.

The first part of this dissertation focuses on establishing …

January 2026, Swosu Rural Health Center

RURAL ROCKS

• Age-Friendly Requirements for Hospital Quality Reporting
• APhA secures key congressional win allowing pharmacists to prescribe buprenorphine with specialized training
• "When the hospital leaves town"
• Med Spa Illicit GLP-1s | Supply Chain Safety
• CMS unveils new model aimed at functional, lifestyle medicine

Glycomedicine: Unveiling The Paracentral Dogma, Wei Wang, Gordan Lauc

Research outputs 2022 to 2026

No abstract provided.

Inflammatory Co-Regulation Of Voltage-Gated Sodium Channels And Na,K-Atpase In Metastatic Breast Cancer, Steven D. Scahill, Kelly Jean Sherman, Dennis Paul

School of Graduate Studies Faculty Publications

Sodium regulation is a potentially major driver of cancer metastasis. Voltage-gated sodium channels (VGSCs) and Na,K-ATPase are sodium transporters that are upregulated in many advanced carcinomas and are implicated as metastatic drivers. However, little is known about what drives this overexpression, how these proteins influence metastatic behavior, or whether these complementary sodium transporters are co-regulated in cancer. Using sodium transporter regulation in healthy neurons as a model, the present study demonstrated that the inflammatory mediator tumor necrosis factor alpha (TNFα) affects the expression of VGSCs and Na,K-ATPase in an in vitro model of metastatic breast cancer. Acute TNFα challenge increased …

The Evolving Therapeutic Landscape Of Nanoscale Cancer Drug Delivery Systems: Future Perspectives, Nafeesa Qudsia Hanif, Bushra Arshad, Anila Fariq, Syed Imam Hussain Abidi, Sohail Ameer Marwat, Aneela Fatima

Journal of Bioresource Management

Cancer is one of the main causes of deaths in the world. Conventional cancer therapeutic approaches such as chemo- and radiotherapy have burdened the cancer patients with arduous physical and psychological challenges. Moreover, in case of onset of this disease, huge amount is required against the medications (chemotherapy and radiotherapy). It is estimated that annually, the increasing cancer disease incidence rate is alarming. In developed countries, the health support is given by the nation. Therefore, the health managements in the developed nations are over-burdened due to heavy expanses against expansive cancer therapy treatments. Interestingly, tumor treatments have undergone a comprehensive …

Microglial Expression Of Serotonin Receptors Reveals Parallel Regulation Of 5-Ht2b And Bdnf In The Rat Hippocampus, Andrei Turkin, Maria Sidorova, Ekaterina Kurilova, Natalia Alenina, Oksana Tuchina, Friederike Klempin

School of Graduate Studies Faculty Publications

Growing evidence suggests that psychiatric disorders are characterized by a prolonged inflammatory state, which may influence the efficacy of compounds targeting serotonin. Serotonin is a key signaling molecule in neuroplasticity of the adult hippocampus and involved in antidepressant action. Recent in vitro studies indicate the neurotransmitter may also facilitate the response to inflammation and potentially modulate microglial function towards neuroprotection. Using Tph2−/− rats depleted of brain serotonin, we examined microglial expression of various serotonin receptors (5-HTRs) in vivo in both the hippocampus and prefrontal cortex and assessed mRNA levels of cytokines and brain-derived neurotrophic factor (BDNF). We observed age-dependent and …

Isg15 Dysregulates Endoplasmic Reticulum-Mitochondrial Contacts And Calcium Homeostasis In Ataxia Telangiectasia, Oygul Mirzalieva, Ryan E. Reed, Arthur L. Haas, Meredith A. Juncker, Patrick Logarbo, Jennifer M. Klein, David Worthylake, Shyamal D. Desai

School of Graduate Studies Faculty Publications

Dysregulation of endoplasmic reticulum and mitochondrial (ER:Mit) contacts and mitochondrial calcium (mitCa2+) homeostasis are found in several neurodegenerative disorders, including Ataxia Telangiectasia (A-T). However, the cellular basis of these defects remains unclear. Previously, we demonstrated that the aberrantly elevated Interferon-Stimulated Gene 15 (ISG15) pathway inhibits protein polyubiquitylation, its dependent protein turnover, and mitophagy pathways in A-T. Literature indicates that silencing of mitochondrial ubiquitin ligase 1 (MUL1) stabilizes mitofusin2 (MFN2) and attenuates mitCa2+ uptake from ER to Mit (mitCa2+influx) in primary neurons. We have replicated these findings in apparently healthy fibroblasts. We hypothesized that elevated ISG15 may inhibit ubiquitin-dependent MUL1-mediated degradation …

Hepatocyte-Specific Lrp1 Silencing Exacerbates Brain Amyloidosis Without Compensatory Ldl Receptor Family Involvement, Brian Carson, Josephine Chu, Devaraj V. Chandrashekar, Jerome Garcia, Rachita K. Sumbria, Derick Han

Pharmacy Faculty Articles and Research

Background

LDL receptor related protein 1 (LRP1) is a major hepatic receptor involved in lipoprotein metabolism, protease degradation, transmembrane receptor modulation, and clearance of excess protein, such as Aβ. Decreased expression of LRP1 due to liver injury can impair receptor-mediated clearance, increasing Aβ availability in the periphery. We investigated the effects of hepato-specific silencing of LRP1 on Aβ deposition in the brain. Additionally, other LDL family members (LRP5, LRP6, and LDLR) that may participate in Aβ clearance were monitored in the liver to ensure non-compensatory effects of LRP1 silencing.

Method

4-month-old male double transgenic (APP/PS1) AD mice were injected with …