Medicine and Health Sciences Commons^™

Microglial Swell1 Deficiency Drives Male-Specific Seizure Vulnerability But Paradoxical Neuroprotection Through Impaired Phagocytosis, Abhijeet S Barath, Aastha Dheer, Laura Montier, Mekenzie M Peshoff, Emily Dale, Flavia Goche, Thanh Thanh Le Nguyen, Mastura Akter, Fangfang Qi, Dimitrios Kleidonas, Lauren Harris, Sarah A Jewanee, Anthony D Umpierre, Dale B Bosco, Koichiro Haruwaka, Rajan Sah, Long-Jun Wu, Rongzhuo Hua, Tejaswani Datla

The Brown Foundation: Institute of Molecular Medicine

The discovery of genes encoding the volume-regulated anion channel (VRAC) has enabled detailed exploration of its cell type-specific roles in the brain. LRRC8A (SWELL1) is the essential VRAC subunit. We observed seizure-induced, subunit-specific changes in microglial VRAC expression and investigated its function using conditional KO (cKO) of LRRC8A in microglia. SWELL1 cKO mice exhibited a male-specific increase in kainate-induced seizure severity, yet showed paradoxical neuroprotection against seizure-associated neuronal loss. Mechanistically, SWELL1 deletion led to a cell-autonomous reduction in microglial density and decreased release of VRAC-permeable neuroactive metabolites, including taurine, GABA, and glutamate in culture. Additionally, impaired phagocytic kinetics and reduced …

Enhancing Teaching Effectiveness Through Professional Development For Part-Time Nursing Faculty, Amanda Moss

Doctor of Nursing Practice Projects

Part-time nursing faculty play a vital role in nursing education; however, many institutions lack standardized professional development opportunities for part-time faculty, resulting in inconsistent preparation and teaching practices. This Doctor of Nursing Practice policy change project examined whether revising an institutional professional development policy to include part-time faculty and implementing a structured faculty development program would improve faculty preparedness, confidence, and comfort with evidence-based teaching practices and instructional strategies that support ACEN faculty development expectations. Guided by the Iowa Model–Revised of Evidence-Based Practice, Kotter’s Organizational Change Theory, and the Plan-Do-Study-Act (PDSA) framework, this quantitative policy change project was conducted over …

An Inf2-Dependent Actin-Mediated Step In Inositol 1,4,5-Trisphosphate Receptor Cluster Formation And Activity, Maite R. Zavala, Amrapali Ghosh, Suresh K. Joseph, Rajarshi Chakrabarti

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Intracellular calcium signaling plays a vital role in regulating various cellular processes including gene regulation, motility, metabolism, and cell death. Inositol 1,4,5-trisphosphate receptors (IP3Rs) on the endoplasmic reticulum (ER) are a major cation channel that regulates stimulus-induced calcium release from the ER. While several molecular players regulate the activity of IP3R, its regulation by actin filaments was uncharacterized. Here, we show that actin filaments polymerized by the specific actin nucleator INF2 facilitate agonist-induced IP3R activity. Our results demonstrate that INF2-mediated actin filaments regulate the formation and/or stability of IP3R clusters on the ER that have been previously shown to be …

Toolkit For Multistate Disease Progression Simulation And Treatment Decision-Making Aid, Can Xie, Ruosha Li, Wael Saber, Jorge E Cortes, Nicholas J Short, Xuelin Huang

Faculty, Staff and Student Publications

Background: The optimal timing of a treatment within therapy lines can maximize its benefit while minimizing risks and side effects. Because patients differ in clinical and biological characteristics, personalized treatment planning can support physicians' decision-making. However, multistate disease progression complicates the comparison of treatment strategies, motivating the development of a user-friendly web tool for multistate disease progression simulation and treatment decision support. Microsimulation is a natural approach for comparing prespecified treatment-timing strategies, where it generates disease trajectories for a large number of virtual patients matched to an individual patient's observed data. In our framework, microsimulation is performed using a multistate …

Enhancing Sleep Quality Through Sleep Hygiene Education Among Adults In A Faith-Based Community, Denielle Earle-Thompson

Doctor of Nursing Practice Projects

Background

Adults between 18 and 64 years of age require at least seven hours of sleep per night; however, many adults do not meet this recommendation, contributing to increased risks for chronic disease, impaired functioning, mood disturbances, and reduced quality of life. Poor sleep quality has been associated with weakened immunity, cardiovascular disease, diabetes, obesity, anxiety, depression, and decreased daytime performance. Obtaining adequate, good-quality sleep is essential for maintaining overall health and well-being. In faith-based communities, combining health education with spiritual support may provide a holistic approach that addresses both physical and emotional contributors to poor sleep.

Purpose

The purpose …

Pruritus Associated With Systemic Sclerosis: A Systematic Review Of Treatment-Based Clinical Trials, Kiana Mortezaei, Rishika Pasula, Meryem Nursoy, Amit Syal, Ioannis Panayiotou, Geeta Kumari, Andreas Chatzitoffis, Pavle Milutinovic, Olajumoke O. Fadugba, Chris T. Derk

Student Papers, Posters & Projects

This paper aims to examine the latest research on treatments for itch (pruritus) in people with systemic sclerosis (SSc), identify areas where information is lacking, and propose suggestions for future studies.A comprehensive literature search was performed in PubMed and Scopus in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify studies evaluating therapeutic interventions for pruritus in SSc. Eligible studies included randomized controlled trials, cohort studies, and case series comprising a minimum of three patients. Data extraction encompassed study design, patient demographics, pruritus assessment instruments including validated and non-validated measures, and clinical outcomes. Studies …

Bottlebrush Polymer Conjugates For Enhanced Antisense Oligonucleotide Therapy In Myotonic Dystrophy Type 1, Yao Li, Gyu Seong Heo, Yongjian Liu, Et Al.

2020-Current year OA Pubs

Oligonucleotides are a promising class of genetic medicine for myotonic dystrophy type 1 (DM1), the most common adult-onset muscular dystrophy. However, poor muscle distribution of nucleic acid drugs following systemic administration has hindered drug development, and no curative treatment currently exists. DM1 pathology requires drug localization to the nucleus, where pathogenic mutant RNA is sequestered, posing additional challenges after cellular internalization regarding endosomal escape and nuclear uptake. Here, we show that a locked nucleic acid oligonucleotide targeting mutant CUG repeat RNA tracts, conjugated to a bottlebrush polymer, exhibits improved muscle distribution and potent correction of DM1-associated splicing dysregulation in a …

Where Evidence-Based Medicine Meets Ai: Promise, Pitfalls, And Practice, Sangil Lee, Joshua Davis, Ken Milne, Christina Shenvi, Lars K. Beattie, Martin Wegman, Laura Melville, Richard D. Shih, Bryan Kane

Department of Emergency Medicine Faculty Papers

No abstract provided.

A Scoping Review Of Preventive Interventions To Reduce Violence Against Women And Girls In The Islamic Republic Of Iran, Wahiba Abu-Ras, Leena Babiker Idris, Shahira Amin, Ashley Butler, Patricia J. Kelly, Basil H. Aboul-Enein

College of Nursing Faculty Papers & Presentations

In Iran, violence against women (VAWG) remains highly prevalent, with reported rates ranging from 22.9% to 66%, underscoring the need for effective, contextually grounded interventions.   This scoping review aimed to systematically identify, map, and critically appraise intervention strategies addressing VAWG in Iran.   Guided by PRISMA-ScR and the PICOS framework, comprehensive searches were conducted across nine databases from 2000 to September 2024. Eligible studies included intervention-based research conducted in Iran that reported outcomes related to violence reduction, psychological well-being, or empowerment. Thirteen studies met the inclusion criteria.   The included studies demonstrated heterogeneous designs, theoretical frameworks, and outcome measures. Four interventions targeted …

Chiari Malformation Type 1 Is Associated With A Smaller Fourth Ventricle Volume - A Multi-Cohort Replication Study, Jarod L Roland, Thanda Meehan, Alexandra Gabliani, Scott Marek, Nico Dosenbach, Joshua S Shimony, Nilay Jakati, Yi Li, Leo Sugrue, Jennifer M Strahle, Chenyang Lu, David D Limbrick, Gabe Haller

2020-Current year OA Pubs

Chiari Malformation Type 1 (CM1) is canonically defined by ectopic position of the cerebellar tonsils with additional anatomic variations described inconsistently. Effect on fourth ventricle volume is controversial with prior studies reporting disparate results and methodologically limited to single institution series that hinder generalizability. This limitation was addressed utilizing multiple data sources, longitudinal replication, and reproducible methods using both FreeSurfer and the deep learning-based DL+DiReCT tools for automated volumetrics. First, we analyzed a local retrospective clinical cohort of individuals with CM1 and controls. Using data from the Adolescent Brain Cognitive Development (ABCD) Study, we analyzed volumes at baseline then replicated …

Program (Pdf), Department Of Orthopaedics

Dept. of Orthopaedics: Robert D. D’Ambrosia Lectureship & Research Day

Program with abstracts for the 22nd Annual Dept of Orthopaedics Annual Robert D. D’Ambrosia Lectureship & Research Day held June 20, 2026.

Reference Values For Intraocular Pressure In Collared Scops Owls (Otus Lettia) Measured Using Rebound Tonometry, Yun-Shan Chiu, Chau-Hwa Chie, Pin-Huan Yu, Chung-Tien Lin

The Thai Journal of Veterinary Medicine

In this study, we aimed to establish species-specific reference values for intraocular pressure (IOP) in clinically healthy collared scops owls (Otus lettia) using rebound tonometry. Twelve free-living owls were included, and twentyfour eyes were examined. All owls were physically restrained in an upright position without sedation. Intraocular pressure was measured in both eyes using rebound tonometry (TONOVET; iCare Finland Oy, Vantaa, Finland) in d mode. No significant difference in IOP was observed between the right and left eyes. The mean IOP values were 10.42 ± 1.24 mmHg (median, 11 mmHg; range, 8–12 mmHg) in the right eye and 10.75 ± …

Pengaruh Intervensi Sigo Terhadap Perbaikan Postur Kerja Dan Penurunan Keluhan Musculoskeletal Disorders Pada Pekerja Sewing Di Cv X Sukoharjo, Sumardiyono Sumardiyono, Tiara Damar Pratiwi, Warda Yussy Rha

National Journal of Occupational Health and Safety

Sewing workers in the garment industry are at high risk of developing non-ergonomic working postures that may lead to musculoskeletal disorders (MSDs), due to prolonged static postures and the use of chairs that are not compatible with workers’ anthropometry. Preliminary surveys indicated complaints of pain in the back, neck, and waist (90%), shoulders and forearms (85%), and upper arms (80%). An ergonomic intervention that can be implemented is the use of ergonomic chairs. This study aims to analyze the effect of using SIGO (Seat Improvement for Garment Operators) as an ergonomic intervention on improving working posture and reducing MSD complaints …

Quality Improvement Project: The Impact Of A Safety Coach Program In A Pediatric Intensive Care Unit, Royanne Lickliter

Doctor of Nursing Practice Projects

Patient safety remains a critical concern in healthcare, with hospital-acquired conditions (HACs) contributing to preventable harm, mortality, and increased costs, particularly in high-acuity settings such as Pediatric intensive care units (PICUs). A recent safety culture survey at a tertiary pediatric hospital identified gaps in proactive safety behaviors, communication, and psychological safety. The primary problem identified was inconsistent engagement in proactive safety practices and limited frontline empowerment to identify and mitigate risks in real time. The purpose of this quality improvement (QI) project was to evaluate the impact of implementing a structured Safety Coach Program in the PICU on HAC rates, …

Prmt5 As A Key Driver Of Stemness And Metastatic Potential In Triple-Negative Breast Cancer, Jae Jin Jeong, Mauli Maniar, Shahrzad Ghane, Sakshi Deshpande, Claire Ellis, Ashakumary Lakshmikuttyamma

College of Pharmacy Faculty Papers

Protein arginine methyltransferase 5 (PRMT5) mediates arginine methylation of a wide range of proteins and plays context-dependent oncogenic or tumor-suppressive roles. In cancer, PRMT5 represses several tumor suppressor genes, including E-cadherin, TP53BP1, ST7, PTEN, and RB (retinoblastoma). Elevated PRMT5 expression has been reported across multiple cancer types, notably triple-negative breast cancer (TNBC). In TNBC, high PRMT5 levels are associated with enhanced cancer stem cell self-renewal, increased tumor growth and metastasis, and reduced patient survival. Mechanistically, PRMT5 promotes breast cancer stem cell maintenance and proliferation through stabilization of the transcription factors KLF4 and KLF5. Disruption of the PRMT5-KLF4 axis results in …

Integration Of Intraoperative Data In Interpretable Machine Learning Models To Predict Postoperative Aki In Noncardiac Surgery Patients, Justin Do, Karan H. Shah, Melissa Xu, Andrew Hyunwoo Kim, Vivaswat Suresh, Nidhir Guggilla, Michael Li, Rishi Kothari

Department of Anesthesiology Faculty Papers

OBJECTIVES: We aimed to (1) quantify changes in discrimination when adding intraoperative data to preoperative data and (2) compare tabular machine learning with feature engineering against a time-aware LSTM-based model.

MATERIALS AND METHODS: Retrospective cohort of 46 204 adults undergoing 57 055 eligible noncardiac surgery in the INSPIRE database. We extracted 38 preoperative and 49 intraoperative variables; acute kidney injury (AKI) was defined by KDIGO serum creatinine criteria and modeled as stage 2/3 postoperative AKI. Models were trained on preoperative-only and combined pre- and intraoperative data. Intraoperative series were summarized using eight statistical features for tabular models or integrated directly …

Quality Improvement Project: Implementation Of The Patient Health Questionnaire-9 Modified For Teens, Hedy Gerber, Leah Buchko, Jennifer Van Winkle

All Faculty and Staff Scholarship

Background: Adolescent depression is a prevalent and significant public health concern, strongly linked to increased suicidality, poor health outcomes, impaired psychosocial functioning, and substantial societal costs. Although measurement‑based care using validated screening instruments is recommended by clinical practice guidelines, routine use of standardized depression screening tools remains limited in mental health settings.

Objective: The purpose of this quality improvement project was to assess the impact of implementing the Patient Health Questionnaire-9 modified for teens (PHQ-9M) in depression screening rates among adolescents aged 11-17 years at an outpatient mental health clinic in Southern Colorado.

Methods: A quantitative, quasi‑experimental pre- and post-intervention …

A Multilevel Analysis Of Hiv Care Outcomes Across Age, Race, And Housing Among United States Women Veterans, Giselle Day, Amber B Amspoker, Alan Z Sheinfil, Liang Chen, Emmanuel Guajardo, Maria E Fernandez, Cici Bauer, Irene Tamí-Maury, Jan Lindsay

Faculty, Staff and Students Publications

Background: Women veterans with HIV represent a growing, diverse population within the Veterans Health Administration (VHA). This study examined HIV care continuum outcomes among women veterans using a multilevel intersectional approach.

Methods: We conducted a retrospective analysis of 1154 women veterans with HIV in VHA care in fiscal year 2022, with outcomes assessed in fiscal year 2023. We applied Multilevel Analysis of Individual Heterogeneity and Discriminatory Accuracy (MAIHDA) to evaluate how combinations of social positions (age, race/ethnicity, housing status) were associated with HIV outcomes.

Results: MAIHDA models showed that younger age (< 45 years) and being unhoused were consistently associated with lower odds of care engagement and viral suppression than midlife (45-64) and older (65+) housed women veterans. Additionally, predicted probability analyses revealed distinct clustering patterns. Younger non-Hispanic White women consistently ranked among the lowest performing strata across all outcomes, while midlife and older Hispanic and non-Hispanic Black women veterans clustered among the highest. Variance Partition Coefficients from null models were modest (1.8-3.0%). Fully adjusted models showed no remaining between-stratum variance, suggesting that the included social positions explained the observed differences in our dataset.

Conclusions: These findings highlight disparities in HIV care …

Air Pollution And Public Health: Global Evidence And Implications, Mohammed Obaid Al-Mansoori

Al-Bahir

Globally, the issue of air pollution keep being one of most serious challenges that affecting environment and human health, coming from emissions of industries, transport, agriculture and also from the fuel people use in homes, in addition to natural events that make the situation worse. This review try to bring together the available evidences about the sources, types, and the health impacts of the main air pollutants, including the gaseous ones like SO₂, O₃, NO₂, and CO, and the particulate matter (PM₁₀, PM₂.₅). Exposure for short or long time to these pollutants is linked with many harmful outcomes, such as …

Intermittent Fasting In Chronic Heart Failure: A Systematic Review Of Safety And Physiological Outcomes, Zulrahman Erlangga, Prenali Dwisthi Sattwika

Journal of the Saudi Heart Association

Interest in intermittent fasting has expanded substantially due to its reported metabolic effects. However, whether such dietary patterns are safe for individuals living with chronic heart failure remains unclear. This issue is particularly relevant for patients who fast for religious observance, including Ramadan. We therefore performed a systematic review to evaluate the clinical safety and physiological implications of intermittent fasting in stable heart failure populations. The review protocol adhered to established reporting standards for systematic reviews. Multiple electronic databases were systematically searched from inception through December 2025 to identify studies evaluating intermittent fasting in adults with chronic heart failure. Both …

Quality Improvement Project: Impact Of Formalized Debriefing On Correctional Health Emergency Response, Angel Woody

Doctor of Nursing Practice Projects

Structured debriefing following medical emergencies has been identified as an evidence-based strategy to improve communication, reflective learning, and staff confidence within high-acuity healthcare settings. Inconsistent debriefing practices within correctional healthcare environments contributed to a gap in emergency response support and staff preparedness. The purpose of this quality improvement project was to evaluate whether implementation of a formalized debriefing protocol following medical emergencies impacted staff confidence during emergency response situations within a correctional healthcare setting. The project was guided by Bandura’s Self-Efficacy Theory and Lewin’s Change Theory. A quantitative one-group pretest-posttest quality improvement design was implemented in a county correctional healthcare …

The Transitional Liver Clinic: Study Protocol For A Stepped-Wedge Cluster Randomized Trial, Lindsay Yoder, Elliot B. Tapper, Richard S. Kalman, Mary Rinella, Nicole Bendin, Manisha Verma, Francis Pike, Naga Chalasani, Neha Nalumasu, Eric S. Orman

Einstein Health Papers

BACKGROUND: Patients with complications of advanced liver disease experience high rates of hospital readmission after discharge. Transitional care models have improved outcomes in other chronic conditions, but their efficacy in liver disease care remains uncertain. This randomized trial evaluates the effectiveness of a tailored transitional care model-the Transitional Liver Clinic (TLC)-in reducing readmissions, improving quality of life, and enhancing patient satisfaction for patients with advanced liver disease.

METHODS: This is a 45-month, stepped-wedge cluster randomized trial enrolling up to 1000 patients with advanced liver disease across 4 academic medical centers. Each site transitions from usual care to the TLC intervention …

Sirt1 And Ifi16 Cooperatively Regulate Hbv Replication Via Epigenetic Modulation And Innate Immune Activation, Zahra Zahid Piracha, Umar Saeed, Neelam Abid, Syed Shahan Gilani, Hafiz Ahmad Bilal Akhtar Chughtai, Areesha Wasti, Muhammad Waseem, Dilber Uzun Ozsahin, Andromeda M. Nauli, Surya M. Nauli

Pharmacy Faculty Articles and Research

Background

Hepatitis B virus (HBV) establishes persistent infection through the formation of a covalently closed circular DNA (cccDNA) minichromosome, which enables immune evasion and sustained viral replication. While SIRT1, IFI16, and STING are known to modulate antiviral pathways, their cooperative role in regulating HBV transcription and host immunity remains poorly defined.

Methods

We investigated the functional interplay between SIRT1, IFI16, and STING using confocal microscopy, chromatin immunoprecipitation (ChIP), gene silencing, and quantitative PCR in HBV-replicating cell models. Interactions with HBV cccDNA and effects on viral transcription and interferon-stimulated gene (ISG) expression were analyzed. Northern blotting and RT-qPCR were used to …

Using United States Medicare Program Claims To Identify Reliable Measures Of Low Value Services Influenced By Primary Care Physician Decisions, Chris Fleming, Dmitriy Poznyak, Rhea E. Powell, Claire Erba, Eunhae Shin, Rui Wang, Claire Burkhart, Arkadipta Ghosh, Eugene C. Rich

Division of Internal Medicine Faculty Papers & Presentations

BACKGROUND: Low-value services (LVS) are those that “… provide little to no benefit to patients….”¹ Among an existing set of 31 LVS are invasive procedures not typically performed by primary care physicians (PCPs), and other LVS that may be commonly provided by specialists. To facilitate research on the role of primary care physicians in low-value care, we sought to identify the reliability of two subsets of LVS measures that are more directly subject to PCPs’ decisions. We refer to these as primary care adjacent (“PCA”) LVS measures.

METHODS: Retrospective observational cohort study to identify which of a 31-item LVS …

Neddylation Maintains Oocyte Quality By Stabilizing Mitochondrial Transcription, Avery A Ahmed, Tessa E Steenwinkel, Bethany K Patton, Peixin Jiang, Matthew D Meyer, Jaspreet K Rishi, Mei Leng, Alexander B Saltzman, Elizabeth S Anaya, Momal Sharif, Laurie J Mckenzie, Laura Detti, Anna Malovannaya, Sean M Hartig, Stephanie A Pangas

Faculty, Staff and Students Publications

Age-related decline in oocyte quality increases the risk of infertility, miscarriage, and birth defects. Mitochondrial dysfunction is a key contributor to this decline. Here, we report that oocyte-specific deletion of Uba3, which encodes the catalytic subunit of the E1 NEDDylation-activating complex, causes sterility in mice. Fully grown, germinal vesicle–stage Uba3 conditional knockout oocytes exhibit mitochondrial dysfunction, including elevated reactive oxygen species, impaired oxidative phosphorylation, and depletion of mitochondrially encoded RNA transcripts. Proteomic analysis identified alterations in mitochondrial-associated proteins, including enrichment of mitochondrial matrix and respiratory chain components and reduced abundance of electron transport chain complexes. These defects were associated …

Targeted Inhibition Of Atr Kinase Promotes Antitumor Immunity In Hnscc Through Enhanced Sting Activation And T Cell Function, Fabio Hb Da Costa, Mutsuki Kawabe, Tsung-You Tsai, Kento Okamoto, Mason D Bartels, Sofia Cortes, Ratna Veeramachaneni, Roberto Rangel, Mitchell J Frederick, Vlad C Sandulache, Andrew G Sikora, Jeffrey N Myers, Abdullah A Osman

Faculty, Staff and Students Publications

Objectives: Oral cavity head and neck squamous cell carcinoma (HNSCC) represents a major global health burden, with over 40,000 new cases annually in the United States and >500,000 worldwide. Despite advances in surgery, radiation therapy, chemotherapy, and immunotherapy, overall survival rates have remained largely stagnant over the past three decades, and over half of patients ultimately die from the disease. Although immune checkpoint inhibitors (ICIs) have improved outcomes for a subset of patients with recurrent or metastatic HNSCC, the majority gain limited benefit. Thus, novel therapeutic strategies that enhance responses to immunotherapy are urgently needed. The ATR-CHK1 signaling pathway has …

Conformational Cycling Of The Wntless Transporter Drives Trafficking And Secretion Of Wnt Morphogens, Yunhui Ge, Taciani De Almeida Magalhaes, Hongjiang Wu, Dick J H Van Den Boomen, Thu Uyen Nguyen, Tongyi Dou, Gaya P Yadav, Sukyeong Lee, Zhao Wang, Andrew Lemoff, Xuemei Luo, Sumitha S Menon, Min Zhang, Jin Wang, Zhicheng Jin, Jiansen Jiang, Adrian Salic, Pengxiang Huang

Faculty, Staff and Students Publications

Wnt proteins are lipid-modified morphogens fundamental in development and disease. During Wnt biogenesis, the G-protein-coupled receptor (GPCR)-like transporter Wntless (WLS) escorts lipidated Wnts from the endoplasmic reticulum to the plasma membrane, then transfers them to extracellular carriers, forming active and soluble morphogen-carrier complexes. To dissect the mechanisms involved, we solve cryo-EM structures of Wnt-bound WLS and unliganded WLS, and perform structure-guided functional experiments. Wnts engage WLS via three conserved hairpins, which are all required for Wnt trafficking to the cell surface and carrier-mediated secretion. Wnt release from cells is driven by dramatic conformational changes in the WLS transmembrane domain, reminiscent …

3d Em Uncovers Mitochondrial Network Remodeling In Residual Triple Negative Breast Cancer After Conventional Chemotherapy Treatments, Mariah J Berner, Heather K Beasley, Benjamin Rodriguez, Audra Lane, Steven W Wall, Andrea G Marshall, Zer Vue, Larry Vang, Mokryun L Baek, Mason Killion, Faben Zeleke, Bryanna Shao, Dominique Parker, Autumn Peterson, Julie Sterling Rhoades, Lacey E Dobrolecki, Amber Crabtree, Annet Kirabo, Sepiso K Masenga, Prasanna Katti, Prasanna Venkhatesh, Chandravanu Dash, Michael T Lewis, Antentor Hinton, Gloria V Echeverria

Faculty, Staff and Students Publications

Mitochondria are hubs of metabolism and signaling. We previously demonstrated the importance of mitochondrial structure and function in chemotherapy-refractory triple-negative breast cancer (TNBC). Herein, we present the first 3D analysis of mitochondrial networks in human tumor tissues. Using serial block face scanning electron microscopy, we reconstructed 3,750 mitochondria and 800 lipid droplets (LDs) in naive and residual tumors persisting after conventional chemotherapies in two orthotopic patient-derived xenografts (PDX). Chemotherapies administered as monotherapy or in combination produced residual tumors that harbored mitochondria with significantly increased areas, volumes, and perimeters. We observed substantial reduction of mitochondrial intratumor heterogeneity following all treatments. Further, …

Targeting Arginine Metabolism Overcomes Chemotherapy Resistance In Aggressive-Variant Prostate Cancers, Elavarasan Subramani, Patrick G Pilié, Rebecca Slack-Tidwell, Paul V Viscuse, Xianghong Kuang, Thirukumaran Kandasamy, Dominik Awad, Jenny J Han, Licai Huang, Christine B Peterson, Amado J Zurita, Sumit K Subudhi, Paul G Corn, Rama Soundararajan, Peter Shepherd, Badrajee Piyarathna, Vasanta Putluri, Nagireddy Putluri, Arun Sreekumar, Yuzhuo Wang, Amina Zoubeidi, Iqbal Mahmud, Sara A Martinez, Lin Tan, Philip L Lorenzi, Sreyashi Basu, Sonali Jindal, Padmanee Sharma, Christopher J Logothetis, Timothy C Thompson, Daniel E Frigo, Ana M Aparicio

Faculty, Staff and Students Publications

Aggressive-variant prostate cancers (AVPCs) respond poorly to anti-androgen therapy but show sensitivity to taxane-platinum chemotherapy, though outcomes remain poor. We conducted a phase 2 trial testing induction cabazitaxel plus carboplatin (CabCarb) followed by olaparib maintenance versus observation in men with AVPC. The primary endpoint of improved progression-free survival (PFS) was not met, likely due to the study being underpowered after 38.5% of patients experienced early progression (ChemoPD) prior to randomization. No genomic alterations predicted ChemoPD; however, transcriptomic analysis revealed the enrichment of metabolic pathways, including arginine metabolism, in ChemoPD tumors. These findings were supported by metabolomics data from preclinical models. …

Strategies For Improving The Drug Importation Control System In Thailand: A Qualitative Investigation, Neeranart Potiyanon, Suntaree Watcharadamrongkun

The Thai Journal of Pharmaceutical Sciences

Background: Drug importation plays a critical role in Thailand’s healthcare system; however, barriers affecting its regulatory control and their public health implications remain inadequately examined. This study compared international drug importation procedures and evaluated Thailand’s control system with strategies for improvement.
Methods: Conducted in Bangkok between 2020 and 2023, this two-phase study employed a qualitative design. Phase 1 involved content analysis comparing drug importation procedures across Thailand, Singapore, Australia and the United States to identify best practices and potential solutions. Phase 2 utilized semistructured, in-depth interviews with 19 key informants from government and private-sector agencies. Data collection was guided by …