Public Health Commons^™

Two Decades Of Diagnostic Safety Research: Advances, Challenges, And Next Steps, Sundas Khan, Andrea Bradford, Christina L Cifra, Hardeep Singh

Faculty, Staff and Students Publications

Since the National Academies of Sciences, Engineering, and Medicine (NASEM) report Improving Diagnosis in Health Care, various research efforts have accelerated progress to understand and improve diagnostic safety. In this opinion piece, we summarize two decades of progress in methods for identifying and learning from diagnostic errors and provide recommendations for future research. Multiple methods have been used to quantify diagnostic errors in various clinical settings, thereby facilitating a deeper understanding of the nature and magnitude of the problem and enabling studies of contributing factors. However, the use of standardized definitions of a diagnostic error and/or diagnostic safety event, …

Foreword: Addressing Diagnostic Error: The First 10 Years, Mark L Graber, Edward P Hoffer, Hardeep Singh

Faculty, Staff and Students Publications

No abstract provided.

Centrally Inserted Central Catheter Placement Using A Novel, Handheld, Image-Guided, Robotic Device: Results Of Initial Feasibility Trial In Patients, James P Herlihy, William E Cohn, Adrian Ebner

Faculty, Staff and Students Publications

Background: Central venous access devices (CVADs) are an essential and widely used tool for the treatment of the critically ill, patients undergoing major surgery, and for many patients requiring hemodialysis. Automation of centrally inserted central catheters (CICCs) could potentially make CVAD placement safer, more effective, and more accessible. A new device that uses ultrasound image-guided, robotic needle placement, in addition to traditional Seldinger technique, to place a CICC is described.

Objective: The device was used in a small, first-in-human, trial for placing non-tunneled hemodialysis catheters (NTHDCs), in order to determine feasibility of clinical use.

Methods: Consecutive patients requiring a NTHDC, …

Molecular Mechanisms In Masld/Mash-Related Hcc, Xiaobo Wang, Liang Zhang, Bingning Dong

Faculty, Staff and Students Publications

Liver cancer is the third leading cause of cancer-related deaths and ranks as the sixth most prevalent cancer type globally. NAFLD or metabolic dysfunction-associated steatotic liver disease, and its more severe manifestation, NASH or metabolic dysfunction-associated steatohepatitis (MASH), pose a significant global health concern, affecting approximately 20%-25% of the population. The increased prevalence of metabolic dysfunction-associated steatotic liver disease and MASH is parallel to the increasing rates of obesity-associated metabolic diseases, including type 2 diabetes, insulin resistance, and fatty liver diseases. MASH can progress to MASH-related HCC (MASH-HCC) in about 2% of cases each year, influenced by various factors such …

Dysregulated Mitochondrial Energy Metabolism Drives The Progression Of Mucosal Field Effects To Invasive Bladder Cancer, Sangkyou Lee, Sung Yun Jung, Pawel Kuś, Jolanta Bondaruk, June Goo Lee, Roman Jaksik, Nagireddy Putluri, Khanh N Dinh, David Cogdell, Huiqin Chen, Yishan Wang, Jiansong Chen, Neema Navai, Colin Dinney, Cathy Mendelsohn, David Mcconkey, Richard R Behringer, Charles C Guo, Peng Wei, Marek Kimmel, Bogdan Czerniak

Faculty, Staff and Students Publications

Multiplatform mutational and gene expression profiling complemented with proteomic and metabolomic spatial mapping were used on the whole-organ scale to identify the molecular profile of bladder cancer evolution from field effects. Analysis of the mutational landscape identified three types of mutations, referred to as α, β, and γ. Time modeling of the mutations revealed that carcinogenesis may span 30 years and can be divided into dormant and progressive phases. The α mutations developed in the dormant phase. The progressive phase lasted 5 years and was signified by expanding β mutations, but it was driven to invasive cancer by γ mutations. …

Pathogenic Xpo1 Variants Cause A Dominant Neurodevelopmental Disorder, Amber S E Van Oirsouw, Pavla Nedbalova, Miroslava Hancarova, Jan Prchal, Darina Prchalova, Marketa Vlckova, Sarka Bendova, Kristin G Monaghan, Lisa M Dyer, Yanmin Chen, Deanna Alexis Carere, Emma A M Te Bogt, Heather Fisher, Angela E Scheuerle, Stephanie Riley, Mahim Jain, Weiyi Mu, Joann N Bodurtha, Albertien M Van Eerde, Marijn F Stokman, Nicola Longo, Meena Balasubramanian, Michael Spiller, Gregory Costain, Charlotte Von Der Lippe, Kristian Tveten, Marianne Jortveit, Øystein L Holla, Bertrand Isidor, Benjamin Cogné, Kevin E Glinton, Blake Vuocolo, Roberta Ann Sierra, Brad Angle, Kelly Bontempo, Klaas Koop, Rachel Rabin, John Pappas, David A Staffenberg, Pascal Joset, Peter Miny, Isabel Filges, Abdulrazak Alali, Kara Vitalone, Jill A Rosenfeld, Weimin Bi, Samuel Bradbrook, Renee Perrier, Subhadra Ramanathan, June-Anne Gold, María Palomares Bralo, María Ángeles Gómez-Cano, Ann Haskins Olney, Shelly Nielsen, Alban Ziegler, Dominique Bonneau, Clément Prouteau, Ange-Line Bruel, Charlotte Caille-Benigni, Laëtitia Lambert, Andrea C Yu, Nathaniel H Robin, Dana Goodloe, Jan Fischer, Joseph Porrmann, Yvonne D Hennig, Rami Abou Jamra, Isabella Herman, Ivy R Johnson, Lucas Hérissant, Guillaume Jouret, Koen L I Van Gassen, Ellen Van Binsbergen, Bert Van Der Zwaag, Alwin Kamermans, Renske Oegema, Zdenek Sedlacek, Michaela Fenckova, Richard H Van Jaarsveld

Faculty, Staff and Students Publications

Purpose: XPO1 functions in key cellular processes, including nucleo-cytoplasmic export and mitosis. The gene is deleted in a subset of patients with the 2p15p16.1 microdeletion syndrome; however, no monogenic XPO1-related disorder has been described to date.

Methods: We collected clinical data of individuals with de novo XPO1 variants through online matchmaking. We used Drosophila to study XPO1 function in development and habituation learning.

Results: A total of 22 individuals met the criteria to be included in the main study cohort. Of these, half have putative loss-of-function variants, and half have coding variants (10 missense and 1 in-frame deletion variant). We …

Glycerol-3-Phosphate Activates Chrebp, Fgf21 Transcription And Lipogenesis In Citrin Deficiency, Vinod Tiwari, Byungchang Jin, Olivia Sun, Edwin D J Lopez Gonzalez, Min-Hsuan Chen, Xiwei Wu, Hardik Shah, Andrew Zhang, Mark A Herman, Cassandra N Spracklen, Russell P Goodman, Charles Brenner

Faculty, Staff and Students Publications

Citrin deficiency (CD) is caused by the inactivation of SLC25A13, a mitochondrial membrane protein required to move electrons from cytosolic NADH to the mitochondrial matrix in hepatocytes. People with CD do not like sweets. Here we show that SLC25A13 loss causes the accumulation of glycerol-3-phosphate (G3P), which activates the carbohydrate response element-binding protein (ChREBP) to transcribe FGF21, which acts in the brain to restrain intake of sweets and alcohol and to transcribe key genes driving lipogenesis. Mouse and human data suggest that G3P-ChREBP is a mechanistic component of the Randle Cycle that contributes to metabolic-dysfunction-associated steatotic liver disease and forms …

Chemical Modulation Of Gut Bacterial Metabolism Induces Colanic Acid And Extends The Lifespan Of Nematode And Mammalian Hosts, Guo Hu, Marzia Savini, Matthew Brandon Cooke, Xin Wei, Dinghuan Deng, Shihong M Gao, Ruyue Alps Xia, Youchen Guan, Alice X Wen, Xin Yu, Jin Wang, Chao Jiang, Christophe Herman, Jiefu Li, Meng C Wang

Faculty, Staff and Students Publications

Microbiota-derived metabolites have emerged as key regulators of longevity. The metabolic activity of the gut microbiota, influenced by dietary components and ingested chemical compounds, profoundly impacts host fitness. While the benefits of dietary prebiotics are well-known, chemically targeting the gut microbiota to enhance host fitness remains largely unexplored. Here, we report a novel chemical approach to induce a pro-longevity bacterial metabolite in the host gut. We discovered that wild-type Escherichia coli strains overproduce colanic acids (CAs) when exposed to a low dose of cephaloridine, leading to an increased life span in the host organism Caenorhabditis elegans. In the mouse gut, …

Using Video Ethnography And Stimulated Recall Interviews To Describe The Diagnostic Process In The Emergency Department, Milisa Manojlovich, Caitlin Cassady, Sarah J Parker, Ellie Davis, Charlotte Ahr, David Ryamukuru, Anna Wang, Kalyan Pasupathy, Hardeep Singh, Prashant Mahajan

Faculty, Staff and Students Publications

Objectives: Understanding how physicians make diagnoses is challenging because cognitive processes are unobservable and partly unconscious, making it difficult for physicians to describe how they arrived at a diagnosis. Physicians who work in emergency departments (EDs) are especially vulnerable to making diagnostic errors because the ED is a fast-paced, dynamic setting where complex decision-making occurs under severe time, information, and resource constraints. The purpose of our study was to describe how the diagnostic process evolves for ED clinicians in both pediatric and adult ED settings.

Methods: We used a qualitative, video ethnography study design to capture in situ, real-time ED …

The Impact Of Social Determinants Of Health On Outcomes Of Brexucabtagene Autoleucel In Adults With Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia, Timothy E O'Connor, Chenyu Lin, Gregory W Roloff, Amy Zhang, Katharine Miller, Ibrahim Aldoss, Noam E Kopmar, Simone E Dekker, Vishal K Gupta, Nikeshan Jeyakumar, Ibrahim N Muhsen, Yannis Valtis, Naveed Ahmed, Katherine Sutherland, Kaitlyn C Dykes, Mohamed Ahmed, Evan Chen, Hector Zambrano, Danielle Bradshaw, Santiago Mercadal, Marc Schwartz, Sean Tracy, Matthew P Connor, Michal Kubiak, Akash Mukherjee, Navneet Majhail, Minoo Battiwalla, Luke Mountjoy, Shahbaz A Malik, John Mathews, Paul Shaughnessy, Betsy Blunk, Aaron C Logan, Abdullah Ladha, Anjali S Advani, Maryann Stefan, Caitlin Guzowski, Rasmus T Hoeg, Talal Hilal, Jozal Moore, Kristen M O'Dwyer, Laquisa C Hill, Joshua Sasine, Caspian Oliai, Melhem M Solh, Catherine J Lee, Vamsi K Kota, Divya Koura, Muthu V Kumaran, Jessica T Leonard, Noelle V Frey, Jae H Park, Marlise R Luskin, Veronika Bachanova, Ahmed Galal, Vinod Pullarkat, Michael R Bishop, Wendy Stock, Ryan D Cassaday, Bijal D Shah, Rawan Faramand, Lori S Muffly, Stephanie B Tsai, Bhagirathbhai Dholaria

Faculty, Staff and Students Publications

Brexucabtagene autoleucel (brexu-cel) is a chimeric antigen receptor T (CAR T) cell therapy approved for adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). We studied the impact of social determinants of health (SDoH) on outcomes of adults with B-ALL receiving brexu-cel. This retrospective analysis included adults (≥18 years) with R/R B-ALL treated with brexu-cel between 2021 and 2023. Cox proportional hazards models evaluated the association of race, ethnicity, and SDoH with progression-free survival (PFS) and overall survival (OS). 189 patients received brexu-cel and 57% were male. 55% were non-Hispanic White, 30% Hispanic, 7% non-Hispanic Black, 6% Asian/Pacific …

Cohesin Haploinsufficiency Is Tolerated In Cbfb::Myh11-Driven Murine Acute Myeloid Leukemia, Shannon E Conneely, Alexis Quezada, Kristen J Kurtz, Nenggang Zhang, Josephine De La Fuente, Nesa Mercer, Jason H Rogers, Rogelio Aguilar, Geraldo Medrano, Margaret A Goodell, Paul P Liu, Debananda Pati, Rachel E Rau

Faculty, Staff and Students Publications

Cohesin gene mutations occur in many malignancies, including acute myeloid leukemia (AML). Loss-of-function mutations in the four major cohesin complex genes (RAD21, SMC3, SMC1a, and STAG2) occur across most major genetic subtypes of AML but are notably absent in AML harboring CBFB::MYH11, suggesting that cohesin mutations yield distinct biological outcomes dependent on the genetic AML driver. We hypothesized that CBFB::MYH11-expressing leukemias would be dependent on intact cohesin genes given their near-mutual exclusivity. To investigate this, we combined either germline or inducible heterozygous deletions in cohesin genes Smc3 or Rad21, respectively, with an inducible murine model of Cbfb::MYH11 AML. This approach …

Distinct Molecular Responses Of Human Intestinal Organoids To Proton And Photon Radiation, Victoria Poplaski, Tajhal D Patel, Hoa Nguyen-Phuc, Amal Kambal, Lawrence Bronk, Mary K Estes, Cristian Coarfa, Sarah E Blutt

Faculty, Staff and Students Publications

Radiation exposure impairs rapidly renewing tissues like the intestinal epithelium, yet translational insights from murine models have been limited by species-specific responses. Here, we use human intestinal organoids (HIOs) derived from jejunal epithelium to evaluate human epithelial responses to low dose proton and photon (gamma) radiation. Gamma irradiation induces a unique developmental and metabolic shift in crypt-like organoids, including enrichment of amino acid metabolism pathways and activation of fetal-associated transcription factors and morphology. Integrated multi-omic profiling reveals serotonin biosynthesis as a central regenerative node. Human intestinal organoids can complement animal models and are emerging as a powerful tool in modeling …

Nasal Microbionts Differentially Colonize And Elicit Cytokines In Human Nasal Epithelial Organoids, Andrea I Boyd, Leah A Kafer, Isabel F Escapa, Amal Kambal, Hira Tariq, Susan G Hilsenbeck, Hoa Nguyen-Phuc, Anubama Rajan, Joshua M Lensmire, Kathryn A Patras, Pedro A Piedra, Sarah E Blutt, Katherine P Lemon

Faculty, Staff and Students Publications

Nasal colonization by Staphylococcus aureus or Streptococcus pneumoniae is associated with an increased risk of infection by these pathobionts, whereas nasal colonization by Dolosigranulum species is associated with health. Human nasal epithelial organoids (HNOs) differentiated at air-liquid interface (ALI) physiologically recapitulate human nasal respiratory epithelium with a robust mucociliary blanket. Due to their natural stem-like properties, HNO lines are a long-term experimental resource that offers genetic diversity based on the different donors. To develop HNOs as a new model system for bacterial nasal colonization, we reproducibly monocolonized HNOs differentiated at ALI with S. aureus, S. pneumoniae, or Dolosigranulum …

Molecular And Cellular Characterization Of Planarian Stem Cell Microenvironments, Frederick G Mann, Carolyn E Brewster, Dung M Vuu, Mol Mir, Riley Galton, Shao-Fu Nien, Enya R Dewars, Carlos Guerrero-Hernández, Jason A Morrison, Mary C Mckinney, Lucinda E Maddera, Melainia L Mcclain, Kate E Hall, Seth Malloy, Shiyuan Chen, Brian D Slaughter, Sean A Mckinney, Stephanie H Nowotarski, Anoja Perera, Blair W Benham-Pyle, Alejandro Sánchez Alvarado

Faculty, Staff and Students Publications

Stem cell niches are essential for regulating stem cell self-renewal and differentiation during tissue repair and regeneration. However, the mechanisms supporting stem cell function in highly regenerative organisms, such as the freshwater planarian Schmidtea mediterranea, remain unclear. Using spatial transcriptomics, we identified two cell types associated with planarian stem cells: secretory cells we term "hecatonoblasts" and intestinal cells. Surprisingly, while hecatonoblasts were in close physical proximity to stem cells in the mesenchyme, they were dispensable for regeneration. In contrast, intestinal cells, despite lacking direct contact with stem cells, regulated both their position and function during regeneration. Electron microscopy revealed diverse …

Association Of Stepping-Up To High Dose Inhaled Corticosteroids And Risk Of Future Asthma Exacerbations: Data From The Us, Trung N Tran, Marjan Kerkhof, Tham T Le, Mina Khezrian, Nicole Zubizarreta, Joshua Enxing, Kirsty Rhodes, Jonatan Hedberg, Bill Cook, Tianshi David Wu, Tim W Harrison

Faculty, Staff and Students Publications

Background: Real-world data on the benefit of high-dose inhaled corticosteroid (ICS) post-exacerbation are limited.

Objective: To investigate whether stepping-up to high-dose inhaled corticosteroid (ICS) post-severe exacerbation reduces future asthma exacerbation risk in a real-world setting.

Methods: This was a retrospective cohort study using the Optum® Clinformatics® database (October 2015-December 2023). Patients with asthma, aged ≥12 years, with ≥1 severe exacerbation and ≥2 ICS maintenance prescriptions in the 12-months pre-, and ≥1 ICS maintenance prescription in the 3-months post-exacerbation were included. Primary and secondary endpoints were annualized asthma exacerbation rate (AAER) and time to first subsequent severe exacerbation, respectively. We compared …

Screening For Trypanosoma Cruzi In Patients Living With The Human Immunodeficiency Virus (Pwh) In The Peruvian Amazon, Silvia Otero-Rodriguez, Martin Casapia-Morales, Lilia-Lorena Pinedo-Ramirez, Esperanza Merino, Eva H Clark, José-Manuel Ramos-Rincón

Faculty, Staff and Students Publications

Introduction: Chagas disease (CD) - Trypanosoma cruzi infection - in people living with HIV (PWH), particularly those with advanced CD4 T cell depletion, can lead to severe syndromes affecting the central nervous system and the heart.

Methods: We performed a cross-sectional study to screen for CD among PWH in Iquitos, Peru, between October 2023 and May 2024, with the objective of understanding the frequency of infection in this population. Adults with confirmed HIV attending outpatient services at two regional hospitals were enrolled. Two ELISA tests (lysate and recombinant) were used, and discordant results were adjudicated by indirect chemiluminescence immunoassay (CLIA). …

Social Vulnerability Associations With Hypopharyngeal Carcinoma Treatment And Prognostic Disparities, Camaren M. Cuenca, David M. Bruss, David J. Fei-Zhang, Jill N. D'Souza, Anthony M. Sheyn, Jeffrey C. Rastatter, Daniel C. Chelius

School of Medicine Faculty Publications

Objectives: Prior studies investigating the impacts of social determinants of health (SDoH) on hypopharyngeal cancer have only assessed the impact of individual factors on patient outcomes. This study uses the CDC's Social Vulnerability Index (SVI) and a national patient cohort to examine how the interrelational influence of SDoH affect hypopharyngeal cancer prognosis, treatment, and follow-up. Methods: This retrospective cohort study analyzed patients from 1975 to 2017 with a diagnosis of hypopharyngeal carcinoma in the NCI-SEER database. Net social vulnerability and its contributions from 15 SDoH variables were ranked and scored across all US counties, yielding a SVI. SVI scores were …

Human Papillomavirus Vaccine Uptake In Ethnically Diverse Women Living With Systemic Lupus Erythematosus, Sebastian Bruera, Yinan Huang, Savannah Bowman, Maria E Suarez-Almazor, Grace H Lo, Maria A Lopez-Olivo, Elizabeth Chiao, Jennifer R Kramer, Frederick A Pereira, Sandeep K Agarwal

Faculty, Staff and Students Publications

Background: Women with systemic lupus erythematosus (SLE) are at an increased risk of infection from the human papillomavirus (HPV) and subsequently HPV-mediated malignancies and genital warts. The HPV vaccine is a highly effective intervention in preventing HPV infection and is recommended in SLE patients. We determined HPV vaccination rates and factors associated with decreased vaccination uptake in women living with SLE.

Methods: We conducted a cross-sectional study in which we enrolled women with SLE (aged 21–45) for whom the HPV vaccine is recommended for by the US Food and Drug Administration (FDA). The primary outcome was self-reported HPV vaccination as …

Compromised Pressure-Generating Capacity Of Diaphragmatic Muscle And Its Interaction With The Lower Rib Cage At High Lung Volume During Airway Occlusion, Aladin M Boriek, Noralis Rodriguez-Santiago, Sanghyun Kim, Aubri Ford, Shari Wynd, Rolf D Hubmayr

Faculty, Staff and Students Publications

The pressure generating capacity of the diaphragm is generally thought to be compromised at high lung volume either due to loss of curvature or loss of its membrane tension. At a state of hyperinflation during airway occlusion at total lung capacity, the diaphragmatic muscle is forced to contract from an initial shorter length, the zone of apposition narrows, insertional force on the chest wall is reduced and abdominal compliance falls. We hypothesize that these altered mechanical conditions at high lung volume lead to a loss of the pressure generating capacity that is mediated by excessive muscle shortening rather than loss …

Stereoelectroencephalography Reveals Neural Signatures Of Multisensory Integration In The Human Superior Temporal Sulcus During Audiovisual Speech Perception, Yue Zhang, John F Magnotti, Xiang Zhang, Zhengjia Wang, Yingjia Yu, Kathryn A Davis, Sameer A Sheth, H Isaac Chen, Daniel Yoshor, Michael S Beauchamp

Faculty, Staff and Students Publications

Human speech perception is multisensory, integrating auditory information from the talker's voice with visual information from the talker's face. BOLD fMRI studies have implicated the superior temporal gyrus (STG) in processing auditory speech and the superior temporal sulcus (STS) in integrating auditory and visual speech, but as an indirect hemodynamic measure, fMRI is limited in its ability to track the rapid neural computations underlying speech perception. Using stereoelectroencephalography (sEEG) electrodes, we directly recorded from the STG and STS in 42 epilepsy patients (25F, 17M). Participants identified single words presented in auditory, visual, and audiovisual formats with and without added auditory …

Resilience And Vulnerabilities Of Tumor Cells Under Purine Shortage Stress, Jianpeng Yu, Chen Jin, Cheng Su, David Moon, Michael A Sun, Hong Zhang, Xue Jiang, Fan Zhang, Nomi Tserentsoodol, Michelle L Bowie, Christopher J Pirozzi, Daniel J George, Robert Wild, Xia Gao, David M Ashley, Yiping He, Jiaoti Huang

Faculty, Staff and Students Publications

Purpose: Purine metabolism is a promising therapeutic target in cancer; however, how cancer cells respond to purine shortage, particularly their adaptation and vulnerabilities, remains unclear.

Experimental design: Using the recently developed purine shortage-inducing prodrug DRP-104 and genetic approaches, we investigated the responses in prostate, lung, and glioma cancer models.

Results: We demonstrate that when de novo purine biosynthesis is compromised, cancer cells employ microtubules to assemble purinosomes, multiprotein complexes of de novo purine biosynthesis enzymes that enhance purine biosynthesis efficiency. Although this process enables tumor cells to adapt to purine shortage stress, it also renders them more susceptible to the …

Addressing Housing As A Health-Related Social Need: Insights And Impacts From Health Share’S Housing Benefit Pilot Program, Monique Gill, Benjamin Gronowski, Megan Holtorf

Articles, Abstracts, and Reports

No abstract provided.

A Safety-Ii Approach To Learn From Practice Variation In The Diagnostic Process In The Emergency Department: An Action Research Study, Rick Roos, Laura Zwaan, Myrthe Maranus, Iwan A Meynaar, Vanessa J Valk, Cees Van Nieuwkoop, Gert-Jan Kamps, Hardeep Singh, Maarten O Van Aken

Faculty, Staff and Students Publications

Objectives: The focus on improving patient safety has mainly been by learning from errors and near misses (Safety-I). We applied a novel Safety-II approach to identify and learn from practice variations in the diagnostic process in the emergency department (ED), and subsequently design and implement practice changes.

Methods: In this single-center study, we used action research (cycles of micro-experiments to study and improve processes with active stakeholder involvement) in the diagnostic process. We used three subsequent observation cycles of the following six steps: observations, gathering of follow-up data, analyses, a co-creation session with involved stakeholders, sharing of best practices, and …

Vaccine And Treatment Evaluation Units: A Historical Perspective, Robert B Belshe, David I Bernstein, Kathryn M Edwards, Sharon E Frey, Wendy A Keitel, Myron M Levine, John J Treanor, Peter F Wright

Faculty, Staff and Students Publications

On 27 February 1962, Surgeon General Luther Terry announced a new vaccine development program within the National Institute of Allergy and Infectious Diseases (NIAID). Initially, the plan had three components: (1) special laboratories and facilities for development of prototype vaccines; (2) pilot lot production facilities and preliminary vaccine trial sites; and (3) larger lot production capacity and expanded human testing. Respiratory viruses were targeted as the top priority for vaccine development. Over 5 decades, this program has evolved and expanded to include multiple academic vaccine evaluation sites within the network, now labeled as the Vaccine and Treatment Evaluation Units (VTEUs). …

Polychlorinated Biphenyls Alter Estrogen Receptor Β-Mediated Epigenetic Regulation, Promoting Endometriosis, Yuri Park, Nuri Sung, Eunsu Kim, Jaeyeong Jeong, Juhee Sim, Mi Jin Park, John P Lydon, Xiaoming Guan, Sang Jun Han

Faculty, Staff and Students Publications

Endometriosis is a pathological condition characterized by the ectopic growth of endometrial cells, leading to chronic pelvic pain and infertility. Epidemiological studies have associated exposure to dioxin-like polychlorinated biphenyls, particularly PCB126, with an increased risk of endometriosis. However, the underlying mechanisms of this association remain poorly understood. We utilized a surgically induced endometriosis mouse model and human endometrial cell lines to assess the impact of PCB126 on endometriosis progression. Mice were exposed to environmentally relevant doses of PCB126. Endometriotic lesion growth, estrogen receptor signaling, receptor tyrosine kinase activity, and gene expression changes induced by PCB126-mediated elevation of DNA methyltransferase 3A …

Dual Targeting Of Orphan Nuclear Receptors Nr4a1 And Nr4a2 For Nonhormonal Endometriosis Therapy, Wai Ning Tiffany Tsui, Yuri Park, Srijana Upadhyay, Da Mi Kim, Lei Zhang, Gus Wright, Amanuel Hailemariam, Arafat Rahman Oany, Sang Jun Han, Stephen Safe

Faculty, Staff and Students Publications

Previous studies show that orphan nuclear receptor 4A1 (NR4A1) regulates endometriotic cell growth, survival, estrogen receptor β (ERβ), mechanistic target of rapamycin signaling and fibrosis. NR4A2 is also expressed in epithelial and stromal derived endometriotic cells, and in this study the effects of 1,1-bis(3'-indolyl)-(3,5-disubstitutedphenyl)methane (DIM-3,5) dual NR4A1/nuclear receptor 4A2 (NR4A2) ligands and knockdown of NR4A1 and NR4A2 were investigated. The dual NR4A1/2 DIM-3,5 analogs inhibited previously identified proendometriotic pathways and gene products, and they also inhibited TWIST1 and multiple markers associated with epithelial-to-mesenchymal transition (EMT). The results show that both NR4A1 and NR4A2 regulate the same pathways, including endometriotic cell …

Phosphorylation Of Ryr1 At Ser2902 Decreases Ca2+ Leak In Skeletal Muscle And Susceptibility To Malignant Hyperthermia And Heat Stroke, Rachel Sue Zhen Yee, Chang Seok Lee, Ting Chang, Sung Yun Jung, Omar Yousif, Courtney Cavazos, John Colyer, Filip Van Petegem, George G Rodney, Susan L Hamilton

Faculty, Staff and Students Publications

The ryanodine receptor 1 (RYR1) is the sarcoplasmic reticulum (SR) Ca2+ release channel required for both skeletal muscle contraction and Ca2+ leak. Mutations in RYR1 cause malignant hyperthermia susceptibility (MHS) and enhanced sensitivity to heat stroke (ESHS), which can result in death due to excessive skeletal muscle thermogenesis upon exposure to volatile anesthetics or heat. Here, we investigated the molecular and physiological functions of phosphorylation of RYR1 at Ser2902 by the kinase SPEG (striated muscle preferentially expressed protein). Muscle from SPEG-deficient mice expressing RYR1 with a Ser2902 →Asp2902 (S2902D) point mutation to mimic phosphorylation by SPEG showed decreased SR Ca2+ …

Strain-Specific Variability In Viral Kinetics, Cytokine Response, And Cellular Damage In Air-Liquid Cultures Of Human Nasal Organoids After Infection With Sars-Cov-2, Gina M Aloisio, Trevor J Mcbride, Letisha Aideyan, Emily M Schultz, Ashley M Murray, Anubama Rajan, Erin G Nicholson, David Henke, Laura Ferlic-Stark, Amal Kambal, Hannah L Johnson, Elina A Mosa, Fabio Stossi, Sarah E Blutt, Pedro A Piedra, Vasanthi Avadhanula

Faculty, Staff and Students Publications

SARS-CoV-2 variants have demonstrated distinct epidemiological patterns and clinical presentations throughout the COVID-19 pandemic. Understanding variant-specific differences at the respiratory epithelium is crucial for understanding their pathogenesis. Here, we utilized human nasal organoid air-liquid interface (HNO-ALI) cell cultures to compare the viral replication kinetics, innate immune response, and epithelial damage of six different strains of SARS-CoV-2 (B.1.2, WA, Alpha, Beta, Delta, and Omicron). All variants replicated efficiently in HNO-ALIs, but with distinct replication kinetic patterns. The Delta variant exhibited delayed replication kinetics, achieving a steady state at 6 days post-infection compared to 3 days for other variants. Cytokine analysis revealed …

Effect Of Establishing A Separate Outpatient Pharmacy Counter On Reducing Waiting Time In Mayapada Hospital, Hanifan Irham, Masyitoh Basabih

Jurnal ARSI : Administrasi Rumah Sakit Indonesia

Pharmacy waiting time is one of the quality indicators that affects patient satisfaction in hospitals. One of the various efforts to reduce drug waiting times is adding outpatient pharmacies. This study aims to see whether the addition of pharmacies based on guarantors can reduce drug waiting times for outpatients. This is an observational study with a cross-sectional design. The sample included 11,703 patients who received prescriptions at Mayapada Hospital Bogor outpatient with insurance and private coverage. Data were collected over four months, two months before and two months after the separation of pharmacies. Waiting time data were obtained from the …

America's Physician Shortage: Look To Pas, Not Abroad, Raquelle Akavan, Laura Juarez

Lynchburg Journal of Medical Science

The United States has long addressed physician shortages by recruiting international medical graduates (IMGs), often from low- and- middle income countries. This "brain drain" deprives already fragile health systems and adds to worldwide health disparities. New state legislation has eased licensing standards for IMGs and generated variable training pathways creating patient safety risk in underserved groups. At the same time, the U.S. has a sustainable, highly trained, and proven ready workforce: physician associates (PA). Created in the 1960s to address physician shortages, PAs undergo intensive graduate-degree education, uniform clinical education, and national certification on par with physicians. Nonetheless, obsolete laws …