Digital Commons Network^™

‘In Texas, Everybody Wants Antibiotics’: Reducing Inappropriate Antibiotic Expectations And Use With A Provider-Patient Communication Tool In Primary Care, Ashley Collazo, Paige Wermuth, Johanan Luna Rodriguez, Kiara Olmeda, Azalia Mancera, Fabrizia Faustinella, Michael K Paasche-Orlow, Roger Zoorob, Barbara Wells Trautner, Larissa Grigoryan

Faculty, Staff and Students Publications

Background/objective: Patients often expect antibiotics for self-limiting diseases, pressuring providers to prescribe antibiotics unnecessarily. These expectations also contribute to the unsafe practice of taking antibiotics without a prescription (non-prescription use), such as pills retained from prior prescriptions or antibiotics from non-medical sources. Previous work shows that non-prescription use is due to strong, widely held misconceptions regarding the curative power of antibiotics. To reduce unnecessary use of antibiotics, we developed and pilot-tested a patient-focused, bilingual (English and Spanish) educational tool with patient and provider stakeholder input. The tool, a trifold brochure, included information on safe antibiotic use, potential antibiotic harms and …

A Multiomics Recovery Factor Predicts Long Covid In The Impacc Study, Gisela Gabernet, Jessica Maciuch, Jeremy P Gygi, John F Moore, Annmarie Hoch, Caitlin Syphurs, Tianyi Chu, Naresh Doni Jayavelu, David B Corry, Farrah Kheradmand, Lindsey R Baden, Rafick-Pierre Sekaly, Grace A Mccomsey, Elias K Haddad, Charles B Cairns, Nadine Rouphael, Ana Fernandez-Sesma, Viviana Simon, Jordan P Metcalf, Nelson I Agudelo Higuita, Catherine L Hough, William B Messer, Mark M Davis, Kari C Nadeau, Bali Pulendran, Monica Kraft, Chris Bime, Elaine F Reed, Joanna Schaenman, David J Erle, Carolyn S Calfee, Mark A Atkinson, Scott C Brakenridge, Esther Melamed, Albert C Shaw, David A Hafler, Alison D Augustine, Patrice M Becker, Al Ozonoff, Steven E Bosinger, Walter Eckalbar, Holden T Maecker, Seunghee Kim-Schulze, Hanno Steen, Florian Krammer, Kerstin Westendorf, Bjoern Peters, Slim Fourati, Matthew C Altman, Ofer Levy, Kinga K Smolen, Ruth R Montgomery, Joann Diray-Arce, Steven H Kleinstein, Leying Guan, Lauren Ir Ehrlich

Faculty, Staff and Students Publications

Background: Following SARS-CoV-2 infection, approximately 10%–35% of patients with COVID-19 experience long COVID (LC), in which debilitating symptoms persist for at least 3 months. Elucidating the biologic underpinnings of LC could identify therapeutic opportunities.

Methods: We utilized machine learning methods on biologic analytes provided over 12 months after hospital discharge from more than 500 patients with COVID-19 in the IMPACC cohort to identify a multiomics “recovery factor,” trained on patient-reported physical function survey scores. Immune profiling data included PBMC transcriptomics, serum O-link and plasma proteomics, plasma metabolomics, and blood mass cytometry by time of flight (CyTOF) protein levels. Recovery factor …

Single-Nucleus Mrna-Sequencing Reveals Dynamics Of Lipogenic And Thermogenic Adipocyte Populations In Murine Brown Adipose Tissue In Response To Cold Exposure, Janina Behrens, Tongtong Wang, Christoph Kilian, Anna Worthmann, Mark A Herman, Joerg Heeren, Lorenz Adlung, Ludger Scheja

Faculty, Staff and Students Publications

Objective and methods: Brown adipose tissue (BAT) comprises a heterogeneous population of adipocytes and non-adipocyte cell types. To characterize these cellular subpopulations and their adaptation to cold, we performed single-nucleus mRNA-sequencing (snRNA-seq) on interscapular BAT from mice maintained at room temperature or exposed to acute (24h) or chronic (10 days) cold (6 °C). To investigate the role of the de novo lipogenesis (DNL)-regulating transcription factor carbohydrate response element-binding protein (ChREBP), we analyzed control and brown adipocyte-specific ChREBP knockout mice.

Results: We identified different cell populations, including seven brown adipocyte subtypes with distinct metabolic profiles. One of them highly expressed ChREBP …

Intravascular Hemolysis As A Converging Mechanism In Hemolytic Disorders, Justin A Courson, Arun Saini

Faculty, Staff and Students Publications

No abstract provided.

From Pachymeningitis Hemorrhagica To Abusive Head Trauma: A Journey Through The Centuries, Oliver Berthold, Flora Blangis, Christopher Spencer Greeley

Faculty, Staff and Students Publications

The development of medical knowledge follows specific principles. These also apply to abusive head trauma. The seminal literature from the early 20th century is based on earlier research from Europe, which is fundamental to understand the evolution of understanding and nomenclature of abusive head trauma. A review of original medical literature on intracranial injuries in children, published in German, English, and French, was conducted using PubMed and Google Scholar for articles before 1950. The primary search focused on subdural hemorrhages and pachymeningitis in children, followed by a snowball search of references. Full texts of available manuscripts were reviewed. Primary literature …

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.

Alterations In Cardiovascular Parameters In 5xfad Murine Model, Andrea G Marshall, Dominique Stephens, Kit Neikirk, Sepiso K Masenga, Bryanna Shao, Amber Crabtree, Zer Vue, Heather K Beasley, Edgar Garza-Lopez, Estevão Scudese, Benjamin I Rodriguez, Han Le, Steven Damo, George E Taffet, Okwute M Ochayi, Ronald Mcmillan, Jeremiah M Afolabi, Vernat Exil, Ashton Oliver, Vineeta Sharma, Pamela Martin, Amadou Gaye, Chanel Harris, Briar Tomeau, Lacara Bell, Markis Hamilton, Taneisha Gillyard, Railyn Webster, Marcus Jackson, Prem Prakash, Shanilah Frierson, Chandravanu Dash, Margaret Mungai, Annet Kirabo, Jennifer A Gaddy, Nelson Wandira, Antentor Hinton, Anilkumar K Reddy

Faculty, Staff and Students Publications

Alzheimer's Disease (AD) is a global health issue, affecting over 6 million people in the United States, with that number expected to increase as the population ages. As a neurodegenerative disorder that affects memory and cognitive functions, it is well established that AD is associated with cardiovascular risk factors beyond only cerebral decline. In this study, we measured hemodynamic parameters related to cardiovascular and cerebrovascular function in 5xFAD mice with AD and their littermates. Specifically, we measured cardiovascular pulse wave velocity parameters, a marker of arterial stiffness and cardiovascular risk, and cerebrovascular pulse wave velocity, a novel technique to measure …

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). …

Xpert Mtb/Rif Ultra Assay For Tuberculosis Disease And Rifampicin Resistance In Children, Alexander W Kay, Maia Madison, Katie Scandrett, Tara Ness, Pauline Amuge, Leeberk Raja Inbaraj, Mukesh Kumar Sathya Narayanan, Lucia González Fernández, Michael Eisenhut, Nazir Ismail, Alexei Korobitsyn, Sabine E Verkuijl, Annemieke Brands, Kerri Viney, Tiziana Masini, Anna M Mandalakas, Karen R Steingart, Yemisi Takwoingi

Faculty, Staff and Students Publications

Background: In 2023, an estimated 1.3 million children (aged 0-14 years) became ill with tuberculosis, and 166,000 children (aged 0-15 years) died from the disease. Xpert MTB/RIF Ultra (Xpert Ultra) is a molecular World Health Organization (WHO)-recommended rapid diagnostic test that detects Mycobacterium tuberculosis complex and rifampicin resistance. This is an update of a Cochrane review first published in 2020 and last updated in 2022. Parts of the current update informed the 2024 WHO updated guidance for the diagnosis of tuberculosis.

Objectives: To assess the diagnostic accuracy of Xpert Ultra for detecting pulmonary tuberculosis, tuberculous meningitis, lymph node tuberculosis, and …

Sperm And Offspring Production In A Nonobstructive Azoospermia Mouse Model Via Testicular Mrna Delivery Using Lipid Nanoparticles, Daisuke Mashiko, Chihiro Emori, Yuki Hatanaka, Daisuke Motooka, Chen Pan, Yuki Kaneda, Martin M Matzuk, Masahito Ikawa

Faculty, Staff and Students Publications

Microsurgical testicular sperm extraction (microTESE) with intracytoplasmic sperm injection (ICSI) represents the current standard treatment for nonobstructive azoospermia (NOA). However, cures remain unavailable for NOA patients lacking retrievable haploid cells. mRNA supplementation could be a potential treatment for genetic defects leading to impaired spermatogenesis. Lipid nanoparticles (LNPs) have emerged as mRNA delivery vehicles with minimal risk of genome integration; however, their ability to selectively deliver mRNA to specific cell types remains limited. To overcome this, microRNA (miRNA) target sequences were incorporated into mRNA constructs to restrict expression specifically to germ cells. Using pyruvate dehydrogenase E1 subunit alpha 2 (PDHA2) knockout …

Everolimus And Low-Dose Tacrolimus After Heart Transplant In Children: A Randomized Clinical Trial, Christopher S Almond, Kevin P Daly, Erin L Albers, Juan C Alejos, Rebecca Ameduri, Scott R Auerbach, Lynsey Barkoff, Aliessa P Barnes, Matthew J Bock, Arene Butto, Waldemar F Carlo, Chesney D Castleberry, Maryanne R Chrisant, Shriprasad R Deshpande, William J Dreyer, Melanie D Everitt, Brian Feingold, Selena Gonzales, Seth A Hollander, Steven J Kindel, Gloria L Klein, Ashwin K Lal, Jacqueline M Lamour, Joanne Lee, Minmin Lu, Irene D Lytrivi, Shelley D Miyamoto, Elfriede Pahl, David M Peng, Thomas D Ryan, Tajinder P Singh, Jennifer A Su, David L Sutcliffe, A Marian Ybarra, Steven Zangwill, Joseph W Rossano, Lynn A Sleeper

Faculty, Staff and Students Publications

Importance: Studies suggest that everolimus may reduce the risk of rejection, cardiac allograft vasculopathy (CAV), chronic kidney disease (CKD), and cytomegalovirus (CMV) after heart transplant. Everolimus use is controversial because of data demonstrating higher infection deaths when everolimus is introduced de novo after transplant. It is unclear whether everolimus is safe and effective when initiated at 6 months posttransplant in children, a population in which median graft survival is limited to 15 years and randomized clinical trials are lacking.

Objective: To evaluate the safety and efficacy of everolimus combined with low-dose tacrolimus to prevent major adverse transplant events (MATEs) in …

Alterations Of The Upper Respiratory Microbiome Among Children Living With Hiv Infection In Botswana, Sweta M Patel, John Farirai, Mohamed Z Patel, Sifelane Boiditswe, Leabaneng Tawe, Shimane Lekalake, Mogomotsi Matshaba, Andrew P Steenhoff, Tonya Arscott-Mills, Kristen A Feemster, Samir S Shah, Nathan Thielman, Coleen K Cunningham, Lawrence A David, David M Murdoch, Matthew S Kelly

Faculty, Staff and Students Publications

Children living with HIV (CLWH) are at high risk of colonization and infection by respiratory pathogens, though this risk can be reduced by other microbes in the upper respiratory microbiome. The impact of HIV infection on the pediatric upper respiratory microbiome is poorly understood, and we sought to address this knowledge gap by identifying associations between HIV infection and the nasopharyngeal microbiomes of Batswana children. We enrolled Batswana CLWH (< 5 years) and age- and sex-matched HIV-exposed, uninfected and HIV-unexposed, uninfected children in a cross-sectional study. We used shotgun metagenomic sequencing to compare nasopharyngeal microbiomes by HIV status. Among the 143 children in this study, HIV and HIV-associated immunosuppression were associated with alterations in nasopharyngeal microbiome composition, including lower abundances of Corynebacterium species associated with resistance to bacterial pathogen colonization. These findings suggest that the upper respiratory microbiome may contribute to the high risk of respiratory infections among CLWH.

Establishing Priority Pediatric Antimicrobial Stewardship Interventions In The Us: Findings From A Delphi Consensus Study, Harry Obeng, Emmanuel Tetteh, Sara Malone, Lauren Walsh, Tyler Walsh, Fernando J Bula-Rudas, Ritu Banerjee, Adam W Brothers, Joshua C Herigon, Katie Namtu, Scott Weissman, Daniel Riggsbee, Jared Olson, Debra Lynn Palazzi, Ann Wirtz, Matthew Sattler, Jessica Tansmore, Brittany A Rodriguez, Monica Abdelnour, Joshua R Watson, Alison C Tribble, Jessica Gillon, Mari Nakamura, Sarah Jones, Jason G Newland, Virginia R Mckay

Faculty, Staff and Students Publications

Background/objectives: Antimicrobial resistance (AMR) is a major global health threat, with children at higher risk due to developmental differences in drug metabolism, limited treatment options and inappropriate antibiotic use. Pediatric antimicrobial stewardship programs (ASPs) face implementation challenges, often relying on adult-based guidelines and limited pediatric-specific evidence. This study aimed to identify and prioritize the most critical areas for pediatric ASP intervention development through a structured, multi-round Delphi consensus process with experts in antimicrobial stewardship and infectious diseases.

Method: A four-round modified Delphi process was conducted to identify and prioritize key pediatric ASP interventions. Experts in antimicrobial stewardship and infectious diseases …

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). …

Practicing With Intent: How To Teach An Old Dogma New Tricks, Matthew C Phillips, Kusha Davar, Sarah Freling, Steven Y C Tong, Todd C Lee, Emily G Mcdonald, Travis B Nielsen, Noah Wald-Dickler, Alfredo J Mena Lora, Rachael A Lee, Fergus Hamilton, Daniel M Musher, Rodrigo P L Costa, Bassam Ghanem, Rachel Baden, Brad Spellberg

Faculty, Staff and Students Publications

Clinicians are constantly bombarded with an onslaught of newly published data, yet they must make clinical decisions despite a dearth of clinical data. Sometimes, they may fall back on clinical practices entrenched by experience, unaware that they are upheld by dogmatic tradition rather than robust evidence. Ideally, the totality of evidence must be assessed and utilized for clinical decision-making, irrespective of entrenched orthodoxy. Here, we explore the questions, how much evidence is needed to revise established clinical practices and, more fundamentally, can data alone truly catalyze such shifts.

Vaccine Value Profile For Schistosomiasis, Gavin Yamey, Kaci Kennedy Mcdade, Roy M Anderson, Sarah M Bartsch, Maria Elena Bottazzi, David Diemert, Peter J Hotez, Bruce Y Lee, Donald Mcmanus, Adebayo J Molehin, Meta Roestenberg, David Rollinson, Afzal A Siddiqui, Miriam Tendler, Joanne P Webster, Hong You, Raphaël M Zellweger, Caroline Marshall

Faculty, Staff and Students Publications

Schistosomiasis is caused by parasitic flatworms (Schistosoma). The disease in humans can be caused by seven different species of Schistosoma: S. mansoni, S. japonicum, S. haematobium, S. malayensis, S. mekongi, S. guineensis and S. intercalatum, as well as by hybrids between species, including livestock schistosome species. People are infected when exposed to infested water and the parasite larvae penetrate the skin. Poor and rural communities are typically the most affected, and the general population who lives in affected areas and is exposed to contaminated water is at risk. Areas with poor access to safe water and adequate sanitation are also …

Nrf2 Hyperactivation As A Driver Of Radiotherapy Resistance And Suppressed Antitumor Immunity In Head And Neck Squamous Cell Carcinoma, Rutulkumar Patel, Kalil Saab, Lixia Luo, Yan Ma, Rashid Abdullah Osman, Nerissa T Williams, Jeffrey Everitt, Maciej J Zelazowski, Patricia Castro, William K Decker, William H Hudson, Jeffrey N Myers, Vlad C Sandulache, Mitchell J Frederick, Yvonne M Mowery, David G Kirsch

Faculty, Staff and Students Publications

Purpose: Alterations in the KEAP1/NFE2L2 (NRF2)/CUL3 pathway occur in ∼20% of human head and neck squamous cell carcinomas (HNSCC) and are associated with resistance to standard-of-care therapy. However, this pathway's role in radiotherapy resistance in HNSCC has not been well studied.

Experimental design: We generated genetically engineered mouse models and developed primary murine cancer cell lines harboring mutations commonly observed in human HNSCC, including inducible activation of PIK3CA and deletion of Trp53, with or without Keap1 loss. Primary tumors were initiated via 4-hydroxytamoxifen injection ± the tobacco carcinogen benzo[a]pyrene (BAP) into the oral buccal mucosa. Tumors were analyzed by Western …

Inhibition Of Ros1 Activity With Lorlatinib Reversibly Suppresses Fertility In Male Mice, Yuki Oyama, Kentaro Shimada, Haruhiko Miyata, Rie Iida-Norita, Chihiro Emori, Maki Kamoshita, Seiya Oura, Ryohei Katayama, Martin M Matzuk, Masahito Ikawa

Faculty, Staff and Students Publications

Background: Inhibition of sperm maturation in the epididymis is a promising post-testicular strategy for short-acting male contraceptives. It has been shown that ROS1, a receptor tyrosine kinase expressed in the epididymis, is essential for epididymal differentiation, sperm maturation, and male fertility in mice. However, it is unknown if inhibition of ROS1 suppresses male fertility reversibly.

Objectives: Our study aimed to investigate the effects of ROS1 inhibitor administration in male mice on sperm function and fertility.

Materials and methods: We used lorlatinib, an anti-cancer drug that inhibits ROS1. We treated 10-week-old sexually mature male mice with lorlatinib for 3 weeks and …

Covid-19 Booster Vaccine Messaging In Emergency Departments: A Cluster Randomized Clinical Trial, Melanie F Molina, Stephanie A Eucker, Kristin L Rising, Efrat R Kean, Zubaid Rafique, Heba Mesbah, David V Glidden, Mireya I Arreguin, Christopher Alvarez, Robert M Rodriguez

Faculty, Staff and Students Publications

Importance: Patient uptake of updated COVID-19 vaccines is crucial for reducing severe outcomes, yet national uptake remains low.

Objective: To determine if tailored messaging or simple inquiry about vaccine acceptance increases 30-day uptake of updated COVID-19 vaccines among emergency department (ED) patients.

Design, setting, and participants: This 3-arm, cluster randomized clinical trial conducted from January 29 to June 18, 2024, enrolled adult ED patients who had not received a COVID-19 vaccine in the prior 6 months across 6 EDs in San Francisco, California; Philadelphia, Pennsylvania; Houston, Texas; and Durham, North Carolina.

Interventions: Intervention M involved tailored messaging about updated COVID-19 …

Liver-Specific Expression Of Hiv-1 Viral Protein R Causes Hepatic Steatosis And Glucose Intolerance In Male Mice, Neeti Agarwal, Pradip Saha, Claudia E Ramirez Bustamante, Sean M Hartig, Mark A Herman, Ashok Balasubramanyam, Jordan E Lake

Faculty, Staff and Students Publications

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized in people with HIV (PWH), with both HIV and antiretroviral therapy contributing to liver damage and glucose intolerance. However, the role of viral proteins derived from reservoirs in this process remains unclear.

Methods: Adeno-associated virus (AAV) constructs encoding a control protein or HIV-1 viral protein R (Vpr) driven by the thyroxine-binding globulin promoter were administered to male mice (n = 5 per group) fed regular chow or a high-fat diet (HFD). Young adult mice underwent intraperitoneal glucose tolerance testing and magnetic resonance imaging, followed by euthanasia. Liver and adipose tissues …

Shrimp Allergy-Distinct Allergen Sensitization Profiles Between Intercontinental Cohorts, Shaymaviswanathan Karnaneedi, Sara Anvari, Shea Brunner, Karen S Tuano, Brenda Bin Su, Saachi Hira, Sahel Heidari, Diamond Hira, Carla M Davis, Andreas L Lopata

Faculty, Staff and Students Publications

No abstract provided.

Cutaneous Tuberculosis With Multisystem Involvement In An Immunocompetent Refugee, Nabor S Mireles, Natalie Garcia, Omid Jalali

Faculty, Staff and Students Publications

Cutaneous tuberculosis (CTB) is an uncommon skin infection that can mimic other dermatologic conditions and delay recognition. Herein, we present a case of TB chancre, a form of CTB caused by exogenous inoculation. A 19-year-old immunocompetent male refugee from Sudan presented with a five-month history of non-healing wounds on his right shoulder and three weeks of bilateral lower extremity weakness. Diagnostic examination revealed the presence of a spinal epidural abscess and lung consolidation, with culture of the spinal abscess positive for Mycobacterium tuberculosis (MTB). Skin biopsy of the shoulder lesion revealed granulomatous dermatitis, with subsequent culture confirming MTB from the …

Strongyloides Seropositivity Among Children Utilizing A Mobile Clinic, Lynda Aririguzo, Aditi Gupta, Norma Castillo, Cassandra Duran, Eva H Clark, Ankona Banerjee, Sanghamitra Misra

Faculty, Staff and Students Publications

Experts recommend screening for or presumptively treating strongyloidiasis in foreign-born immigrant children, though prevalence is unknown. Health care providers encounter barriers to following this recommendation. We aimed to describe Strongyloides seropositivity and risk factors among pediatric patients on a mobile clinic. Participants completed a written survey and provided blood for absolute eosinophil count (AEC) and Strongyloides IgG enzyme-linked immunosorbent assay (ELISA). From October 2022 to June 2023, 206 patients participated; 201 (97.6%) were born outside the United States; 97.1% (n = 200) were Hispanic. Most (68.9%) arrived less than 1 year before study enrollment. Four (1.9%) and 3 (1.5%) had …

Cyp1b1 Mediates Cigarette Smoke-Induced Lipid Accumulation In Alveolar Type 2 Cells, Yin Zhu, Siddhika Gamare, Francesca Polverino, Caroline A Owen, Payaningal R Somanath, Xiaoyun Wang, Duo Zhang

Faculty, Staff and Students Publications

Alterations in lipid profiles have been shown in patients with chronic obstructive pulmonary disease (COPD), but the underlying molecular mechanisms remain unclear. In this study, we aimed to investigate the role of cytochrome P450 family-1 subfamily B member 1 (CYP1B1) in cigarette smoke (CS)-induced lipid accumulation in alveolar type II epithelial (AT2) cells. We observed a steady increase in CYP1B1 protein levels in AT2 cells from COPD patients. Additionally, CS exposure induced CYP1B1 expression in AT2 cells of murine lungs. In vitro, treatment with cigarette smoke extract (CSE) not only upregulated CYP1B1 expression but also triggered lipid accumulation in AT2-like …

Pediatric Heart Failure: A Practical Guide For Primary Care Providers Supporting Families Across The Care Continuum, Shahnawaz Amdani, Kriti Puri, Julie Glickstein, Joseph A Spinner, Jonathan N Johnson, Ashraf S Harahsheh, Majd Makhoul, Susan Denfield

Faculty, Staff and Students Publications

Background/Objectives: Pediatric heart failure (HF) is a complex clinical syndrome with diverse etiologies and presentations. Primary care providers (PCPs) are critical in early recognition, family education, and coordination of ongoing care in collaboration with pediatric cardiologists. This review provides a comprehensive guide for PCPs to understand the causes, symptoms, treatments, and longitudinal considerations for children with HF.

Methods: We conducted a narrative review synthesizing published evidence and expert consensus guidelines, focusing on the clinical presentation, treatment options, and longitudinal care strategies in children with HF.

Results: HF in children most commonly results from congenital heart disease and …

Sorting Nexin 3 Promotes Ischemic Retinopathy Through Rip1- And Rip3-Mediated Myeloid Cell Necroptosis And Mitochondrial Fission, Jiaojiao Wang, Chunhong Zhou, Kai Zhuang, Jiami Zou, Wanlu Qiu, Mei Jin, Weile Ye, Pinglian Yang, Zhihua Zheng, Qing Zhou, Zunnan Huang, Yuanxiang Wang, Peiqing Liu, Jing Lu, Yuqing Huo, Zhiping Liu

Faculty, Staff and Students Publications

Proliferative retinopathy is a leading cause of irreversible blindness in humans; however, the molecular mechanisms behind the immune cell–mediated retinal angiogenesis remain poorly elucidated. Here, using single-cell RNA sequencing in an oxygen-induced retinopathy (OIR) model, we identified an enrichment of sorting nexin (SNX)-related pathways, with SNX3, a member of the SNX family that is involved in endosomal sorting and trafficking, being significantly upregulated in the myeloid cell subpopulations of OIR retinas. Immunostaining showed that SNX3 expression is markedly increased in the retinal microglia/macrophages of mice with OIR, which is mainly located within and around the neovascular tufts. Myeloid cell-specific deficiency …

Human Toxocariasis, Susana Lopez-Alamillo, Pravallika Padyala, Megan Carey, Megan M Duffey, Jill E Weatherhead

Faculty, Staff and Students Publications

Human toxocariasis is a globally prevalent zoonotic parasitic infection caused by larvae of Toxocara species, primarily Toxocara canis and Toxocara cati. Toxocariasis is commonly transmitted to humans through the ingestion of embryonated Toxocara eggs found in contaminated soil, water, or on surfaces contaminated with animal feces. Unlike in dogs and cats, humans are not definitive hosts for Toxocara spp., and, as a result, Toxocara larvae do not complete their life cycle in humans. Instead, following accidental oral ingestion of embryonated eggs, Toxocara larvae undergo an aberrant larval migratory cycle to various organs including the lungs, liver, muscles, and central …

Testis Expressed 50 Is Essential For Maintaining Sperm Acrosome Integrity During Epididymal Transit, Saori Haga, Kaori Nozawa, Ferheen Abbasi, Katarzyna Kent, Naoko Nagasawa, Tsutomu Endo, Haruhiko Miyata, Masahito Ikawa, Martin M Matzuk, Yoshitaka Fujihara

Faculty, Staff and Students Publications

In mammals, sperm formation is completed in the seminiferous tubules within the testis, and sperm maturation occurs during the epididymal transit of the spermatozoa. Sperm morphology drastically changes when abnormal spermatozoa migrate from the testis to the epididymis. Detailed molecular mechanisms for sperm survival in the epididymis have not been determined yet. Globozoospermia is a cause of male infertility and is characterized by round-headed spermatozoa without acrosomes, an abnormal sperm nuclear membrane, and sperm midpiece defects. Testis expressed 50 (Tex50) is a testis-enriched gene that is expressed in mice and humans. Using CRISPR-Cas9, we generated Tex50 knockout (KO) …

Amoxicillin Vs Ceftriaxone To Treat Pneumonia Caused By Amoxicillin-Non-Susceptible Streptococcus Pneumoniae, Daniel M Musher

Faculty, Staff and Students Publications

Although the article by J Càmara, I Grau, A González-Díaz, N Santos, et al. (Antimicrob Agents Chemother 69:e00237-25, 2025, https://doi.org/10.1128/aac.00237-25) suggests that ceftriaxone is greatly superior to amoxicillin in treating pneumonia due to pneumococci with an MIC > 2 mg/L, much of the difference in efficacy of the two drugs may have been due to dosage, route, and times of administration of the amoxicillin.