Digital Commons Network^™

Evaluating Eosinophilic Colitis As A Unique Disease Using Colonic Molecular Profiles: A Multi-Site Study, Tetsuo Shoda, Margaret H Collins, Mark Rochman, Ting Wen, Julie M Caldwell, Lydia E Mack, Garrett A Osswald, John A Besse, Yael Haberman, Seema S Aceves, Nicoleta C Arva, Kelley E Capocelli, Mirna Chehade, Carla M Davis, Evan S Dellon, Gary W Falk, Nirmala Gonsalves, Sandeep K Gupta, Ikuo Hirano, Paneez Khoury, Amy Klion, Calies Menard-Katcher, John Leung, Vincent A Mukkada, Philip E Putnam, Jonathan M Spergel, Joshua B Wechsler, Guang-Yu Yang, Glenn T Furuta, Lee A Denson, Marc E Rothenberg, Consortium Of Eosinophilic Gastrointestinal Diseases Researchers (Cegir)

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Colonic eosinophilia, an enigmatic finding often referred to as eosinophilic colitis (EoC), is a poorly understood condition. Whether EoC is a distinct disease or a colonic manifestation of eosinophilic gastrointestinal diseases (EGIDs) or inflammatory bowel disease (IBD) is undetermined.

METHODS: Subjects with EoC (n = 27) and controls (normal [NL, n = 20], Crohn's disease [CD, n = 14]) were enrolled across sites associated with the Consortium of Eosinophilic Gastrointestinal Disease Researchers. EoC was diagnosed as colonic eosinophilia (ascending ≥100, descending ≥85, sigmoid ≥65 eosinophils/high-power field) with related symptoms. Colon biopsies were subjected to RNA sequencing. Associations …

Primer For Development Of Guidelines For Helicobacter Pylori Therapy Using Antimicrobial Stewardship, David Y Graham, Jyh-Ming Liou

Faculty, Staff and Students Publications

We provide a primer to assist in the difficult transition of Helicobacter pylori therapy guidelines to those that adhere to the principles of antimicrobial stewardship. This transition will entail abandonment of many of the principles that heretofore formed the basis of treatment guidelines and recommendations. The goals of antimicrobial stewardship include optimization of the use of antibiotics while reducing antimicrobial resistance. The critical outcome measure is absolute cure rate which largely restricts comparative trials to those which reliably produce high cure rates (eg, ∼95%). Therapies that fail to achieve at least a 90% cure rate should be abandoned as unacceptable. …

Heightened Levels Of Plasma Growth Differentiation Factor 15 In Men Living With Hiv, Neeti Agarwal, Claudia E Ramirez Bustamante, Huaizhu Wu, Reina Armamento-Villareal, Jordan E Lake, Ashok Balasubramanyam, Sean M Hartig

Faculty, Staff and Students Publications

Plasma biomarkers that reflect energy balance disorders in people living with HIV (PLWH) remain limited. Growth differentiation factor 15 (GDF15) abundance in plasma of mice and humans induces negative energy balance but also becomes highly elevated in obesity and other metabolic diseases. We sought to compare plasma GDF15 levels in PLWH and HIV-negative persons and mouse models expressing the HIV accessory protein Vpr (that recapitulate HIV-associated metabolic disorders) and determine their relationship to metabolic parameters. We measured liver Gdf15 mRNA levels and plasma GDF15 levels in male Vpr mice and littermate controls. In parallel, we analyzed plasma GDF15 levels in …

Temporal Trends In Outcomes In Patients With Adrenocortical Carcinoma: A Multidisciplinary Referral-Center Experience, Marilyne Daher, Jeena Varghese, Stephen K Gruschkus, Camilo Jimenez, Steven G Waguespack, Sara Bedrose, Lina Altameemi, Hadil Bazerbashi, Aung Naing, Vivek Subaiah, Matthew T Campbell, Amishi Y Shah, Miao Zhang, Rahul A Sheth, Jose A Karam, Christopher G Wood, Nancy D Perrier, Paul H Graham, Jeffery E Lee, Mouhammed Amir Habra

Faculty, Staff and Students Publications

CONTEXT: Reporting temporal trends in adrenocortical carcinoma (ACC) helps guide management strategies.

OBJECTIVE: This work aimed to report the trends in disease burden and clinical outcomes over time that cannot be adequately captured from individual clinical trials.

METHODS: A retrospective study was held of ACC patients seen at a referral cancer center between February 1998 and August 2019. Clinical outcomes were compared between an early cohort (February 1998-June 2007) and a late cohort (July 2007-August 2019).

RESULTS: A total of 621 patients included with a median age at diagnosis of 49.3 years (range, 0.5-86.6 years). There were 285 (45.9%) patients …

Emergency Department Antimicrobial Use In A Low-Resource Setting: Results From A Retrospective Observational Study At A Referral Hospital In Liberia, Sojung Yi, Anu Ramachandran, Lane Epps, Alex Mayah, Taylor W Burkholder, Michael Senyu Jaung, Ahson Haider, Paul Whesseh, John Shakpeh, Kayla Enriquez, Corey Bills

Faculty, Staff and Students Publications

OBJECTIVE: Data on antimicrobial use in low-income and middle-income countries (LMICs) remain limited. In Liberia, the absence of local data impedes surveillance and may lead to suboptimal treatment, injudicious use and resistance against antimicrobials. This study aims to examine antimicrobial prescribing patterns for patients in the emergency department (ED) of a large Liberian public hospital. Secondarily, this prescribing was compared with WHO prescribing indicators.

DESIGN: Retrospective observational study.

SETTING: An adult ED of a large public hospital in Monrovia, Liberia.

PARTICIPANTS: A total of 1082 adult patients (>18 years of age) were recorded in the ED, from 1 January …

Envisioning Future Urinary Tract Infection Diagnostics, Robin Patel, Christopher R Polage, Jennifer Dien Bard, Larissa May, Francesca M Lee, Valeria Fabre, Mary K Hayden, Sarah D B Doernberg, David A Haake, Barbara W Trautner, Larissa Grigoryan, Ephraim L Tsalik, Kimberly E Hanson

Faculty, Staff and Students Publications

Urinary tract infections (UTIs) are among the most common bacterial infections in the United States and are a major driver of antibiotic use, both appropriate and inappropriate, across healthcare settings. Novel UTI diagnostics are a strategy that might enable better UTI treatment. Members of the Antibacterial Resistance Leadership Group Laboratory Center and the Infectious Diseases Society of America Diagnostics Committee convened to envision ideal future UTI diagnostics, with a view towards improving delivery of healthcare, patient outcomes and experiences, and antibiotic use, addressing which types of UTI diagnostics are needed and how companies might approach development of novel UTI diagnostics.

Clinical Presentation, Treatment, And Genetic And Histopathological Analysis Of Juvenile Cataracts And Secondary Glaucoma In A Rhesus Macaque (Macaca Mulatta), M Isabel Casanova, Rui Chen, Laura M Garzel, Katherine J Olstad, Soohyun Kim, Ronald Alan Harris, Yumei Li, Muthuswamy Raveendran, Qingnan Liang, Jun Wang, Glenn Yiu, John Timothy Stout, Jeffrey A Roberts, Jeffrey Rogers, Ala Moshiri, Sara M Thomasy

Faculty, Staff and Students Publications

This report describes the clinical and histological findings, genetic study, and treatment in a 1.3-year-old rhesus macaque with bilateral cataracts and unilateral secondary glaucoma. Intravitreal injection of gentamicin decreased the intraocular pressure from 56 to <2 mm Hg. A putative genetic cause of the cataracts was not identified.

Single-Cell Transcriptional Profiling Of Murine Conjunctival Immune Cells Reveals Distinct Populations Expressing Homeostatic And Regulatory Genes, Jehan Alam, Ghasem Yazdanpanah, Rinki Ratnapriya, Nicholas Borcherding, Cintia S De Paiva, Dequan Li, Stephen C Pflugfelder

Faculty, Staff and Students Publications

Immune cells in the exposed conjunctiva mucosa defend against environmental and microbial stresses. Expression profiling by single-cell RNA sequencing was performed to identify conjunctival immune cell populations expressing homeostatic and regulatory genes. Fourteen distinct clusters were identified, including myeloid cells (neutrophils, monocytes, macrophages), dendritic cells (DC), and lymphoid cells (B, T, γδT, ILC2, and NK) lineages. Novel neutrophil [lipocalin (Lcn2) high and low), and MHCIIlo macrophage (MP) clusters were identified. More than half of the cells map to myeloid and dendritic cell populations with differential expression profiles that include genes with homeostatic and regulatory functions: Serpinb2 (MHCIIlo macrophage), …

Vestibular Rehabilitation For Peripheral Vestibular Hypofunction: An Updated Clinical Practice Guideline From The Academy Of Neurologic Physical Therapy Of The American Physical Therapy Association, Courtney D Hall, Susan J Herdman, Susan L Whitney, Eric R Anson, Wendy J Carender, Carrie W Hoppes, Stephen P Cass, Jennifer B Christy, Helen S Cohen, Terry D Fife, Joseph M Furman, Neil T Shepard, Richard A Clendaniel, J Donald Dishman, Joel A Goebel, Dara Meldrum, Cynthia Ryan, Richard L Wallace, Nakia J Woodward

Faculty, Staff and Students Publications

BACKGROUND: Uncompensated vestibular hypofunction can result in symptoms of dizziness, imbalance, and/or oscillopsia, gaze and gait instability, and impaired navigation and spatial orientation; thus, may negatively impact an individual's quality of life, ability to perform activities of daily living, drive, and work. It is estimated that one-third of adults in the United States have vestibular dysfunction and the incidence increases with age. There is strong evidence supporting vestibular physical therapy for reducing symptoms, improving gaze and postural stability, and improving function in individuals with vestibular hypofunction. The purpose of this revised clinical practice guideline is to improve quality of care …

Antimicrobial Susceptibility Testing For Helicobacter Pylori Is Now Widely Available: When, How, Why, David Y Graham, Steven F Moss

Faculty, Staff and Students Publications

No abstract provided.

Differences In Covid-19-Related Testing And Healthcare Utilization By Race And Ethnicity In The Veterans Health Administration, Javad Razjouyan, Drew A Helmer, Ang Li, Aanand D Naik, Christopher I Amos, Venkata Bandi, Amir Sharafkhaneh

Faculty, Staff and Students Publications

IMPORTANCE: Recent reports indicate differences in COVID-19-related care and outcomes between Black and White Americans.

OBJECTIVE: We examine the COVID-19-related healthcare utilization and mortality by race and ethnicity of patients tested for SARS-CoV-2 in the Veterans Health Administration (VHA).

DESIGN: A retrospective cohort study.

SETTING: We used the VHA COVID-19 shared data resources between February 1 and June 30, 2020.

PARTICIPANTS: Veterans tested for SARS-CoV-2 virus by VHA.

EXPOSURE(S): Three racial-ethnicity groups of Black, Hispanic, and White (as reference) veterans.

MAIN OUTCOME(S) AND MEASURE(S): Main outcomes are testing rate, positivity rate, hospitalization rate, ICU admission rate, and in-hospital mortality. Controlling …

Peppermint Oil Effects On The Gut Microbiome In Children With Functional Abdominal Pain, Santosh Thapa, Ruth Ann Luna, Bruno P Chumpitazi, Numan Oezguen, Susan M Abdel-Rahman, Uttam Garg, Salma Musaad, James Versalovic, Gregory L Kearns, Robert J Shulman

Faculty, Staff and Students Publications

Peppermint oil (PMO) is effective in the treatment of functional abdominal pain disorders, but its mechanism of action is unclear. Evidence suggests PMO has microbicidal activity. We investigated the effect of three different doses of PMO on gut microbiome composition. Thirty children (7-12 years of age) with functional abdominal pain provided a baseline stool sample prior to randomization to 180, 360, or 540 mg of enteric coated PMO (10 participants per dose). They took their respective dose of PMO (180 mg once, 180 mg twice, or 180 mg thrice daily) for 1 week, after which the stool collection was repeated. …

Derivation And Validation Of A Novel Risk Assessment Tool To Identify Children Aged 2–59 Months At Risk Of Hospitalised Pneumonia-Related Mortality In 20 Countries, Chris A Rees, Tim Colbourn, Shubhada Hooli, Carina King, Norman Lufesi, Eric D Mccollum, Charles Mwansambo, Clare Cutland, Shabir Ahmed Madhi, Marta Nunes, Joseph L Matthew, Emmanuel Addo-Yobo, Noel Chisaka, Mumtaz Hassan, Patricia L Hibberd, Prakash M Jeena, Juan M Lozano, William B Macleod, Archana Patel, Donald M Thea, Ngoc Tuong Vy Nguyen, Cissy B Kartasasmita, Marilla Lucero, Shally Awasthi, Ashish Bavdekar, Monidarin Chou, Pagbajabyn Nymadawa, Jean-William Pape, Glaucia Paranhos-Baccala, Valentina S Picot, Mala Rakoto-Andrianarivelo, Vanessa Rouzier, Graciela Russomando, Mariam Sylla, Philippe Vanhems, Jianwei Wang, Rai Asghar, Salem Banajeh, Imran Iqbal, Irene Maulen-Radovan, Greta Mino-Leon, Samir K Saha, Mathuram Santosham, Sunit Singhi, Sudha Basnet, Tor A Strand, Shinjini Bhatnagar, Nitya Wadhwa, Rakesh Lodha, Satinder Aneja, Alexey W Clara, Harry Campbell, Harish Nair, Jennifer Falconer, Shamim A Qazi, Yasir B Nisar, Mark I Neuman, World Health Organization Prepare Study Group

Faculty, Staff and Students Publications

INTRODUCTION: Existing risk assessment tools to identify children at risk of hospitalised pneumonia-related mortality have shown suboptimal discriminatory value during external validation. Our objective was to derive and validate a novel risk assessment tool to identify children aged 2-59 months at risk of hospitalised pneumonia-related mortality across various settings.

METHODS: We used primary, baseline, patient-level data from 11 studies, including children evaluated for pneumonia in 20 low-income and middle-income countries. Patients with complete data were included in a logistic regression model to assess the association of candidate variables with the outcome hospitalised pneumonia-related mortality. Adjusted log coefficients were calculated for …

Considerations For The Use Of Phage Therapy In Clinical Practice, Gina A Suh, Thomas P Lodise, Pranita D Tamma, Jane M Knisely, Jose Alexander, Saima Aslam, Karen D Barton, Erica Bizzell, Katherine M C Totten, Joseph L Campbell, Benjamin K Chan, Scott A Cunningham, Katherine E Goodman, Kerryl E Greenwood-Quaintance, Anthony D Harris, Shayla Hesse, Anthony Maresso, Veronique Nussenblatt, David Pride, Michael J Rybak, Zoe Sund, David Van Duin, Daria Van Tyne, Robin Patel

Faculty, Staff and Students Publications

Increasing antimicrobial resistance and medical device-related infections have led to a renewed interest in phage therapy as an alternative or adjunct to conventional antimicrobials. Expanded access and compassionate use cases have risen exponentially but have varied widely in approach, methodology, and clinical situations in which phage therapy might be considered. Large gaps in knowledge contribute to heterogeneity in approach and lack of consensus in many important clinical areas. The Antibacterial Resistance Leadership Group (ARLG) has convened a panel of experts in phage therapy, clinical microbiology, infectious diseases, and pharmacology, who worked with regulatory experts and a funding agency to identify …

Atomic Structure Of The Predominant Gii4 Human Norovirus Capsid Reveals Novel Stability And Plasticity, Liya Hu, Wilhelm Salmen, Rong Chen, Yi Zhou, Frederick Neill, James E Crowe, Robert L Atmar, Mary K Estes, B V Venkataram Prasad

Faculty, Staff and Students Publications

Human noroviruses (HuNoVs) cause sporadic and epidemic viral gastroenteritis worldwide. The GII.4 variants are responsible for most HuNoV infections, and GII.4 virus-like particles (VLPs) are being used in vaccine development. The atomic structure of the GII.4 capsid in the native T = 3 state has not been determined. Here we present the GII.4 VLP structure with T = 3 symmetry determined using X-ray crystallography and cryo-EM at 3.0 Å and 3.8 Å resolution, respectively, which reveals unanticipated novel features. A novel aspect in the crystal structure determined without imposing icosahedral symmetry is the remarkable adaptability of the capsid protein VP1 …

Factors Associated With Penicillin Allergy Labels In Electronic Health Records Of Children In 2 Large Us Pediatric Primary Care Networks, Margaret G Taylor, Torsten Joerger, Yun Li, Michael E Scheurer, Michael E Russo, Jeffrey S Gerber, Debra L Palazzi

Faculty, Staff and Students Publications

IMPORTANCE: Penicillin allergy labels influence clinical decision-making, yet most children who are labeled do not have type 1 hypersensitivity allergic reactions and instead have a history of predictable adverse reactions or unspecified illness symptoms while receiving penicillin for viral infections. Studies describing penicillin allergy labeling in the pediatric outpatient setting are lacking.

OBJECTIVE: To describe the epidemiology and factors associated with penicillin allergy labels across 2 large US pediatric primary care networks.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective, longitudinal birth cohort study was conducted in 90 primary care pediatric practices serving a diverse population of children across Houston, Texas, Austin, …

Prognostic And Predictive Biomarkers In Patients With Coronavirus Disease 2019 Treated With Tocilizumab In A Randomized Controlled Trial, Jennifer Tom, Min Bao, Larry Tsai, Aditi Qamra, David Summers, Montserrat Carrasco-Triguero, Jacqueline Mcbride, Carrie M Rosenberger, Celia J F Lin, William Stubbings, Kevin G Blyth, Jordi Carratalà, Bruno François, Thomas Benfield, Derrick Haslem, Paolo Bonfanti, Cor H Van Der Leest, Nidhi Rohatgi, Lothar Wiese, Charles Edouard Luyt, Farrah Kheradmand, Ivan O Rosas, Fang Cai

Faculty, Staff and Students Publications

OBJECTIVES: To explore candidate prognostic and predictive biomarkers identified in retrospective observational studies (interleukin-6, C-reactive protein, lactate dehydrogenase, ferritin, lymphocytes, monocytes, neutrophils, d-dimer, and platelets) in patients with coronavirus disease 2019 pneumonia after treatment with tocilizumab, an anti-interleukin-6 receptor antibody, using data from the COVACTA trial in patients hospitalized with severe coronavirus disease 2019 pneumonia.

DESIGN: Exploratory analysis from a multicenter, randomized, double-blind, placebo-controlled, phase 3 trial.

SETTING: Hospitals in North America and Europe.

PATIENTS: Adults hospitalized with severe coronavirus disease 2019 pneumonia receiving standard care.

INTERVENTION: Randomly assigned 2:1 to IV tocilizumab 8 mg/kg or placebo.

MEASUREMENTS AND MAIN …

Otosyphilis: A Rare Cause Of Reversible Hearing Loss In A Teenage Male, Shan He, Anna H Messner, Gayatri Mirani

Faculty, Staff and Students Publications

A high index of suspicion and a thorough neurotologic examination at the onset of presentation are imperative to generate the diagnosis of otosyphilis. Complete audiologic recovery is rare but possible in approximately 20%-25% of patients after appropriate treatment. We present a case of reversible hearing loss secondary to otosyphilis in a teenage male patient with a new diagnosis of human immunodeficiency virus (HIV). Audiology findings were consistent with mixed hearing loss. Lumbar puncture results were consistent with neurosyphilis. Prompt treatment with a 14-day course of intravenous penicillin led to the complete recovery of hearing. In this case report, the pathophysiology, …

Identifying Causative Microorganisms In Left Ventricular Assist Device Infections As A Guide For Developing Bacteriophage Therapy, Ishan Kamat, Harveen Lamba, Casey Hines-Munson, Samuel Hudson, Kenneth Liao, Kenneth L Muldrew, Sabrina Green, Austen Terwilliger, Heidi B Kaplan, Robert F Ramig, Anthony Maresso, Barbara W Trautner

Faculty, Staff and Students Publications

BACKGROUND: As more left ventricular-assist devices (LVADs) are implanted, multidrug-resistant LVAD infections are becoming increasingly common, partly due to bacterial biofilm production. To aid in developing bacteriophage therapy for LVAD infections, we have identified the most common bacterial pathogens that cause LVAD driveline infections (DLIs) in our heart transplant referral center.

MATERIALS AND METHODS: We studied a retrospective cohort of patients who received LVADs from November 2003 to August 2017 to identify the common causative organisms of LVAD infection. We also studied a prospective cohort of patients diagnosed with DLIs from October 2018 to May 2019 to collect bacterial strains …

Cross-Roads For Meta-Analysis And Network Meta-Analysis Of H Pylori Therapy, David Y Graham, Ruben Hernaez, Theodore Rokkas

Faculty, Staff and Students Publications

Helicobacter pylori infections are responsible for tremendous morbidity and mortality worldwide, leading to efforts to eradicate the organism. However, the effectiveness of antimicrobial therapy has been undermined by the progressive development of antimicrobial resistance. Treatments and treatment guidelines have been based on traditional pairwise meta-analyses of randomized controlled trials. More recently, network meta-analyses have also been utilized in an attempt to provide useful information to the clinician regarding which therapies appear best and which to avoid as the least efficacious. However, both forms of meta-analysis have been undermined by the same problems including the poor quality of the clinical trials …

Novel Role Of Ghrelin Receptor In Gut Dysbiosis And Experimental Colitis In Aging, Ji Yeon Noh, Chia-Shan Wu, Jennifer A A Deluca, Sridevi Devaraj, Arul Jayaraman, Robert C Alaniz, Xiao-Di Tan, Clinton D Allred, Yuxiang Sun

Faculty, Staff and Students Publications

Chronic low-grade inflammation is a hallmark of aging, which is now coined as inflamm-aging. Inflamm-aging contributes to many age-associated diseases such as obesity, type 2 diabetes, cardiovascular disease, and inflammatory bowel disease (IBD). We have shown that gut hormone ghrelin, via its receptor growth hormone secretagogue receptor (GHS-R), regulates energy metabolism and inflammation in aging. Emerging evidence suggests that gut microbiome has a critical role in intestinal immunity of the host. To determine whether microbiome is an integral driving force of GHS-R mediated immune-metabolic homeostasis in aging, we assessed the gut microbiome profiles of young and old GHS-R global knockout …

Repair-Assisted Damage Detection Reveals Biological Disparities In Prostate Cancer Between African Americans And European Americans, Kimiko L Krieger, Jie H Gohlke, Kevin J Lee, Danthasinghe Waduge Badrajee Piyarathna, Patricia D Castro, Jeffrey A Jones, Michael M Ittmann, Natalie R Gassman, Arun Sreekumar

Faculty, Staff and Students Publications

African Americans (AA) are two times more likely to be diagnosed with and succumb to prostate cancer (PCa) compared to European Americans (EA). There is mounting evidence that biological differences in these tumors contribute to disparities in patient outcomes. Our goal was to examine the differences in DNA damage in AA and EA prostate tissues. Tissue microarrays with matched tumor-benign adjacent pairs from 77 AA and EA PCa patients were analyzed for abasic sites, oxidative lesions, crosslinks, and uracil content using the Repair Assisted Damage Detection (RADD) assay. Our analysis revealed that AA PCa, overall, have more DNA damage than …

Fully Resolved Assembly Of Cryptosporidium Parvum, Vipin K Menon, Pablo C Okhuysen, Cynthia L Chappell, Medhat Mahmoud, Medhat Mahmoud, Qingchang Meng, Harsha Doddapaneni, Vanesa Vee, Yi Han, Sejal Salvi, Sravya Bhamidipati, Kavya Kottapalli, George Weissenberger, Hua Shen, Matthew C Ross, Kristi L Hoffman, Sara Javornik Cregeen, Donna M Muzny, Ginger A Metcalf, Richard A Gibbs, Joseph F Petrosino, Fritz J Sedlazeck

Faculty, Staff and Students Publications

BACKGROUND: Cryptosporidium parvum is an apicomplexan parasite commonly found across many host species with a global infection prevalence in human populations of 7.6%. Understanding its diversity and genomic makeup can help in fighting established infections and prohibiting further transmission. The basis of every genomic study is a high-quality reference genome that has continuity and completeness, thus enabling comprehensive comparative studies.

FINDINGS: Here, we provide a highly accurate and complete reference genome of Cryptosporidium parvum. The assembly is based on Oxford Nanopore reads and was improved using Illumina reads for error correction. We also outline how to evaluate and choose from …

Reducing Influenza Virus Transmission: The Potential Value Of Antiviral Treatment, Frederick G Hayden, Jason Asher, Benjamin J Cowling, Aeron C Hurt, Hideyuki Ikematsu, Klaus Kuhlbusch, Annabelle Lemenuel-Diot, Zhanwei Du, Lauren Ancel Meyers, Pedro A Piedra, Takahiro Takazono, Hui-Ling Yen, Arnold S Monto

Faculty, Staff and Students Publications

Prompt antiviral treatment has the potential to reduce influenza virus transmission to close contacts, but rigorous data on the magnitude of treatment effects on transmission are limited. Animal model data indicate that rapid reductions in viral replication after antiviral treatment reduce the risk of transmission. Observational and clinical trial data with oseltamivir and other neuraminidase inhibitors indicate that prompt treatment of household index patients seems to reduce the risk of illness in contacts, although the magnitude of the reported effects has varied widely across studies. In addition, the potential risk of transmitting drug-resistant variants exists with all approved classes of …

Depletion Of The Apical Endosome In Response To Viruses And Bacterial Toxins Provides Cell-Autonomous Host Defense At Mucosal Surfaces, Keiko Maeda, Nicholas C Zachos, Megan H Orzalli, Stefanie S Schmieder, Denis Chang, Katlynn Bugda Gwilt, Michele Doucet, Nicholas W Baetz, Sun Lee, Sue E Crawford, Mary K Estes, Jonathan C Kagan, Jerrold R Turner, Wayne I Lencer

Faculty, Staff and Students Publications

Polarized epithelial cells form an essential barrier against infection at mucosal surfaces. Many pathogens breach this barrier to cause disease, often by co-opting cellular endocytosis mechanisms to enter the cell through the lumenal (apical) cell surface. We recently discovered that the loss of the cell polarity gene PARD6B selectively diminishes apical endosome function. Here, we find that in response to the entry of certain viruses and bacterial toxins into the epithelial cells via the apical membrane, PARD6B and aPKC, two components of the PARD6B-aPKC-Cdc42 apical polarity complex, undergo rapid proteasome-dependent degradation. The perturbation of apical membrane glycosphingolipids by toxin- or …

Sars-Cov-2 Anti-Spike Antibodies After Vaccination In Pediatric Heart Transplantation: A First Report, Joseph A Spinner, Christopher L Julien, Lily Olayinka, William J Dreyer, Claire E Bocchini, Flor M Munoz, Sridevi Devaraj

Faculty, Staff and Students Publications

BACKGROUND: BACKGROUND: There is a paucity of data regarding the antibody response to SARS-CoV-2 vaccination in children after solid organ transplant.

METHODS: We retrospectively reviewed the SARS-CoV-2 Anti-Spike IgG antibodies measured following SARS-CoV-2 vaccination at our pediatric heart transplant (HTx) center.

RESULTS: Among patients (median age 17.1 years) in whom antibody testing was performed (median 118 days post-vaccine completion), a SARS-CoV-2 Anti-Spike IgG antibody was detected in 28 of 40 (70%) post-HTx recipients (median antibody level 10.9 AU/ml). Neutropenia, diabetes mellitus, and previous use of rituximab were associated with absence of a detectable antibody. All 7 post-HTx patients with a …

Fecal Microbiota Transplantation Commonly Failed In Children With Co-Morbidities, Richard Kellermayer, Qinglong Wu, Dorottya Nagy-Szakal, Karen Queliza, Faith D Ihekweazu, Claire E Bocchini, Abria R Magee, Numan Oezguen, Jennifer K Spinler, Emily B Hollister, Robert J Shulman, James Versalovic, Ruth Ann Luna, Tor C Savidge

Faculty, Staff and Students Publications

OBJECTIVES: Fecal microbiota transplantation (FMT) is arguably the most effective treatment for recurrent Clostridioides difficile infection (rCDI). Clinical reports on pediatric FMT have not systematically evaluated microbiome restoration in patients with co-morbidities. Here, we determined whether FMT recipient age and underlying co-morbidity influenced clinical outcomes and microbiome restoration when treated from shared fecal donor sources.

METHODS: Eighteen rCDI patients participating in a single-center, open-label prospective cohort study received fecal preparation from a self-designated (single case) or two universal donors. Twelve age-matched healthy children and four pediatric ulcerative colitis (UC) cases from an independent serial FMT trial, but with a shared …

Maternal Lactobacillus Reuteri Supplementation Shifts The Intestinal Microbiome In Mice And Provides Protection From Experimental Colitis In Female Offspring, Mahesh Krishna, Melinda Engevik, Karen Queliza, Savini Britto, Rajesh Shah, Wenly Ruan, Hongtao Wang, James Versalovic, Richard Kellermayer

Faculty, Staff and Students Publications

The purpose of our experiment was to explore how stochastic (inter-individual variation) gut microbiome composition may link to inflammatory bowel disease (IBD) susceptibility and guide the development of a perinatal preventative probiotic. Dextran sodium sulfate (DSS) was introduced to C57BL/BJ mice to induce acute colitis as a model of IBD. Potentially protective bacteria were identified using a discovery-validation cohort approach toward stochastic DSS susceptibility.

Extensive Identification Of Genes Involved In Congenital And Structural Heart Disorders And Cardiomyopathy, Nadine Spielmann, Gregor Miller, Tudor I Oprea, Chih-Wei Hsu, Gisela Fobo, Goar Frishman, Corinna Montrone, Hamed Haseli Mashhadi, Jeremy Mason, Violeta Munoz Fuentes, Stefanie Leuchtenberger, Andreas Ruepp, Matias Wagner, Dominik S Westphal, Cordula Wolf, Agnes Görlach, Adrián Sanz-Moreno, Yi-Li Cho, Raffaele Teperino, Stefan Brandmaier, Sapna Sharma, Isabella Rikarda Galter, Manuela A Östereicher, Lilly Zapf, Philipp Mayer-Kuckuk, Jan Rozman, Lydia Teboul, Rosie K A Bunton-Stasyshyn, Heather Cater, Michelle Stewart, Skevoulla Christou, Henrik Westerberg, Amelia M Willett, Janine M Wotton, Willson B Roper, Audrey E Christiansen, Christopher S Ward, Jason D Heaney, Corey L Reynolds, Jan Prochazka, Lynette Bower, David Clary, Mohammed Selloum, Ghina Bou About, Olivia Wendling, Hugues Jacobs, Sophie Leblanc, Hamid Meziane, Tania Sorg, Enrique Audain, Arthur Gilly, Nigel W Rayner, Impc Consortium, Genomics England Research Consortium;, Marc-Phillip Hitz, Eleftheria Zeggini, Eckhard Wolf, Radislav Sedlacek, Steven A Murray, Karen L Svenson, Robert E Braun, Jaqueline K White, Lois Kelsey, Xiang Gao, Toshihiko Shiroishi, Ying Xu, Je Kyung Seong, Fabio Mammano, Glauco P Tocchini-Valentini, Arthur L Beaudet, Terrence F Meehan, Helen Parkinson, Damian Smedley, Ann-Marie Mallon, Sara E Wells, Harald Grallert, Wolfgang Wurst, Susan Marschall, Helmut Fuchs, Steve D M Brown, Ann M Flenniken, Lauryl M J Nutter, Colin Mckerlie, Yann Herault, K C Kent Lloyd, Mary E Dickinson, Valerie Gailus-Durner, Martin Hrabe De Angelis

Faculty, Staff and Students Publications

Clinical presentation of congenital heart disease is heterogeneous, making identification of the disease-causing genes and their genetic pathways and mechanisms of action challenging. By using in vivo electrocardiography, transthoracic echocardiography and microcomputed tomography imaging to screen 3,894 single-gene-null mouse lines for structural and functional cardiac abnormalities, here we identify 705 lines with cardiac arrhythmia, myocardial hypertrophy and/or ventricular dilation. Among these 705 genes, 486 have not been previously associated with cardiac dysfunction in humans, and some of them represent variants of unknown relevance (VUR). Mice with mutations in Casz1, Dnajc18, Pde4dip, Rnf38 or Tmem161b genes show developmental cardiac structural abnormalities, …

Metabolism Of A Selective Serotonin And Norepinephrine Reuptake Inhibitor Duloxetine In Liver Microsomes And Mice, Xuan Qin, John M Hakenjos, Kevin R Mackenzie, Mercedes Barzi, Hemantkumar Chavan, Pranavanand Nyshadham, Jin Wang, Sung Yun Jung, Joie Z Guner, Si Chen, Lei Guo, Partha Krishnamurthy, Karl-Dimiter Bissig, Stephen Palmer, Martin M Matzuk, Feng Li

Faculty, Staff and Students Publications

Duloxetine (DLX) is a dual serotonin and norepinephrine reuptake inhibitor, widely used for the treatment of major depressive disorder. Although DLX has shown good efficacy and safety, serious adverse effects (e.g., liver injury) have been reported. The mechanisms associated with DLX-induced toxicity remain elusive. Drug metabolism plays critical roles in drug safety and efficacy. However, the metabolic profile of DLX in mice is not available, although mice serve as commonly used animal models for mechanistic studies of drug-induced adverse effects. Our study revealed 39 DLX metabolites in human/mouse liver microsomes and mice. Of note, 13 metabolites are novel, including five …