Digital Commons Network^™

Antibiotic-Driven Intestinal Dysbiosis In Pediatric Short Bowel Syndrome Is Associated With Persistently Altered Microbiome Functions And Gut-Derived Bloodstream Infections, Robert Thänert, Anna Thänert, Jocelyn Ou, Adam Bajinting, Carey-Ann D Burnham, Holly J Engelstad, Maria E Tecos, I Malick Ndao, Carla Hall-Moore, Colleen Rouggly-Nickless, Mike A Carl, Deborah C Rubin, Nicholas O Davidson, Phillip I Tarr, Barbara B Warner, Gautam Dantas, Brad W Warner

Open Access Publications

Surgical removal of the intestine, lifesaving in catastrophic gastrointestinal disorders of infancy, can result in a form of intestinal failure known as short bowel syndrome (SBS). Bloodstream infections (BSIs) are a major challenge in pediatric SBS management. BSIs require frequent antibiotic therapy, with ill-defined consequences for the gut microbiome and childhood health. Here, we combine serial stool collection, shotgun metagenomic sequencing, multivariate statistics and genome-resolved strain-tracking in a cohort of 19 patients with surgically-induced SBS to show that antibiotic-driven intestinal dysbiosis in SBS enriches for persistent intestinal colonization with BSI causative pathogens in SBS. Comparing the gut microbiome composition of …

Paeonol Ameliorates Chronic Itch And Spinal Astrocytic Activation Via Cxcr3 In An Experimental Dry Skin Model In Mice, Wen Wang, Qiaoyun Li, Zhongqiu Zhao, Yutong Liu, Yi Wang, Hui Xiong, Zhinan Mei

Open Access Publications

Paeonol is a bioactive phenol presents mainly in

Discovery Of Novel Reductive Elimination Pathway For 10-Hydroxywarfarin, Dakota L Pouncey, Dustyn A Barnette, Riley W Sinnott, Sarah J Phillips, Noah R Flynn, Howard P Hendrickson, S Joshua Swamidass, Grover P Miller

Open Access Publications

Coumadin (R/S-warfarin) anticoagulant therapy is highly efficacious in preventing the formation of blood clots; however, significant inter-individual variations in response risks over or under dosing resulting in adverse bleeding events or ineffective therapy, respectively. Levels of pharmacologically active forms of the drug and metabolites depend on a diversity of metabolic pathways. Cytochromes P450 play a major role in oxidizing R- and S-warfarin to 6-, 7-, 8-, 10-, and 4'-hydroxywarfarin, and warfarin alcohols form through a minor metabolic pathway involving reduction at the C11 position. We hypothesized that due to structural similarities with warfarin, hydroxywarfarins undergo reduction, possibly impacting their pharmacological …

Perceptions Of Clinical Dental Students Toward Online Education During The Covid-19 Crisis: An Egyptian Multicenter Cross-Sectional Survey, Reham Hassan, Ayman R Khalifa, Tarek Elsewify, Mohamed G Hassan

Open Access Publications

No abstract provided.

Superior Verbal Memory Outcome After Stereotactic Laser Amygdalohippocampotomy, Daniel L Drane, Jon T Willie, Et Al

Open Access Publications

No abstract provided.

Care Gaps And Recommendations In Vestibular Migraine: An Expert Panel Summit, Monica P Mallampalli, Joel A Goebel, Et Al

Open Access Publications

Vestibular migraine (VM) is an increasingly recognized pathology yet remains as an underdiagnosed cause of vestibular disorders. While current diagnostic criteria are codified in the 2012 Barany Society document and included in the third edition of the international classification of headache disorders, the pathophysiology of this disorder is still elusive. The Association for Migraine Disorders hosted a multidisciplinary, international expert workshop in October 2020 and identified seven current care gaps that the scientific community needs to resolve, including a better understanding of the range of symptoms and phenotypes of VM, the lack of a diagnostic marker, a better understanding of …

Association Of Inventory To Measure And Assess Image Disturbance - Head And Neck Scores With Clinically Meaningful Body Image-Related Distress Among Head And Neck Cancer Survivors, David Macias, Patrik Pipkorn, Et Al

Open Access Publications

No abstract provided.

Factors Influencing Implementation Of Blood Transfusion Recommendations In Pediatric Critical Care Units, Katherine M Steffen, Philip C Spinella, Laura M Holdsworth, Mackenzie A Ford, Grace M Lee, Steven M Asch, Enola K Proctor, Allan Doctor

Open Access Publications

No abstract provided.

Academic Performance Of Children With Sickle Cell Disease In The United States: A Meta-Analysis, Andrew M Heitzer, Latacha Hamilton, Claire Stafford, Jeffrey Gossett, Lara Ouellette, Ana Trpchevska, Allison A King, Guolian Kang, Jane S Hankins

Open Access Publications

No abstract provided.

Encephalitic Arboviruses Of Africa: Emergence, Clinical Presentation And Neuropathogenesis, Robyn S Klein

Open Access Publications

Many mosquito-borne viruses (arboviruses) are endemic in Africa, contributing to systemic and neurological infections in various geographical locations on the continent. While most arboviral infections do not lead to neuroinvasive diseases of the central nervous system, neurologic diseases caused by arboviruses include flaccid paralysis, meningitis, encephalitis, myelitis, encephalomyelitis, neuritis, and post-infectious autoimmune or memory disorders. Here we review endemic members of the

Rubella Virus Infected Macrophages And Neutrophils Define Patterns Of Granulomatous Inflammation In Inborn And Acquired Errors Of Immunity, Ludmila Perelygina, Amy Musiek, Et Al

Open Access Publications

Rubella virus (RuV) has recently been found in association with granulomatous inflammation of the skin and several internal organs in patients with inborn errors of immunity (IEI). The cellular tropism and molecular mechanisms of RuV persistence and pathogenesis in select immunocompromised hosts are not clear. We provide clinical, immunological, virological, and histological data on a cohort of 28 patients with a broad spectrum of IEI and RuV-associated granulomas in skin and nine extracutaneous tissues to further delineate this relationship. Combined immunodeficiency was the most frequent diagnosis (67.8%) among patients. Patients with previously undocumented conditions, i.e., humoral immunodeficiencies, a secondary immunodeficiency, …

Global Parity: Study Design For A Multi-Centered, International Point Prevalence Study To Estimate The Burden Of Pediatric Acute Critical Illness In Resource-Limited Settings, Qalab Abbas, Kenneth E Remy, Et Al

Open Access Publications

Background: The burden of pediatric critical illness and resource utilization by children with critical illness in resource limited settings (RLS) are largely unknown. Without specific data that captures key aspects of critical illness, disease presentation, and resource utilization for pediatric populations in RLS, development of a contextual framework for appropriate, evidence-based interventions to guide allocation of limited but available resources is challenging. We present this methods paper which describes our efforts to determine the prevalence, etiology, hospital outcomes, and resource utilization associated with pediatric acute, critical illness in RLS globally.

Methods: We will conduct a prospective, observational, multicenter, multinational point …

A Real-World Observation Of Antipsychotic Effects On Brain Volumes And Intrinsic Brain Activity In Schizophrenia, Yifan Chen, Fay Y Womer, Ruiqi Feng, Xizhe Zhang, Yanbo Zhang, Jia Duan, Miao Chang, Zhiyang Yin, Xiaowei Jiang, Shengnan Wei, Yange Wei, Yanqing Tang, Fei Wang

Open Access Publications

Background: The confounding effects of antipsychotics that led to the inconsistencies of neuroimaging findings have long been the barriers to understanding the pathophysiology of schizophrenia (SZ). Although it is widely accepted that antipsychotics can alleviate psychotic symptoms during the early most acute phase, the longer-term effects of antipsychotics on the brain have been unclear. This study aims to look at the susceptibility of different imaging measures to longer-term medicated status through real-world observation.

Methods: We compared gray matter volume (GMV) with amplitude of low-frequency fluctuations (ALFFs) in 89 medicated-schizophrenia (med-SZ), 81 unmedicated-schizophrenia (unmed-SZ), and 235 healthy controls (HC), and the …

Seizures In Fragile X Syndrome: Associations And Longitudinal Analysis Of A Large Clinic-Based Cohort, Elizabeth Berry-Kravis, Robyn A Filipink, Richard E Frye, Sailaja Golla, Stephanie M Morris, Howard Andrews, Tse-Hwei Choo, Walter E Kaufmann, Et Al

Open Access Publications

Fragile X syndrome (FXS), the most common inherited cause of intellectual disability, learning disability, and autism spectrum disorder, is associated with an increased prevalence of certain medical conditions including seizures. The goal of this study was to better understand seizures in individuals with FXS using the Fragile X Online Registry with Accessible Research Database, a multisite observational study initiated in 2012 involving FXS clinics in the Fragile X Clinic and Research Consortium. Seizure data were available for 1,607 participants, mostly male (77%) and white (74.5%). The overall prevalence of at least one seizure was 12%, with this rate being significantly …

Development And Testing Of A Spray-Dried Tuberculosis Vaccine Candidate In A Mouse Model, Mellissa Gomez, Mushtaq Ahmed, Shibali Das, Leah Mellett, Rosemary Swanson, Ananya Gupta, Shabaana A Khader, Et Al

Open Access Publications

Converting a vaccine into a thermostable dry powder is advantageous as it reduces the resource burden linked with the cold chain and provides flexibility in dosage and administration through different routes. Such a dry powder presentation may be especially useful in the development of a vaccine towards the respiratory infectious disease tuberculosis (TB). This study assesses the immunogenicity and protective efficacy of spray-dried ID93+GLA-SE, a promising TB vaccine candidate, against

Druggable Lipid Binding Sites In Pentameric Ligand-Gated Ion Channels And Transient Receptor Potential Channels, Wayland W L Cheng, Mark J Arcario, John T Petroff

Open Access Publications

Lipids modulate the function of many ion channels, possibly through direct lipid-protein interactions. The recent outpouring of ion channel structures by cryo-EM has revealed many lipid binding sites. Whether these sites mediate lipid modulation of ion channel function is not firmly established in most cases. However, it is intriguing that many of these lipid binding sites are also known sites for other allosteric modulators or drugs, supporting the notion that lipids act as endogenous allosteric modulators through these sites. Here, we review such lipid-drug binding sites, focusing on pentameric ligand-gated ion channels and transient receptor potential channels. Notable examples include …

Understanding Drivers Of Coronavirus Disease 2019 (Covid-19) Racial Disparities: A Population-Level Analysis Of Covid-19 Testing Among Black And White Populations, Aaloke Mody, Kristin Pfeifauf, Cory Bradley, Branson Fox, Matifadza G. Hlatshwayo, Will Ross, Vetta Sanders-Thompson, Karen Joynt Maddox, Mat Reidhead, Mario Schootman, William G. Powderly, Elvin H. Geng

Open Access Publications

BACKGROUND: Disparities in coronavirus disease 2019 (COVID-19) testing-the pandemic's most critical but limited resource-may be an important but modifiable driver of COVID-19 inequities.

METHODS: We analyzed data from the Missouri State Department of Health and Senior Services on all COVID-19 tests conducted in the St Louis and Kansas City regions. We adapted a well-established tool for measuring inequity-the Lorenz curve-to compare COVID-19 testing rates per diagnosed case among Black and White populations.

RESULTS: Between 14/3/2020 and 15/9/2020, 606 725 and 328 204 COVID-19 tests were conducted in the St Louis and Kansas City regions, respectively. Over time, Black individuals consistently …

Extracorporeal Life Support For Cardiogenic Shock With Either A Percutaneous Ventricular Assist Device Or An Intra-Aortic Balloon Pump, Tomohiro Nakajima, Yuki Tanaka, Irene Fischer, Kunal Kotkar, Ralph J Damiano Jr, Marc R Moon, Muhammad F Masood, Akinobu Itoh

Open Access Publications

Extracorporeal life support (ECLS) can result in complications due to increased left ventricular (LV) afterload. The percutaneous ventricular assist device (PVAD) and intra-aortic balloon pump (IABP) are both considered to be effective means of LV unloading. This study describes the efficacy of LV unloading and related outcomes with PVAD or IABP during ECLS. From January 2010 to April 2018, all cardiogenic shock patients who underwent ECLS plus simultaneous PVAD or IABP were analyzed. Forty-nine patients received ECLS + PVAD, while 91 received ECLS + IABP. At 48 hours, mean pulmonary artery pressure was significantly reduced in both groups [34 mm …

A Clinical Epidemiology And Molecular Attribution Evaluation Of Adenoviruses In Pediatric Acute Gastroenteritis: A Case-Control Study, Kanti Pabbaraju, Raymond Tellier, Xiao-Li Pang, Jianling Xie, Bonita E Lee, Linda Chui, Ran Zhuo, Otto G Vanderkooi, Samina Ali, Phillip I Tarr, Anna Funk, Stephen B Freedman

Open Access Publications

The objective of this study was to characterize the etiological role of human adenovirus (HAdV) serotypes in pediatric gastroenteritis. Using a case-control design, we compared the frequencies of HAdV serotypes between children with ≥3 episodes of vomiting or diarrhea within 24 h and <7 days of symptoms (i.e., cases) and those with no infectious symptoms (i.e., controls). Stool samples and/or rectal swabs underwent molecular serotyping with cycle threshold (Ct) values provided by multiplex real-time reverse transcription-PCR testing. Cases without respiratory symptoms were analyzed to calculate the proportion of disease attributed to individual HAdV serotypes (i.e., attributable fraction). Between December 2014 and August 2018, adenoviruses were detected in 18.8% (629/3,347) of cases and 7.2% (97/1,355) of controls, a difference of 11.6% (95% confidence interval [CI], 9.6%, 13.5%). In 96% (95% CI, 92 to 98%) of HAdV F40/41 detections, the symptoms could be attributed to the identified serotype; when serotypes C1, C2, C5, and C6 were detected, they were responsible for symptoms in 52% (95% CI, 12 to 73%). Ct values were lower among cases than among controls (

Comparison Of Upper Respiratory Viral Load Distributions In Asymptomatic And Symptomatic Children Diagnosed With Sars-Cov-2 Infection In Pediatric Hospital Testing Programs, Larry K Kociolek, Bijal A Parikh, Ariel Hernandez-Leyva, Et Al

Open Access Publications

The distribution of upper respiratory viral loads (VL) in asymptomatic children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. We assessed PCR cycle threshold (Ct) values and estimated VL in infected asymptomatic children diagnosed in nine pediatric hospital testing programs. Records for asymptomatic and symptomatic patients with positive clinical SARS-CoV-2 tests were reviewed. Ct values were (i) adjusted by centering each value around the institutional median Ct value from symptomatic children tested with that assay and (ii) converted to estimated VL (numbers of copies per milliliter) using internal or manufacturer data. Adjusted Ct values and estimated VL …

Discoidin Domain Receptor 1 Activation Links Extracellular Matrix To Podocyte Lipotoxicity In Alport Syndrome, Jin-Ju Kim, Jeffrey H Miner, Et Al

Open Access Publications

BACKGROUND: Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase that is activated by collagens that is involved in the pathogenesis of fibrotic disorders. Interestingly, de novo production of the collagen type I (Col I) has been observed in Col4a3 knockout mice, a mouse model of Alport Syndrome (AS mice). Deletion of the DDR1 in AS mice was shown to improve survival and renal function. However, the mechanisms driving DDR1-dependent fibrosis remain largely unknown.

METHODS: Podocyte pDDR1 levels, Collagen and cluster of differentiation 36 (CD36) expression was analyzed by Real-time PCR and Western blot. Lipid droplet accumulation and content …

A Study Protocol For A Multicentre, Prospective, Before-And-After Trial Evaluating The Feasibility Of Implementing Targeted Sedation After Initiation Of Mechanical Ventilation In The Emergency Department (The Ed-Sed Pilot Trial), Brian M Fuller, Brian W Roberts, Nicholas M Mohr, Ryan D Pappal, Robert J Stephens, Yan Yan, Chris Carpenter, Marin H Kollef, Michael Simon Avidan

Open Access Publications

INTRODUCTION: Sedation is a cornerstone therapy in the management of patients receiving mechanical ventilation and is highly influential on outcome. Early sedation depth appears especially influential, as early deep sedation is associated with worse outcome when compared with light sedation. Our research group has shown that patients receiving mechanical ventilation in the emergency department (ED) are exposed to deep sedation commonly, and ED sedation depth is impactful on intensive care unit (ICU) care and clinical outcomes. While extensive investigation has occurred for patients in the ICU, comparatively little data exist from the ED. Given the influence that ED sedation seems …

Self-Administered Questionnaire To Screen For Polycystic Ovarian Syndrome, Bronwyn S Bedrick, Ashley M Eskew, Jorge E Chavarro, Emily S Jungheim

Open Access Publications

No abstract provided.

Coronary Computed Tomography Angiography Compared With Single Photon Emission Computed Tomography Myocardial Perfusion Imaging As A Guide To Optimal Medical Therapy In Patients Presenting With Stable Angina: The Rescue Trial, Arthur E Stillman, Constantine Gatsonis, Joao A C Lima, Tao Liu, Bradley S Snyder, Jean Cormack, Vinay Malholtra, Mitchell D Schnall, James E Udelson, Udo Hoffmann, Pamela K Woodard, Rescue Investigators

Open Access Publications

Background The RESCUE (Randomized Evaluation of Patients with Stable Angina Comparing Utilization of Noninvasive Examinations) trial was a randomized, controlled, multicenter, comparative efficacy outcomes trial designed to assess whether initial testing with coronary computed tomographic angiography (CCTA) is noninferior to single photon emission computed tomography (SPECT) myocardial perfusion imaging in directing patients with stable angina to optimal medical therapy alone or optimal medical therapy with revascularization. Methods and Results The end point was first major adverse cardiovascular event (MACE) (cardiac death or myocardial infarction), or revascularization. Noninferiority margin for CCTA was set a priori as a hazard ratio (HR) of …

Associations Between Atrial Cardiopathy And Cerebral Amyloid: The Aric-Pet Study, Michelle C Johansen, Thomas H Mosley, David S Knopman, Dean F Wong, Chiadi Ndumele, Amil M Shah, Scott D Solomon, Rebecca F Gottesman

Open Access Publications

Background Atrial fibrillation (AF) is a risk factor for cognitive decline, possibly from silent brain infarction. Left atrial changes in structure or function (atrial cardiopathy) can lead to AF but may impact cognition independently. It is unknown if AF or atrial cardiopathy also acts on Alzheimer disease-specific mechanisms, such as deposition of β-amyloid. Methods and Results A total of 316 dementia-free participants from the ARIC (Atherosclerosis Risk in Communities) study underwent florbetapir positron emission tomography, electrocardiography, and 2-dimensional echocardiography. Atrial cardiopathy was defined as ≥1: (1) left atrial volume index >34 mL/m

Comparative Evaluation Of Clinical Manifestations And Risk Of Death In Patients Admitted To Hospital With Covid-19 And Seasonal Influenza: Cohort Study, Yan Xie, Benjamin Bowe, Geetha Maddukuri, Ziyad Al-Aly

Open Access Publications

No abstract provided.

Protocol For The Prognosticating Delirium Recovery Outcomes Using Wakefulness And Sleep Electroencephalography (P-Drows-E) Study: A Prospective Observational Study Of Delirium In Elderly Cardiac Surgical Patients, S Kendall Smith, Thomas Nguyen, Alyssa K Labonte, Mohammadmehdi Kafashan, Orlandrea Hyche, Christian S Guay, Elizabeth Wilson, Courtney W Chan, Anhthi Luong, L Brian Hickman, Bradley A Fritz, Daniel Emmert, Thomas J Graetz, Spencer J Melby, Brendan P Lucey, Yo-El S Ju, Troy S Wildes, Michael S Avidan, Ben J A Palanca

Open Access Publications

INTRODUCTION: Delirium is a potentially preventable disorder characterised by acute disturbances in attention and cognition with fluctuating severity. Postoperative delirium is associated with prolonged intensive care unit and hospital stay, cognitive decline and mortality. The development of biomarkers for tracking delirium could potentially aid in the early detection, mitigation and assessment of response to interventions. Because sleep disruption has been posited as a contributor to the development of this syndrome, expression of abnormal electroencephalography (EEG) patterns during sleep and wakefulness may be informative. Here we hypothesise that abnormal EEG patterns of sleep and wakefulness may serve as predictive and diagnostic …

Yap And Taz Maintain Prox1 Expression In The Developing Lymphatic And Lymphovenous Valves In Response To Vegf-C Signaling, Boksik Cha, Yen-Chun Ho, Xin Geng, Md Riaj Mahamud, Lijuan Chen, Yeunhee Kim, Dongwon Choi, Tae Hoon Kim, Gwendalyn J Randolph, Xinwei Cao, Hong Chen, R Sathish Srinivasan

Open Access Publications

Lymphatic vasculature is an integral part of digestive, immune and circulatory systems. The homeobox transcription factor PROX1 is necessary for the development of lymphatic vessels, lymphatic valves (LVs) and lymphovenous valves (LVVs). We and others previously reported a feedback loop between PROX1 and vascular endothelial growth factor-C (VEGF-C) signaling. PROX1 promotes the expression of the VEGF-C receptor VEGFR3 in lymphatic endothelial cells (LECs). In turn, VEGF-C signaling maintains PROX1 expression in LECs. However, the mechanisms of PROX1/VEGF-C feedback loop remain poorly understood. Whether VEGF-C signaling is necessary for LV and LVV development is also unknown. Here, we report for the …

Single-Arm Prospective Interventional Study Assessing Feasibility Of Using Gallium-68 Ventilation And Perfusion Pet/Ct To Avoid Functional Lung In Patients With Stage Iii Non-Small Cell Lung Cancer, Nicholas Bucknell, Amir Iravani, Et Al

Open Access Publications

BACKGROUND: In the curative-intent treatment of locally advanced lung cancer, significant morbidity and mortality can result from thoracic radiation therapy. Symptomatic radiation pneumonitis occurs in one in three patients and can lead to radiation-induced fibrosis. Local failure occurs in one in three patients due to the lungs being a dose-limiting organ, conventionally restricting tumour doses to around 60 Gy. Functional lung imaging using positron emission tomography (PET)/CT provides a geographic map of regional lung function and preclinical studies suggest this enables personalised lung radiotherapy. This map of lung function can be integrated into Volumetric Modulated Arc Therapy (VMAT) radiotherapy planning …

Macrophage-Derived Vascular Endothelial Growth Factor-A Is Integral To Neuromuscular Junction Reinnervation After Nerve Injury, Chuieng-Yi Lu, Katherine B. Santosa, Albina Jablonka-Shariff, Bianca Vannucci, Anja Fuchs, Isaiah Turnbull, Deng Pan, Matthew D. Wood, Alison K. Snyder-Warwick

Open Access Publications

Functional recovery in the end target muscle is a determinant of outcome after peripheral nerve injury. The neuromuscular junction (NMJ) provides the interface between nerve and muscle and includes non-myelinating terminal Schwann cells (tSCs). After nerve injury, tSCs extend cytoplasmic processes between NMJs to guide axon growth and NMJ reinnervation. The mechanisms related to NMJ reinnervation are not known. We used multiple mouse models to investigate the mechanisms of NMJ reinnervation in both sexes, specifically whether macrophage-derived vascular endothelial growth factor-A (Vegf-A) is crucial to establishing NMJ reinnervation at the end target muscle. Both macrophage number and Vegf-A expression increased …