Histone Deacetylase Inhibition by Gut Microbe-Generated Short-Chain Fatty Acids Entrains Intestinal Epithelial Circadian Rhythms.

Background & Aims: The circadian clock orchestrates ∼24-hour oscillations of gastrointestinal epithelial structure and function that drive diurnal rhythms in gut microbiota. Here, we use experimental and computational approaches in intestinal organoids to reveal reciprocal effects of gut microbial metabolites on epithelial timekeeping by an epigenetic mechanism.

Methods: We cultured enteroids in media supplemented with sterile supernatants from the altered Schaedler Flora (ASF), a defined murine microbiota.

Intrathecal Fentanyl With a Myofascial Plane Block in Open Lumbar Surgeries: A Case Series.

Background: Acute postoperative pain control after lumbar surgery is imperative to minimizing long-term narcotic use and associated adverse sequela. The safety of intrathecal morphine for postoperative pain management in spine surgery has been investigated; however, to date, no studies have investigated the safety of intrathecal fentanyl with a myofascial plane (MP) block in lumbar procedures.

Objective: To assess the safety profile of intrathecal fentanyl with a MP block administered during lumbar surgery and the subsequent utilization of postoperative intravenous opioids.

Prevalence and Risk Factors for Kidney Disease and Elevated BP in 2-Year-Old Children Born Extremely Premature.

Background And Objectives: Extremely low gestational age neonates born <28 weeks gestation are at risk for chronic disease. We sought to describe the prevalence of kidney outcomes by gestational age and determine risk factors for their development.

Design, Setting, Participants, & Measurements: The Recombinant Erythropoietin for Protection of Infant Renal Disease (REPAIReD) study examined kidney outcomes of extremely low gestational age neonates enrolled in the Preterm Epo NeuroProtection Trial (PENUT) study.

Digital Inhalers and Remote Patient Monitoring for Asthma.

Digital inhaler systems, remote patient monitoring, and remote therapeutic monitoring offer great promise as diagnostic tools and therapeutic interventions to improve adherence and inhaler technique for patients with difficult-to-control asthma. In turn, improvements in adherence and inhaler technique may translate into decreasing the need for high side effect treatments such as oral corticosteroids and costly therapies including biologics. Although more clinical trials are needed, studies that use digital inhaler systems to collect objective real-time data on medication-taking behavior via electronic medication monitors and feed this data back to patients on their mobile asthma app, and to health care professionals on the clinician dashboard to counsel patients, show positive outcomes.

Hemostasis and tumor immunity.

Significant data have accumulated demonstrating a reciprocal relationship between cancer and the hemostatic system whereby cancer promotes life-threatening hemostatic system dysregulation (e.g., thromboembolism, consumptive coagulopathy), and hemostatic system components directly contribute to cancer pathogenesis.

Gender Disparities in Academic Productivity and Promotion Among Endocrine Surgery Faculty.

Introduction: Academic rank and metrics such as total publications (pubs) and H-index are indicators to measure academic achievement. This study aims to determine whether there are gender differences in academic productivity or faculty appointments among endocrine surgeons in the United States.

Methods: A database was generated from the American Association of Endocrine Surgeons (AAES) website.

Gestational Age at Delivery and Neonatal Outcomes among Infants with Gastroschisis in the Children's Hospitals Neonatal Consortium (CHNC).

Objective: The effect of gestational age (GA) on gastroschisis outcomes is unclear and delivery timing varies in practice. We aimed to correlate clinical outcomes of infants with gastroschisis and GA at delivery in the Children's Hospitals Neonatal Consortium (CHNC).

Study Design: This was a retrospective multicenter cohort study of infants with gastroschisis admitted to CHNC neonatal intensive care units (NICUs) from 2010 to 2016.

Differential CXCR4 expression on hematopoietic progenitor cells versus stem cells directs homing and engraftment.

Gene therapy involves a substantial loss of hematopoietic stem and progenitor cells (HSPC) during processing and homing. Intra-BM (i.b.

Single-cell RNA-Seq of human esophageal epithelium in homeostasis and allergic inflammation.

Inflammation of the esophageal epithelium is a hallmark of eosinophilic esophagitis (EoE), an emerging chronic allergic disease. Herein, we probed human esophageal epithelial cells at single-cell resolution during homeostasis and EoE. During allergic inflammation, the epithelial differentiation program was blocked, leading to loss of KRT6hi differentiated populations and expansion of TOP2hi proliferating, DSPhi transitioning, and SERPINB3hi transitioning populations; however, there was stability of the stem cell-enriched PDPNhi basal epithelial compartment.

Management of Acute Kidney Injury in Extremely Low Birth Weight Infants.

Acute kidney injury (AKI) is a common problem in the neonatal intensive care unit (NICU). Neonates born at <1,000 g (extremely low birth weight, ELBW) are at an increased risk of secondary associated comorbidities such as intrauterine growth restriction, prematurity, volume restriction, ischaemic injury, among others. Studies estimate up to 50% ELBW infants experience at least one episode of AKI during their NICU stay.

Mucosal healing with methotrexate versus azathioprine treatment in pediatric Crohn's disease as reflected by fecal calprotectin.

Background/objectives: The current treatment goal for inflammatory bowel disease (IBD) is achievement of mucosal healing (MH). While established with biologic or azathioprine (AZA) therapies, the data on MH with methotrexate (MTX( treatment is scarce. We aimed to compare MH rate as reflected by FC in children with Crohn's disease (CD) treated with either MTX or thiopurines monotherapy.

Eicosatetraynoic Acid and Butyrate Regulate Human Intestinal Organoid Mitochondrial and Extracellular Matrix Pathways Implicated in Crohn's Disease Strictures.

Background: Perturbagen analysis of Crohn's disease (CD) ileal gene expression data identified small molecules including eicosatetraynoic acid (ETYA), which may exert an antifibrotic effect. We developed a patient-specific human intestinal organoid (HIO) model system to test small molecule regulation of mitochondrial and wound-healing functions implicated in stricturing behavior.

Methods: HIOs were made from CD induced pluripotent stem cells with and without a loss-of-function haplotype in the DUOX2 gene implicated in ileal homeostasis and characterized under basal conditions and following exposure to butyrate and ETYA using RNA sequencing, flow cytometry, and immunofluorescent and polarized light microscopy.

A randomized double-blind, placebo-controlled pilot trial of mirtazapine for anxiety in children and adolescents with autism spectrum disorder.

This study was a 10-week double-blind, placebo-controlled pilot trial of mirtazapine for anxiety in youth with autism spectrum disorder (ASD). Participants were ages 5 to 17 years with ASD and clinically significant anxiety (Pediatric Anxiety Rating Scale [PARS] score ≥10). Thirty participants were randomized to mirtazapine (7.

Getting the Most out of Consent: Patient-Centered Consent for an Acute Stroke Trial.

Informed consent for clinical trials in acute stroke is characterized by challenges related to urgency, cognitive impairment, and geographical separation. Context-appropriate approaches are needed for this setting. We conducted a mixed-methods project involving focus groups and interviews as well as collaboration with a patient advisory panel and a central institutional review board (CIRB) to design and implement a patient-driven consent process for a multicenter trial incorporating adaptive randomization.

Meta-analysis defines predominant shared microbial responses in various diseases and a specific inflammatory bowel disease signal.

Background: Gut microbial alteration is implicated in inflammatory bowel disease but is noted in other diseases. Systematic comparison to define similarities and specificities is hampered since most studies focus on a single disease.

Results: We develop a pipeline to compare between disease cohorts starting from the raw V4 16S amplicon sequence variants.

Effect of combining aspirin and rivaroxaban on atherosclerosis in mice.

Background And Aims: The platelet inhibitor aspirin reduces inflammation and atherosclerosis in both apolipoprotein E deficient (apoE) mice and low-density lipoprotein receptor deficient (Ldlr) mice. Similarly, the factor Xa inhibitor rivaroxaban reduces atherosclerosis in both apoE and Ldlr mice. We tested the hypothesis that the combination of aspirin and rivaroxaban reduces atherosclerosis in mice to a greater extent than either agent alone.

Clinical Characteristics and Etiology of Community-acquired Pneumonia in US Children, 2015-2018.

Background: Pneumonia has a major impact on childhood health and health care costs. This study was designed to obtain contemporary information on the clinical characteristics and etiology of community-acquired pneumonia (CAP) in children from both inpatient and outpatient settings in the USA.

Methods: We conducted a prospective, multicenter, observational study of CAP among previously healthy children 2 months to 18 years of age in 6 children's hospitals in Ohio from 2015 to 2018.

A track record of diversity: Medical schools ranked by successful black applicants to orthopaedic residencies.

Background: Orthopaedic surgery is the least diverse surgical subspecialty in medicine. However, to date, there is no literature that shows which medical schools have successfully contributed to improving orthopaedic surgeon diversity.

Objective: The purpose of this study is to identify the top U.

Effector memory CD4 T cells induce damaging innate inflammation and autoimmune pathology by engaging CD40 and TNFR on myeloid cells.

Cytokine storm and sterile inflammation are common features of T cell-mediated autoimmune diseases and T cell-targeted cancer immunotherapies. Although blocking individual cytokines can mitigate some pathology, the upstream mechanisms governing overabundant innate inflammatory cytokine production remain unknown. Here, we have identified a critical signaling node that is engaged by effector memory T cells (T) to mobilize a broad proinflammatory program in the innate immune system.

Telemedicine Lessons Learned During the COVID-19 Pandemic.

Purpose Of Review: Prior to the SARS-CoV-2 novel coronavirus (COVID-19) pandemic, access and utilization of telemedicine in the USA was negligeable, with very little interest from both the public and healthcare sectors. Since that time, telemedicine technology and services have undergone explosive growth and investment and are poised to change the way healthcare is delivered now and in the future. But has telemedicine truly changed the way healthcare is delivered or is it merely a temporary fix for a temporary pandemic?

Recent Findings: This global public health emergency has exposed vulnerabilities in our healthcare system and telemedicine has proven to be an effective tool to help increase access to care and improve affordability for patients across all racial, economic, geographic, and technological demographics.

Gut microbiome development in early childhood is affected by day care attendance.

The human gut microbiome develops during the first years of life, followed by a relatively stable adult microbiome. Day care attendance is a drastic change that exposes children to a large group of peers in a diverse environment for prolonged periods, at this critical time of microbial development, and therefore has the potential to affect microbial composition. We characterize the effect of day care on the gut microbial development throughout a single school year in 61 children from 4 different day care facilities, and in additional 24 age-matched home care children (n = 268 samples, median age of entering the study was 12 months).

Bcl-2 Is Necessary to Counteract Bim and Promote Survival of TCRαβCD8αα Intraepithelial Lymphocyte Precursors in the Thymus.

The precursors of TCRαβCD8αα intraepithelial lymphocytes (IEL) arise in the thymus through a complex process of agonist selection. We and others have shown that the proapoptotic protein, Bim, is critical to limit the number of thymic IEL precursors (IELp), as loss of Bim at the CD4CD8 double-positive stage of development drastically increases IELp. The factors determining this cell death versus survival decision remain largely unknown.

Structural lung disease in preschool children with cystic fibrosis: An 18 month natural history study.

Background: This study was performed to describe the natural history of CF lung disease in young children over an 18 month period to assess the use of CT scanning as an outcome measure for intervention trials.

Methods: Chest CT scans were obtained at baseline and after 18 months in 42 two- to six-year-old children with CF. CT scans were scored by 2 experienced radiologists for the presence and severity of bronchiectasis, mucous plugging, and air trapping.