Accumulation of immune-suppressive CD4 + T cells in aging - tempering inflammaging at the expense of immunity.

The 'immune risk profile' has been shown to predict mortality in the elderly, highlighting the need to better understand age-related immune dysfunction. While aging leads to many defects affecting all arms of the immune system, this review is focused on the accrual of immuno-suppressive CD4 + T cell populations, including FoxP3 + regulatory T cells, and subsets of IL-10-producing T follicular helper cells. New data suggest that such accumulations constitute feedback mechanisms to temper the ongoing progressive low-grade inflammation that develops with age, the so-called "inflammaging", and by doing so, how they have the potential to promote healthier aging.

It Takes a Village: Optimal Graduate Medical Education Requires a Deliberately Developmental Organization.

Coaching is proposed as a means of improving the learning culture of medicine. By fostering trusting teacher-learner relationships, learners are encouraged to embrace feedback and make the most of failure. This paper posits that a cultural shift is necessary to fully harness the potential of coaching in graduate medical education.

Prospective study of an amino acid-based elemental diet in an eosinophilic gastritis and gastroenteritis nutrition trial.

Background: Eosinophilic gastritis/gastroenteritis (EoG/EoGE) are rare disorders with pathologic gastric and/or small intestinal eosinophilia lacking an approved therapy. An allergic mechanism is postulated but underexplored mechanistically and therapeutically.

Objective: We evaluated the effectiveness of a food allergen-free diet (elemental formula) in controlling gastrointestinal eosinophilia in adult EoG/EoGE.

Microglia-derived TGF-β1 ligand maintains microglia homeostasis via autocrine mechanism and is critical for normal cognitive function in adult mouse brain.

While TGF-β signaling is essential for microglial function, the cellular source of TGF-β ligand and its spatial regulation remains unclear in the adult CNS. Our data support that microglia, not astrocytes or neurons, are the primary producers of TGF-β1 ligands needed for microglial homeostasis. Microglia (MG)- inducible knockout (iKO) leads to the activation of microglia featuring a dyshomeostatic transcriptomic profile that resembles disease-associated microglia (DAMs), injury-associated microglia, and aged microglia, suggesting that microglial self-produced TGF-β1 ligands are important in the adult CNS.

Viral Detection Is Associated With Severe Disease in Children With Suspected Community-Acquired Pneumonia.

Objective: To evaluate the role of virus detection on disease severity among children presenting to the emergency department (ED) with suspected community-acquired pneumonia (CAP).

Methods: We performed a single-center prospective study of children presenting to a pediatric ED with signs and symptoms of a lower respiratory tract infection and who had a chest radiograph performed for suspected CAP. We included patients who had virus testing, with results classified as negative for virus, human rhinovirus, respiratory syncytial virus (RSV), influenza, and other viruses.

Impact of Adjunct Corticosteroid Therapy on Quality of Life for Children With Suspected Pneumonia.

Objective: To determine the association between adjunct corticosteroid therapy and quality of life (QoL) outcomes in children with signs and symptoms of lower respiratory tract infection and clinical suspicion for community-acquired pneumonia (CAP) in the emergency department (ED).

Methods: Secondary analysis from a prospective cohort study of children aged 3 months to 18 years with signs and symptoms of LRTI and a chest radiograph for suspected CAP in the ED, excluding children with recent (within 14 days) systemic corticosteroid use. The primary exposure was receipt of corticosteroids during the ED visit.

Strategies to Counteract Impact of Harmful Bias in Selection of Medical Residents.

Human biases impact medical care in ways that perpetuate health disparities. Research has demonstrated that biases negatively affect patient outcomes and stifle diversity across the physician workforce, further compounding health disparities by worsening patient-physician concordance. Taken as one, the application, interview, recruitment, and selection processes employed by residency programs has been one of the critical junctures where bias has exacerbated inequities among future physicians.

FOXA2 Cooperates with Mutant KRAS to Drive Invasive Mucinous Adenocarcinoma of the Lung.

Unlabelled: The endoderm-lineage transcription factor FOXA2 has been shown to inhibit lung tumorigenesis in in vitro and xenograft studies using lung cancer cell lines. However, FOXA2 expression in primary lung tumors does not correlate with an improved patient survival rate, and the functional role of FOXA2 in primary lung tumors remains elusive. To understand the role of FOXA2 in primary lung tumors in vivo, here, we conditionally induced the expression of FOXA2 along with either of the two major lung cancer oncogenes, EGFRL858R or KRASG12D, in the lung epithelium of transgenic mice.

Incorporation of biomarkers into a prediction model for paediatric radiographic pneumonia.

Objective: The aim of this study was to evaluate biomarkers to predict radiographic pneumonia among children with suspected lower respiratory tract infections (LRTI).

Methods: We performed a single-centre prospective cohort study of children 3 months to 18 years evaluated in the emergency department with signs and symptoms of LRTI. We evaluated the incorporation of four biomarkers (white blood cell count, absolute neutrophil count, C-reactive protein (CRP) and procalcitonin), in isolation and in combination, with a previously developed clinical model (which included focal decreased breath sounds, age and fever duration) for an outcome of radiographic pneumonia using multivariable logistic regression.

Thermoneutral housing shapes hepatic inflammation and damage in mouse models of non-alcoholic fatty liver disease.

Introduction: Inflammation is a common unifying factor in experimental models of non-alcoholic fatty liver disease (NAFLD) progression. Recent evidence suggests that housing temperature-driven alterations in hepatic inflammation correlate with exacerbated hepatic steatosis, development of hepatic fibrosis, and hepatocellular damage in a model of high fat diet-driven NAFLD. However, the congruency of these findings across other, frequently employed, experimental mouse models of NAFLD has not been studied.

Trajectories of Executive Functions After Early Childhood Traumatic Brain Injury: Teacher Ratings in the Initial 81 Months Postinjury.

Objective: To explore teacher-rated trajectories of executive functioning (EF) after early childhood traumatic brain injury (TBI) and to identify injury-related, academic, and family factors associated with growth trajectories using latent class growth analysis.

Participants: A total of 121 children who sustained a TBI or orthopedic injury (OI) between the ages of 3 and 7 years were recruited from 3 tertiary care children's hospitals and a general hospital in Ohio, including 57 with moderate or severe TBI and 64 with OI.

Design: Assessments were completed at baseline (0-3 months postinjury) and an average of 6, 12, 18, and 81 months postinjury.

Intestinal epithelial HDAC3 and MHC class II coordinate microbiota-specific immunity.

Aberrant immune responses to resident microbes promote inflammatory bowel disease and other chronic inflammatory conditions. However, how microbiota-specific immunity is controlled in mucosal tissues remains poorly understood. Here, we found that mice lacking epithelial expression of microbiota-sensitive histone deacetylase 3 (HDAC3) exhibited increased accumulation of commensal-specific CD4+ T cells in the intestine, provoking the hypothesis that epithelial HDAC3 may instruct local microbiota-specific immunity.

Iron status and burden of anemia in children with recessive dystrophic epidermolysis bullosa.

Background And Objectives: To describe the prevalence, severity, and management of anemia in a cohort of children with recessive dystrophic epidermolysis bullosa (RDEB) and to highlight the use of soluble transferrin receptor (sTfR) to diagnose iron deficiency in this chronic inflammatory state.

Methods: We studied a cohort of 114 patients with RDEB followed at a pediatric hospital-based Epidermolysis Bullosa Center from 2010 to 2020; data were prospectively tracked in a comprehensive clinical database that captured all visits, laboratory tests, iron infusions, and transfusions. The primary outcome was occurrence of anemia, which was assessed by age and sex, with and without transfusion support.

Mucosal Microbiota Associated With Eosinophilic Esophagitis and Eosinophilic Gastritis.

Objective: The aim of the study was to determine the mucosal microbiota associated with eosinophilic esophagitis (EoE) and eosinophilic gastritis (EoG) in a geographically diverse cohort of patients compared to controls.

Methods: We conducted a prospective study of individuals with eosinophilic gastrointestinal disease (EGID) in the Consortium of Eosinophilic Gastrointestinal Disease Researchers, including pediatric and adult tertiary care centers. Eligible individuals had clinical data, mucosal biopsies, and stool collected.

Good intentions gone wrong: The B cell block to epithelial repair.

Cellular dynamics that influence mucosal healing are not well understood. In this issue of Immunity, Frede, Czarnewski, Monasterio et al. find that B cells accumulate in the colon following intestinal injury.

Customized Postoperative Therapy Improves Bile Drainage in Biliary Atresia: A Single Center Preliminary Report.

Background: Controversies in management of biliary atresia (BA) after hepatoportoenterostomy (HPE) lead to variable treatment protocols. We implemented standardized medical management after HPE, customizing the use of antibiotics and corticosteroids based on patient-specific factors.

Methods: In this retrospective analysis, 20 consecutive infants underwent HPE for BA and were compared to a historical cohort.

Thrombin-mediated activation of PAR1 enhances doxorubicin-induced cardiac injury in mice.

The chemotherapeutic drug doxorubicin is cardiotoxic and can cause irreversible heart failure. In addition to being cardiotoxic, doxorubicin also induces the activation of coagulation. We determined the effect of thrombin-mediated activation of protease-activated receptor 1 (PAR1) on doxorubicin-induced cardiac injury.

Trial of Training to Reduce Driver Inattention in Teens with ADHD.

Background: Teens with attention deficit-hyperactivity disorder (ADHD) are at increased risk for motor vehicle collisions. A computerized skills-training program to reduce long glances away from the roadway, a contributor to collision risk, may ameliorate driving risks among teens with ADHD.

Methods: We evaluated a computerized skills-training program designed to reduce long glances (lasting ≥2 seconds) away from the roadway in drivers 16 to 19 years of age with ADHD.

A randomized, controlled trial of ZYN002 cannabidiol transdermal gel in children and adolescents with fragile X syndrome (CONNECT-FX).

Background: Fragile X syndrome (FXS) is associated with dysregulated endocannabinoid signaling and may therefore respond to cannabidiol therapy.

Design: CONNECT-FX was a double-blind, randomized phase 3 trial assessing efficacy and safety of ZYN002, transdermal cannabidiol gel, for the treatment of behavioral symptoms in children and adolescents with FXS.

Methods: Patients were randomized to 12 weeks of ZYN002 (250 mg or 500 mg daily [weight-based]) or placebo, as add-on to standard of care.

Antibiotic use and outcomes among children hospitalized with suspected pneumonia.

Background: Although viral etiologies predominate, antibiotics are frequently prescribed for community-acquired pneumonia (CAP).

Objective: We evaluated the association between antibiotic use and outcomes among children hospitalized with suspected CAP.

Designs, Settings And Participants: We performed a secondary analysis of a prospective cohort of children hospitalized with suspected CAP.

Naturally-aged microglia exhibit phagocytic dysfunction accompanied by gene expression changes reflective of underlying neurologic disease.

Age-associated microglial dysfunction contributes to the accumulation of amyloid-β (Aβ) plaques in Alzheimer's disease. Although several studies have shown age-related declines in the phagocytic capacity of myeloid cells, relatively few have examined phagocytosis of normally aged microglia. Furthermore, much of the existing data on aging microglial function have been generated in accelerated genetic models of Alzheimer's disease.

Dietary phytate primes epithelial antibacterial immunity in the intestine.

Although diet has long been associated with susceptibility to infection, the dietary components that regulate host defense remain poorly understood. Here, we demonstrate that consuming rice bran decreases susceptibility to intestinal infection with , a murine pathogen that is similar to enteropathogenic infection in humans. Rice bran naturally contains high levels of the substance phytate.