Adult microglial TGFβ1 is required for microglia homeostasis via an autocrine mechanism to maintain cognitive function in mice.

While TGF-β signaling is essential for microglial function, the cellular source of TGF-β1 ligand and its spatial regulation remains unclear in the adult CNS. Our data supports that microglia but not astrocytes or neurons are the primary producers of TGF-β1 ligands needed for microglial homeostasis. Microglia-Tgfb1 KO leads to the activation of microglia featuring a dyshomeostatic transcriptome that resembles disease-associated, injury-associated, and aged microglia, suggesting microglial self-produced TGF-β1 ligands are important in the adult CNS.

INTRODUCTION: Securing Reproductive Justice After .

When we conceptualized this symposium, was still the law of the land, albeit precariously. We aimed to commemorate its fiftieth anniversary by exploring historical, legal, medical, and related dimensions of access to abortion as well as the challenges ahead to secure reproductive justice. With the leak of the U.

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.

Fetal allotransplant recipients are resistant to graft-versus-host disease.

In utero hematopoietic cell transplantation (IUHCT) is an experimental treatment for congenital hemoglobinopathies, including Sickle cell disease and thalassemias. One of the principal advantages of IUHCT is the predisposition of the developing fetus toward immunologic tolerance. This allows for engraftment across immune barriers without immunosuppression and, potentially, decreased susceptibility to graft-versus-host disease (GVHD).

Schizophrenia-associated differential DNA methylation in brain is distributed across the genome and annotated to MAD1L1, a locus at which DNA methylation and transcription phenotypes share genetic variation with schizophrenia risk.

DNA methylation (DNAm), the addition of a methyl group to a cytosine in DNA, plays an important role in the regulation of gene expression. Single-nucleotide polymorphisms (SNPs) associated with schizophrenia (SZ) by genome-wide association studies (GWAS) often influence local DNAm levels. Thus, DNAm alterations, acting through effects on gene expression, represent one potential mechanism by which SZ-associated SNPs confer risk.

ICU delirium burden predicts functional neurologic outcomes.

Background: We investigated the effect of delirium burden in mechanically ventilated patients, beginning in the ICU and continuing throughout hospitalization, on functional neurologic outcomes up to 2.5 years following critical illness.

Methods: Prospective cohort study of enrolling 178 consecutive mechanically ventilated adult medical and surgical ICU patients between October 2013 and May 2016.

How rare and common risk variation jointly affect liability for autism spectrum disorder.

Background: Genetic studies have implicated rare and common variations in liability for autism spectrum disorder (ASD). Of the discovered risk variants, those rare in the population invariably have large impact on liability, while common variants have small effects. Yet, collectively, common risk variants account for the majority of population-level variability.

Linking childhood trauma and cytokine levels in depressed adolescents.

Background: Evidence supports raised circulating levels of inflammatory mediators, such as interleukin-6 (IL-6) and tumor necrosis factor (TNFα), among clinically depressed adults, although preliminary findings in adolescents are mixed. Independently, meta-analyses identify correlations between childhood trauma and elevated cytokine levels in adulthood. Here, we examine the possible role of individual differences in exposure to childhood trauma in contributing to variability in cytokine levels in depressed adolescents.

Emotion-based decision-making as a predictor of alcohol-related consequences in college students.

Student drinking during the college years can result in many adverse outcomes. Emotion-based decision-making (EBDM), or the use of emotional information to influence future plans and behavior, may lead to increased harmful consequences of alcohol. The current study examined both the number of types and total frequency of alcohol consequences as a function of EBDM.

A pilot randomized controlled trial of smartphone-assisted mindfulness-based intervention with contingency management for smokers with mood disorders.

Unlabelled: Cigarette smoking disproportionately affects individuals with mood disorders, but smoking cessation interventions have modest effects in this population. Home mindfulness practice during abstinence incentivized via contingency management (CM) may help those in affective distress quit smoking.

Method: Adult smokers receiving outpatient psychiatric treatment for mood disorders were randomized to receive a smartphone-assisted mindfulness-based smoking cessation intervention with contingency management (SMI-CM, = 25) or enhanced standard treatment (EST, = 24) with noncontingent rewards.

Neonatal necrotizing enterocolitis-associated DNA methylation signatures in the colon are evident in stool samples of affected individuals.

Neonatal necrotizing enterocolitis (NEC) is a deadly and unpredictable gastrointestinal disease, for which no biomarker exists. We aimed to describe the methylation patterns in stool and colon from infants with NEC. We performed a high-resolution genome-wide epigenomic analysis using solution-phase hybridization and next-generation sequencing of bisulfite-converted DNA.

Transcriptome alterations are enriched for synapse-associated genes in the striatum of subjects with obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a chronic and severe psychiatric disorder for which effective treatment options are limited. Structural and functional neuroimaging studies have consistently implicated the orbitofrontal cortex (OFC) and striatum in the pathophysiology of the disorder. Recent genetic evidence points to involvement of components of the excitatory synapse in the etiology of OCD.

Global hypermethylation of intestinal epithelial cells is a hallmark feature of neonatal surgical necrotizing enterocolitis.

Background: Necrotizing enterocolitis (NEC) remains one of the overall leading causes of death in premature infants, and the pathogenesis is unpredictable and not well characterized. The aim of our study was to determine the molecular phenotype of NEC via transcriptomic and epithelial cell-specific epigenomic analysis, with a specific focus on DNA methylation.

Methods: Using laser capture microdissection, epithelial cell-specific methylation signatures were characterized by whole-genome bisulfite sequencing of ileal and colonic samples at the time of surgery for NEC and after NEC had healed at reanastomosis (n = 40).

Associations between mindfulness and mental health outcomes: A systematic review of ecological momentary assessment research.

Objectives: Psychological science has taken up investigations of the effectiveness of mindfulness-based programs (MBPs) and mechanisms through which people benefit from mindfulness. Reliable and valid psychometric tools are essential components of psychological science, and efforts have been made to produce tools for the accurate measurement of mindfulness as a construct. However, trait measurement methods, which are commonly used, may not adequately assess mindfulness and mental health outcomes in a way that allows for mechanisms to be adequately tested.

More beads, more peristaltic reserve, better outcomes: factors predicting postoperative dysphagia after magnetic sphincter augmentation.

Introduction: Magnetic sphincter augmentation (MSA) offers a minimally invasive anti-reflux alternative to fundoplication for gastroesophageal reflux disease. The most common side effect of MSA is dysphagia, which may require dilation or even device removal. The incidence of dysphagia may be reduced by MSA sizing and preoperative motility studies.

Non-invasive epigenomic molecular phenotyping of the human brain via liquid biopsy of cerebrospinal fluid and next generation sequencing.

Our goal was to undertake a genome-wide epigenomic liquid biopsy of cerebrospinal fluid (CSF) for the comprehensive analysis of cell-free DNA (cfDNA) methylation signatures in the human central nervous system (CNS). Solution-phase hybridization and massively parallel sequencing of bisulfite converted human DNA was employed to compare methylation signatures of cfDNA obtained from CSF with plasma. Recovery of cfDNA from CSF was relatively low (68-840 pg/mL) compared to plasma (2720-8390 pg/mL) and cfDNA fragments from CSF were approximately 20 bp shorter than their plasma-derived counterparts.

High-resolution epigenomic liquid biopsy for noninvasive phenotyping in pregnancy.

Objective: We explored the potential of genome-wide epigenomic liquid biopsy for the comprehensive analysis of cell-free DNA (cfDNA) methylation signatures in maternal plasma in early gestation.

Method: We used solution phase hybridization for targeted region capture of bisulfite-converted DNA obtained from plasma of pregnant women in early gestation and nonpregnant female controls.

Results: Targeted sequencing of ~80.

Longitudinal relationships of cytokines, depression and anhedonia in depressed adolescents.

Background: Depression has been associated with low-grade elevation of plasma cytokines (e.g. interleukin-6, IL-6; tumor necrosis factor alpha, TNFα) in both cross-sectional and longitudinal studies in adults.

Regulatory T cells promote alloengraftment in a model of late-gestation in utero hematopoietic cell transplantation.

In utero hematopoietic cell transplantation (IUHCT) has the potential to cure congenital hematologic disorders including sickle cell disease. However, the window of opportunity for IUHCT closes with the acquisition of T-cell immunity, beginning at approximately 14 weeks gestation, posing significant technical challenges and excluding from treatment fetuses evaluated after the first trimester. Here we report that regulatory T cells can promote alloengraftment and preserve allograft tolerance after the acquisition of T-cell immunity in a mouse model of late-gestation IUHCT.

No pain is gain: A prospective evaluation of strict non-opioid pain control after pediatric appendectomy.

Introduction: Opiates are often prescribed after pediatric operations despite safety concerns and lack of evidence confirming superiority compared to other pain control modalities. In this study, we use daily parental surveys to prospectively evaluate a strict non-opioid pain control strategy after laparoscopic appendectomy.

Methods: After IRB approval, children who underwent laparoscopic appendectomy for nonperforated acute appendicitis were recruited to the study.

Rare variants and biological pathways identified in treatment-refractory depression.

Individuals diagnosed with major depressive disorder not responding to at least two adequate treatments are defined as treatment-refractory major depressive disorder (TR-MDD). Some TR-MDD patients have altered metabolic phenotypes that may be pharmacologically reversed. The characterization of these phenotypes and their underlying etiologies is paramount, particularly their genetic components.

Age dependent association of inbreeding with risk for schizophrenia in Egypt.

Background: Self-reported consanguinity is associated with risk for schizophrenia (SZ) in several inbred populations, but estimates using DNA-based coefficients of inbreeding are unavailable. Further, it is not known whether recessively inherited risk mutations can be identified through homozygosity by descent (HBD) mapping.

Methods: We studied self-reported and DNA-based estimates of inbreeding among Egyptian patients with SZ (n = 421, DSM IV criteria) and adult controls without psychosis (n = 301), who were evaluated using semi-structured diagnostic interview schedules and genotyped using the Illumina Infinium PsychArray.