GJA1 (connexin43) is a key regulator of Alzheimer's disease pathogenesis.

GJA1 (connexin43) has been predicted as the top key driver of an astrocyte enriched subnetwork associated with Alzheimer's disease (AD). In this study, we comprehensively examined GJA1 expression across 29 transcriptomic and proteomic datasets from post-mortem AD and normal control brains. We demonstrated that GJA1 was strongly associated with AD amyloid and tau pathologies and cognitive functions.

Genome-wide de novo risk score implicates promoter variation in autism spectrum disorder.

Whole-genome sequencing (WGS) has facilitated the first genome-wide evaluations of the contribution of de novo noncoding mutations to complex disorders. Using WGS, we identified 255,106 de novo mutations among sample genomes from members of 1902 quartet families in which one child, but not a sibling or their parents, was affected by autism spectrum disorder (ASD). In contrast to coding mutations, no noncoding functional annotation category, analyzed in isolation, was significantly associated with ASD.

Temporal proteomic profiling of postnatal human cortical development.

Healthy cortical development depends on precise regulation of transcription and translation. However, the dynamics of how proteins are expressed, function and interact across postnatal human cortical development remain poorly understood. We surveyed the proteomic landscape of 69 dorsolateral prefrontal cortex samples across seven stages of postnatal life and integrated these data with paired transcriptome data.

Endoscopic Ultrasound Assessment of Pancreatic Duct Diameter Predicts Neuroendocrine Tumors and Other Pancreas Masses.

Objectives: Distinguishing neuroendocrine tumors (NETs) and other pancreas lesions from adenocarcinomas via endoscopic ultrasound (EUS) requires additional tissue for special staining and processing. Our aim was to determine if main pancreatic duct (PD) diameter on EUS helps to differentiate NET and other unusual tumors from adenocarcinoma.

Methods: We evaluated 30 consecutive patients diagnosed with NET or other pancreas lesions by EUS with 90 matched patients who were found to have adenocarcinoma.

Gaining Medicaid Coverage During ACA Implementation: Effects on Access to Care and Preventive Services.

Objective: The continued expansion of Medicaid is under debate; it is critical to evaluate the effect of obtaining Medicaid on access to preventive care.

Methods: We analyzed longitudinal data from the 2013-2014 Medical Expenditure Panel Survey and applied a difference-in-differences approach. Our treatment group included low-income, non-pregnant, non-disabled adults aged 18-64 with no insurance in 2013 who received Medicaid in 2014; the comparison group included individuals who did not have insurance in either year.

High-risk symptoms do not predict gastric cancer precursors.

Background & Study Aims: Gastric intestinal metaplasia (GIM) is the most common precursor of gastric cancer. Our aim is to determine if presenting symptoms predict gastric cancer precursor lesions in a high-risk population.

Patient And Methods: Consecutive unique patients evaluated by endoscopy for upper gastrointestinal symptoms at the Los Angeles County Hospital between 2010 and 2014 were evaluated.

Volumetric Analysis of the Basal Ganglia and Cerebellar Structures in Patients with Phelan-McDermid Syndrome.

Objective: Phelan-McDermid syndrome is caused by haploinsufficiency of SHANK3 on terminal chromosome 22. Knowledge about altered neuroanatomic circuitry in Phelan-McDermid syndrome comes from mouse models showing striatal hypertrophy in the basal ganglia, and from humans with evidence of cerebellar atrophy. To date, no studies have performed volumetric analysis on Phelan-McDermid syndrome patients.

Association of Autism Spectrum Disorder With Prenatal Exposure to Medication Affecting Neurotransmitter Systems.

Importance: Prenatal exposure to certain medications has been hypothesized to influence the risk of autism spectrum disorders (ASD). However, the underlying effects on the neurotransmitter systems have not been comprehensively assessed.

Objective: To investigate the association of early-life interference with different neurotransmitter systems by prenatal medication exposure on the risk of ASD in offspring.

Update on the Prevention of Post-ERCP Pancreatitis.

Purpose Of Review: Endoscopic retrograde cholangiopancreatography (ERCP) is a commonly performed procedure to manage pancreaticobiliary disease. Post-ERCP pancreatitis (PEP) is the most common adverse event of ERCP with a significant burden of morbidity and cost.

Recent Findings: Appropriate indication and counseling is mandatory especially for patients at increased risk for PEP such as those with suspected sphincter of Oddi dysfunction, pancreatic indications, and a prior history of PEP.

Behavioral Phenotyping of an Improved Mouse Model of Phelan-McDermid Syndrome with a Complete Deletion of the Gene.

Phelan-McDermid syndrome (PMS) is a rare genetic disorder in which one copy of the gene is missing or mutated, leading to a global developmental delay, intellectual disability (ID), and autism. Multiple intragenic promoters and alternatively spliced exons are responsible for the formation of numerous isoforms. Many genetically-modified mouse models of PMS have been generated but most disrupt only some of the isoforms.

Genetic risk for schizophrenia and autism, social impairment and developmental pathways to psychosis.

While psychotic experiences (PEs) are assumed to represent psychosis liability, general population studies have not been able to establish significant associations between polygenic risk scores (PRS) and PEs. Previous work suggests that PEs may only represent significant risk when accompanied by social impairment. Leveraging data from the large longitudinal IMAGEN cohort, including 2096 14-year old adolescents that were followed-up to age 18, we tested whether the association between polygenic risk and PEs is mediated by (increasing) impairments in social functioning and social cognitive processes.

De Novo Sequence and Copy Number Variants Are Strongly Associated with Tourette Disorder and Implicate Cell Polarity in Pathogenesis.

We previously established the contribution of de novo damaging sequence variants to Tourette disorder (TD) through whole-exome sequencing of 511 trios. Here, we sequence an additional 291 TD trios and analyze the combined set of 802 trios. We observe an overrepresentation of de novo damaging variants in simplex, but not multiplex, families; we identify a high-confidence TD risk gene, CELSR3 (cadherin EGF LAG seven-pass G-type receptor 3); we find that the genes mutated in TD patients are enriched for those related to cell polarity, suggesting a common pathway underlying pathobiology; and we confirm a statistically significant excess of de novo copy number variants in TD.

The Mount Sinai cohort of large-scale genomic, transcriptomic and proteomic data in Alzheimer's disease.

Alzheimer's disease (AD) affects half the US population over the age of 85 and is universally fatal following an average course of 10 years of progressive cognitive disability. Genetic and genome-wide association studies (GWAS) have identified about 33 risk factor genes for common, late-onset AD (LOAD), but these risk loci fail to account for the majority of affected cases and can neither provide clinically meaningful prediction of development of AD nor offer actionable mechanisms. This cohort study generated large-scale matched multi-Omics data in AD and control brains for exploring novel molecular underpinnings of AD.

GLUCAGON PRESCRIPTIONS FOR DIABETES PATIENTS AFTER EMERGENCY DEPARTMENT VISITS FOR HYPOGLYCEMIA.

Objective: To determine the proportion of prescription fills for glucagon within 90 days of an emergency department (ED) visit for hypoglycemia.

Methods: This was a retrospective research study of glucagon prescriptions filled after an ED visit for hypoglycemia (from January 2011 to June 2014) by people with type 1 diabetes (T1D) or type 2 diabetes (T2D) taking insulin who did not already have an unexpired glucagon prescription within the Truven Health MarketScan Research Database.

Results: Less than 10% (T1D: 10.

Identification of rare de novo epigenetic variations in congenital disorders.

Certain human traits such as neurodevelopmental disorders (NDs) and congenital anomalies (CAs) are believed to be primarily genetic in origin. However, even after whole-genome sequencing (WGS), a substantial fraction of such disorders remain unexplained. We hypothesize that some cases of ND-CA are caused by aberrant DNA methylation leading to dysregulated genome function.

Gene expression in cord blood links genetic risk for neurodevelopmental disorders with maternal psychological distress and adverse childhood outcomes.

Prenatal exposure to maternal stress and depression has been identified as a risk factor for adverse behavioral and neurodevelopmental outcomes in early childhood. However, the molecular mechanisms through which maternal psychopathology shapes offspring development remain poorly understood. We applied transcriptome-wide screens to 149 umbilical cord blood samples from neonates born to mothers with posttraumatic stress disorder (PTSD; n = 20), depression (n = 31) and PTSD with comorbid depression (n = 13), compared to carefully matched trauma exposed controls (n = 23) and healthy mothers (n = 62).

FUN-LDA: A Latent Dirichlet Allocation Model for Predicting Tissue-Specific Functional Effects of Noncoding Variation: Methods and Applications.

We describe a method based on a latent Dirichlet allocation model for predicting functional effects of noncoding genetic variants in a cell-type- and/or tissue-specific way (FUN-LDA). Using this unsupervised approach, we predict tissue-specific functional effects for every position in the human genome in 127 different tissues and cell types. We demonstrate the usefulness of our predictions by using several validation experiments.

Delineation of the genetic and clinical spectrum of Phelan-McDermid syndrome caused by point mutations.

Background: Phelan-McDermid syndrome (PMS) is a neurodevelopmental disorder characterized by psychiatric and neurological features. Most reported cases are caused by 22q13.3 deletions, leading to haploinsufficiency, but also usually encompassing many other genes.