Stress and gonadal steroid influences on alcohol drinking and withdrawal, with focus on animal models in females.

Sexually dimorphic effects of alcohol, following binge drinking, chronic intoxication, and withdrawal, are documented at the level of the transcriptome and in behavioral and physiological responses. The purpose of the current review is to update and to expand upon contributions of the endocrine system to alcohol drinking and withdrawal in females, with a focus on animal models. Steroids important in the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-adrenal axes, the reciprocal interactions between these axes, the effects of chronic alcohol use on steroid levels, and the genomic and rapid membrane-associated effects of steroids and neurosteroids in models of alcohol drinking and withdrawal are described.

Systematic benchmarking of single-cell ATAC-sequencing protocols.

Single-cell assay for transposase-accessible chromatin by sequencing (scATAC-seq) has emerged as a powerful tool for dissecting regulatory landscapes and cellular heterogeneity. However, an exploration of systemic biases among scATAC-seq technologies has remained absent. In this study, we benchmark the performance of eight scATAC-seq methods across 47 experiments using human peripheral blood mononuclear cells (PBMCs) as a reference sample and develop PUMATAC, a universal preprocessing pipeline, to handle the various sequencing data formats.

Long-term drinking stability in the open-access self-administration monkey model.

The Non-Human Primate (NHP) model for the study of Alcohol Use Disorders (AUD) as developed in our laboratories is critical to our understanding of the pathophysiology of voluntary, chronic, ethanol consumption. Previous work in this model established categories of ethanol consumption that parallel reported categories of human consumption across a spectrum spanning low drinking, binge drinking, heavy drinking, and very heavy drinking, albeit at generally higher daily intakes across categories than documented in people. Original categories assigned to ethanol consumption patterns were established using a limited cohort of rhesus macaques.

Environmental enrichment promotes adaptive responding during tests of behavioral regulation in male heterogeneous stock rats.

Organisms must regulate their behavior flexibly in the face of environmental challenges. Failure can lead to a host of maladaptive behavioral traits associated with a range of neuropsychiatric disorders, including attention deficit hyperactivity disorder, autism, and substance use disorders. This maladaptive dysregulation of behavior is influenced by genetic and environmental factors.

A Multicenter Assessment of Interreader Reliability of LI-RADS Version 2018 for MRI and CT.

Background Various limitations have impacted research evaluating reader agreement for Liver Imaging Reporting and Data System (LI-RADS). Purpose To assess reader agreement of LI-RADS in an international multicenter multireader setting using scrollable images. Materials and Methods This retrospective study used deidentified clinical multiphase CT and MRI and reports with at least one untreated observation from six institutions and three countries; only qualifying examinations were submitted.

An open protocol for modeling T Cell Clonotype repertoires using TCRβ CDR3 sequences.

T cell receptor repertoires can be profiled using next generation sequencing (NGS) to measure and monitor adaptive dynamical changes in response to disease and other perturbations. Genomic DNA-based bulk sequencing is cost-effective but necessitates multiplex target amplification using multiple primer pairs with highly variable amplification efficiencies. Here, we utilize an equimolar primer mixture and propose a single statistical normalization step that efficiently corrects for amplification bias post sequencing.

Machine Learning Algorithm Detection of Confluent B-Lines.

Objective: B-lines are a ring-down artifact of lung ultrasound that arise with increased alveolar water in conditions such as pulmonary edema and infectious pneumonitis. Confluent B-line presence may signify a different level of pathology compared with single B-lines. Existing algorithms aimed at B-line counting do not distinguish between single and confluent B-lines.

Early Clinical Variables Associated With Refractory Convulsive Status Epilepticus in Children.

Background And Objectives: The objective of this study was to determine patient-specific factors known proximate to the presentation to emergency care associated with the development of refractory convulsive status epilepticus (RSE) in children.

Methods: An observational case-control study was conducted comparing pediatric patients (1 month-21 years) with convulsive SE whose seizures stopped after benzodiazepine (BZD) and a single second-line antiseizure medication (ASM) (responsive established status epilepticus [rESE]) with patients requiring more than a BZD and a single second-line ASM to stop their seizures (RSE). These subpopulations were obtained from the pediatric Status Epilepticus Research Group study cohort.

Targets and study design for symptom-focused trials aimed at patients with cirrhosis: An expert consensus.

Background: Symptom-focused trials are critically needed for patients with cirrhosis. However, this work would benefit from standard processes and validated measures.

Methods: A writing group was formed among hepatologists, nurses, palliative care providers, pharmacists, and clinical trial experts focused on symptom management in patients with cirrhosis to define the key (1) components of trial design, (2) symptom targets, (3) measurement, and (4) outcomes for each target.

Heightened adolescent emotional reactivity in the brain is associated with lower future distress tolerance and higher depressive symptoms.

Distress tolerance, the ability to persist while experiencing negative psychological states, is essential for regulating emotions and is a transdiagnostic risk/resiliency trait for multiple psychopathologies. Studying distress tolerance during adolescence, a period when emotion regulation is still developing, may help identify early risk and/or protective factors. This study included 40 participants (mean scan age = 17.

Rhesus macaque fetal and placental growth demographics: A resource for laboratory animal researchers.

Rhesus macaques (Macaca mulatta) are amongst the most common nonhuman primate species used in biomedical research. These animals provide a precious resource for translational studies and opportunities to maximize rhesus data use are encouraged. Here we compile data produced from 10 years of investigator-driven pregnancy studies conducted at the Oregon National Primate Research Center (ONPRC).

The association between food desert severity, socioeconomic status, and metabolic state during pregnancy in a prospective longitudinal cohort.

Poor metabolic health during pregnancy is associated with health concerns for pregnant individuals and their offspring. Lower socioeconomic status (SES) is one risk factor for poor metabolic health, and may be related to limited access to healthful and affordable foods (e.g.

Effects of alcohol and PARP inhibition on RNA ribosomal engagement in cortical excitatory neurons.

We report on the effects of ethanol (EtOH) and Poly (ADP-ribose) polymerase (PARP) inhibition on RNA ribosomal engagement, as a proxy for protein translation, in prefrontal cortical (PFC) pyramidal neurons. We hypothesized that EtOH induces a shift in RNA ribosomal-engagement (RE) in PFC pyramidal neurons, and that many of these changes can be reversed using a PARP inhibitor. We utilized the translating ribosome affinity purification (TRAP) technique to isolate cell type-specific RNA.

Deletion of the mRNA stability factor (HuR) in pancreatic cancer cells disrupts the tumor microenvironment integrity.

Stromal cells promote extensive fibrosis in pancreatic ductal adenocarcinoma (PDAC), which is associated with poor prognosis and therapeutic resistance. We report here for the first time that loss of the RNA-binding protein human antigen R (HuR, ) in PDAC cells leads to reprogramming of the tumor microenvironment. In multiple models, CRISPR deletion of in PDAC cells resulted in a decrease of collagen deposition, accompanied by a decrease of stromal markers (i.

Adolescent Substance Use Is Associated With Altered Brain Response During Processing of Negative Emotional Stimuli.

Objective: Substance misuse is often associated with emotional dysregulation. Understanding the neurobiology of emotional responsivity and regulation as it relates to substance use in adolescence may be beneficial for preventing future use.

Method: The present study used a community sample, ages 11-21 years old ( = 130, = 17), to investigate the effects of alcohol and marijuana use on emotional reactivity and regulation using an Emotional Go-NoGo task during functional magnetic resonance imaging.

HIV rapidly targets a diverse pool of CD4 T cells to establish productive and latent infections.

Upon infection, HIV disseminates throughout the human body within 1-2 weeks. However, its early cellular targets remain poorly characterized. We used a single-cell approach to retrieve the phenotype and TCR sequence of infected cells in blood and lymphoid tissue from individuals at the earliest stages of HIV infection.

Alcohol-induced changes in mesostriatal resting-state functional connectivity are linked to sensation seeking in young adults.

Background: Studies in animals and humans suggest that greater levels of sensation seeking and alcohol use are related to individual differences in drug-induced dopamine release. However, it remains unclear whether drug-induced alterations in the functional synchrony between mesostriatal regions are related to sensation seeking and alcohol use.

Methods: In this within-subject masked-design study, 21-year-old participants (n = 34) underwent functional magnetic resonance imaging to measure ventral tegmental area (VTA) resting-state functional connectivity to the striatum after receiving alcohol (target blood alcohol concentration 0.

Static Perimetry in the Rate of Progression in USH2A-related Retinal Degeneration (RUSH2A) Study: Assessment Through 2 Years.

Purpose: To evaluate disease progression using static perimetry (SP) in patients with USH2A-related retinal degeneration, including Usher syndrome type 2 (USH2) and nonsyndromic autosomal recessive retinitis pigmentosa.

Design: Prospective, observational cohort study.

Methods: A total of 102 patients with biallelic disease-causing sequence variants in USH2A with baseline best-corrected visual acuity (BCVA) letter score ≥54 were recruited from 16 clinical sites in Europe and North America.

Alcohol Dependence Modifies Brain Networks Activated During Withdrawal and Reaccess: A c-Fos-Based Analysis in Mice.

Background: High-level alcohol consumption causes neuroplastic changes in the brain that promote pathological drinking behavior. Some of these changes have been characterized in defined brain circuits and cell types, but unbiased approaches are needed to explore broader patterns of adaptations.

Methods: We used whole-brain c-Fos mapping and network analysis to assess patterns of neuronal activity during alcohol withdrawal and following reaccess in a well-characterized model of alcohol dependence.

Preclinical and clinical evidence for suppression of alcohol intake by apremilast.

Treatment options for alcohol use disorders (AUDs) have minimally advanced since 2004, while the annual deaths and economic toll have increased alarmingly. Phosphodiesterase type 4 (PDE4) is associated with alcohol and nicotine dependence. PDE4 inhibitors were identified as a potential AUD treatment using a bioinformatics approach.

A DNA methylation atlas of normal human cell types.

DNA methylation is a fundamental epigenetic mark that governs gene expression and chromatin organization, thus providing a window into cellular identity and developmental processes. Current datasets typically include only a fraction of methylation sites and are often based either on cell lines that underwent massive changes in culture or on tissues containing unspecified mixtures of cells. Here we describe a human methylome atlas, based on deep whole-genome bisulfite sequencing, allowing fragment-level analysis across thousands of unique markers for 39 cell types sorted from 205 healthy tissue samples.

Exploratory Study of the Brain Response in Facial Synkinesis after Bell Palsy with Systematic Review and Meta-analysis of the Literature.

Background: Facial synkinesis, characterized by unintentional facial movements paired with intentional movements, is a debilitating sequela of Bell palsy.

Purpose: Our aim was to determine whether persistent peripheral nerve changes arising from Bell palsy result in persistent altered brain function in motor pathways in synkinesis.

Data Sources: A literature search using terms related to facial paralysis, Bell palsy, synkinesis, and fMRI through May 2021 was conducted in MEDLINE and EMBASE.

Sex differences in hippocampal structural plasticity and glycosaminoglycan disaccharide levels after neonatal handling.

In this study we investigated the effects of a neonatal handling protocol that mimics the handling of sham control pups in protocols of neonatal exposure to brain insults on dendritic arborization and glycosaminoglycan (GAG) levels in the developing brain. GAGs are long, unbranched polysaccharides, consisting of repeating disaccharide units that can be modified by sulfation at specific sites and are involved in modulating neuronal plasticity during brain development. In this study, male and female Sprague-Dawley rats underwent neonatal handling daily between post-natal day (PD)4 and PD9, with brains analyzed on PD9.