Cholangiocyte pathobiology.

Cholangiocytes, the epithelial cells lining the intrahepatic and extrahepatic bile ducts, are highly specialized cells residing in a complex anatomic niche where they participate in bile production and homeostasis. Cholangiocytes are damaged in a variety of human diseases termed cholangiopathies, often causing advanced liver failure. The regulation of cholangiocyte transport properties is increasingly understood, as is their anatomical and functional heterogeneity along the biliary tract.

Glial activation and inflammation along the Alzheimer's disease continuum.

Background: Neuronal and glial cell interaction is essential for synaptic homeostasis and may be affected in Alzheimer's disease (AD). We measured cerebrospinal fluid (CSF) neuronal and glia markers along the AD continuum, to reveal putative protective or harmful stage-dependent patterns of activation.

Methods: We included healthy controls (n = 36) and Aβ-positive (Aβ+) cases (as defined by pathological CSF amyloid beta 1-42 (Aβ42)) with either subjective cognitive decline (SCD, n = 19), mild cognitive impairment (MCI, n = 39), or AD dementia (n = 27).

Activated dendritic cells and monocytes in HIV immunological nonresponders: HIV-induced interferon-inducible protein-10 correlates with low future CD4+ recovery.

Objective: To explore monocyte and dendritic cell immune responses, and their association with future CD4 gain in treated HIV patients with suboptimal CD4 recovery.

Design: A cross-sectional study of HIV-infected, virally suppressed individuals on antiretroviral therapy for at least 24 months; 41 immunological nonresponders (INRs) (CD4 cell count <400 cells/μl) and 26 immunological responders (CD4 cell count >600 cells/μl). Ten HIV-infected antiretroviral therapy-naive and 10 HIV-negative healthy persons served as controls.

Performance measures for endoscopy services: A European Society of Gastrointestinal Endoscopy (ESGE) quality improvement initiative.

The European Society of Gastrointestinal Endoscopy (ESGE) and United European Gastroenterology present a list of key performance measures for endoscopy services. We recommend that these performance measures be adopted by all endoscopy services across Europe. The measures include those related to the leadership, organization, and delivery of the service, as well as those associated with the patient journey.

Dendritic cell targeted Ccl3- and Xcl1-fusion DNA vaccines differ in induced immune responses and optimal delivery site.

Fusing antigens to chemokines to target antigen presenting cells (APC) is a promising method for enhancing immunogenicity of DNA vaccines. However, it is unclear how different chemokines compare in terms of immune potentiating effects. Here we compare Ccl3- and Xcl1-fusion vaccines containing hemagglutinin (HA) from influenza A delivered by intramuscular (i.

Single-Cell Transcriptomics of Regulatory T Cells Reveals Trajectories of Tissue Adaptation.

Non-lymphoid tissues (NLTs) harbor a pool of adaptive immune cells with largely unexplored phenotype and development. We used single-cell RNA-seq to characterize 35,000 CD4 regulatory (Treg) and memory (Tmem) T cells in mouse skin and colon, their respective draining lymph nodes (LNs) and spleen. In these tissues, we identified Treg cell subpopulations with distinct degrees of NLT phenotype.

Mosaic deletion patterns of the human antibody heavy chain gene locus shown by Bayesian haplotyping.

Analysis of antibody repertoires by high-throughput sequencing is of major importance in understanding adaptive immune responses. Our knowledge of variations in the genomic loci encoding immunoglobulin genes is incomplete, resulting in conflicting VDJ gene assignments and biased genotype and haplotype inference. Haplotypes can be inferred using IGHJ6 heterozygosity, observed in one third of the people.

Dynamic susceptibility contrast and diffusion MR imaging identify oligodendroglioma as defined by the 2016 WHO classification for brain tumors: histogram analysis approach.

Purpose: According to the revised World Health Organization (WHO) Classification of Tumors of the Central Nervous System (CNS) of 2016, oligodendrogliomas are now defined primarily by a specific molecular signature (presence of IDH mutation and 1p19q codeletion). The purpose of our study was to assess the value of dynamic susceptibility contrast MR imaging (DSC-MRI) and diffusion-weighted imaging (DWI) to characterize oligodendrogliomas and to distinguish them from astrocytomas.

Methods: Seventy-one adult patients with untreated WHO grade II and grade III diffuse infiltrating gliomas and known 1p/19q codeletion status were retrospectively identified and analyzed using relative cerebral blood volume (rCBV) and apparent diffusion coefficient (ADC) maps based on whole-tumor volume histograms.

Radicular cyst in a primary molar following pulp therapy with gutta percha: A case report and literature review.

A radicular cyst (RC) in deciduous dentition is relatively rare. This clinical report presents a case of RC that condition derived from a primary molar undergone an endodontic treatment with gutta-percha approximately one year ago. In addition, we also considered whether intracanal medicaments and gutta-percha filling material related to the formation and development of the cyst or not.

Inflammatory markers are altered in severe mental disorders independent of comorbid cardiometabolic disease risk factors.

Background: Inflammation and immune activation have been implicated in the pathogenesis of severe mental disorders and cardiovascular disease (CVD). Despite high level of comorbidity, many studies of the immune system in severe mental disorders have not systematically taken cardiometabolic risk factors into account.

Methods: We investigated if inflammatory markers were increased in schizophrenia (SCZ) and affective (AFF) disorders independently of comorbid CVD risk factors.

Mitochondrial stress response triggered by defects in protein synthesis quality control.

Mitochondria have a compartmentalized gene expression system dedicated to the synthesis of membrane proteins essential for oxidative phosphorylation. Responsive quality control mechanisms are needed to ensure that aberrant protein synthesis does not disrupt mitochondrial function. Pathogenic mutations that impede the function of the mitochondrial matrix quality control protease complex composed of AFG3L2 and paraplegin cause a multifaceted clinical syndrome.

Adipokine levels are associated with insulin resistance in antipsychotics users independently of BMI.

Background: The prevalence of obesity, metabolic syndrome and type 2 diabetes mellitus is increased among patients with severe mental disorders, and particularly use of second generation antipsychotic drugs is associated with metabolic side effects. Antipsychotics have been found to alter levels of adipokines which regulate insulin sensitivity, but their role in antipsychotic-associated insulin resistance is not established, and it is unclear whether adipokines affect insulin resistance independently of body mass index (BMI).

Methods: We included 1050 patients with severe mental disorders and 112 healthy controls aged 18-65 years from the Oslo area, Norway.

B cell depletion in the treatment of multiple sclerosis.

Introduction: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. The latest development of B-cell depletion by anti-CD20 monoclonal antibodies has been a large step forward in the treatment of this devastating disease.

Areas Covered: In this manuscript, we review mechanisms of action, efficacy, safety, and tolerance of anti-CD20 therapies for MS, including rituximab, ocrelizumab, and ofatumumab.

Plasma Cells Are the Most Abundant Gluten Peptide MHC-expressing Cells in Inflamed Intestinal Tissues From Patients With Celiac Disease.

Background & Aims: Development of celiac disease is believed to involve the transglutaminase-dependent response of CD4 T cells toward deamidated gluten peptides in the intestinal mucosa of individuals with specific HLA-DQ haplotypes. We investigated the antigen presentation process during this mucosal immune response.

Methods: We generated monoclonal antibodies (mAbs) specific for the peptide-MHC (pMHC) complex of HLA-DQ2.

Performance measures for endoscopic retrograde cholangiopancreatography and endoscopic ultrasound: A European Society of Gastrointestinal Endoscopy (ESGE) Quality Improvement Initiative.

The European Society of Gastrointestinal Endoscopy (ESGE) and United European Gastroenterology present a short list of key performance measures for endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP). We recommend that endoscopy services across Europe adopt the following seven key and one minor performance measures for EUS and ERCP, for measurement and evaluation in daily practice at centre and endoscopist level: Adequate antibiotic prophylaxis before ERCP (key performance measure, at least 90%); antibiotic prophylaxis before EUS-guided puncture of cystic lesions (key performance measure, at least 95%); bile duct cannulation rate (key performance measure, at least 90%); tissue sampling during EUS (key performance measure, at least 85%); appropriate stent placement in patients with biliary obstruction below the hilum (key performance measure, at least 95%); bile duct stone extraction (key performance measure, at least 90%); post-ERCP pancreatitis (key performance measure, less than 10%); and adequate documentation of EUS landmarks (minor performance measure, at least 90%). This present list of quality performance measures for ERCP and EUS recommended by the ESGE should not be considered to be exhaustive; it might be extended in future to address further clinical and scientific issues.

GPCR-specific autoantibody signatures are associated with physiological and pathological immune homeostasis.

Autoantibodies have been associated with autoimmune diseases. However, studies have identified autoantibodies in healthy donors (HD) who do not develop autoimmune disorders. Here we provide evidence of a network of immunoglobulin G (IgG) autoantibodies targeting G protein-coupled receptors (GPCR) in HD compared to patients with systemic sclerosis, Alzheimer's disease, and ovarian cancer.

Cryopreservation of primary B cells minimally influences their signaling responses.

Phospho flow is a powerful approach to detect cell signaling aberrations, identify biomarkers and assess pharmacodynamics, and can be performed using cryopreserved samples. The effects of cryopreservation on signaling responses and the reproducibility of phospho flow measurements are however unknown in many cell systems. Here, B lymphocytes were isolated from healthy donors and patients with the B cell malignancy chronic lymphocytic leukemia and analyzed by phospho flow using phospho-specific antibodies targeting 20 different protein epitopes.

Preassociation between the 5-HT serotonin receptor and G protein G: molecular determinants and association with low potency activation of adenylyl cyclase.

According to early models of GPCR signaling, G proteins only interact with activated receptors. However, some GPCRs were shown to assemble with G proteins before receptor activation, in accordance with more recent models. Previously, we found that the 5-HT receptor, as opposed to the 5-HT receptor, was preassociated with G, but the molecular determinants for this interaction are still elusive.

Personality Traits in Patients with Myocardial Infarction with Nonobstructive Coronary Arteries.

Objective: The purpose of this study was to describe type A behavior pattern and trait anger in patients with myocardial infarction with nonobstructive coronary arteries (MINOCA) and compare them with patients with coronary heart disease and healthy controls. Type A behavior pattern and anger have been linked to coronary heart disease in previous studies. This is the first study to assess type A behavior pattern and trait anger in MINOCA patients.

Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder.

Attention deficit/hyperactivity disorder (ADHD) is a highly heritable childhood behavioral disorder affecting 5% of children and 2.5% of adults. Common genetic variants contribute substantially to ADHD susceptibility, but no variants have been robustly associated with ADHD.

Hypokalemia-Induced Arrhythmias and Heart Failure: New Insights and Implications for Therapy.

Routine use of diuretics and neurohumoral activation make hypokalemia (serum K < 3. 5 mM) a prevalent electrolyte disorder among heart failure patients, contributing to the increased risk of ventricular arrhythmias and sudden cardiac death in heart failure. Recent experimental studies have suggested that hypokalemia-induced arrhythmias are initiated by the reduced activity of the Na/K-ATPase (NKA), subsequently leading to Ca overload, Ca/Calmodulin-dependent kinase II (CaMKII) activation, and development of afterdepolarizations.