Human liver-derived CXCR6 NK cells are predominantly educated through NKG2A and show reduced cytokine production.

NK cells have been implicated to affect the outcome of numerous liver diseases. In particular, members of the killer-cell Ig-like receptor (KIR) family, predominantly expressed by NK cells, have been associated with the outcome of hepatitis C virus infection and clearance of hepatocellular carcinoma. Inhibitory KIRs tune NK cell function through interaction with HLA class I, a process termed education.

Two vs four puffs of albuterol: does dose change bronchodilator response?

Background: Reversible obstruction on spirometry may be used to diagnose asthma. As per 2005 American Thoracic Society (ATS) guidelines, our pulmonary center began using 360 µg (four puffs) of albuterol rather than 180 µg (two puffs) to determine reversibility on spirometry starting in 2009.

Hypothesis: We hypothesized that fewer patients would respond to two puffs of albuterol than four puffs during spirometric testing.

Extended Infusion of β-Lactams for Bloodstream Infection in Patients With Liver Cirrhosis: An Observational Multicenter Study.

Background: We analyzed the impact of continuous/extended infusion (C/EI) vs intermittent infusion of piperacillin-tazobactam (TZP) and carbapenems on 30-day mortality of patients with liver cirrhosis and bloodstream infection (BSI).

Methods: The BICRHOME study was a prospective, multicenter study that enrolled 312 cirrhotic patients with BSI. In this secondary analysis, we selected patients receiving TZP or carbapenems as adequate empirical treatment.

Th17 cell frequency is associated with low bone mass in primary sclerosing cholangitis.

Background & Aims: Osteoporotic fractures are a major cause of morbidity and reduced quality of life in patients with primary sclerosing cholangitis (PSC), a progressive bile duct disease of unknown origin. Although it is generally assumed that this pathology is a consequence of impaired calcium homeostasis and malabsorption, the cellular and molecular causes of PSC-associated osteoporosis are unknown.

Methods: We determined bone mineral density by dual-X-ray absorptiometry and assessed bone microstructure by high-resolution peripheral quantitative computed tomography in patients with PSC.

Predniso(lo)ne Dosage and Chance of Remission in Patients With Autoimmune Hepatitis.

Background & Aims: Patients with autoimmune hepatitis (AIH) commonly receive induction therapy with predniso(lo)ne followed by maintenance therapy with azathioprine. European Association for Study of the Liver clinical practice guidelines advise a predniso(lo)ne dose range of 0.50-1 mg/kg/day, which leaves room for practice variation.

Rate of Spleen Length Progression Is a Marker of Outcome in Patients With Primary Sclerosing Cholangitis.

Patients with primary sclerosing cholangitis (PSC) tend to develop progressive liver fibrosis and end-stage liver disease within 10-20 years. The International PSC Study Group declared research on surrogate endpoints a high-priority task not least for ongoing clinical trials on novel treatment options. The spleen in patients with PSC often enlarges even before cirrhosis develops.

Hyperplastic polyps and nonadvanced adenomas, but not advanced polypoid lesions, are detected more frequently in the presence of colonic diverticula during screening colonoscopies.

Hintergrund:  Die bisher veröffentlichte Studienlage zur Assoziation von Kolondivertikeln und kolorektalen Polypen einschließlich des kolorektalen Karzinoms (KRK) ist konträr. Ziel der Studie war es, die Assoziation für sämtliche relevanten histologischen Polypensubtypen, d. h.

HVEM and CD160: Regulators of Immunopathology During Malaria Blood-Stage.

CD8 T cells are key players during infection with the malaria parasite ANKA (PbA). While they cannot provide protection against blood-stage parasites, they can cause immunopathology, thus leading to the severe manifestation of cerebral malaria. Hence, the tight control of CD8 T cell function is key in order to prevent fatal outcomes.

Colitis Promotes a Pathological Condition of the Liver in the Absence of Foxp3 Regulatory T Cells.

Inflammatory bowel disease is associated with extraintestinal diseases such as primary sclerosing cholangitis in the liver. Interestingly, it is known that an imbalance between Foxp3 regulatory T cells (Treg) and Th17 cells is involved in inflammatory bowel disease and also in primary sclerosing cholangitis. To explain these associations, one hypothesis is that intestinal inflammation and barrier defects promote liver disease because of the influx of bacteria and inflammatory cells to the liver.

AIRR Community Standardized Representations for Annotated Immune Repertoires.

Increased interest in the immune system's involvement in pathophysiological phenomena coupled with decreased DNA sequencing costs have led to an explosion of antibody and T cell receptor sequencing data collectively termed "adaptive immune receptor repertoire sequencing" (AIRR-seq or Rep-Seq). The AIRR Community has been actively working to standardize protocols, metadata, formats, APIs, and other guidelines to promote open and reproducible studies of the immune repertoire. In this paper, we describe the work of the AIRR Community's Data Representation Working Group to develop standardized data representations for storing and sharing annotated antibody and T cell receptor data.

Sequencing HIV-neutralizing antibody exons and introns reveals detailed aspects of lineage maturation.

The developmental pathways of broadly neutralizing antibodies (bNAbs) against HIV are of great importance for the design of immunogens that can elicit protective responses. Here we show the maturation features of the HIV-neutralizing anti-V1V2 VRC26 lineage by simultaneously sequencing the exon together with the downstream intron of VRC26 members. Using the mutational landscapes of both segments and the selection-free nature of the intron region, we identify multiple events of amino acid mutational convergence in the complementarity-determining region 3 (CDR3) of VRC26 members, and determine potential intermediates with diverse CDR3s to a late stage bNAb from 2 years prior to its isolation.

Sex-related factors in autoimmune liver diseases.

Autoimmune diseases are a broad range of diseases in which the immune system produces an inappropriate response to self-antigens. This results in inflammation, damage, or dysfunction of tissues and/or organs. Many autoimmune diseases are more common in women and differences between female and male immune and autoimmune responses have been well documented.

Mucosal Autoimmunity to Cell-Bound GP2 Isoforms Is a Sensitive Marker in PSC and Associated With the Clinical Phenotype.

Zymogen granule glycoprotein 2 (GP2) was demonstrated as first autoimmune mucosal target in primary sclerosing cholangitis (PSC) associated with disease severity. Autoantibodies to four GP2 isoforms (aGP2) were found in patients with inflammatory bowel diseases but reactivity against specific GP2 epitopes has not been investigated in PSC yet. Hence, the prevalence of aGP2 and their association with the PSC phenotype for risk prediction were examined.

Repeated hot water and steam disinfection of Pari LC Plus® nebulizers alter nebulizer output.

Currently, cystic fibrosis patients require daily nebulized treatments to achieve optimal lung health. Growth of pathogenic bacteria in patient nebulizers is well known, and disinfection guidelines have been established. In this short communication, we sought to discover what effect, if any, repeated nebulization/disinfection cycles had on nebulizer output.

Beyond Hot Spots: Biases in Antibody Somatic Hypermutation and Implications for Vaccine Design.

The evolution of antibodies in an individual during an immune response by somatic hypermutation (SHM) is essential for the ability of the immune system to recognize and remove the diverse spectrum of antigens that may be encountered. These mutations are not produced at random; nucleotide motifs that result in increased or decreased rates of mutation were first reported in 1992. Newer models that estimate the propensity for mutation for every possible 5- or 7-nucleotide motif have emphasized the complexity of SHM targeting and suggested possible new hot spot motifs.

Risk of endoscopic biliary interventions in primary sclerosing cholangitis is similar between patients with and without cirrhosis.

Background: Endoscopic retrograde cholangiography (ERC) is a mainstay of therapy in patients with primary sclerosing cholangitis (PSC) and obstructive cholestasis. Patients with liver cirrhosis have an increased risk of surgical complications and are more susceptible to infections. Since PSC often progresses to cirrhosis, we aimed to assess whether ERC is associated with increased risk of complications in patients with PSC and cirrhosis.

Interactions Between KIR3DS1 and HLA-F Activate Natural Killer Cells to Control HCV Replication in Cell Culture.

Killer-cell immunoglobulin-like receptors (KIRs) are transmembrane glycoproteins expressed by natural killer (NK) cells. Binding of KIR3DS1 to its recently discovered ligand, HLA-F, activates NK cells and has been associated with resolution of hepatitis C virus (HCV) infection. We investigated the mechanisms by which KIR3DS1 contributes to the antiviral immune response.

Tissue-resident NK cells differ in their expression profile of the nutrient transporters Glut1, CD98 and CD71.

Metabolism is a critical basis for immune cell functionality. It was recently shown that NK cell subsets from peripheral blood modulate their expression of nutrient receptors following cytokine stimulation, demonstrating that NK cells can adjust to changes in metabolic requirements. As nutrient availability in blood and tissues can significantly differ, we examined NK cells isolated from paired blood-liver and blood-spleen samples and compared expression of the nutrient transporters Glut1, CD98 and CD71.

Prospective comparison of diffusion-weighted MRI and dynamic Gd-EOB-DTPA-enhanced MRI for detection and staging of hepatic fibrosis in primary sclerosing cholangitis.

Purpose: To assess the diagnostic value of multiparametric magnetic resonance imaging (MRI) including dynamic Gd-EOB-DTPA-enhanced (DCE) and diffusion-weighted (DW) imaging for diagnosis and staging of hepatic fibrosis in primary sclerosing cholangitis (PSC) using transient elastography as a standard reference.

Material And Methods: Multiparametric MRI was prospectively performed on a 3.0-Tesla scanner in 47 patients (age 43.

Web-Based Immersive Patient Simulator as a Curricular Tool for Objective Structured Clinical Examination Preparation in Surgery: Development and Evaluation.

Background: Objective Structured Clinical Examination is a standard method of testing declarative and process knowledge in clinical core competencies. It is desirable that students undergo Objective Structured Clinical Examination training before participating in the exam. However, establishing Objective Structured Clinical Examination training is resource intensive and therefore there is often limited practice time.

Early-life antibiotics attenuate regulatory T cell generation and increase the severity of murine house dust mite-induced asthma.

Introduction: Early-life exposure to antibiotics (ABX) has been linked to increases in asthma severity and prevalence in both children and laboratory animals. We explored the immunologic mechanisms behind this association using a mouse model of house dust mite (HDM)-induced asthma and early-life ABX exposure.

Methods: Mice were exposed to three short courses of ABX following weaning and experimental asthma was thereafter induced.

Jules Joseph Dejerine: an outstanding neurologist and Charcot's enemy.

Jules Joseph Dejerine (1849-1917) became renowned for his many contributions to neurology, including his anatomical and anatomo-functional studies, particularly those in the field of language and the peripheral nervous system. A disciple of Vulpian and a rival of Charcot, Dejerine progressed rapidly in the academic world, reaching the peak of his career in 1911, when he was appointed to the chair of Nervous System Diseases at the Salpêtrière Hospital after defeating Pierre Marie (1853-1940), one of the most distinguished pupils of Jean-Martin Charcot (1825-1893).