Adverse childhood experiences (ACEs) have diverse effects on physical development and mental health. This study aimed to clarify the relationship between the quantity of ACE exposure, type of ACE exposure, and subjective level of stress felt, correlated with event-related potential activity across the scalp, while controlling for relevant confounding variables. Fifty-three participants aged 18-32 years completed questionnaires assessing their current mental health, self-regulation, childhood socioeconomic status, and history of traumatic events.
View Article and Find Full Text PDFBackground: Portal hypertension (PH) resulting from static and dynamic intrahepatic changes drives liver-related complications even after removing the underlying aetiological factor.
Objective: We investigated the impact of inflammation on the dynamic component of PH during disease regression in animal models of toxin-induced cirrhosis and patients with alcohol-related cirrhosis.
Methods: In mice, cirrhosis was induced via toxin application for 12 weeks followed by toxin-withdrawal allowing for one or 2 weeks of regression.
In this position statement, we explore the intricate relationship between alcohol intake and metabolic dysfunction in the context of the 2023 nomenclature update for steatotic liver disease (SLD). Recent and lifetime alcohol use should be accurately assessed in all patients with SLD to facilitate classification of alcohol use in grams of alcohol per week. Alcohol biomarkers (i.
View Article and Find Full Text PDFBackground: Metabolic dysfunction-associated steatotic liver disease (MASLD) is considered multifactorial with a number of predisposing gene polymorphisms known.
Methods: The occurrence of MASLD in 7 and 10 year old siblings, one without classical risk factors and one with type 2 diabetes suggested a monogenic etiology and prompted next-generation sequencing. Exome sequencing was performed in the proband, both parents and both siblings.
Background & Aims: In clinical practice, the diagnosis of alcohol-associated hepatitis (AH) is mostly based on non-invasive criteria, which were defined at a consensus conference by the National Institute on Alcohol Abuse and Alcoholism (NIAAA). These criteria were recently modified by adding C-reactive protein (CRP) and termed NIAAAm-CRP criteria, which showed superior diagnostic accuracy for presence of alcohol-associated steatohepatitis (ASH) on liver histology. The aim of our study was to validate the diagnostic accuracy of both original NIAAA criteria and NIAAAm-CRP criteria for presence of ASH on liver histology in an independent cohort.
View Article and Find Full Text PDFThe association between granulomas and vaccine-derived rubella virus (VDRV) in people with primary immunodeficiencies has raised concerns about the ability of immunoglobulin preparations to neutralize VDRVs. We investigated the capacity of immunoglobulin to neutralize rubella vaccine virus and 4 VDRV strains. As expected, the rubella vaccine virus itself was potently neutralized by immunoglobulin preparations, but the VDRV isolates from patients after intrahost evolution, 2-6 times less so.
View Article and Find Full Text PDFBiochim Biophys Acta Mol Basis Dis
March 2024
High fructose diets are associated with an increased risk of liver cancer. Previous studies in mice suggest increased lipogenesis is a key mechanism linking high fructose diets to liver tumour growth. However, these studies administered fructose to mice at supraphysiological levels.
View Article and Find Full Text PDFAlcohol-related liver disease (ALD) encompasses a range of pathological conditions that are complex to study at the clinical and preclinical levels. Despite the global burden of ALD, there is a lack of effective treatments, and mortality is high. One of the reasons for the unsuccessful development of novel therapies is that experimental studies are hindered by the challenge of recapitulating this multifactorial disorder in vitro, including the contributions of hepatotoxicity, impaired lipid metabolism, fibrosis and inflammatory cytokine storm, which are critical drivers in the pathogenesis of ALD in patients and primary targets for drug development.
View Article and Find Full Text PDFThe Centre for Disease Control recommends vaccination of children against SARS-CoV-2 to reduce the severity of COVID-19 disease and reduce the likelihood of associated complications. Vaccination of children requires the consent of parents or guardians, and levels of consent may ebb and flow over the course of the pandemic. This exploratory study examines predictors of parental intentions to vaccinate their children and the speed with which they would have them vaccinated during the fifth wave of the pandemic when vaccines were just being approved for use in children using a convenience sample of 641 parents reporting on 962 children.
View Article and Find Full Text PDFNicotine exposure is associated with negative consequences on the developing brain, both in utero and after birth. We investigated the relationship between perinatal nicotine exposure and electroencephalographic brain activity recorded during an emotional faces Go/No-Go task among adolescents. Seventy-one adolescents aged 12-15 years completed a Go/No-Go task using fearful and happy faces.
View Article and Find Full Text PDFSecondary infections contribute significantly to covid-19 mortality but driving factors remain poorly understood. Autopsies of 20 covid-19 cases and 14 controls from the first pandemic wave complemented with microbial cultivation and RNA-seq from lung tissues enabled description of major organ pathologies and specification of secondary infections. Lethal covid-19 segregated into two main death causes with either dominant diffuse alveolar damage (DAD) or secondary pneumonias.
View Article and Find Full Text PDFObjective: Hepatocellular carcinoma (HCC) often develops in patients with alcohol-related cirrhosis at an annual risk of up to 2.5%. Some host genetic risk factors have been identified but do not account for the majority of the variance in occurrence.
View Article and Find Full Text PDFImmune globulin (IG) is administered as measles postexposure prophylaxis (PEP) in people with primary immunodeficiency disorders or individuals not eligible for live virus vaccination. However, measles virus (MeV) neutralizing antibody (nAb) levels in plasma for fractionation and IG products fractionated thereof have declined. Here, the feasibility of producing a measles hyperimmune globulin (HIG) for PEP of high-risk individuals was investigated.
View Article and Find Full Text PDFBackground & Aims: Diagnostic histological criteria for autoimmune hepatitis (AIH) have not been clearly established. Previously published criteria focused mainly on chronic AIH, in which inflammatory changes mainly occur in portal/periportal regions and may not be applicable to acute presentation of AIH, in which inflammatory changes are typically predominantly lobular in location. International consensus criteria for the diagnosis and assessment of disease severity in both acute and chronic AIH are thus urgently needed.
View Article and Find Full Text PDFBackground & Aims: Histologically assessed hepatocyte ballooning is a key feature discriminating non-alcoholic steatohepatitis (NASH) from steatosis (NAFL). Reliable identification underpins patient inclusion in clinical trials and serves as a key regulatory-approved surrogate endpoint for drug efficacy. High inter/intra-observer variation in ballooning measured using the NASH CRN semi-quantitative score has been reported yet no actionable solutions have been proposed.
View Article and Find Full Text PDFObjective: Alcohol-related liver disease (ALD) ranges from never-decompensated ALD (ndALD) to the life-threatening decompensated phenotype, known as alcohol-related hepatitis (AH). A multidimensional study of the clinical, histological and molecular features of these subtypes is lacking.
Design: Two large cohorts of patients were recruited in an international, observational multicentre study: a retrospective cohort of patients with ndALD (n=110) and a prospective cohort of patients with AH (n=225).
Focal nodular hyperplasia (FNH) is a polyclonal tumour-like hepatic lesion characterised by parenchymal nodules, connective tissue septa without interlobular bile ducts, pronounced ductular reaction and inflammation. It may represent a response to local arterial hyperperfusion and hyperoxygenation resulting in oxidative stress. We aimed at obtaining closer insight into the pathogenesis of FNH with its characteristic morphologic features.
View Article and Find Full Text PDFThe functioning of microbial ecosystems has important consequences from global climate to human health, but quantitative mechanistic understanding remains elusive. The components of microbial ecosystems can now be observed at high resolution, but interactions still have to be inferred e.g.
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