Seamless Management of Juvenile Autoimmune Liver Disease: Long-Term Medical and Social Outcome.

Objectives: To report baseline features and long-term medical/social outcomes of juvenile autoimmune liver disease, including autoimmune hepatitis (AIH) and autoimmune sclerosing cholangitis (ASC), managed in a single tertiary center.

Study Design: Retrospective study of children diagnosed in 2000-2004 with AIH/ASC followed up to date. Patients with abnormal cholangiogram were classified as ASC.

Critical roles of conventional dendritic cells in autoimmune hepatitis via autophagy regulation.

Autoimmune hepatitis (AIH) is a necroinflammatory disease associated with interactive cell populations of the innate and adaptive immune systems. The contribution of conventional dendritic cells (cDCs) to AIH and the underlying mechanism remain poorly understood. The frequency of peripheral mature cDCs increased in AIH patients and was positively correlated with disease severity.

Childhood and Adolescent Nonalcoholic Fatty Liver Disease: Is It Different from Adults?

Paediatric nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in childhood and adolescence. Although the condition is similar in many ways to NAFLD in adults, there are important differences in predisposition, presentation, differential diagnosis and potentially also in optimal management. Antenatal and early childhood exposures and the particular vulnerabilities to environmental influences in a growing child, present unique opportunities for intervention and modification of risk.

Journey to multimorbidity: longitudinal analysis exploring cardiovascular risk factors and sociodemographic determinants in an urban setting.

Objective: To study the social determinants and cardiovascular risk factors for multimorbidity and the acquisition sequence of multimorbidity.

Design: Longitudinal study based on anonymised primary care data.

Setting: General practices in an urban multiethnic borough in London, UK.

Concomitant systemic lupus erythematosus might have a negative impact on the biochemical responses to treatment in patients with primary biliary cholangitis.

Background: Primary biliary cholangitis (PBC) is often overlapping with other autoimmune conditions, including systemic lupus erythematosus (SLE). Since the concomitant PBC and SLE are rare, the impacts of SLE on the response and prognosis in ursodeoxycholic acid (UDCA)-treated patients with PBC remain unclear.

Methods: A PBC database of 769 patients at West China hospital was used to identify 26 patients with concomitant PBC and SLE.

Sickle cell disease and thalassaemia antenatal screening programme in England over 10 years: a review from 2007/2008 to 2016/2017.

Objectives: To evaluate the antenatal sickle cell and thalassaemia screening programme in England over 10 years from 1 April 2007 to 31 March 2017.

Methods: Four routine data sources were used: antenatal screening laboratory data; key performance indicator data from maternity trusts; prenatal diagnosis (PND) laboratory data and data from screening incidents.

Results: For the 10 years examined a total of 6608 575 booking samples were reported as screened, and 154 196 pregnant women required further testing.

Hypoglycaemia Awareness Restoration Programme for People with Type 1 Diabetes and Problematic Hypoglycaemia Persisting Despite Optimised Self-care (HARPdoc): protocol for a group randomised controlled trial of a novel intervention addressing cognitions.

Introduction: Severe hypoglycaemia (SH), when blood glucose falls too low to support brain function, is the most feared acute complication of insulin therapy for type 1 diabetes mellitus (T1DM). 10% of people with T1DM contribute nearly 70% of all episodes, with impaired awareness of hypoglycaemia (IAH) a major risk factor. People with IAH may be refractory to conventional approaches to reduce SH, with evidence for cognitive barriers to hypoglycaemia avoidance.

Tailoring drug release rates in hydrogel-based therapeutic delivery applications using graphene oxide.

Graphene oxide (GO) is increasingly used for controlling mass diffusion in hydrogel-based drug delivery applications. On the macro-scale, the density of GO in the hydrogel is a critical parameter for modulating drug release. Here, we investigate the diffusion of a peptide drug through a network of GO membranes and GO-embedded hydrogels, modelled as porous matrices resembling both laminated and 'house of cards' structures.

The Envelope Gene of Transmitted HIV-1 Resists a Late Interferon Gamma-Induced Block.

Type I interferon (IFN) signaling engenders an antiviral state that likely plays an important role in constraining HIV-1 transmission and contributes to defining subsequent AIDS pathogenesis. Type II IFN (IFN-γ) also induces an antiviral state but is often primarily considered to be an immunomodulatory cytokine. We report that IFN-γ stimulation can induce an antiviral state that can be both distinct from that of type I interferon and can potently inhibit HIV-1 in primary CD4 T cells and a number of human cell lines.

ASH1L (a histone methyltransferase protein) is a novel candidate globin gene regulator revealed by genetic study of an English family with beta-thalassaemia unlinked to the beta-globin locus.

In 1993, we described an English family with beta-thalassaemia that was not linked to the beta-globin locus. Whole genome sequence analyses revealed potential causative mutations in 15 different genes, of which 4 were consistently and uniquely associated with the phenotype in all 7 affected family members, also confirmed by genetic linkage analysis. Of the 4 genes, which are present in a centromeric region of chromosome 1, ASH1L was proposed as causative through functional mRNA knock-down and chromatin-immunoprecipitation studies in human erythroid progenitor cells.

Resistance of Transmitted Founder HIV-1 to IFITM-Mediated Restriction.

Interferon-induced transmembrane proteins (IFITMs) restrict the entry of diverse enveloped viruses through incompletely understood mechanisms. While IFITMs are reported to inhibit HIV-1, their in vivo relevance is unclear. We show that IFITM sensitivity of HIV-1 strains is determined by the co-receptor usage of the viral envelope glycoproteins as well as IFITM subcellular localization within the target cell.

The induction of autoimmune hepatitis in the human leucocyte antigen-DR4 non-obese diabetic mice autoimmune hepatitis mouse model.

Autoimmune hepatitis (AIH) is a chronic liver disease characterized by progressive inflammation, female preponderance and seropositivity for autoantibodies such as anti-smooth muscle actin and/or anti-nuclear, anti-liver kidney microsomal type 1 (anti-LKM1) and anti-liver cytosol type 1 (anti-LC1) in more than 80% of cases. AIH is linked strongly to several major histocompatibility complex (MHC) alleles, including human leucocyte antigen (HLA)-DR3, -DR7 and -DR13. HLA-DR4 has the second strongest association with adult AIH, after HLA-DR3.

Age-related aspects of human IgM(+) B cell heterogeneity.

The CD27(+) IgD(+) B cell population, known as IgM memory, reduces with age. It is thought that this population is responsible for pneumococcal polysaccharide T-independent responses, and that the age-related reduction might be partially responsible for the increased susceptibility of older people to bacterial pathogens. There are other IgM(+) B cell populations that do not express IgD.