Gut microbiota depletion aggravates bile acid-induced liver pathology in mice with a human-like bile acid composition.

Cyp2c70-deficient mice have a human-like bile acid (BA) composition due to their inability to convert chenodeoxycholic acid (CDCA) into rodent-specific muricholic acids (MCAs). However, the hydrophobic BA composition in these animals is associated with liver pathology. Although Cyp2c70-ablation has been shown to alter gut microbiome composition, the impact of gut bacteria on liver pathology in Cyp2c70-/- mice remains to be established.

Bile Acid Sequestration via Colesevelam Reduces Bile Acid Hydrophobicity and Improves Liver Pathology in Mice with a Human-like Bile Acid Composition.

Bile acids (BAs) and their signaling pathways have been identified as therapeutic targets for liver and metabolic diseases. We generated (KO) mice that were not able to convert chenodeoxycholic acid into rodent-specific muricholic acids (MCAs) and, hence, possessed a more hydrophobic, human-like BA pool. Recently, we have shown that KO mice display cholangiopathic features with the development of liver fibrosis.

Low production of 12α-hydroxylated bile acids prevents hepatic steatosis in Cyp2c70 mice by reducing fat absorption.

Bile acids (BAs) play important roles in lipid homeostasis, and BA signaling pathways serve as therapeutic targets for nonalcoholic fatty liver disease (NAFLD). Recently, we generated cytochrome P450, family 2, subfamily C, polypeptide 70 (Cyp2c70) mice with a human-like BA composition lacking mouse-/rat-specific muricholic acids to accelerate translation from mice to humans. We employed this model to assess the consequences of a human-like BA pool on diet-induced obesity and NAFLD development.

Gender differences between adolescents with autism in emergency psychiatry.

Among adolescents seen for psychiatric emergency consultation, the percentage of adolescents with autism is increasing over the years. This applies even more to girls than to boys. We collected data of 1378 adolescents aged 12-18 years who were seen for urgent consultation by mobile psychiatric emergency services in the Netherlands.

Increased prevalence of intellectual disabilities in higher-intensity mental healthcare settings.

Background: It has been suggested that people with intellectual disabilities have a higher likelihood to develop psychiatric disorders, and that their treatment prognosis is relatively poor.

Aims: We aimed to establish the prevalence of intellectual disability in different mental healthcare settings, and estimate percentage of cognitive decline. We hypothesised that the prevalence of intellectual disabilities increases with intensity of care.

The Impact of Antipsychotic Formulations on Time to Medication Discontinuation in Patients with Schizophrenia: A Dutch Registry-Based Retrospective Cohort Study.

Background: Many patients with schizophrenia discontinue antipsychotic medication, frequently with adverse outcomes. Although different antipsychotic formulations are associated with different times to discontinuation, not much is known about discontinuation rates with oral-weekly formulations. Such a formulation of penfluridol is available in both the Netherlands and several other countries.

Increased insulin sensitivity and diminished pancreatic beta-cell function in DNA repair deficient Ercc1 mice.

Background: Type 2 diabetes (T2DM) is an age-associated disease characterized by hyperglycemia due to insulin resistance and decreased beta-cell function. DNA damage accumulation has been associated with T2DM, but whether DNA damage plays a role in the pathogenesis of the disease is unclear. Here, we used mice deficient for the DNA excision-repair gene Ercc1 to study the impact of persistent endogenous DNA damage accumulation on energy metabolism, glucose homeostasis and beta-cell function.

Cholangiopathy and Biliary Fibrosis in Cyp2c70-Deficient Mice Are Fully Reversed by Ursodeoxycholic Acid.

Background And Aims: Bile acids (BAs) aid intestinal fat absorption and exert systemic actions by receptor-mediated signaling. BA receptors have been identified as drug targets for liver diseases. Yet, differences in BA metabolism between humans and mice hamper translation of pre-clinical outcomes.

Spontaneous liver disease in wild-type C57BL/6JOlaHsd mice fed semisynthetic diet.

Mouse models are frequently used to study mechanisms of human diseases. Recently, we observed a spontaneous bimodal variation in liver weight in C57BL/6JOlaHsd mice fed a semisynthetic diet. We now characterized the spontaneous variation in liver weight and its relationship with parameters of hepatic lipid and bile acid (BA) metabolism.

A Qualitative Study of the Working Alliance between Patient and Community Mental Health Nurse during Interpersonal Community Psychiatric Treatment.

In the Netherlands, long-term community psychiatric treatment for patients with a severe mental illness (SMI) is poorly developed and lacks a structured, goal-centered approach. Often this form of treatment is provided by community mental health nurses (CMHN's).Especially in the group of nonpsychotic patients with SMI, it often leads to care-as-usual with limited proven interventions and an unstructured treatment.

A human-like bile acid pool induced by deletion of hepatic modulates effects of FXR activation in mice.

Bile acids (BAs) facilitate intestinal absorption of lipid-soluble nutrients and modulate various metabolic pathways through the farnesoid X receptor (FXR) and Takeda G-protein-coupled receptor 5. These receptors are targets for therapy in cholestatic and metabolic diseases. However, dissimilarities in BA metabolism between humans and mice complicate translation of preclinical data.

Glucose-6-Phosphate Regulates Hepatic Bile Acid Synthesis in Mice.

It is well established that, besides facilitating lipid absorption, bile acids act as signaling molecules that modulate glucose and lipid metabolism. Bile acid metabolism, in turn, is controlled by several nutrient-sensitive transcription factors. Altered intrahepatic glucose signaling in type 2 diabetes associates with perturbed bile acid synthesis.

Mental health professionals' knowledge, skills and attitudes on domestic violence and abuse in the Netherlands: cross-sectional study.

Background: Despite the high prevalence of domestic violence and abuse (DVA) among patients with psychiatric conditions, detection rates are low. Limited knowledge and skills on DVA in mental healthcare (MHC) professionals might contribute to poor identification.AimsTo assess the level of, and factors associated with, DVA knowledge and skills among MHC professionals.

AAV8-mediated gene transfer of microRNA-132 improves beta cell function in mice fed a high-fat diet.

MicroRNAs have emerged as essential regulators of beta cell function and beta cell proliferation. One of these microRNAs, miR-132, is highly induced in several obesity models and increased expression of miR-132 in vitro modulates glucose-stimulated insulin secretion. The aim of this study was to investigate the therapeutic benefits of miR-132 overexpression on beta cell function in vivo.

Lymphocyte-Derived Exosomal MicroRNAs Promote Pancreatic β Cell Death and May Contribute to Type 1 Diabetes Development.

Type 1 diabetes is an autoimmune disease initiated by the invasion of pancreatic islets by immune cells that selectively kill the β cells. We found that rodent and human T lymphocytes release exosomes containing the microRNAs (miRNAs) miR-142-3p, miR-142-5p, and miR-155, which can be transferred in active form to β cells favoring apoptosis. Inactivation of these miRNAs in recipient β cells prevents exosome-mediated apoptosis and protects non-obese diabetic (NOD) mice from diabetes development.

Treatment results for severe psychiatric illness: which method is best suited to denote the outcome of mental health care?

Background: The present study investigates the suitability of various treatment outcome indicators to evaluate performance of mental health institutions that provide care to patients with severe mental illness. Several categorical approaches are compared to a reference indicator (continuous outcome) using pretest-posttest data of the Health of Nation Outcome Scales (HoNOS).

Methods: Data from 10 institutions and 3189 patients were used, comprising outcomes of the first year of treatment by teams providing long-term care.

Employment Rates in Flexible Assertive Community Treatment Teams in The Netherlands: An Observational Study.

We determined the proportions of clients treated in Flexible Assertive Community Treatment teams who were unemployed and gained employment and who were employed and lost employment. Secondly, we explored the demographical and clinical factors associated with employment. Data were collected during routine outcome monitoring.

Associations between psychiatric symptoms and seclusion use: Clinical implications for care planning.

Findings from an increasing number of studies suggest that incorporating systematic short-term risk assessments in treatment planning could lead to safer practice on psychiatric admissions wards. The aim of the present study was to investigate the associations between the scores of three structured observation tools - the Kennedy Axis V (K-Axis-V), the Brief Psychiatric Rating Scale (BPRS), and the Social Dysfunction and Aggression Scale (SDAS) - and seclusion. In total, 1840 weekly risk assessments with these observation scales were collected over 2342 admission weeks.

Different Perspectives of Clinicians and Patients with Severe Mental Illness on Motivation for Treatment.

Unlabelled: The present study assessed motivation for engaging in treatment as rated by clinicians (n = 57) and patients with severe mental illness (SMI, n = 294) using measures based on three different motivation theories. Questionnaires were derived from self-determination theory, the transtheoretical model and the integral model of treatment motivation. It was investigated to which extent clinicians of patients with SMI were able to estimate their patient's perspective on motivation for engaging in treatment, to which extent they agreed on the patient's motivation and which factors were associated with estimation and agreement on treatment motivation.

Cost effectiveness of interpersonal community psychiatric treatment for people with long-term severe non-psychotic mental disorders: protocol of a multi-centre randomized controlled trial.

Background: This study aims for health gain and cost reduction in the care for people with long-term non-psychotic psychiatric disorders. Present care for this population has a limited evidence base, is often open ended, little effective, and expensive. Recent epidemiological data shows that 43.

Flexible ACT & Resource-group ACT: Different Working Procedures Which Can Supplement and Strengthen Each Other. A Response.

This article is a response to Nordén and Norlander's 'Absence of Positive Results for Flexible Assertive Community Treatment. What is the next approach?'[1], in which they assert that 'at present [there is] no evidence for Flexible ACT and… that RACT might be able to provide new impulses and new vitality to the treatment mode of ACT'. We question their analyses and conclusions.