Damaging mutations in liver X receptor-α are hepatotoxic and implicate cholesterol sensing in liver health.

Liver X receptor-α (LXRα) regulates cellular cholesterol abundance and potently activates hepatic lipogenesis. Here we show that at least 1 in 450 people in the UK Biobank carry functionally impaired mutations in LXRα, which is associated with biochemical evidence of hepatic dysfunction. On a western diet, male and female mice homozygous for a dominant negative mutation in LXRα have elevated liver cholesterol, diffuse cholesterol crystal accumulation and develop severe hepatitis and fibrosis, despite reduced liver triglyceride and no steatosis.

Guidelines for evaluating and reporting social isolation and loneliness interventions.

Given the unpleasant nature of social isolation and loneliness (SIL) and their negative effects on health and wellbeing, interventions are needed. However, persistent issues in the design, evaluation, and reporting of SIL interventions preclude conclusive evidence and commentary on the effectiveness of SIL interventions. Here, we propose guidelines for evaluating SIL interventions, firstly by operationalising them into two categories: (1) interventions aiming to reduce SIL as a primary outcome and (2) interventions aiming to improve non-SIL outcomes in the lives of individuals experiencing SIL.

Selenoprotein deficiency disorder predisposes to aortic aneurysm formation.

Aortic aneurysms, which may dissect or rupture acutely and be lethal, can be a part of multisystem disorders that have a heritable basis. We report four patients with deficiency of selenocysteine-containing proteins due to selenocysteine Insertion Sequence Binding Protein 2 (SECISBP2) mutations who show early-onset, progressive, aneurysmal dilatation of the ascending aorta due to cystic medial necrosis. Zebrafish and male mice with global or vascular smooth muscle cell (VSMC)-targeted disruption of Secisbp2 respectively show similar aortopathy.

[Social, emotional and existential loneliness among nursing home residents with somatic problems].

Relatively little is known about loneliness in nursing homes. The aim of this study is to gain insight in the prevalence of social, emotional and existential loneliness among nursing home residents and in the relationship between loneliness and participation in activities and having contacts. Data is collected among nursing home residents in the province of Zeeland in the Netherlands (N = 101; age range = 42 to 103 years; median = 83 years; 71% female).

Older adults' mentioned practices for coping with loneliness.

In recent years, loneliness has been receiving increasing attention, yet there remains a lot to learn about how older adults cope with loneliness. In this study, the practices older adults consider for coping with loneliness and the relationship between various types of coping practices, loneliness, and personal resources are examined. Several hypotheses about the relationship between social and emotional loneliness, personal resources, and mentioning coping practices are formulated.