Obesity-associated MRAP2 variants impair multiple MC4R-mediated signaling pathways.

The melanocortin-4 receptor (MC4R) is a G protein-coupled receptor expressed at hypothalamic neurons that has an important role in appetite suppression and food intake. Mutations in MC4R are the most common cause of monogenic obesity and can affect multiple signaling pathways including Gs-cAMP, Gq, ERK1/2, β-arrestin recruitment, internalization and cell surface expression. The melanocortin-2 receptor accessory protein 2 (MRAP2), is a single-pass transmembrane protein that interacts with and regulates signaling by MC4R.

The modern use of hydroxyurea for children with sickle cell anemia.

Over the past 40 years, the introduction and refinement of hydroxyurea therapy has led to remarkable progress for the care of individuals with sickle cell anemia (SCA). From initial small proof-of-principle studies to multi-center Phase 3 controlled clinical trials and then numerous open-label studies, the consistent benefits of once-daily oral hydroxyurea have been demonstrated across the lifespan. Elevated fetal hemoglobin (HbF) serves as the most important treatment response, as HbF delays sickle hemoglobin polymerization and reduces erythrocyte sickling.

Caring for young adult men with inflammatory bowel disease: Clinician and patient perspectives.

Inflammatory bowel disease (IBD) presents unique challenges for young adult men that extend beyond physical symptoms, encompassing psychosocial dimensions affecting all aspects of life. This article draws insights from a roundtable discussion facilitated by the Crohn's and Colitis Young Adults Network (CCYAN), focusing on the experiences of young men living with IBD. It sheds light on the intersections of IBD and men's sexual and reproductive health, fertility, and mental well-being while identifying gaps in care.

Diagnostic interobserver variability of atypia assessment in columnar cell lesions among a group of expert breast pathologists in the United Kingdom and the Republic of Ireland, on behalf of the UK national coordinating committee for breast pathology.

Aims: Atypical ductal hyperplasia and flat epithelial atypia (FEA) have defined diagnostic criteria, yet there is variation in the interpretation of these criteria, particularly when the atypia is present in a background of columnar cell lesions (CCLs). This study focuses upon cases which are especially challenging or difficult to classify reproducibly according to existing criteria.

Methods And Results: Thirteen breast pathology experts were asked to classify 10 challenging cases with CLLs as atypical or non-atypical.

Qualitative evaluation of my life today - A co-produced personal tool from the IDEAL programme to help people with dementia monitor valued aspects of their lives.

Self-management of chronic conditions can help individuals take control of their health, both improving well-being and reducing the burden on health and social care resources. This study explored the potential of our co-produced self-management tool, My Life Today (MLT), to help people with dementia identify, plan and monitor aspects of their lives that are important to them and that help to maintain or improve well-being. We asked people with dementia to try using MLT.