Overexpression of Glucocorticoid Receptor ß Enhances Myogenesis and Reduces Catabolic Gene Expression.

Unlike the glucocorticoid receptor α (GRα), GR ß (GRß) has a truncated ligand-binding domain that prevents glucocorticoid binding, implicating GRα as the mediator of glucocorticoid-induced skeletal muscle loss. Because GRß causes glucocorticoid resistance, targeting GRß may be beneficial in impairing muscle loss as a result of GRα activity. The purpose of this study was to determine how the overexpression of GRß affects myotube formation and dexamethasone (Dex) responsiveness. We measured GR isoform expression in C2C12 muscle cells in response to Dex and insulin, and through four days of myotube formation. Next, lentiviral-mediated overexpression of GRß in C2C12 was performed, and these cells were characterized for cell fusion and myotube formation, as well as sensitivity to Dex via the expression of ubiquitin ligases. GRß overexpression increased mRNA levels of muscle regulatory factors and enhanced proliferation in myoblasts. GRß overexpressing myotubes had an increased fusion index. Myotubes overexpressing GRß had lower forkhead box O3 (Foxo3a) mRNA levels and a blunted muscle atrophy F-box/Atrogen-1 (MAFbx) and muscle ring finger 1 (MuRF1) response to Dex. We showed that GRß may serve as a pharmacological target for skeletal muscle growth and protection from glucocorticoid-induced catabolic signaling. Increasing GRß levels in skeletal muscle may cause a state of glucocorticoid resistance, stabilizing muscle mass during exposure to high doses of glucocorticoids.

A Web-Based Peer Support Network to Help Care Partners of People With Serious Illness: Co-Design Study.

BACKGROUND: Care partners of people with serious illness experience significant challenges and unmet needs during the patient's treatment period and after their death. Learning from others with shared experiences can be valuable, but opportunities are not consistently available. OBJECTIVE: This study aims to design and prototype a regional, facilitated, and web-based peer support network to help active and bereaved care partners of persons with serious illness be better prepared to cope with the surprises that arise during serious illness and in bereavement. METHODS: An 18-member co-design team included active care partners and those in bereavement, people who had experienced serious illness, regional health care and support partners, and clinicians. It was guided by facilitators and peer network subject-matter experts. We conducted design exercises to identify the functions and specifications of a peer support network. Co-design members independently prioritized network specifications, which were incorporated into an early iteration of the web-based network. RESULTS: The team prioritized two functions: (1) connecting care partners to information and (2) facilitating emotional support. The design process generated 24 potential network specifications to support these functions. The highest priorities included providing a supportive and respectful community; connecting people to trusted resources; reducing barriers to asking for help; and providing frequently asked questions and responses. The network platform had to be simple and intuitive, provide technical support for users, protect member privacy, provide publicly available information and a private discussion forum, and be easily accessible. It was feasible to enroll members in the ConnectShareCare web-based network over a 3-month period. CONCLUSIONS: A co-design process supported the identification of critical features of a peer support network for care partners of people with serious illnesses in a rural setting, as well as initial testing and use. Further testing is underway to assess the long-term viability and impact of the network.