Antonio Melillo

Bipolar disorders (BD) are associated with high disability, comorbidities, and premature mortality, yet diagnosis is often delayed by several years. Research has identified bipolar at-risk states (BARS), but no study has tested the feasibility and acceptability of a dedicated specialist service. Consequently, evidence is lacking on optimal service set up, outreach strategies, and referral pathways required to effectively implement a BD prevention service. Outreach and Support in South London (OASIS)-BAR was piloted for 18 months as the first National Health Service (NHS)-funded standalone specialist service for individuals at risk of BD. The service, co-designed with experts by experience, operated in Lambeth, London, a socially deprived and ethnically diverse borough. Feasibility was evaluated through service set up, efficiency (outreach performance, waiting times, detection rates, treatment provision), and continuity of care (successful discharge planning). Acceptability was assessed through service engagement and qualitative feedback from service users and stakeholders. Of 28 referrals, 17 were assessed and 10 (58, 8%) met SIBARS criteria. The mean waiting time from referral to complete assessment was 22.4 days. All service users received medical reviews (100%), while most received psychotherapy (66, 7%) and occupational support (77, 8%). Engagement was satisfactory (mean length = 271 days). Service users expressed high satisfaction, and professional stakeholders emphasised the service’s role in addressing unmet needs and alleviating caseload burden on other services. OASIS-BAR pilot implementation demonstrated the feasibility and acceptability of a standalone service for BD prevention within the NHS. Findings support the development of similar innovative services, which may strengthen early detection and preventive care, ultimately improving long-term outcomes for many young people.

The p53 transcription factor plays a critical role in cellular responses to stress. Its activation in response to DNA damage leads to cell growth arrest, allowing for DNA repair, or directs cellular senescence or apoptosis, thereby maintaining genome integrity. Senescence is a permanent cell-cycle arrest that has a crucial role in aging, and it also represents a robust physiological antitumor response, which counteracts oncogenic insults. In addition, senescent cells can also negatively impact the surrounding tissue microenvironment and the neighboring cells by secreting pro-inflammatory cytokines, ultimately triggering tissue dysfunction and/or unfavorable outcomes. This review focuses on the characteristics of senescence and on the recent advances in the contribution of p53 to cellular senescence. Moreover, we also discuss the p53-mediated regulation of several pathophysiological microenvironments that could be associated with senescence and its development.