Cerebral preconditioning (PC) confers endogenous brain protection after stroke. Ischemic stroke patients with a prior transient ischemic attack (TIA) may potentially be in a preconditioned state. Although PC has been associated with the activation of pro-survival signals, the mechanism by which preconditioning confers neuroprotection is not yet fully clarified. Recently, we have described that PC-mediated neuroprotection against ischemic insult is promoted by p53 destabilization, which is mediated by its main regulator MDM2. Moreover, we have previously described that the human Tp53 Arg72Pro single nucleotide polymorphism (SNP) controls susceptibility to ischemia-induced neuronal apoptosis and governs the functional outcome of patients after stroke. Here, we studied the contribution of the human Tp53 Arg72Pro SNP on PC-induced neuroprotection after ischemia. Our results showed that cortical neurons expressing the Pro72-p53 variant exhibited higher PC-mediated neuroprotection as compared with Arg72-p53 neurons. PC prevented ischemia-induced nuclear and cytosolic p53 stabilization in Pro72-p53 neurons. However, PC failed to prevent mitochondrial p53 stabilization, which occurs in Arg72-p53 neurons after ischemia. Furthermore, PC promoted neuroprotection against ischemia by controlling the p53/active caspase-3 pathway in Pro72-p53, but not in Arg72-p53 neurons. Finally, we found that good prognosis associated to TIA within 1month prior to ischemic stroke was restricted to patients harboring the Pro72 allele. Our findings demonstrate that the Tp53 Arg72Pro SNP controls PC-promoted neuroprotection against a subsequent ischemic insult by modulating mitochondrial p53 stabilization and then modulates TIA-induced ischemic tolerance.
AIM:To examine the conceptual ambiguity of nursing leadership, particularly in relation to management roles, and to propose a multilevel competency framework that redefines leadership as a core dimension of nursing practice. The paper introduces an innovative hybrid Iceberg-Alles model that integrates observable competencies with deeper motivational, ethical and personality-based attributes. DESIGN:Integrative review. METHODS:Two-stage evidence identification process informed by theoretical reflection and existing evidence on nursing leadership and management. DATA SOURCES:A literature search was conducted in targeted databases such as PubMed, Scopus, Web of Science, CINAHL and extended to Google Scholar and grey literature. IMPLICATIONS FOR NURSING:Current understandings of nursing leadership are fragmented and often limited to managerial skills, overlooking crucial aspects such as ethical commitment, personal values, interpersonal skills and relational capacities. The hybrid Iceberg-Alles model reconceptualizes leadership as a multidimensional construct that balances visible skills with underlying drivers such as motivation, self-awareness and value alignment, offering a more comprehensive basis for leadership development. CONCLUSIONS:Nursing leadership should be understood as a relational and value-based process embedded across all levels of practice, not confined to formal administrative positions. The proposed model enhances conceptual clarity and provides a transferable framework that can be adapted across diverse health systems, roles and organisational structures. IMPACT:Broadening the scope of nursing leadership can reduce role ambiguity, highlight the unique contribution of nurses to healthcare systems, and strengthen the profession's influence in policy and decision-making. The hybrid model provides concrete guidance for educational programmes, competency-based curricula and organisational strategies aimed at preparing future nurse leaders to manage complexity, promote collaboration and improve patient care. REPORTING METHOD:This manuscript followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines (PRISMA-ScR). PATIENT OR PUBLIC CONTRIBUTION:This study did not include patient or public involvement in its design, conduct or reporting.
Healthcare systems worldwide face mounting pressure to deliver high-quality care while enhancing efficiency and sustainability. Nurse-led interventions have emerged as promising strategies to optimize care delivery, particularly within value-based health systems. However, a comprehensive understanding of their clinical impact and economic value remains limited. This systematic review conducted following PRISMA guidelines, searched nine international databases to identify and synthesize formally evaluated nurse-led interventions, programs, and strategies. Twenty-eight studies were included, encompassing diverse care settings and patient populations. Most studies reported improvements in clinical outcomes, including reduced hospital readmissions, enhanced quality of life, and improved chronic disease management. Several interventions analyzed effectiveness, particularly those involving advanced nursing roles such as nurse practitioners and case managers. Findings suggest that clinical effectiveness does not necessarily translate into increased professional authority: nurse-led interventions consistently generate value across patient, organizational, and systemic dimensions, yet nursing leadership remains structurally subordinate within healthcare governance. A systematic agenda for rigorous economic evaluation embedded in nursing research programs is urgently needed, alongside structural reforms that redistribute authority-not merely develop competencies-within healthcare organizations.
Abstract Aims To characterize the long-term physiological, symptomatic, psychological, and functional outcomes in patients with obstructive sleep apnea (OSA) and excessive daytime sleepiness (EDS) treated with continuous positive airway pressure (CPAP), and to identify residual limitations despite optimal therapy. Methods Prospective multicenter cohort including 616 adults with OSA and EDS assessed at baseline, 6, 12, and 24 months. Evaluations included polysomnography (apnea-hypopnea index [AHI], CT90, mean SpO₂), Epworth Sleepiness Scale (ESS), EuroQol-5D (EQ-5D), Functional Outcomes of Sleep Questionnaire (FOSQ), Hospital Anxiety and Depression Scale (HADS), and CPAP adherence. Longitudinal descriptive analyses were performed. Results Mean age was 55.6 ± 11.5 years; 65.6% were male. At baseline, most patients had severe OSA (mean AHI 39.5 ± 25.9/h) with significant hypoxic burden (CT90 21.7 ± 23.1%) and marked clinical impairment (ESS 10.9 ± 5.5; HADS 12.1 ± 7.2; FOSQ 92.1 ± 24.4; EQ-5D 71.0 ± 16.9). CPAP treatment resulted in early and statistically significant improvement across all symptomatic, psychological, and functional domains at 6 months (ESS 7.95 ± 4.6; HADS 4.17 ± 6.6; FOSQ 100.1 ± 21.3; all p < 0.001), together with marked physiological correction (AHI 3.2 ± 5.0/h; CT90 0.5%; mean SpO₂ 95%). Improvements were sustained at 12 months (ESS 7.19 ± 4.2; HADS 2.04 ± 4.8; FOSQ 101.5 ± 21.0), with excellent adherence (90.8% of patients using CPAP >4 h/night). Despite overall recovery, selected functional domains—particularly general activity—showed incomplete improvement, despite optimal physiological correction. Preliminary 24-month data, although limited, suggested maintenance of symptomatic and functional benefit. Conclusions In patients with OSA and EDS, CPAP provides rapid and sustained improvements in physiological, symptomatic, psychological, and functional outcomes over long-term follow-up with excellent adherence. However, persistent functional limitations in selected domains suggest that CPAP alone may be insufficient to fully restore daily functioning in this phenotype, supporting the need for comprehensive, multidimensional follow-up strategies and potential adjunctive interventions beyond CPAP monotherapy. This abstract is funded by: SEPAR, SES, BIOPROJET,
