Lifestyle habits, cognitive reserve, and affective reserve (secure attachment, extraversion, psychological resilience) predict resilience in the oldest-old, though the underlying biological mechanisms remain unclear. This study explored relationships between these protective factors, 120 + NULISA CNS blood biomarkers, and multidimensional health outcomes (global cognition, mental health, walking speed) in 401 dementia-free participants (age 83-87) from the InveCe.Ab study. Using sparse partial least squares (sPLS) regression, eight biomarkers were stably associated with the protective factors: HBA1, DDC, IFNG, IL15, GOT1, ACHE, SNAP25, and SNCB. Structural equation modeling (SEM) showed that the three protective factors exerted an independent and domain-specific effect on health outcomes. Moreover, lifestyle habits were associated with ACHE (β = 0.26), IL15 (β = 0.22), and GOT1 (β = 0.28); affective reserve showed inverse associations with IFNG (β = -0.13) and IL15 (β = -0.31), and GOT1 (β = -0.18). Regarding health domains, SNAP25 was inversely related to global cognition (β = -0.10), while SNCB was associated with global cognition (β = 0.16) and walking speed (β = 0.13). Notably, no significant mediated effects were found, suggesting that the clinical benefits observed were not directly driven by the aforementioned biological pathways. The present study paves the way for further investigations on the biological mechanisms underlying resilient aging, while further demonstrating the key protective role of individual habits and psychosocial characteristics during the life course.

To explore how neonatal nurses in Level III (high-acuity) neonatal intensive care units recognise, interpret, and escalate early signs of clinical deterioration.

A qualitative interpretive description study underpinned by critical realism.

Twenty-two registered nurses were purposively recruited from four Level III units in the Jouf Region of northern Saudi Arabia using criterion-based maximum-variation sampling. Semi-structured interviews were conducted in Arabic or English and analysed in their original language. Situation awareness and invisible work scholarship served as sensitising lenses. Rigour was supported through member reflection, negative-case analysis, peer debriefing and an audit trail.

Four interrelated themes were identified: (1) 'the infant tells you before the monitor does', reflecting recognition of subtle deviation from the infant's baseline; (2) 'building the case', in which nurses tested and assembled evidence to make concern clinically credible before escalation; (3) 'the escalation calculus', describing how anticipated physician responses, hierarchy and previous dismissal shaped escalation and (4) 'the unit works against you', showing how alarm burden, documentation demands and staffing variability constrained vigilance. Recognition and escalation formed a cyclical, organisationally situated process rather than a single response to abnormal observations.

Escalation involved interpretive, relational and legitimising work before early concern became actionable. Participants' accounts suggest that timely response depends on clinical expertise and environments that protect bedside attention and legitimise early escalation.

Neonatal services should protect surveillance capacity through staffing and workload design, alarm reduction, simulation of ambiguous deterioration and constructive escalation feedback.

The study identifies case-building as a distinct stage between noticing deterioration and escalating concern and indicates how organisational conditions may constrain early nursing surveillance.

Consolidated Criteria for Reporting Qualitative Research.

Patients and the public were not involved.

Individuals with autosomal dominant frontotemporal dementia (FTD) exhibit considerable variability in disease onset and progression. Both modifiable and non-modifiable factors-such as sex, educational attainment or geographic region of residence-may contribute to this heterogeneity, potentially through their influence on cognitive reserve. The aim of the present study was to investigate the role of cognitive reserve modulators within the Genetic Frontotemporal dementia Initiative (GENFI) cohort. To this end, we used functional MRI (i.e. spatial chronnectome measures) and neurodegenerative markers (i.e. plasma neurofilament light chains levels) to determine disease stage using a Discriminative Event-Based Model (DEBM). We then examined how potential modulators influence the relationship between disease stage and cognitive performance. We analysed a total of 711 participants, including 106 patients with genetic FTD, 325 presymptomatic mutation carriers and 280 non-carriers healthy controls. Female participants showed a weaker association between disease stage and cognitive performance compared to males (P < 0.001), with difference becoming progressively more pronounced across symptomatic stages. Educational attainment exhibited a similar effect: individuals with higher education demonstrated an attenuated association compared to those with secondary or primary schooling (P < 0.001), with differences already detectable at prodromal disease stages. The effect of geographical region of residence was associated with education levels, but appeared to have an indirect and less strong influence. In summary, sex and educational attainment significantly affect the development and maintenance of cognitive reserve in individuals with genetic FTD. These findings underscore the importance of identifying disease-modifying interventions since the presymptomatic stages of the disease.

Schizophrenia imposes significant economic and social burdens, often resulting in prolonged inpatient length of stay (LOS), particularly for treatment-resistant cases. This study aimed to identify clinical, demographic, and social factors associated with prolonged LOS in a Canadian tertiary schizophrenia inpatient unit to highlight modifiable drivers and inform targeted interventions.

A retrospective chart review of 120 consecutive discharges from January 2021 to May 2023 was conducted. Data on demographics, clinical history, and discharge delays were analyzed using ANOVA and t-tests to identify factors associated with prolonged LOS. Prolonged LOS was examined while differentiating between discharge delays and extended hospital stays.

The mean LOS was 200.43 days (SD = 285.67, median = 100 days). Fifty percent of patients (n = 60) experienced discharge delays, defined as >10 days between readiness and actual discharge. Housing instability was the leading cause (56.67%, n = 34), including patients seeking housing (40%) or awaiting long-term care (16.67%). Longer illness duration (p = 0.048) and treatment-resistant schizophrenia (TRS, indicated by clozapine use; p = 0.011) were significantly associated with length of delayed discharge. Sex, relationship status, and family or community support were not significantly associated with length of delayed discharge. Illness complexity/severity was the primary reason for extended hospital stay in all cases (100%, n = 12).

This exploratory study highlights distinct clinical and system-level contributors to prolonged hospitalization. Housing instability, chronic illness, and TRS are key contributors to delays in discharge. Early discharge planning, enhanced housing support, and specialized TRS care pathways are essential to reduce LOS and optimize inpatient care.

Reliable data on population-level need for rehabilitation services and assistive products (AP) across different settings are lacking. The Functional Needs Assessment Tool (FNAT) is a new survey method for estimating the prevalence of functional difficulties/impairment and the need for services and AP. It combines self-report, clinical impairment and functional assessments across seven domains: vision, hearing, mobility, communication, cognition, self-care, and mental health. Data are collected using a bespoke mobile application and web-based platform. The FNAT methodology is presented in the first paper in this series.

The FNAT was pilot-tested in Kalungu District, Uganda, between March and July 2023 to assess the feasibility of the methodology and the functionality of the mobile data collection application.

Two pilot studies were conducted across 18 communities/villages, including 305 (pilot 1) and 550 (pilot 2) participants aged 2 years and older. Participants were identified using a two-stage cluster sampling method and underwent assessments using standardised tools to evaluate functional difficulties/impairments and the need for services and AP.

The pilot studies identified several key learnings, such as the need for questionnaire revisions and improvements to the application programming. It confirmed the feasibility of completing the two-stage assessments over 2 days with a cluster size of 45 participants (participants aged 2 years and older) while including visual acuity screening for all participants.

The FNAT is a feasible approach for estimating the prevalence of functional difficulties and the need for and coverage of related services and AP, with lessons learned for future development, and should be tested at scale. The field-test study is presented in the final paper in this series.

Healthcare professionals in intensive care units face substantial psychological stress, yet structured educational approaches to promote mental health during early training remain underdeveloped. While current recommendations advocate early integration of psychosocial support into onboarding, they have not been translated into competency-based educational frameworks aligned with modern health professions education.

To develop a competency-based educational framework for ICU onboarding that integrates mental health promotion into structured learning objectives across knowledge, reflection, and action domains.

A mixed-methods design was applied, combining a structured consensus process with competency-based curricular mapping. Guiding questions were iteratively refined using a two-stage rapid consensus process involving a multidisciplinary panel of clinicians, educators, and external experts in psychology and occupational health. Consensus was defined as the absence of substantial disagreement. The resulting content was mapped to competency dimensions informed by competency-based medical education principles and aligned with Miller's Pyramid, a hierarchical model of clinical competence ranging from knowledge to action.

The process resulted in a competency-based framework comprising eight educational domains: relevance of mental health, ICU-specific stressors, conceptual understanding of stress, resilience and coping, the second victim phenomenon (the psychological impact on healthcare professionals following adverse events), structural support systems, professional self-reflection, and shared responsibility. Each domain was operationalized into competency levels (knowledge to evaluation), enabling constructive alignment between learning objectives, teaching formats, and potential assessment strategies. The framework integrates individual, team, and organizational perspectives and provides a structured basis for embedding psychosocial competencies into onboarding curricula.

This study may contribute to advancing health professions education and supports constructive alignment among learning objectives, teaching formats, and assessment strategies. It operationalizes existing recommendations into actionable educational components and supports constructive alignment in curriculum design. Implementation and evaluation studies are warranted to assess its impact on learning outcomes, behavioral change, and clinical practice.

Healthcare maintenance plays a vital role in the long-term management of patients with inflammatory bowel disease (IBD), particularly those receiving immunosuppressive therapies. This review emphasizes the importance of maintaining up-to-date vaccinations, regular bone and mental health assessments, and appropriate cancer screening in this population. It also highlights the added complexity of preventive care in immunosuppressed patients, outlining specific modifications to vaccination and screening strategies required to ensure safe and effective disease management. Gastroenterologists and other clinicians involved in IBD care should remain familiar with current guidelines and consistently integrate preventive health measures into routine clinical practice.

Abstract.

Depression is a pervasive mental health disorder that has been extensively studied, but effective treatment remains elusive. This is due to the lack of understanding regarding the underlying molecular mechanisms. Antidepressants usually target the monoaminergic system, but studies show that other neurotransmitters, such as acetylcholine (ACh), may be involved. Many clinical and preclinical studies show that increased ACh levels are associated with depression. Particularly, acetylcholinesterase (AChE) activity is shown to decrease in depression and antidepressants are known to increase it. However, it is not known whether this effect is direct or downstream.

To check whether antidepressants can directly modulate AChE activity, we evaluated the effect of various classes of antidepressants on ex vivo AChE activity in the frontal cortex, hippocampus and striatum of male and female rats.

Briefly, sertraline (SER), escitalopram (ESC), amitriptyline (AT), duloxetine (DUL), bupropion (BUP) and ketamine (KET) were incubated with the brain tissue homogenates in a 96-well plate for 30 min, following which AChE activity was evaluated by modified Ellman's method.

SER and ESC increased AChE activity in the frontal cortex, while AT, DUL, BUP and KET did not affect it.

This points to a novel mechanism of action of selective serotonin reuptake inhibitors (SSRIs) and a potential target for developing new therapeutics with better efficacy and lower side effect profiles.