To explore the experiences and perceptions of health and healthcare of clients of a co-designed, community-based service for people with frequent hospital admissions.

This qualitative study used semi-structured interviews guided by a schedule that covered each participant's experience and perception of their health and healthcare and experience of receiving care from the service; what is important to them when receiving care; and what, if any, effect being a client of the service had on their health and well-being. Interviews took place in participants' homes, were audio-recorded, transcribed verbatim and checked for accuracy. Participants were able to amend their transcript. Using thematic analysis informed by grounded theory, data were independently and iteratively analysed by two investigators and data saturation was reached. The study was guided by principles of qualitative rigour.

A nurse-led, multidisciplinary, community-based service comprising a nurse manager, GP, social worker, allied health assistant and administration assistant for people with frequent admissions at a public hospital in Tasmania, Australia.

Any past or existing client was eligible to participate. Twenty were interviewed. Their median age was 78 years, 50% were female and 55% lived alone.

Three themes were identified: (i) the challenges of ageing, (ii) complex care needs require intensive multidisciplinary holistic care and (iii) relationships are central to care and healthcare delivery. The three themes together formed a central organising theme: time to care. Having 'time to care' enabled healthcare workers to provide biomedical and psychosocial care and support and help participants address their challenges of ageing. It also allowed the development of trusting and respectful relationships that were essential to participants when receiving care.

To understand and support people with frequent admissions 'time to care' was essential. A range of healthcare workers were required to provide relational aspects of care, as well as individualised and time-intensive care that spanned medical, spiritual, mental and socio-economic dimensions across tertiary, social and community services. Diverse strategies may be needed to allow healthcare workers 'time to care'.

Burnout among healthcare professionals remains a critical public health issue linked to impaired cognition, emotional exhaustion and diminished clinical performance. Structured breathing practices have demonstrated promise in improving autonomic regulation and cerebral oxygenation, yet their feasibility, acceptability and implementation in real-world healthcare settings remain underexplored.

This single-arm pilot feasibility trial aims to evaluate the feasibility, acceptability and implementation appropriateness of a structured breathing-based intervention for healthcare professionals across community-based Mayo Clinic Health System (MCHS) sites. Secondary objectives include assessing usability and engagement with the mobile breathing platform, while exploratory analyses will describe magnitude of variability and feasibility of collecting psychological and cerebral haemodynamic measures. This study will commence in November 2025 and is expected to be completed by June 2026.

A total of 40 clinicians (MD/DO/MBBS/PA) and nurses reporting moderate or greater burnout will be enrolled across four MCHS sites. Participants will complete a 4-month structured breathing programme delivered primarily online, supported by a mobile application for practice tracking. Assessments will occur at baseline, 2 months and 4 months, with functional near-infrared spectroscopy (fNIRS) measures of cerebral oxygenation collected at baseline and 4 months in a population subset. Primary outcomes include (1) recruitment yield, retention and adherence rates; (2) acceptability and participant satisfaction (survey and qualitative feedback); and (3) implementation appropriateness measured by the Acceptability of Intervention Measure (AIM), Intervention Appropriateness Measure (IAM) and Feasibility of Intervention Measure (FIM). Secondary outcomes include digital engagement and usability through mobile analytics and the System Usability Scale. Exploratory outcomes are psychological indicators (burnout, depression, anxiety, perceived stress, sleep, fatigue, professional fulfilment and resilience) and physiological endpoints (fNIRS). Analyses will be descriptive, summarising feasibility metrics with 95% CIs. Progression criteria (recruitment≥75%, retention≥80%, adherence≥70%, AIM/IAM/FIM≥4.0) will determine readiness for a definitive hybrid effectiveness-implementation trial.

The study is approved by the Mayo Clinic Institutional Review Board (IRB # 25-009320). All participants will provide informed consent. Study procedures ensure confidentiality, cultural sensitivity and participant safety. Data will be securely stored in REDCap and disseminated through peer-reviewed publications and scientific conference TRIAL REGISTRATION NUMBER: NCT07218458.

Patients with advanced cancer are increasingly encouraged to self-manage the medical, psychosocial, and practical consequences of their illness. However, the impact of self-management skills on patient outcomes and healthcare utilisation remains unclear. Therefore, we examined self-management skills among patients with advanced cancer and their associations with depressive symptoms, quality of life, and formal and informal healthcare utilisation.

We embedded a cross-sectional questionnaire study in a Dutch nationwide prospective observational cohort study (eQuiPe study).

464 patients with advanced cancer (response rate 42.1%). 50% of the participants were women, and the mean age was 66 years (SD = 10).

Self-management skills were assessed using three scales of the Health Education Impact Questionnaire: Skill and technique acquisition (STA), Self-monitoring and insight (SMI), and Health services navigation (HSN) (range: 1-4). Multivariate linear and logistic regression analyses were performed to examine associations (adjusting for sociodemographic and medical characteristics) between self-management skills and depressive symptoms (Hospital Anxiety and Depression Scale), quality of life (European Organisation for Research and Treatment of Cancer), and healthcare utilisation in the past month (healthcare organisations and disciplines; hospital admissions; emergency care visits; informal care).

Mean (SD) scores were 3.0 (0.5) for STA, 3.2 (0.4) for SMI, and 3.4 (0.5) for HSN. Higher scores of self-management skills on all three scales were significantly associated with fewer depressive symptoms (STA: β = -2.36, 95% CI -2.98 to -1.69; SMI: β = -2.88, 95% CI -3.64 to -2.09; HSN: β = -2.06, 95% CI -2.76 to -1.37). Patients with higher levels of STA and SMI reported better quality of life (β = 8.54, 95% CI 5.84 to 11.01 and β = 8.41, 95% CI 4.75 to 11.99, respectively). Regarding healthcare utilisation, only HSN showed a significant association, with higher scores being associated with increased nurse contact (β = 1.65, 95% CI 1.09 to 2.56).

Greater self-management skills were associated with fewer depressive symptoms and improved quality of life in patients with advanced cancer. However, self-management skills were hardly associated with healthcare utilisation.

Netherlands Trial Register; NTR6584.

Depression is a mental disorder characterized by high incidence and relapse rates, and the search for effective treatments has been continuously pursued. To assess the effectiveness of existing studies, recent research advances are summarized with an emphasis on potential pathophysiological mechanisms through specific pathways of intestinal flora affecting depression, including microbial and metabolic activities, neuroendocrine regulation, immune and inflammatory responses, and microbial dysbiosis. This review also presents current therapeutic strategies targeting intestinal flora in depression and provides potential directions for future research.

Air pollution is a major global public health threat associated with increased morbidity and premature mortality. Growing evidence suggests that air pollution may also adversely affect brain health, contributing to cognitive impairment and mental disorders. However, most existing studies are observational and therefore vulnerable to residual confounding and reverse causation. Mendelian randomization (MR), which uses genetic variants as instrumental variables, offers a framework to strengthen causal inference regarding the neurological effects of air pollution. We conducted a 2-sample MR study using large-scale genome-wide association study data to investigate the causal effects of air pollution on neurodevelopmental and mental health outcomes. Exposures included ambient air pollutants (PM2.5, PM10, PM2.5-10, NO2, and NOx) and workplace-related air pollution, including self-reported "very dusty" workplace exposure, chemical or other fumes, and diesel exhaust. Neurodevelopmental and mental health outcomes comprised 17 genome-wide association studies datasets across 6 domains: cognitive function and intelligence, educational attainment, psychiatric disorders, emotional and behavioral disorders in children and adolescents, attention-deficit/hyperactivity disorder (ADHD), and neuroticism. Genetically proxied higher PM2.5 exposure was associated with lower intelligence and cognitive performance, reduced educational attainment, and increased risks of schizophrenia, depression, panic attacks, and vulnerability during youth. Elevated NOx exposure was associated with poorer cognition, lower educational attainment, and increased risks of anxiety, panic disorder, and attention-deficit/hyperactivity disorder. Higher NO2 levels were associated with an increased risk of schizophrenia and higher neuroticism scores. Workplace-related air pollution exposures were also associated with adverse outcomes. Self-reported "very dusty" workplace exposure was associated with poorer cognitive performance and educational attainment, while chemical fumes and diesel exhaust were linked to reduced academic achievement and increased risks of selected psychiatric outcomes. This MR study provides evidence supporting potential causal relationships between air pollution exposure and a wide range of neurodevelopmental and mental health outcomes, underscoring the importance of reducing air pollution exposure, particularly among vulnerable populations.

Maternal mental health during pregnancy has been linked to early neurodevelopment, but the unique contributions of maternal and paternal psychosocial risk and protective factors to neonatal brain structure remain unclear. This study examined associations between prenatal parental psychosocial factors and neonatal brain morphometry (intracranial and subcortical volumes) and white matter microstructure.

Structural and diffusion MRI data were acquired at 2-5 weeks postnatal age in n=174 neonates (M gestational age=39.9 ± 1.2 weeks) from the FinnBrain Birth Cohort. Psychosocial data were collected via questionnaires from n=173 mothers and n=116 fathers during pregnancy. Latent risk and protective constructs were derived using exploratory factor analysis. Associations with neonatal brain metrics: intracranial volume, bilateral hippocampal/amygdala volumes, and white matter microstructure (fractional anisotropy and mean diffusivity in key tracts) were tested using structural equation modeling, adjusted for covariates and FDR correction.

Four maternal (mental health and well-being, early relationships, pregnancy-related anxiety, attachment) and two paternal (mental health and well-being, social bonding) latent factors were identified. Greater maternal mental health and well-being was associated with larger neonatal intracranial volume. Greater paternal mental health and well-being was associated with lower fractional anisotropy in the hippocampal cingulum and inferior fronto-occipital fasciculus, and higher mean diffusivity in the latter.

Findings suggest that prenatal parental psychosocial health is associated with subtle deviations in neonatal brain architecture. These results underscore the need for holistic research on parental mental health, paving the way for care models that integrate psychosocial well-being to promote better health outcomes across generations.

Parkinson's disease (PD) is a complex neurodegenerative disorder with both genetic and environmental contributions. Over the past two and a half decades, advances in genetics, genomics and molecular biology have uncovered several monogenic forms of PD, linked to mutations in a number PD genes (collectively called PARK genes) such as SNCA, LRRK2, PRKN, PINK1, and DJ-1. To date there are 26 PARK genes reported with more than 100 genetic variants that increase the risk of PD. These genetic mutations and variants influence disease onset, progression, and therapeutic responses, making them critical for understanding the precise molecular pathways that drive preferential dopaminergic neurodegeneration in PD. These discoveries have not only deepened our understanding of PD pathogenesis but also provided avenues for stratifying patients based on their genetic profiles and provided remarkable insights crucial in tailoring individualised therapeutic approaches. This review updates recent findings on monogenic causes of PD, genetic variants which are risk factors for developing the disease and their mechanistic implications in PD neuropathological landscape. In the later part of the review, we described how these monogenic discoveries have reshaped PD into a set of mechanistic subtypes that are amenable to stratification and precision therapeutics of personalised medicine for PD patients. A list of currently developing individualised disease-modifying therapies including small molecules, antisense oligonucleotide, siRNA and CRISPR based products and targeted immunotherapies are included followed by a discussion on current challenges in developing these medications. Translating this personalised therapeutic promise into routine clinical benefit will require parallel advances in science, trial methodology and regulation, financing and social policy. Crucially, these advances must be pursued with an explicit commitment to equity, robust ethical safeguards, and stakeholder engagement so that genotype-driven care becomes accessible and beneficial across global populations rather than an exclusive privilege for a few.

To investigate whether behavioral factors and substance use influence the oral disease burden at 40 years of age in a population-based birth cohort.

This longitudinal study drew data from the 1982 Pelotas Birth Cohort, Brazil. At age 40, 453 participants were examined. Oral disease burden was modeled as a latent construct including decayed teeth, periodontal probing depth ≥4 mm, clinical attachment level ≥3 mm, and bleeding on probing. Exposures included prior sugar intake, alcohol, tobacco, and cannabis use. Models were adjusted for sex, family income at birth, common mental disorders, dental visits, and dental flossing. Associations were estimated using structural equation modeling.

Higher sugar intake (SC = 0.269, 95% CI: 0.168-0.370) and tobacco use (SC = 0.432, 95% CI: 0.336-0.527) were associated with an increased oral disease burden at age 40. Dental flossing (SC = -0.450, 95% CI: -0.605 to -0.294) and regular dental visits (SC = -0.311, 95% CI: -0.426 to -0.197) were protective. Cannabis use showed an apparent protective effect (SC = -0.259, 95% CI: -0.389 to -0.129), likely due to correlation with tobacco. Alcohol use was not associated with the outcome.

Behavioral factors and substance use at age 30 significantly influenced oral disease burden at age 40.

The long-term impact of behavioral trajectories on oral health is underscored by these findings. Clinical and policy interventions prioritizing the stabilization of healthy habits during early adulthood are essential to mitigate the cumulative burden of chronic oral diseases later in life.

Selective serotonin reuptake inhibitors (SSRIs) are a recommended first line medication for the treatment of major depressive disorder, due to higher tolerability and lower risk of adverse effects than other antidepressants. The mechanisms by which SSRIs reduce depressive symptoms are not well understood, but are hypothesised to include direct effects on serotonin signalling and synaptic remodelling, and indirect effects on inflammation. Indirect or off-target effects may be detectable in blood and can be investigated using methylome- and transcriptome-wide approaches.

The Staged Treatment in Early Psychosis (STEP) clinical trial included a 6-month long randomised, placebo-controlled trial of the SSRI fluoxetine in a cohort of young people at ultra-high risk for psychosis. A methylome-wide association study (MWAS; N_{Total (before/after/both)} = 104 (52/52/44), N_{SSRI (before/after/both)} = 45 (21/24/18)) and differential expression analysis were performed on longitudinal blood samples collected at the start and end of the 6 months to identify changes in DNA-methylation and gene expression associated with medium-term SSRI exposure.

Four methylation CpGs (cg26253898, cg09719563, cg22216017, cg26017656) were significantly associated with SSRI exposure (FDR < 0.1, 2 CpGs at FDR < 0.05) and annotated to genes involved in glucose metabolism, synaptic remodelling and inflammation (GCG, COL23A1, PEG10, SGCE, MFGE8). Gene-set enrichment analyses of genes annotated to the top 100 CpGs identified significant tissue-specific enrichments in artery, adipose and spleen tissues, and in the 'postsynaptic density' GO term. No genes were differentially expressed, including genes annotated to the significant methylation CpGs.

Medium-term SSRI use during the STEP trial was associated with changes in DNA-methylation that may partially explain the potential antidepressant mechanisms and adverse effects of SSRIs, however replication in other cohorts is necessary to establish if these changes are generalisable to SSRI use more broadly.

Adolescent major depressive disorder (MDD) is a widespread mental health condition for which treatment outcomes remain suboptimal. For adolescents, it remains unclear whether fluoxetine monotherapy or fluoxetine combined with cognitive-behavioral therapy (CBT) is more effective as an initial treatment. Additionally, no research has compared augmentation versus switching strategies after initial fluoxetine failure.

We conducted a multistep, multicenter, pragmatical clinical trial with a partially randomized design. In step 1, patients had the opportunity to choose treatment with fluoxetine monotherapy or combined fluoxetine and CBT treatment. In step 2, nonresponders were randomized to switch to sertraline, vortioxetine, or duloxetine, or to augment fluoxetine with aripiprazole, olanzapine, or lithium. The primary outcome was the response rate. Secondary outcomes included changes in depression, anxiety, global severity, sleep quality, and quality of life scores. Safety was assessed through mania, suicidality, and adverse events.

No significant differences were observed between treatment strategies in terms of primary outcomes or adverse events. In exploratory analysis, olanzapine augmentation showed greater improvement in sleep quality compared to duloxetine switching, and similar result were found in post hoc comparisons. Aripiprazole augmentation aenhanced life of quality compared to duloxetine switching.

Limitations include a small sample size and lack of control and blinding.

In this study, fluoxetine combined with CBT showed no significant advantage over fluoxetine monotherapy. All strategies in step 2 were feasible and acceptable. Our findings supported the feasibility of th sequential treatment pathway for adolescent MDD and provided insights for future adequately powered trials.