To evaluate perspectives of counseling and decision making among birthing parents who chose termination or hospice birth due to a fetal congenital heart defect (CHD).

Qualitative analysis of semi-structured interviews with birthing parents who chose either termination or hospice birth due to severe fetal CHD. Participants were recruited from a purposive sample of those who received multidisciplinary counseling at a tertiary congenital heart surgical center between 2019-2023. Thematic analysis was conducted in five stages, using an integrated deductive-inductive approach.

In total, 20 individuals were eligible; 10 completed interviews. Identified themes were categorized in two domains: Experiences During Counseling and Individual Factors Affecting Decision Making. Themes in the first domain included: areas for improvement during counseling, perceived strengths of counseling, patient attributes affecting counseling, and views on provider recommendations. Themes in the second domain included: emotions affecting decision making, value for reproductive autonomy, family factors, internal factors, outside input, and desire for resources.

In this study, birthing parents who chose termination or hospice for fetal CHD appreciated information extending beyond clinical outcomes to include family and financial impacts. Their value for reproductive autonomy reflects the need for clinicians to gain skills in empathetic and neutral counseling of all management options.

This study performs untargeted metabolomics on mouse serum and quantitative proteomics on xenograft tumors to explore the potential anti-tumor mechanisms of Inonotus obliquus polysaccharides (IOPs) against non-small cell lung cancer (NSCLC), revealing candidate pathways that warrant further experimental validation. Building on our prior discovery of IOP-induced apoptosis, we combined functional assays with multi-omics analyses using a well-characterized IOPs preparation (average molecular weight: 4.5 × 10⁴ Da; polysaccharide content: 70.3%; primarily composed of glucose). IOPs potently inhibited proliferation (MTT/colony formation) in LLC and H520 cells and suppressed tumor growth in an allograft model. Untargeted metabolomics of mouse serum revealed IOP-driven downregulation of lipid metabolism. Quantitative proteomics of tumors showed that IOPs regulate nuclear processes (transcription, DNA repair) and modulate the tumor immune microenvironment, as evidenced by enriched pathways of neutrophil extracellular trap (NET) formation, cell adhesion molecules, and Th1/Th2 cell differentiation. Collectively, these findings propose a potential working model in which IOPs may exert anti-tumor effects through coordinated nuclear regulation, metabolic reprogramming, and immune modulation. Our results provide preliminary evidence that IOPs may act beyond direct cytotoxicity, potentially involving systemic regulatory pathways. Further studies are needed to validate these findings and to assess its therapeutic potential in NSCLC.

The renin-angiotensin system (RAS) is a pivotal system for regulating blood volume, electrolyte balance, and systemic vascular resistance. The system exerts its functions through various central targets, particularly those located in the brain. Among these, the subfornical organ (SFO) plays a unique and integrative role. High permeability and the lack of a functional blood-brain barrier (BBB) enable the organ to monitor changes in body fluid composition and transduce these signals into autonomic and behavioral outputs. Its extensive neural projections facilitate the monitoring of circulating factors. The interaction between the RAS and the SFO has gained great attention regarding the activation of different receptors, including angiotensin AT1 and AT2 receptors, and molecular pathways such as protein kinase C, mitogen-activated protein kinase, and growth factor receptor pathways. These interactions are involved in disorders including hypertension and chronic kidney disease. This review summarizes current evidence on RAS-SFO interactions and their pathological significance.

Drugs that inhibit phosphodiesterase 10A (PDE10A) activity have shown efficacy in animal models. However, clinical trials of PDE10A inhibitors in patients with schizophrenia have failed to provide clinically significant results up to this point. Our study investigated whether alofropodect (previously referred to as CPL'36 or CPL500036), a PDE10A inhibitor with an improved pharmacological profile compared with other PDE10A inhibitors, including a fast dissociation rate and high activity, could improve symptoms of acute schizophrenia.

In this phase 2, randomised, double-blind, placebo-controlled, parallel-group trial (11 centres, three countries), investigators randomly assigned hospitalised patients with acute schizophrenia to treatment or placebo groups. The main inclusion criteria were age 18-65 years, a documented diagnosis of schizophrenia for at least 2 years before screening and a positive and negative syndrome scale (PANSS) total score ≥ 80. Participants were randomly assigned (1:1:1) to receive oral alofropodect (20 mg or 40 mg) or placebo administered once daily in the morning for 4 weeks. The primary endpoint of the study was an improvement in the PANSS positive subscale at week 4. The secondary endpoints included improvements in PANSS total and negative subscale scores, along with other efficacy and safety assessments. Clinical responders were defined as those with a ≥ 30% reduction in PANSS total score from baseline at week 4.

Between 24 May 2021 and 8 May 2024, investigators randomised 189 patients into three groups: 58 into the alofropodect 20 mg group, 66 into the alofropodect 40 mg group and 65 into the placebo group. The mean age was 41.7 years (standard deviation (SD) 10.1), and 119 (63%) participants were men, 70 (37%) were women. All participants were White. We measured the difference in PANSS positive subscale before and after treatment, and the change met the primary endpoints at week 4 with the group where alofropodect 20 mg was compared with placebo (- 3.70 [90% CI - 5.51 to - 1.89]; p < 0.001) and alofropodect 40 mg versus placebo (- 6.35 [90% CI - 8.12 to - 4.57]; p = 0.001). Both the 20-mg and 40-mg doses of alofropodect were effective in improving the total PANSS score compared with placebo and met most secondary efficacy endpoints. A clinical response was observed in 2 of 53 patients (3.8%) in the placebo group, 8 of 52 patients (15.4%) in the 20 mg group and 22 of 52 patients (42.3%) in the 40 mg group at week 4. The compound was well tolerated, with only a few serious adverse events. The discontinuation rates were similar in the placebo and treatment arms. Extrapyramidal symptoms (EPS) occurred only in the active treatment groups, but rates were low overall. Somnolence was also reported only in alofropodect groups. Vital signs and biochemical parameters remained unaffected by either dose at any time point. Specifically, blood glucose, total cholesterol and triglycerides did not increase at any dose compared with placebo within our study window.

Alofropodect was effective in the treatment of acute schizophrenia symptoms and was well-tolerated, warranting further investigation in larger clinical studies.

Clinicaltrials.gov identifier: NCT05278156; registration date: 2022-02-09.

Bulimia nervosa (BN) is common and has a global presence and burden. BN shares features with anorexia nervosa and binge eating disorder, but its cardinal feature is recurrent binge eating followed by extreme weight control or compensatory behaviours in association with high levels of weight and shape, and other body image and eating, preoccupations. The last three decades have seen advances in understanding the risk factors and psychobehavioural mechanisms of BN. These advances have informed primary prevention programmes that are effective in preventing the onset of risk factors and, in one selective programme, the onset of BN itself. First-line treatment for BN is psychological therapy, namely cognitive behaviour therapy for eating disorders. However, the challenge of a large treatment gap and the need to improve prevention and early detection of BN remains. Adaptations of treatments to increase their accessibility and reduce cost, alongside the growth of co-design and incorporation of lived experience expertise in research, are assisting in developing programmes that may effectively close this treatment gap. An increasingly sophisticated approach to understanding the neuroscience of BN has the potential to inform novel treatments in both psychological and biological spheres.

Trajectories of age-related neurocognitive decline are nonuniform, and are impacted by numerous environmental and physiological factors. Earlier life phases set the stage for later life neurocognitive function, with midlife marking a critical transition characterized by increasing variability in cognitive, affective, and physiological functioning. Despite its importance, this turbulent period remains underrepresented in open neuroimaging data resources. To address this gap, the Nathan Kline Institute - Rockland Sample (NKI-RS) created 'Mapping Interindividual Variation in the Aging Connectome' (MIVAC), an openly shared, multimodal dataset designed to map brain aging trajectories beginning in midlife and assess the influence of key modifiable factors linked to dementia prevention such as cardiorespiratory fitness, sleep, and mood. This longitudinal investigation includes 348 community-ascertained participants aged 38 to 71 years at baseline, with 219 participants completing 3 annual timepoints. Data collection incorporated deep phenotyping, including detailed assessment of cognitive, behavioral, medical, and cardiorespiratory fitness domains, to compliment multimodal neuroimaging (resting-state fMRI, diffusion MRI, morphometric MRI, and arterial spin labeling) and biospecimen collection. The protocol harmonizes with prior NKI-RS sub studies, enabling lifespan cross-sectional or longitudinal questions, while incorporating age-specific considerations for cognitive and neural aging. The full dataset is openly available.

People with disabilities, including Deaf and hard-of-hearing (DHH) individuals, face disproportionate disaster risks due to communication barriers. Emergency alert systems are predominantly auditory-based, limiting their effectiveness for DHH populations. This gap is especially critical during armed conflict, where timely alerts can be life-saving.

This study examined emergency alert system accessibility and associated psychological distress among DHH adults during active armed conflict.

A cross-sectional online survey was conducted in Israel (October-November 2023) during the early phase of the Israel-Hamas War among DHH adults (N = 167), assessing daytime and nighttime alert accessibility and psychological distress. Analyses included McNemar's test, repeated-measures ANOVA with Bonferroni correction, independent-samples t-tests, and one- and two-way ANOVA. Effect sizes were reported throughout.

Participants included 87 Deaf (52.1%), 73 hard-of-hearing (43.7%), and 7 (4.2%) identifying as "other," with a mean age of 55.3 years (SD = 16.4). While 69.5% received alerts via the national application during daytime, only 32.3% did so at night, indicating a substantial nighttime accessibility gap. Alert accessibility was only partially associated with psychological distress. Women reported significantly higher distress than men (p < .019). No significant differences emerged between Deaf and hard-of-hearing participants in alert use or distress levels. Education level did not predict alert accessibility, suggesting structural rather than user-dependent barriers.

DHH individuals face systematic barriers to accessing emergency alerts, particularly at night. Equitable disaster preparedness requires multimodal systems incorporating visual, vibration, and text-based channels. Culturally accessible mental health support should be integrated into emergency response protocols.

Parkinson's disease (PD) affects individuals across diverse cultural, linguistic, and socioeconomic backgrounds worldwide. While non-motor symptoms (NMS) are among the most disabling features of PD, the influence of culture on their recognition, reporting, and management remains underexplored. This review examines cultural factors that shape the experience and care of NMS in PD, with particular attention to Asian populations, which have historically received limited focus in health disparities literature. Drawing on evidence from diverse global populations, we explore how cultural beliefs, stigma, family dynamics, spirituality, language, and trust in healthcare systems influence symptom interpretation, help-seeking behaviors, treatment engagement, caregiving, and end-of-life decision-making. Sensitive symptoms such as bladder, bowel and sexual dysfunction, as well as mental health symptoms may be underreported because of stigma, shame, or cultural norms. Immigrant populations may avoid "bothering" healthcare providers, while language barriers and mistrust can further impede communication and access to care. Cultural values also influence decision-making preferences. In contrast to Western models that prioritize individual autonomy, some patients prefer family-centered decision-making, with designated family members guiding healthcare choices. Concepts such as filial piety, "familismo", and culturally defined gender roles (superwoman schema and stoic masculinity) shape caregiving and acceptance of treatment recommendations. Culturally enabled care is essential to equitable and person-centered PD management and can improve communication, reduce disparities, foster trust, and enhance quality of life for people living with PD and their families. Further research is urgently needed to better understand how culture intersects with NMS management and to develop culturally enabled models of care.

To explore the cross-sectional and longitudinal associations of poverty, assessed by deprivation index (DI) and income, with anxiety and stress among adults DESIGN: Longitudinal cohort observational study SETTING: A cohort of adults established in 2014-2015 (T1) in Hong Kong.

493 participants (177 men, median age 56 years) were followed up in the third wave of household survey in 2021-2022 (T3).

Self-reported equivalised household income and DI, measured as material and social deprivation, were recorded. Anxiety and stress were assessed using the Depression, Anxiety and Stress Scale-21 items (Chinese) version.

Being deprived in T3 is significantly associated with higher anxiety and stress score in T3 as compared with being non-deprived cross-sectionally. Income status did not show significant association with anxiety and stress score cross-sectionally in T3. Increased deprivation status since baseline is significantly associated with higher anxiety and stress score in T3 than persistent non-deprivation. Being able to afford one less basic necessity throughout T1-T3 is significantly associated with 0.31-unit higher anxiety score (95% CI 0.18 to 0.45) and 0.36-unit higher stress score (95% CI 0.18 to 0.55) across time.Subgroup analyses further showed that income-poor younger adults aged less than 60 years tended to have higher anxiety and stress scores than their non-income-poor counterparts in the same age group in T3 cross-sectionally. Younger adults with occasional non-income-poverty throughout T1-T3 also had higher anxiety and stress scores in T3 than persistently non-income-poor younger adults. This relationship of income-poverty with anxiety and stress was not significant among older adults aged 60 years or above.

Individual deprivation and increased deprivation over time were associated with higher anxiety and stress scores in T3 cross-sectionally and longitudinally respectively. Young adults' anxiety and stress scores tended to be more affected by income-poverty than their older counterparts. Nevertheless, sample attrition may occur as a proportion of participants dropped out throughout the 7 years of follow-up.Age-specific poverty measurement tools may be developed to assess the age-specific standard of living. Policymakers may consider deprivation, in addition to income, as well as change in poverty status, in healthcare and social welfare policymaking to better address the mental health of the population and health inequality in the region.

This paper constitutes an intervention development paper, illustrating the application of the person-based approach to planning and developing a digital transdiagnostic intervention to support Portuguese adults in managing their stress and emotions, thereby enhancing their mental health.

A multi-method intervention development study following the person-based approach (Phase I: collating and analysing evidence; Phase II: creating the intervention plan). Evidence from three quantitative studies, examining emotional schemas, psychological flexibility, and mental health in the context of stress, a qualitative study, exploring stress-coping experiences, and a scoping review of digital interventions designed for stress, were combined with experts' consultation to facilitate the creation of the guiding principles and the logic model. This guided the development of prototype intervention.

Community-based recruitment across Portugal, collected online and at hospitals, senior universities and patient organisations.

Quantitative studies used a convenience sample (Study 1, n=666; Study 2, n=583; Study 3, n=276). 29 adults purposively sampled from the Study 3' highest and lowest stress quartiles took part in semi-structured interviews. In the scoping review, 5867 articles were identified, and 131 studies of digital psychological interventions for stress were included. Six experts in stress, cognitive behavioural therapy, acceptance and commitment therapy, emotional schema therapy, digital interventions, intervention development and public health reviewed the draft intervention plan.

Stress responses, more than stressor type, were the strongest predictor of both positive and negative mental health, with emotional schemas (negative evaluation of emotions, difficulties in reappraisal) and psychological flexibility (behavioural awareness, valued action, openness to experience) acting as mediators. Qualitative interviews highlighted maladaptive thoughts as the main barrier and emotional management as the main facilitator to coping, alongside preferences for intervention content and delivery. The scoping review found common components in existing digital interventions for stress, but none integrated the emotional schemas model. Together with expert consultation, these findings led to the development of EmOcean prototype, a guided self-help digital intervention comprising eight integrated and five optional modules, tailored to users' needs, characteristics and preferences, which are completed sequentially on a weekly basis. Modules include psychoeducation and exercises on topics such as stress, emotions, cognitive reframing, mindfulness, acceptance, values, activities, problem-solving, time management, physical exercise, sleep, social support, assertiveness and emotional management.

Combining empirical, theoretical and person-based evidence supported the development of EmOcean, an intervention hypothesised to support stress and emotion management and enhance mental health. Its acceptability, feasibility and efficacy will be evaluated in future studies.