Background/Objectives: Schizophrenia is a chronic psychiatric disorder traditionally associated with early adulthood; however, an increasing number of individuals are now reaching older age, highlighting the need to better understand the aging process in this population. Emerging evidence suggests that schizophrenia may be associated with accelerated aging, characterized by an earlier onset of age-related conditions and increased vulnerability to physical and cognitive decline. Methods: We provide an integrative overview of aging in schizophrenia, focusing on biological mechanisms, clinical manifestations, and psychosocial dimensions. Results: Key biological processes, including oxidative stress, mitochondrial dysfunction, chronic immune activation, and dysregulation of stress-response systems, are discussed as potential contributors to accelerated aging. Clinically, older individuals with schizophrenia present a high burden of cardiometabolic comorbidities, persistent cognitive impairment, and increased functional dependency, often compounded by the complexity of pharmacological management in this age group. In addition, psychosocial factors such as social isolation, stigma, and caregiver burden play a critical role in shaping health outcomes and quality of life. Conclusions: Despite growing recognition of these challenges, aging in schizophrenia remains an underexplored area, with significant gaps in longitudinal research and limited focus on older populations. A comprehensive approach that integrates biological, clinical, and psychosocial perspectives is essential to better characterize aging trajectories and to inform more effective and person-centered care strategies in this vulnerable population.

The proportion of suspected adverse drug reactions (ADRs) that are formally reported to official pharmacovigilance databases is unclear, although this is essential for patient safety. This systematic literature review aimed to compare the level of formal reporting of ADRs to pharmacovigilance databases with the level of informal reporting of ADRs identified in clinical settings. Further, it aimed to investigate factors that could influence formal ADR reporting. A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. A review protocol was registered a priori. Embase and Medline were searched for studies published between 1st January 2015 and 17th June 2025 that were based on original data and provided quantitative comparisons between formal and informal ADR reports for any medication type. Reviews, meta-analyses, randomized controlled trials, case reports, case studies, letters to editors, and nonhuman studies were excluded. Four independent reviewers screened the studies and extracted the data pairwise. For each study, we calculated the proportion of identified suspected ADRs that were not formally reported to pharmacovigilance databases and presented them using median and interquartile range (IQR). Risk of bias was assessed using the Critical Appraisal Skills Programme (CASP) checklist. The certainty of evidence was rated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Of the 12,558 studies identified, 11 cross-sectional studies were included in the review. These studies included a total of 38,962 patients across all age groups (range 0-96 years) and investigated different medications. The nonreporting estimates ranged between 71.7 and 100%, with a median rate of 98.05% (IQR 95.5-99.3). Formal ADR reporting was low regardless of severity or seriousness, suggesting that these factors did not meaningfully influence reporting rates. The studies were heterogeneous and had considerable risk of bias according to CASP. The overall certainty of evidence was rated as very low. A large proportion of ADRs suspected in clinical settings are not formally reported to pharmacovigilance databases. This could constitute a patient safety risk, and future studies should identify key factors that influence formal ADR reporting in order to guide improvements.

Antibody-drug conjugates (ADCs) have revolutionized HER2-positive breast cancer treatment, yet resistance to next-generation agents such as SHR-A1811 (trastuzumab rezetecan) remains a major challenge arising from poor intratumoral delivery, enhanced DNA damage repair, and an immunosuppressive tumor microenvironment (TME). Here, we engineered HER2-targeted AIE780-A1811 nanoparticles (NPs) by covalently conjugating the mitochondria-directed NIR photosensitizer AIE780 with SHR-A1811 via EDC/Sulfo-NHS-mediated amide coupling. These core-shell NPs exhibit an optimal size for EPR-mediated tumor accumulation, high photothermal conversion efficiency, and stable NIR fluorescence for real-time imaging. Upon 660 nm irradiation, AIE780-A1811 NPs generate robust ROS and potent photothermal effects, inducing tumor cell death and stimuli-responsive SHR-A1811 release to amplify DNA double-strand breaks. Mechanistically, this combination therapy activates the NLRP3 inflammasome-GSDMD axis, driving immunogenic pyroptosis and the release of damage-associated molecular patterns. Concurrently, it reprograms tumor-associated macrophages from an M2-like to an M1-like phenotype, enhances CD8⁺ T cell infiltration, and reduces regulatory T cells, thereby remodeling the immunosuppressive TME. AIE780-A1811 NPs demonstrate potent antitumor efficacy across SHR-A1811-resistant cell lines, patient-derived organoids, and mouse xenografts, achieving near-complete tumor regression with negligible systemic toxicity. This multimodal strategy integrating targeted chemotherapy, photothermal therapy, and immunomodulation offers a promising translational approach to overcome ADC resistance in refractory HER2-positive breast cancer.

The use of ketamine as a treatment for mood disorders continues to grow in popularity. However, the differences between individuals consuming ketamine within clinical settings and those self-medicating in casual, non-clinical settings has not been yet characterized. Using the 2023 Global Psychedelic Survey, this study aimed to examine the demographic and clinical characteristics, as well as the self-reported effectiveness and hallucination-related side effects, of ketamine use by comparing individuals using ketamine with and without medical supervision. Compared to clinical ketamine consumers (n = 238), non-clinical consumers (n = 222) were more experienced in use of various psychedelic (p < .0001) and non-psychedelic recreational substances (p < .001), and lifetime use of ketamine (p < .0001). Both groups presented with similar mild depression and anxiety symptoms at the time of the survey collection (p = .22, p = .46). Ketamine was similarly and highly rated in effectiveness within both groups when rated on a scale of 0-100 (83.3 ± 15.0 clinical, 81.2 ± 16.6 non-clinical; p = .45). Non-clinical consumers presented higher odds of reporting long-term hallucinations following ketamine use (OR = 2.58, 95% CI: 1.08-6.31). The results of this study indicate a high self-reported effectiveness of ketamine in clinical and non-clinical settings while emphasizing the potential risks of side effects when used without medical supervision.

Mental health conditions are prevalent among graduate health professions students and can negatively impact academic performance, well-being, and relationships. This systematic review evaluated the effectiveness of mind-body therapies (MBTs) on anxiety, burnout, depression, and stress in graduate health professions students.

Five healthcare/academic databases were searched from 2008 through August 25, 2023.

1) graduate health professions students; 2) MBT interventions; and 3) anxiety, burnout, depression, and/or stress outcomes. Title/abstract screening, full-text review, level of evidence, and quality assessment were performed by author pairs.

Of 2,511 screened records, 24 met inclusion criteria, representing 2,220 students across 6 health professions programs. Studies described 8 anxiety, 2 burnout, 7 depression, and 10 stress outcomes. The average QuADS score was 73.64% (range 53.85-100%). Fifteen studies reported significant improvements in at least 1 anxiety, depression, or stress outcome. Of 9 studies that measured anxiety, 5 demonstrated reductions. Depression results were inconsistent, with only 1 of 7 studies showing improvements. Stress outcomes improved most frequently, with 13 of 22 studies reporting benefits. None of the 3 burnout studies showed positive results.

MBTs such as mindfulness, meditation, yoga, and breathing exercises show promise in reducing anxiety and stress. Evidence supporting improvements in burnout and depression remains quite limited.

In vitro fertilization (IVF) can affect quality of life and psychological well-being in both female and male patients, but stage-specific patterns across different stages of IVF cycle remain incompletely characterized. We examined sex differences and stage-specific variation in fertility-related quality of life (FertiQoL) and psychological distress measured with the Patient Health Questionnaire-4 (PHQ-4). We analyzed 444 paired FertiQoL and PHQ-4 responses from 320 patients (202 females and 118 males) undergoing IVF at 11 centers in Taiwan. Assessments were available before IVF initiation, ovum pick-up (OPU), embryo transfer (ET), and the pregnancy test. Sex differences were evaluated, and stage-specific associations were estimated with linear mixed-effects models. Males had higher total FertiQoL scores than females (mean 72.78 vs. 69.14, p = 0.008), particularly in the emotional (71.39 vs. 64.08, p < 0.001) and mind/body (mean 77.91 vs. 69.36, p < 0.001) domains. Females had higher anxiety scores (Generalized Anxiety Disorder-2, GAD-2: mean 1.71 vs. 1.32, p < 0.001) and total PHQ-4 scores (mean 2.66 vs. 2.23, p = 0.006) compared to males. Nominal increases in PHQ-2 and PHQ-4 scores before embryo transfer (ET) and a nominal decrease in Tolerability scores before the pregnancy test were observed; however, these differences did not remain statistically significant after correction. Sex-related differences in selected quality-of-life domains and anxiety were observed during IVF, while stage-specific trends were also suggested. These findings highlight the importance of monitoring mental health and providing targeted psychological support and underscore the need for prospective, stage-standardized studies with linked couple data and more comprehensive clinical characterization.

Parkinson's disease (PD) is characterized by the accumulation of Lewy bodies (LBs) in the brain, predominantly consisting of aggregated and phosphorylated α-synuclein (α-Syn). Consequently, strategies to suppress α-Syn expression offer substantial therapeutic potential for PD. This study explores heteroduplex oligonucleotides (HDOs), an innovative gene-silencing technology utilizing DNA/RNA or DNA/DNA hybrids. We designed two HDOs targeting α-Syn: α-Syn-HDO-1 (DNA/RNA) and α-Syn-HDO-2 (DNA/DNA). Both demonstrated robust silencing of α-Syn expression in mice. In AAV-hSyn-human SNCA-treated mice, these α-Syn-HDOs exerted neuroprotective effects on dopaminergic neurons. Furthermore, they reduced aberrant α-Syn accumulation in α-Syn-HEK293 cells and in mice treated with α-Syn preformed fibrils (PFFs). The neuroprotective effects of α-Syn-HDOs were linked to activation of the brain-derived neurotrophic factor (BDNF)-tyrosine kinase B (TrkB) signaling pathway. Moreover, BDNF overexpression diminished abnormal α-Syn aggregation in both PFFs-treated α-Syn-HEK293 cells and PFFs-treated mice. These results highlight the capacity of α-Syn-HDOs to protect dopaminergic neurons by enhancing BDNF-TrkB signaling through the inhibition of abnormal elevated α-Syn. Our findings position α-Syn-HDOs as promising therapeutic candidates for PD and suggest BDNF as a potential diagnostic biomarker or indicator of treatment efficacy.

Aggression and violence remain persistent challenges in inpatient mental health services, with significant implications for patient safety, staff wellbeing, therapeutic relationships and the continued use of restrictive practices. Although de-escalation is widely promoted as a first-line, non-coercive response to distress and behavioural escalation, its implementation remains inconsistent and the evidence base is fragmented across relational, educational, organisational and policy literatures. This paper reports a structured critical narrative synthesis of United Kingdom-relevant empirical, theoretical, policy and practice literature examining de-escalation, staff training, restrictive-practice reduction and organisational responses to aggression and violence in adult inpatient mental health care. Literature published between January 2014 and March 2024 was identified through searches of Scopus, CINAHL, PubMed/MEDLINE, ProQuest and Web of Science, supplemented by reference-list screening and targeted grey-literature searches. Sources were selected for their relevance to adult inpatient mental health settings and their contribution to understanding how de-escalation is enacted, supported and sustained. Given the heterogeneity of the evidence, design-appropriate appraisal principles informed by the Critical Appraisal Skills Programme and Mixed Methods Appraisal Tool were used to support interpretation. The synthesis identified three interdependent domains shaping de-escalation practice: People, Capability and Context (PCC). Therapeutic relationships, communication, emotional intelligence and service-user involvement underpinned early recognition of distress and relationally attuned responses. Workforce capability was strengthened through simulation, reflective learning, team rehearsal and practice-proximal evaluation. Organisational context, including staffing, leadership, ward environment, safety culture, equity safeguards and wider structural determinants, shaped whether de-escalation could be enacted consistently and safely. These findings generated the PCC framework as a practice-facing model that conceptualises de-escalation as an emergent practice arising from alignment between relational processes, workforce capability and organisational conditions. The framework offers a practical basis for guiding restrictive-practice reduction, quality improvement, equity-sensitive monitoring and future empirical research in inpatient mental health care.

What is this summary about? This is a summary of the latest 2023 European guideline on the diagnosis and management of insomnia disorder in adults aged 18 and older. The guideline provides up-to-date recommendations to healthcare professionals on how best to diagnose, manage, and treat adults with insomnia, focusing on insomnia disorder. Insomnia disorder is defined as a long-term difficulty of falling asleep or staying asleep three or more nights a week for at least three months, despite adequate opportunity for sleep, and which impacts the ability to function well during the day. This summary provides an overview of how insomnia disorder is diagnosed and managed and the recommended treatment options.

Childhood anxiety is a prevalent mental health concern, and much research has focused on the development of related interventions. The Supportive Parenting for Anxious Childhood Emotions (SPACE) program is a parent-only intervention that focuses on reducing child anxiety by targeting family accommodations (FA). The current study aims to explore parents' perspectives of attending the intervention, with a specific focus on the temporal progression of parents' sense-making relating to their child's anxiety and family accommodations.

Ten parents who attended a SPACE intervention were interviewed at two time points, pre-intervention and post-intervention. Semi-structured interviews were analysed using a Longitudinal Interpretative Phenomenological Analysis (LIPA) approach.

Two superordinate themes emerged: (1) 'It's hard not to intervene' - The evolution of parent responding highlighted progressions of parent narratives about child anxiety, and accommodating behaviours across the time points, while (2) From doubt to self-efficacy - Parents' journey through the intervention reflected evolution of parental experiences throughout the intervention.

Findings suggested shifts in parents' conceptualization of their child's anxiety, and changes in their responding from Time 1 to Time 2. These insights contribute to the growing evidence base for SPACE, and have implications for clinical practice. Directions for future research are discussed.