To examine sociodemographic and episode-of-care characteristics among individuals presenting with suicidal behaviour who re-present to emergency departments in Tasmania, Australia.

Emergency department presentations related to suicidal behaviour from 1 January 2017 to 31 December 2023 were identified across four public hospitals in Tasmania. The primary outcome of interest was the number, rate and risk of re-presentations, defined as a subsequent visit within 7 days, 28 days or at any time during the study period. Analyses also assessed the total presentation frequency per individual across these timeframes. Concordance in episode-of-care characteristics, including arrival mode, was compared between the index and first re-presentation.

A total of 12,659 presentations related to suicidal behaviour were recorded among 7,426 Tasmanian individuals, of which 5,409 had a single presentation, and 2,017 had one or more re-presentations. Re-presentation within 7 days, 28 days and across the study period was associated with younger age, higher triage urgency and specific departure modalities. The highest concordance between index and repeat presentations was observed for arrival by ambulance (51.63%), afternoon arrival (40.33%), triage category 3 (66%) and leaving at own risk after clinician assessment (65.05%). Individuals with multiple re-presentations were more likely to be female and from lower socioeconomic areas.

Re-presentations to the emergency department for suicidal behaviour were more common among younger individuals, those triaged as more urgent and those who left the emergency department without seeing a health professional. Higher re-presentation rates were also observed among females and individuals from disadvantaged socioeconomic areas. These findings highlight key sociodemographic and care-related factors that can inform targeted interventions, improved service planning and enhanced mental health resource allocation to reduce repeat emergency department presentations.

Evidence of regional differences in clinical outcomes after intracerebral hemorrhage (ICH) is still scarce. We quantified differential outcomes and response to early intensive blood pressure lowering treatment by region in the Blood pressure in Acute Stroke Collaboration ICH data set.

This was an observational analysis of pooled individual participant data from 16 completed randomized controlled trials of blood pressure-lowering treatment in acute ICH, based on the Blood pressure in Acute Stroke Collaboration data set. Generalized linear mixed models with inverse probability of treatment weighting (IPTW) were used to determine the association between regions (Asia [primarily East and South Asia] versus non-Asia) and clinical outcomes including neurological deterioration within 7 days, hematoma expansion at 24 hours (absolute ≥6 mL or relative ≥33%), and death or dependency (modified Rankin Scale scores, 3-6), major disability(modified Rankin Scale score, 3-5), death alone at 90 days.

Among 6221 patients (age, 63.3±13.0 years; female 36.4%), 3494 (56.2%) were from Asia. ICH participants from Asia had a significantly reduced risk of death or dependency (unadjusted odds ratio [OR], 0.44 [95% CI, 0.39-0.51]; IPTW-weighted OR, 0.67 [95% CI, 0.58-0.77]); and major disability (unadjusted OR, 0.49 [95% CI, 0.42-0.56]; IPTW-weighted OR, 0.67 [95% CI, 0.57-0.78]) at 90 days, neurological deterioration (unadjusted OR, 0.63 [95% CI, 0.52-0.77]; IPTW-weighted OR, 0.70 [95% CI, 0.56-0.89]) within 7 days, in comparison to those from non-Asia regions. However, there were no differences for hematoma expansion (P=0.97) at 24 hours or death (P=0.23) at 90 days using IPTW. Additionally, there were no significant interactions between blood pressure-lowering treatment and region (Asia versus non-Asia) for either outcome using IPTW.

Participants from East and South Asia had a favorable functional recovery and a lower risk of neurological deterioration compared with those from non-Asian regions after adjustment for confounders, with no differences in hematoma expansion at 24 hours after ICH. These findings suggest that future ICH studies on clinical outcomes should consider regional differences.

Alternative splicing of MAPT exon 10 generates 4R- and 3R-Tau isoforms, and its dysregulation is associated with tauopathies including Alzheimer's disease (AD), for which effective treatments remain lacking. Here, we identify HuR as a novel repressor of MAPT exon 10 alternative splicing. Mechanistically, the RRM1 domain of HuR is critical for mediating its splicing inhibitory effect. HuR binds to the U-rich region downstream of intron 9 in MAPT together with FUBP1, KHSRP, hnRNPD, hnRNPAB, hnRNPDL, and TIAL1. The expression of HuR shows a negative association with that of FUBP1, KHSRP, hnRNPD, and TIAL1. Finally, we demonstrate that HuR regulates the expression and alternative splicing of genes involved in autophagy and apoptosis, pathways dysregulated in AD. Collectively, these findings establish HuR as a regulator of AD-relevant transcriptomic networks and provide a mechanistic basis for exploring HuR-targeted strategies in AD.

Most adolescents living with type 1 diabetes (T1D) do not reach targeted levels of hemoglobin A1c (HbA1c), which increases risk for diabetes-related complications. Suboptimal diabetes management may be associated with the burden of coping with T1D for adolescents who are simultaneously adjusting to physical, cognitive, and socioemotional changes. Mindfulness-based interventions (MBIs) are associated with improved coping skills and could be useful for adolescents with T1D.

This was a pilot randomized controlled study to examine the feasibility and acceptability of a virtual MBI in adolescents aged 15-17 years with T1D. Enrollment took place in two iterations: 1) patients were approached in clinic by a physician; 2) letters were mailed and follow-up phone calls were made by research staff. Enrolled participants were given the option of 2 different weekly times for participation and were assigned to one of two study arms: diabetes education + MBI (DE+MBI) or DE only. For each arm, 12 virtual group sessions were held weekly. Feasibility measures included time-to-recruit, program enrollment, and study retention. Acceptability was assessed by attendance and survey completion. Exploratory outcomes included HbA1c and responses to quality of life and mental health questionnaires.

By design, the first 60 eligible participants who agreed to participate were enrolled. Sixty of 164 approached (37%) consented to enroll. Fifty percent of these (n=30; DE+MBI=15, DE=15) participated in at least one group session; the mean attendance was 7 + 3 sessions. All participants reported managing at least one area of life better post-intervention (coping with stress, sleep, physical symptoms, self-care, school, emotion regulation, getting along with others). Survey completion was 87% pre-intervention and 60% post-intervention. There was no change in mean HbA1c for either the DE+MBI or the DE arms.

More study is warranted to investigate ways to increase the feasibility for implementing complementary therapies such as MBI in a diabetes clinic for adolescents with T1D.

The ventral hippocampus plays a crucial role in regulating emotional and motivated behaviors. However, the molecular mechanisms underlying its dysfunction in major depressive disorder (MDD) remain poorly understood. Here, we identified elevated expression of vitamin D binding protein (VDBP) in the hippocampi of chronic unpredictable mild stress (CUMS)-susceptible mice, which correlated with the severity of depression-like behaviors. Notably, VDBP up-regulation was specifically in ventral CA3 excitatory (vCA3^CaMKIIα) neurons. CA3^CaMKIIα VDBP overexpression led to inhibited neuronal activity, synaptic and dendritic impairments, and, ultimately, depression-like behaviors. Conversely, vCA3^CaMKIIα-specific VDBP knockdown enhanced resilience to chronic stress. Mechanistically, VDBP directly interacted with PIK3R3 to inhibit the PI3K-Akt-mTOR pathway in a cell-autonomous manner, leading to excessive autophagy and subsequent neuronal dysfunction. Chemogenetic activation, intervention using the Akt-specific activator SC79, and site-specific mutation disrupting the VDBP-PIK3R3 interaction ameliorated vCA3^CaMKIIα VDBP-induced depression-like phenotypes. Collectively, these findings underscore the critical involvement of vCA3^CaMKIIα neuron-derived VDBP in stress-induced depressive pathology and highlight its potential as a therapeutic target for MDD.

Insomnia disorder (ID) is a common sleep-wake disorder marked by persistent dissatisfaction with sleep quality or quantity. Previous studies have shown that sleep plays a critical role in emotion regulation, particularly in fear extinction. This study aims to characterize ID using estimates of the sympathetic arousal state derived from skin conductance (SC)-based observations, and to compare two observation models: the marked point process (MPP) model and the MPP coupled with continuous (MPP+Cont) model. We utilize SC data from a fear conditioning and extinction procedure involving 24 individuals with ID and 24 good sleepers (GS). The SC measurements are deconvolved to extract autonomic nervous system (ANS) activations and the tonic component. The MPP observation model uses only the extracted ANS activations, while the MPP+Cont model incorporates both ANS activations and the tonic component. Both models are employed to estimate the underlying arousal state over time and compute a high arousal index (HAI). We compare the estimated arousal states and HAI between the ID and GS groups to assess alterations in arousal associated with ID. Our results reveal that ID may be associated with impaired fear extinction learning and recall. Notably, the distinction between ID and GS emerges only under the MPP+Cont model, indicating the critical role of the tonic component in arousal estimation. Overall, this study highlights the potential of arousal state estimation for understanding autonomic dysregulation in ID, thereby supporting interventions for fear-centered comorbidities and improving quality of life.

The Five Factor Model (FFM) personality meta-traits, stability and plasticity, are thought to capture broad individual differences in the parameters of goal-directed, cybernetic mechanisms in the brain, which have implications for transdiagnostic psychopathology risk. It remains unknown whether these meta-traits represent genetically coherent dimensions. Here we conduct a genomic investigation into the FFM meta-traits and characterize their association with 11 psychiatric conditions.

We combined recent genome-wide association study (GWAS) summary statistics with data from the 23andMe Research Institute (European ancestry; total N = 279,240-682,707) and applied Genomic Structural Equation Modelling to conduct a multivariate GWAS of the FFM meta-traits. We then conducted transcriptome-wide association studies (TWAS) and stratified linkage disequilibrium score regression (S-LDSC) to prioritize candidate effector genes and brain cell types for personality traits. Finally, we used LDSC regression and CAUSE Mendelian randomization to characterize the relationship between personality traits and 11 psychiatric conditions.

We identified 83 (14 novel) and 13 (4 novel) independent genome-wide significant loci for stability and plasticity respectively. TWAS prioritized hundreds of candidate effector genes for personality, and S-LDSC showed heritability enrichment across several neuronal cell types. Finally, genetic correlation and Mendelian randomization analyses provided genetic evidence suggesting bidirectional links between stability and psychopathology: higher genetic propensity for stability was protective against psychopathology, whereas greater genetic liability to psychopathology was associated with reduced stability.

The personality meta-traits capture modest shared architecture across personality, with genetic liability for lower stability potentially representing a broad transdiagnostic link between personality and psychiatric vulnerability.

Non-communicable diseases (NCDs) are a major public health challenge in the United Kingdom (UK), placing strain on the National Health Service (NHS). While Western medicine dominates NCD care, the use of complementary and alternative medicine (CAM), such as Ayurveda, is increasing. The objective of this study was to explore the experiences and perspectives of Ayurvedic practitioners in the UK regarding the use of Ayurveda for managing NCDs.

Seventeen UK-based Ayurvedic practitioners participated in semi-structured qualitative interviews that were audio-recorded, transcribed verbatim, and analysed thematically.

Three key themes were identified. First, Ayurvedic practitioners viewed their role as complementary to Western medicine, providing holistic, individualised, and patient-centred care to support NCD management. Second, they faced multiple barriers in the UK, including structural challenges (limited integration, poor institutional support, and restricted patient access) and financial constraints (high treatment costs, lack of NHS coverage, and import regulations). Finally, professional associations played a vital role in providing legal and regulatory guidance, promoting continuous professional development, and supporting research to strengthen evidence and legitimacy.

Although Ayurvedic practitioners face considerable challenges in the UK, they play a unique role in negotiating legitimacy, professional recognition, and the epistemological challenges of practising within a Western-dominated healthcare system. Professional associations help legitimise and advance their practice, supporting culturally congruent, patient-centred care that complements conventional NCD management. Despite structural barriers, Ayurvedic practitioners have maintained their presence and have navigated a complex, structurally Western-centric healthcare landscape, offering insights into integrative approaches to NCD care.