Cerebral infarction (CI) is associated with high incidence and mortality rates. This study aimed to investigate the role and molecular mechanism of arachidonate 15-lipoxygenase (ALOX15) in oxygen-glucose deprivation/reoxygenation (OGD/R)-induced SK-N-SH cells.

An in vitro OGD/R model was established using SK-N-SH cells. The gene expression levels were assessed by RT-qPCR and western blotting. Cell proliferation and apoptosis were evaluated using the 5-Ethynyl-2'-deoxyuridine (EdU) assay and flow cytometry. Ferroptosis-related markers, including reactive oxygen species (ROS), Fe²⁺, and malondialdehyde (MDA), were measured. Bioinformatics analysis, dual-luciferase reporter, and chromatin immunoprecipitation (ChIP) assays were used to validate the transcriptional regulation of ALOX15 by SP1. The interaction between ELAV-like RNA-binding protein 1 (ELAVL1) and ALOX15 was analyzed using RNA-binding protein database analysis. In vivo, a middle cerebral artery occlusion (MCAO) model was used to assess the effects of ALOX15 silencing on cerebral infarct volume and neurological deficits.

ALOX15 was upregulated in CI patient tissues and OGD/R-treated SK-N-SH cells. Silencing ALOX15 alleviated OGD/R-induced SK-N-SH cell injury and ferroptosis. Specificity protein 1 (SP1) transcriptionally activated ALOX15 expression, promoting cell damage and ferroptosis. Additionally, ELAVL1 stabilized ALOX15 mRNA, further enhancing its expression and contributing to OGD/R-induced injury and ferroptosis. In the MCAO model, ALOX15 knockdown reduced infarct volume and improved neurological outcomes.

SP1 and ELAVL1 regulated ALOX15 to drive OGD/R-induced SK-N-SH cell injury and ferroptosis. These findings highlight the SP1/ELAVL1-ALOX15 axis as a potential therapeutic target for mitigating brain injury in CI, providing a translational basis for future interventions.

This letter comments on the longitudinal study by Schaeffer et al. (Child and Adolescent Mental Health, 2025) regarding emotional reactivity, parent-child conflict resolution, and suicidal ideation among Hispanic/Latino adolescents. While confirming the predictive role of emotional reactivity, the study's nonsignificant finding regarding parent-child conflict resolution invites critical reflection. We argue that this result may stem from the limitations of generic assessment tools, such as the PACHIQ-R, in capturing culturally nuanced relational processes. Core cultural values, particularly familismo, respeto, and simpatía, fundamentally shape conflict navigation, often through harmony, indirect communication, and nonverbal understanding, rather than the explicit problem-solving that standard scales measure. This measurement gap may lead to an incomplete understanding of protective family processes and limit the relevance of clinical interventions. We therefore call for future research to adopt culturally grounded measures and multi-method assessments to more accurately elucidate the role of family factors in adolescent suicide risk, advancing more inclusive and precise research practices.

Health-related quality of life (HRQoL) is a key patient-reported outcome in people living with HIV, reflecting physical, psychological and social well-being. This study aimed to evaluate HRQoL among people living with HIV in Türkiye using the PozQoL scale and to examine sociodemographic, clinical and treatment-related factors associated with HRQoL.

This cross-sectional, hospital-based study was conducted between May and August 2025 among 299 people living with HIV followed at the Tepecik Training and Research Hospital HIV Clinic in Izmir. The validated Turkish version of the PozQoL scale was administered to assess psychological, social, health concerns and functional domains. Sociodemographic and clinical variables, including comorbidities and polypharmacy, were analysed using t tests, Mann-Whitney U tests and multiple linear regression.

Participants had a mean age of 39.0 ± 11.8 years; 88.3% were male and 86.4% had virological suppression. The mean total PozQoL score was 47.83 ± 11.83. Multivariable analyses showed that depression was the only variable independently associated with lower total PozQoL scores (p = 0.009). In the psychological domain model, gender (p = 0.031), marital status (p = 0.022) and depression (p = 0.014) remained significantly associated with psychological well-being. Overall, unmarried participants, women/trans participants and those with depression had lower psychological domain scores. No significant associations were observed with HIV RNA suppression or transmission route.

Among virologically suppressed people living with HIV, higher PozQoL scores indicate better HRQoL. In this virologically suppressed cohort, HRQoL was primarily associated with social factors (gender, marital status), psychosocial factors (e.g., depression) and comorbidity burden rather than immunovirological indicators. Routine use of patient-reported outcome measures such as PozQoL can help identify treatable factors-including depression and polypharmacy-and support the integration of mental health and multimorbidity management into person-centred HIV care.

Growing evidence suggests that physical environmental features at the neighborhood level are linked to brain structure during human development. In a context of accelerated urbanization, climate change and technological transformations, assessing how environmental changes relate to brain development is critical. Most studies to date, however, used cross-sectional data only and focused on a reduced set of environmental and brain features. The present study investigates whether macroenvironmental and brain changes are associated during adolescence. We used structural equation models and regularized multivariate path analysis to identify macroenvironmental features that predict changes in whole-brain structural features in a sample of 368 individuals from the IMAGEN study (https://www.imagen-project.org/), who were assessed at 14 and 22 years of age. We observed characteristic brain developmental changes and substantial individual differences in change in 15 macroenvironmental features. Path analysis showed that changes in a handful of these variables, for instance tree cover density, presence of water bodies and air pollution, significantly predict changes in cortical thickness, structural connectivity and gray and white matter volumes over adolescence.

Studies show an association between elevated blood pressure, obesity, and insulin resistance with an higher risk of developing diabetes. As sodium is closely linked to elevated blood pressure and hypertension, and potassium is a counterbalancing nutrient to sodium, this study examines the association between intake of sodium, potassium, and sodium: potassium (Na:K) ratio and the incidence of diabetes.

Retrospective data analysis of dietary intake measured by a validated food frequency questionnaire in a prospective cohort of veterans participating in the Million Veteran Program (MVP) between 2011 and 2020, who were free of diabetes at baseline.

The main outcome is clinically diagnosed diabetes defined by phenotyping algorithms applied to electronic health records.

In this study of 198,049 veterans (mean age: 63.8 ± 13.1 years, 89% male), 7,260 were diagnosed with diabetes over a mean follow-up of 4.3 years. The mean sodium intake was 1218 mg/day. A higher sodium intake was associated with an 11% higher rate of developing diabetes (hazard ratio, HR) comparing extreme quintiles: 1.11, 95% CI: 1.03-1.20). Gs. The average daily potassium intake was 2589 mg and theighest quintile of potassium intake was associated with a 13% lower rate of diabetes (HR: 0.87, 95% CI: 0.81, 0.94) compared to the lowest quintile of potassium. Highest quintile of Na:K ratio was associated with a 21% higher rate for diabetes (HR:1.21, 95%CI: 1.12, 1.30). The pattern of associations between Na:K ratio and diabetes closely followed the pattern of dietary sodium intake and diabetes associations.

A higher sodium intake and a higher Na:K ratio were associated with a higher risk of diabetes in this large cohort of Veterans. These findings may be applied in future work to identify personalized lifestyle and dietary supports to prevent and treat T2DM.

Sleep phase delay (SPD) is a common comorbidity in patients with obsessive-compulsive disorder (OCD) and may affect the severity of OC symptoms and treatment response. This study aimed to explore the concentration of neurometabolites in the anterior cingulate cortex (ACC) of OCD patients with sleep phase delay, with a particular focus on the mediating role of ACC glutamate concentration to further understand the relationship between sleep phase delay and OCD.

94 participants (61 OCD patients and 33 healthy controls) underwent clinical assessments and imaging tests. Resting-state and functional-state magnetic resonance spectroscopy (MRS) was conducted to assess ACC neurochemical profiles. We compared clinical features and ACC neurometabolites among healthy controls, OCD patients with and without sleep phase delay. Mediation models were constructed to examine the mediating role of ACC glutamate.

Compared with OCD patients without sleep phase delay, OCD patients with sleep phase delay had higher PSQI scores, lower MEQ scores, higher Y-BOCS scores, and a higher proportion of treatment-resistant cases. In both resting-state and functional-state MRS, the concentrations of Glu and Glx in OCD patients with sleep phase delay were significantly higher than those in patients without sleep phase delay, but were not significantly different from those in healthy controls. Mediation analysis showed that resting-state Glu mediated the association between sleep phase delay treatment resistance in OCD.

Our findings indicate that glutamate concentration in the ACC serves as a key mediator in the relationship between delayed sleep phase and treatment resistance in OCD. Specifically, delayed sleep phase may exacerbate treatment resistance in OCD by elevating ACC glutamate levels, thereby identifying a novel neurobiological pathway.

Non-suicidal self-injury (NSSI) is prevalent in adolescents with major depressive disorder (MDD), yet the neuroendocrine mechanisms underlying NSSI remain poorly understood. This study examined the associations between hypothalamic-pituitary-thyroid (HPT) axis parameters, NSSI, and clinical symptoms in adolescents with MDD.

In this retrospective study, 110 adolescents with MDD (aged 12-17 years) were categorized into NSSI n = 45) and non-NSSI (n = 65) groups. Serum thyroid hormones (TSH, T3, T4, FT3, FT4) were measured via electrochemiluminescence immunoassay. Covariate-adjusted analyses compared thyroid function between groups and evaluated correlations with anxiety (HAMA) and depression (HAMD-24) symptom domains.

After adjusting for age, gender, BMI, illness duration, and antidepressant dose, the NSSI group exhibited significantly higher free thyroxine (FT4) levels compared to non-NSSI controls (17.01 ± 2.22 vs. 15.91 ± 2.25 pmol/L; p = 0.029). No differences were observed in TSH, T3, T4, FT3, or FT3/FT4 ratio (p > 0.05). Within the NSSI group, FT3 negatively correlated with somatic anxiety (r = -0.307, p = 0.040), while T4 inversely associated with psychomotor retardation (r = -0.299, p = 0.046).

Elevated FT4 levels suggest potential HPT axis dysregulation that may be associated with NSSI in adolescents with MDD. FT3 inversely correlated with somatic anxiety and T4 with psychomotor retardation, suggesting that thyroid hormones may play differential modulatory roles within depressive pathology.

Psychedelic use has greatly increased within clinical and recreational settings over recent years. While demonstrating a favorable safety profile within certain clinical populations, little empirical research has explored safety of psychedelic use within real-world samples. Using the World Health Organization (WHO) VigiBase, a comprehensive global pharmacovigilance database with voluntary spontaneous reporting of adverse events (AEs) from real-world clinical and recreational populations, we examined reports for classic psychedelics and MDMA. Most reports were made for MDMA (n = 1573) and LSD (n = 394), while psilocybin (n = 56), DMT (n = 18), and mescaline (n = 15) had fewer reports. The most common AEs for all substances were psychiatric in nature, specifically surrounding substance or drug abuse and dependence. Reports of overdose constituted 1.1 to 1.7 % of total AEs. Pregnancy-related and congenital disorders were rare. Compared to the acetaminophen control, LSD and MDMA were associated with significantly greater odds for the reported AEs of alcohol abuse (LSD: ROR=45.7, 95 % CI: 27.2 - 76.9; MDMA: ROR=19.2, 95 % CI: 12.2 - 30.4), substance use disorder (LSD: ROR=71.1, 95 % CI: 36.3 - 139.2; MDMA: ROR=129.9, 95 % CI: 78.4 - 215.5) and substance dependence (LSD: ROR=215.1, 95 % CI: 69.0 - 670.3; MDMA: ROR=76.8, 95 % CI: 25.5 - 231.8). These reports were also greater than those associated with the external positive control, oxycodone. Taken together, this exploratory study provides the first analysis of AEs associated with psychedelics reported to a global pharmacovigilance database and can inform their real-world safety. Findings should be considered in light of limitations surrounding co-use of other substances and potential deterrence towards reporting use of illicit substances.

Agitated depression, conventionally associated with bipolar disorder, may also constitute a clinically significant subtype within unipolar major depressive disorder (MDD). Nevertheless, the interrelationship between agitation and anxiety symptoms and their clinical implications in unipolar depression remain largely unexamined.

We examined three large, independent cohorts of patients with MDD from the GSRD (n = 1588), STAR*D (n = 1532), and PANDORA (n = 244) studies. A composite agitation-anxiety score was computed by summing relevant items of the retrospective Montgomery-Äsberg depression rating scale (rMADRS) in GSRD, the Hamilton Depression Rating Scale 17-items (HAM-D) in PANDORA and the 30-item Inventory for Depressive Symptomatology, Clinician-rated (IDS-C₃₀) in STAR*D. Patients were then stratified into patients with agitation-anxiety (AA+) and without agitation-anxiety (AA-) based on the median scores of each cluster. Associations between agitation-anxiety features and depression severity, suicidal ideation, disease duration, treatment response, and family history of bipolar disorder were evaluated using univariate and multivariate analyses.

A total of 3364 participants were analyzed. AA+ patients showed significantly greater baseline depression severity (independent from agitation-anxiety items) across all datasets. Moreover, agitation-anxiety features correlated with higher rates of suicidal ideation (STAR*D, GSRD), longer disease duration (GSRD), and lower treatment response (STAR*D), independent of age and sex. No significant associations with family history of bipolar disorder were found.

Features of agitated depression define a more severe depressive phenotype within depressive episodes and may represent a clinically relevant dimension in unipolar MDD. A transdiagnostic approach may enhance future research and treatment strategies.

Patients who define themselves as claustrophobic are often unwilling to undergo closed magnetic resonance imaging (MRI). The aim of this research is to determine the effectiveness of immersive entertainment glasses and person-centred care to successfully perform an MRI and to reduce anxiety levels in individuals who identify themselves as having claustrophobia.

A randomized clinical trial was conducted in 2022 in an imaging department of a University Hospital. The MRI scans were performed using a 1.5T Signa Explorer MRI. Participants were randomly assigned to either the control group (CG), which received specific person-centred care for claustrophobia, or the intervention group (IG), which received specific person-centred nursing care plus immersive entertainment glasses. The sample size was 226 individuals (114 IG and 112 CG).

A total of 189 participants (83.6 %) successfully completed the test from a cohort where previously 49,7 % couldn't complete the MRI. Lower body weight was associated with a higher likelihood of completing the MRI than higher body weight (p = 0.01). No statistically significant differences in anxiety were observed between the groups, nor in anxiety level changes during or after the test.

The high result in completing the test may be attributed to the fact that the actual impact is the person-centred approach more than immersive entertainment glasses.

Patients who were previously unable to undergo MRI can now successfully complete the procedure in a significantly higher proportion of cases because of patient-centred care. This advancement improves diagnostic accuracy and supports better clinical decision-making and patient outcomes.

ClinicalTrials.gov with ID NCT05304143 TRIAL AND PROTOCOL REGISTRATION: Clinical trial registration is at Clinicaltrials.gov with ID: NCT05304143 (https://trial.medpath.com/clinical-trial/e85ba4987305ba9e/nct05304143-efficacy-immersive-entertainment-glasses-magnetic-resonance-imaging).