Danon disease (DD) is a rare X-linked dominant lysosomal storage disorder caused by mutations in the LAMP2 gene. It is typically characterized by a triad of intellectual disability, skeletal myopathy, and cardiomyopathy. Due to the X-linked inheritance pattern, males often present with more severe manifestations. We report an atypical presentation of DD in a young male with isolated cardiomyopathy, incidentally diagnosed during evaluation of an abnormal electrocardiogram showing a pseudo-left bundle branch block in the setting of a Wolff-Parkinson-White pattern. Further workup revealed heart failure with reduced ejection fraction on echocardiography, and cardiac MRI demonstrated late gadolinium enhancement of the left ventricular walls with sparing of the basal septum. Genetic testing confirmed the diagnosis of DD. The patient was managed with guideline-directed medical therapy and received an implantable cardioverter-defibrillator for primary prevention of arrhythmia. He ultimately underwent heart transplantation with a satisfactory clinical outcome. This case underscores the importance of maintaining a high index of suspicion and pursuing comprehensive cardiac and genetic evaluation in young patients with unexplained cardiomyopathy, as early diagnosis of underlying conditions like DD can enable timely and potentially life-saving interventions.

Lactococcus garvieae bloodstream infection in a woman in Germany resulted in spondylodiscitis and bioprosthetic mitral valve endocarditis. Six weeks of ceftriaxone followed by 10 days of doxycycline led to sustained clinical and microbiological resolution. This case highlights the need for thorough diagnostic testing and individualized, shared decision-making in infective endocarditis cases.

Hypertension serves as a pivotal risk factor for myocardial ischemia reperfusion injury (MIRI). Reciprocally, MIRI exacerbates hypertension by inducing oxidative stress, inflammatory responses, cardiomyocyte death, fibrosis-associated myocardial remodeling, and RAAS system disruption, forming a vicious feedback cycle. This study aimed to investigate the regulatory role and underlying molecular mechanism of the lactate-related signaling axis in cardiomyocyte ferroptosis during MIRI, and to identify novel potential therapeutic targets for interrupting this detrimental feedback loop.

In vivo mouse MIRI models, in vitro cardiomyocyte oxygen‒glucose deprivation/reoxygenation (OGD/R) models, and spontaneously hypertensive rat (SHR) models were successfully established. Oxaloacetate and β-alanine were administered to inhibit lactate production and protein lactylation, respectively. Hematoxylin‒eosin (HE) and Masson staining were performed to evaluate myocardial histopathological damage and fibrosis. Immunohistochemistry (IHC) and Western blotting were used to detect the protein expression levels of lysine lactylation (Kla), H3K18la, alanyl-tRNA synthetase 1 (AARS1), and acyl-CoA synthetase long-chain family member 4 (ACSL4). An enzyme-linked immunosorbent assay (ELISA) was adopted to quantify the lactate content and ferroptosis-related marker levels. Transmission electron microscopy (TEM), immunofluorescence staining, and chromatin immunoprecipitation (ChIP) assays were separately utilized to observe the mitochondrial ultrastructure, assess cellular lipid peroxidation, and verify gene promoter enrichment.

Lactate, Kla, and H3K18la levels were markedly elevated in the MIRI and OGD/R models, accompanied by severe myocardial injury, fibrosis, and excessive cardiomyocyte ferroptosis. Inhibition of lactate production effectively reduced lactylation levels and mitigated ferroptosis as well as myocardial structural damage. Mechanistically, H3K18la was enriched in the promoter region of ACSL4 to facilitate its transcriptional activation, and knockdown of ACSL4 markedly reversed OGD/R-triggered cardiomyocyte ferroptosis. AARS1 overexpression strengthened lactylation and ACSL4 expression to promote ferroptosis, while its mutant did not. Notably, hypertension aggravated MIRI, promotes further increases in the level of histone lactylation mediated by AARS1, and exacerbates ferroptosis. Pharmacological intervention with β-alanine blocked the lactate/AARS1/H3K18la/ACSL4 axis and attenuated MIRI-induced myocardial damage.

Abnormal lactate accumulation facilitates H3K18la modification via AARS1-dependent regulation, which transcriptionally activates ACSL4 and modulates cardiomyocyte ferroptosis, ultimately contributing to the pathological progression of MIRI. Targeting the lactate/AARS1/H3K18la/ACSL4 regulatory axis is a promising and viable therapeutic strategy for MIRI intervention.

The Cavβ4 subunit of voltage-gated Cav1.2 channels regulates gene expression in neurons and cardiac cells. It increases the expression of interferon-β-related genes in H9c2 cardiomyocytes derived from rat ventricular tissue, but the possibility that it also regulates the expression of microRNAs (miRs) remains unexplored. Furthermore, its role in cardiac hypertrophy is unknown. Although the mechanisms underlying cardiac hypertrophy have been studied extensively, the antihypertrophic response is poorly understood. We conducted quantitative reverse-transcriptase polymerase chain reaction, western blot, and immunofluorescence experiments with H9c2 cardiomyocytes to examine the effects of Cavβ4 overexpression on isoproterenol-induced hypertrophy; the protein abundance of the transcription factors nuclear receptor 4A2 (NR4A2) and forkhead box O1 (FOXO1), which counter agonist-induced hypertrophic growth; and the expression of miR-183-5p, which targets NR4A2 and FOXO1 mRNAs. We found that the Cavβ4 subunit prevented the development of H9c2 cardiomyocyte hypertrophy, down-regulating miR-183-5p expression and increasing the protein abundance of NR4A2 and FOXO1. We also observed a transient decrease in Cavβ4 mRNA expression in rat ventricles at 6 h after isoproterenol injection. These results suggest that the Cavβ4 subunit plays a channel-independent role in the antihypertrophic response in cardiac muscle cells.

Violent conflict can affect worker's mental health and labor productivity, with implications for agricultural production and food security. Hired farm workers are particularly vulnerable because they often rely on daily wages, have limited assets, and face insecure employment, yet evidence on how conflict affects their mental health and productivity remains limited. This study examines the associations between conflict exposure, mental health, and labor productivity among hired farm workers in Myanmar.

We conducted a cross-sectional phone survey of 1,504 hired farm workers across Myanmar. The survey collected information on workers' demographic characteristics, work activities during the past 12 months, absenteeism, self-reported labor productivity (presenteeism), agricultural labor market conditions, job characteristics, job and life satisfaction, mental health, workplace harassment, and access to information. These primary survey data were matched with conflict event data from the Armed Conflict Location & Event Data (ACLED). Mediation analysis was used to examine whether mental health mediates the relationship between conflict exposure and labor productivity outcomes.

Overall, 39% of workers were exposed to conflict and 20% met the criteria for trauma. Compared with non-exposed workers, conflict-exposed workers were more likely to experience trauma (27% vs. 17%), more frequently absent from work (28% vs. 23%), and reported lower work performance (7.0 vs. 7.4). In multivariable mediation analyses, conflict exposure was associated with a 7-percentage-point higher likelihood of absenteeism and a 0.15-point lower work performance score. Trauma significantly mediated these associations, increasing the total association between conflict exposure and absenteeism by approximately 18%.

Our findings highlight the need for greater research and policy attention to the socio-psychological implications of conflict, which can erode labor productivity. They also reinforce the case for increased investment in mental health interventions, which have been severely reduced amid widespread budget cuts despite their potentially high cost-effectiveness.

Previous studies have shown that work-privacy conflict (WPC) can have detrimental effects on mental and physical health, interpersonal relationships, and family functioning. However, these detrimental effects vary widely between individuals. At the same time, there is evidence that the Big Five personality traits interact with how people cope with stress and conflict, so they may partly explain these differences. Thus, this study aims to examine the moderating role of the Big Five personality traits in the association between WPC and relationship satisfaction in mothers and fathers.

Data from 686 mothers and 702 fathers were derived from a longitudinal cohort study from Eastern Germany. Established questionnaires were used to measure personality at eight weeks, WPC at 14 months, and relationship satisfaction at two years after childbirth. Hierarchical linear regression analyses were performed including relevant confounding variables.

WPC alone did not predict maternal relationship satisfaction, whereas it significantly interacted with neuroticism. Mothers with average and high neuroticism levels showed consistently low relationship satisfaction, irrespective of their perceived WPC. Mothers with low neuroticism levels had low relationship satisfaction when their WPC was high. For fathers, WPC alone significantly negatively predicted relationship satisfaction, yet there was no significant interaction effect with personality.

The present findings indicate a complex interplay between WPC, neuroticism, and relationship satisfaction in mothers, including that average or high neuroticism scores alone are a potential risk factor for relationship satisfaction. Additionally, our results suggest that WPC may have a detrimental effect on relationship satisfaction in fathers, regardless of their personality traits. Based on our results we recommend developing and expanding measures related to work-family benefits to ensure balance between both domains. We also suggest prevention and intervention in the field of positive psychology.

The diagnosis of major depressive disorder (MDD) currently relies on subjective clinical assessments, highlighting a critical need for objective biological markers. The sphingosine-1-phosphate (S1P) signaling pathway, a pivotal regulator of neuro-immune interactions, has emerged as a potential contributor to MDD pathophysiology, yet its role remains incompletely understood. This study aimed to investigate plasma levels of S1P and its key receptors, S1PR1 and S1PR3, as potential diagnostic and predictive biomarkers for MDD, with a specific focus on sex differences and treatment effects.

Patients with MDD (n = 56) underwent an 8-week treatment protocol were enrolled, alongside 42 healthy controls (HCs). Depression severity was evaluated using the Hamilton Depression Rating Scale (HAMD-24) and Patient Health Questionnaire (PHQ-9) at baseline and 8-week visit. The plasma levels of S1P, S1PR1 and S1PR3 were measured at baseline and week 8.

At baseline, plasma concentrations of S1P, S1PR1, and S1PR3 were significantly elevated in patients with MDD compared to HCs. All three markers significantly decreased and trended toward normal levels after 8 weeks of antidepressant treatment. Notably, a significant sex-specific difference was observed for the receptors, baseline elevations of S1PR1 and S1PR3 were more obvious in female patients than in male patients. Furthermore, baseline S1P levels significantly predicted symptom improvement-as measured by changes in both HAMD-24 and PHQ-9 scores-whereas baseline S1PR levels alone did not. In addition, a combined panel of S1P, S1PR1, and S1PR3 yielded high diagnostic accuracy, with an area under the receiver operating characteristic curve (AUC) of 0.9575.

Our data demonstrate a significant, sex-dependent dysregulation of the peripheral S1P signaling pathway in MDD, which is responsive to antidepressant treatment. The ability of baseline S1P to predict clinical outcomes and the encouraging diagnostic precision of the S1P-S1PR1-S1PR3 panel strongly support their potential as clinically applicable biomarkers. These results imply that the S1P pathway plays a crucial role in the pathophysiology of depression, offering new possibilities for diagnosis and personalized treatment strategies in psychiatry.

Children of parents with depression, hereafter referred to as high-risk youth, are at elevated risk for mental illness, yet the mechanisms underlying this vulnerability remain unclear. Biased interpretation of ambiguous information and altered stress responses in this population have been proposed as potential pathways. As no previous study has examined these factors together, we investigated interpretation bias and endocrinological and affective stress responses as potential markers of depression vulnerability in high-risk children. We hypothesised that children of parents with depression would show more negative interpretation bias, altered cortisol stress responses and greater affective reactivity and prolonged recovery compared to children of parents with no mental illness. Across the sample, associations between interpretation bias and stress responses were expected.

Participants were 80 high-risk (parental depression) and 77 low-risk (no parental mental illness) youth aged 10 to 14 years. Mental health was assessed using structured clinical interviews. Interpretation bias was measured using the Scrambled Sentences Task, and stress reactivity and recovery were indexed by salivary cortisol and self-reported affect across six time points. Group differences were tested with t-tests and analyses of covariance. Regressions examined the unique contribution of familial risk status beyond other relevant factors, including depression, anxiety, childhood trauma, pubertal status, and sex. Correlations examined associations between interpretation bias and cortisol and affective stress indices.

Groups did not differ in interpretation bias, or cortisol or affective stress responses. Children's own symptoms of psychopathology (depression slightly more so than anxiety) positively predicted their interpretation bias but not their cortisol or affective stress responses. Exploratory moderation analyses showed that higher baseline cortisol strengthened the relationship between depression and interpretation bias. Interpretation bias correlated with cortisol reactivity and recovery within the high-risk but not the low-risk group.

Contrary to theoretical accounts, high-risk youth did not exhibit cognitive, affective, or endocrinological vulnerabilities relative to low-risk peers. Interpretation bias was found to be a promising target, robustly linked to clinical outcomes and tentatively to cortisol stress responses, though its absence in high-risk youth is in support of a more selective intervention approach.

The study was preregistered under the Deutsches Register Klinischer Studien DRKS00028842 on August 19, 2022.

The treatment of neuromyelitis optica spectrum disorder (NMOSD) has entered the era of targeted biological agents. While relapse control has improved substantially, patient-reported outcomes (PROs) remain understudied. This study aimed to explore real-world patient-reported perceptions of inebilizumab therapy in AQP4-IgG-positive NMOSD.

We conducted a nationwide cross-sectional survey of AQP4-IgG-positive NMOSD patients receiving inebilizumab using an anonymous online questionnaire (April-September 2025). Data collected included demographics, medication history, and multidimensional quality-of-life changes following inebilizumab initiation. Descriptive statistics and correlation analyses were performed. Key outcomes were patient-reported without objective validation.

A total of 275 valid questionnaires were analyzed. Respondents were predominantly female (90.5%) with a mean age of 39.7 ± 11.8 years. Mean inebilizumab treatment duration was 14.5 ± 8.4 months. Of all patients, 33.1% received inebilizumab as initial maintenance therapy, 42.9% had previously used conventional immunosuppressants, and 24.0% had switched from other biologics. Among respondents, 92.4% reported meaningful symptom improvement across multiple domains including bodily pain and mental health. Overall, 96.4% expressed willingness to continue therapy, with symptom improvement cited as the predominant reason (91.7%). Correlation analysis revealed weak associations between treatment duration and satisfaction (r = 0.12, p < 0.05) and between medication cost burden and satisfaction (r = - 0.24, p < 0.01).

In this cross-sectional survey, Chinese patients with AQP4-IgG-positive NMOSD receiving inebilizumab reported high satisfaction, perceived multidimensional benefit, and strong treatment continuation willingness. These findings provide exploratory patient-reported evidence regarding the acceptability of inebilizumab in routine practice. However, the observed improvements are self-reported and associative rather than causal; interpretation should account for the cross-sectional, non-comparative design, potential selection and recall biases, and lack of objective outcome validation. Prospective controlled studies are required to confirm these preliminary findings.

Individuals with psychosis and depression show widespread alterations in brain resting-state functional connectivity (rs-FC), affecting both sensory and higher-order brain regions. In this study, we investigate disruptions in the hierarchical organization of brain functional networks in individuals with psychotic and affective disorders. We derived functional brain gradients, low dimensional representations of rs-FC that capture cortical hierarchy, in a sample of 1071 (56.3% female) participants, including clinical high-risk for psychosis (CHR-P) individuals, recent-onset psychosis (ROP) patients, recent-onset depression (ROD) patients, and healthy controls (HC). We examined regional alterations, network-level alterations and functional differentiation and their relationship to clinical symptoms. In addition, we linked case-control differences to receptor expression maps to explore underlying neurobiological mechanisms. All clinical groups exhibited alterations in the visual-to-sensorimotor gradient, while only ROP patients showed alterations in the sensory-to-association gradient. CHR-P and ROP individuals exhibited lower values in the ventral attention network. Clinical groups combined showed higher values in the somatomotor network, a reduced gradient range and altered between-network dispersion. ROD patients showed reduced within-network dispersion in the attentional networks and a reduced range. Correlational analysis revealed weak associations of gradient measures with functioning, visual dysfunctions and cognition. Case-control differences showed associations to receptor expression maps, suggesting the involvement of neurotransmitter systems in these disruptions. Our findings reveal transdiagnostic and disease-specific alterations of hierarchical brain organization. These alterations indicate deficits in functional integration across psychiatric diseases, highlighting the role of attentional and sensory networks in disease processes.