Aortic aneurysms, including thoracic aortic aneurysms (TAA) and abdominal aortic aneurysms (AAA), represent a group of severe vascular lesions with insidious onset and high mortality. Currently, effective diagnostic markers and pharmacological interventions remain lacking in clinical practice. Extracellular vesicles (EVs), as key mediators of intercellular communication, have attracted increasing attention in the research on aortic aneurysms due to their high content of bioactive molecules, favorable biocompatibility, low immunogenicity, and inherent targeting capacity. This review systematically elaborated on the research progress on EVs in TAA and AAA, highlighting their significant role in the development and progression of aortic aneurysms. EVs play a crucial role by mediating core pathological processes, including endothelial dysfunction, phenotypic transformation of vascular smooth muscle cells, inflammatory immune responses, and extracellular matrix remodeling. Additionally, this review discussed the potential of disease-specific molecules carried by EVs as novel liquid biopsy markers for the early diagnosis of aortic aneurysms. Furthermore, this review evaluated the application prospects of EVs as natural drug delivery platforms and EV-based therapeutic strategies for aortic aneurysm through engineering modifications (such as targeting peptide modification and biomaterial integration). In particular, "cell-free" immunomodulatory therapies, which enhance targeting capacity to lesion sites through engineering modifications and focus strategically on regulating the phenotype and function of key immune cells (such as macrophages), are increasingly emerging as a cutting-edge direction with the greatest translational potential in this field. Despite challenges such as targeted delivery, the integration of engineering technologies with nanomedicine holds promise for opening new avenues for the precise prevention and treatment of aortic aneurysms through EV-based integrated diagnostic and therapeutic strategies.

Artificial intelligence (AI) is entering the study of hypertension, serving both primarily clinical purposes - to assist practicing physicians - and research objectives. Hypertension presents certain specific characteristics that should be carefully considered when using AI. The measured value of blood pressure is an extremely variable parameter that is difficult to standardize and measure with precision. At present, AI is able to provide very simple, clear, and well-documented answers to clinical questions regarding the management of patients with hypertension. Its role in research is perhaps somewhat less well developed. Several studies have been published on the use of AI in identifying patients with secondary hypertension, on the risk of future hypertension in normotensive individuals, and on the risk of heart failure and other complications of hypertension. A common issue with all these studies is the relative paucity of controlled clinical trials comparing AI with traditional procedures drawing on medical literature and clinical experience ("natural intelligence"), precisely designed to quantify the potential superiority of AI over natural intelligence on key end-points of real clinical value. This is similar to the approach currently taken when testing a new diagnostic or therapeutic procedure. Obviously, these considerations should be viewed as encouragement, not as a barrier, to continuing clinical research in the field of AI in hypertension. It is also important that scientific articles on AI published in medical journals be written using terms that doctors can understand, to ensure transparency and interpretability.

Accidental hypothermia is an underdiagnosed condition with a significant impact on public health. With the aim of providing the basis for a comprehensive care framework, 12 panelists from 3 Spanish scientific societies (SEDAR, SEMES and SEMICYUC) developed this multidisciplinary consensus document. Through a systematic search and the final synthesis of 281 articles including 1,704,632 patients, 37 recommendations were developed through a 2-round Delphi process, distributed across 8 application domains based on the organization of a rescue chain: prehospital prevention, initial evaluation, management and transport, hospital detection, care of the polytraumatized patient, hospital rewarming, cardiac arrest, and resuscitation. Robust consensus among panelists (>75% agreement) and excellent internal consistency (ω = 0.913) were achieved, providing a solid document that may serve as a basis for the implementation of standardized protocols.

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.