Mineralocorticoid receptor antagonists (MRAs) are a well-established treatment option for the management of heart failure (HF) with reduced ejection fraction. However, high-quality evidence for the effect of MRAs in the treatment of heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) has been limited until recent years. The nonsteroidal MRA finerenone has demonstrated efficacy in this population and was approved for treatment in July 2025 by the U.S. Food and Drug Administration. A call to action is needed to increase the use of guideline-directed medical therapy in HFmrEF/HFpEF with simultaneous or rapid sequence initiation of a combination therapy. This review provides an overview of MRAs approved for use in HF management, with particular focus on HFmrEF/HFpEF. Guideline recommendations and HF label indications are discussed, highlighting practical considerations for the safe use of MRAs in clinical practice. In addition, the therapeutic management of patients with HFmrEF/HFpEF and concomitant cardiovascular, kidney, and metabolic diseases is considered.

Prospective cohort studies documenting long-term dietary trends across multiple world regions are lacking.

To evaluate 15-y (2007-2022) changes in food and beverage consumption among adults aged 35-70 y living in 626 urban and rural communities across 16 high-income (HIC), middle-income (MIC) and low-income (LIC) countries.

In the Prospective Urban Rural Epidemiology Study, dietary intake was assessed using an abbreviated food-frequency questionnaire approximately every 3 y across four follow-up visits over a 15-y calendar period (2007-2022). Linear mixed-effect models and mixed-effect multinomial logistic regression were used to evaluate changes in food and beverage consumption over time. Dietary changes <0.05 servings/d (s/d) are presented as servings/wk (s/wk). Changes of <0.2 s/d change over the study period were considered modest. Participant demographics (age, sex, urban/rural residence, and education) closely matched national distributions in each country.

A total of 120 782 participants provided at least one dietary assessment (median follow-up: 12.1 y). Consumption of animal-based products has generally increased, with clear regional differences. Milk increased in China (+0.21 s/d, +0.15 to +0.26), and in LICs (+0.08 s/d, +0.05 to +0.11); decreased in HICs (-0.10 s/d, -0.12 to -0.07) and in MICs (-0.21 s/wk, -0.28 to -0.15). Eggs increased in HICs, MICs, and in China up to 0.12 eggs/d (+0.11 to +0.14); no change in LICs. All regions increased chicken intake. Only HICs increased cooked fish consumption (0.28 s/wk, +0.06 to +0.50). By contrast, plant-based food intake has generally decreased, but these changes were generally small, and there was some regional variation. Fruit consumption decreased in HICs (-0.16 s/d, -0.18 to -0.14) and MICs (-0.09 s/d, -0.10 to -0.07); increased in China (+0.13 s/d, +0.11 to +0.14) and LICs (+0.22 s/wk, +0.16 to +0.29). Fresh and cooked vegetable consumption decreased in HICs (-0.05 s/d [-0.06, -0.04] and -0.17 s/wk [-0.30 to -0.03], respectively), MICs (-0.19 s/wk [-0.23 to -0.16] and -0.08 s/d [-0.09 to -0.07], respectively), and in China (-0.07 s/d [-0.08 to -0.06] and -0.31 s/wk [-0.40 to -0.23], respectively). In LICs, fresh vegetable consumption increased (+0.19 s/wk, +0.12 to +0.26); cooked vegetable intake was unchanged. Rice consumption decreased in all regions.

In this international prospective study, dietary changes for most foods and beverages during the 15-y (2007-2022) study period were modest in size (most changes <0.2 s/d), but varied by region. Animal-source food intake generally increased, particularly in rapidly developing economies, while plant-based food intake decreased. As these shifts remain below the magnitude usually associated with measurable changes in disease risk, their clinical importance is uncertain.

Massive weight loss (MWL) is becoming more common, yet there is limited knowledge about the sociodemographic and clinical features of women undergoing post-mastectomy breast reconstruction following MWL. This study compared women with and without prior MWL who are undergoing breast reconstruction.

This nationwide, population-based case-control study used prospectively collected Swedish national registry data. Women who underwent bariatric surgery between 2007 and 2022 and subsequently received implant-based breast reconstruction after mastectomy were identified and matched by age and body mass index to controls without previous bariatric surgery, with at least 3 controls per patient. Sociodemographic characteristics, specialist-care diagnoses, and dispensed drugs were compared between groups.

Eighty-one women with MWL were matched with 993 controls. Women with MWL had lost an average of 30.6 kg before reconstruction. They were more frequently separated or divorced and had lower educational attainment, although the educational difference did not remain significant after Bonferroni correction. Employment and income levels were similar between groups. Diagnoses from specialist care were generally more common among women with MWL: diabetes, cardiovascular, gastrointestinal, rheumatic, and psychiatric diseases occurred at more than twice the frequency compared to controls, although most differences were not significant after correction. Women with MWL also had higher usage of several types of drugs. Differences in dispensed vitamins and minerals and anemia drugs remained significant after Bonferroni correction.

Women undergoing breast reconstruction after MWL form a distinct subgroup with higher medical and psychosocial complexity than women without MWL. Recognising these differences can aid patient assessment and perioperative planning.

This review synthesizes recent literature on cell type-specific roles for BRD4 in cardiac homeostasis and disease, emphasizing functions for this chromatin 'reader protein' in mediating pathologic gene signatures in heart failure.

Paradoxically, although knockout of BRD4 in cardiomyocytes is catastrophic, pharmacological inhibition of BRD4 blocks pathological cardiac remodeling via salutary effects in cardiomyocytes as well as in cardiac fibroblasts and macrophages. Mechanistically, dynamic targeting of BRD4 to gene enhancers and promoters governs stress-induced pathogenic transcriptional programs across myocyte and non-myocyte cell populations in the heart. Recent findings support roles for BRD4 in promoting pro-hypertrophic, pro-inflammatory, and pro-fibrotic gene expression via cell autonomous and non-autonomous actions in multiple cardiac cell types. Advancements in understanding the mechanisms by which BRD4 controls pathological gene expression in the heart should facilitate efforts to develop effective agents to target this epigenetic reader for the treatment of heart failure.

Obesity has become a global public health crisis in recent years, with its continuous rise posing significant health risks. It is associated with a range of chronic diseases, including cardiovascular disease, type 2 diabetes, and certain types of cancer. Additionally, obesity leads to poor health outcomes and reduces life expectancy. The lymphatic system, a critical part of the circulatory system, has traditionally been recognized for its primary functions in immune surveillance and maintaining tissue fluid balance. Lymphatics also play a more complex role in lipid metabolism, immune regulation, and inflammation control, which significantly influences metabolic health. Despite these insights, the specific mechanisms of interaction between lymphatic dysfunction and obesity, as well as the directionality of causality, are not yet fully understood. This review aims to systematically synthesize and evaluate existing evidence regarding the interrelationship between lymphatic dysfunction and obesity. Its goal is to provide novel perspectives for developing innovative preventative and therapeutic strategies targeting lymphatic function in obesity.

Dilated cardiomyopathy (DCM) is a leading cause of heart failure. Due to its complex pathogenesis, effective treatment strategies remain limited. Therefore, it is particularly important to identify novel candidate biomarkers from the pathogenesis level. In recent years, lactylation modification plays an important role in various cardiovascular diseases; however, its specific involvement in DCM remains unclear. Therefore, it is of great significance to identify lactylation-related biomarkers associated with DCM to provide insights for future mechanistic investigations. The DCM gene expression datasets were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes and co-expression modules were identified using differential expression analysis and weighted gene co-expression network analysis (WGCNA). Lactylation-related gene sets (LRGs) were obtained from the MSigDB database. The intersection of these results was further analysed using machine learning algorithms: Least Absolute Shrinkage and Selection Operator (LASSO), Random Forest (RF), and Support Vector Machine (SVM). CIBERSORT algorithm was used to analyse the immune infiltration characteristics of DCM, and DCM was divided into two subtypes by unsupervised consensus clustering. Mendelian randomization (MR) analysis was employed to evaluate potential causal associations between the candidate genes and DCM or heart failure progression. Finally, the candidate genes were verified by the GSE57338 database and β₁-AA-induced heart failure model with DCM characteristics. Through comprehensive transcriptomic analysis integrating WGCNA and LRGs, 38 characteristic genes associated with DCM and lactylation were finally identified. Subsequently, 18 key genes were selected by machine learning. The risk prediction model based on these genes demonstrated good predictive performance for DCM. Immune infiltration analysis revealed dysregulated inflammatory responses in DCM patients, and 18 key genes were significantly related to CD8⁺ T cells, CD4⁺ T cells, neutrophils, and Natural killer T cell infiltration. Unsupervised consensus clustering divided DCM patients into two distinct subtypes (C1 and C2), with marked differences in gene expression. Subtype C1 was characterized by activation of CD8⁺ T cells and Natural Killer T cells, whereas C2 mainly exhibited CD4⁺ T cells and neutrophils activation. Furthermore, Mendelian randomization analysis suggested that EXT1 may be associated with heart failure, while IER3 was potentially associated with DCM. Finally, the external validation set GSE57338 and the heart failure model with DCM characteristics were used to verify the two genes identified. The results showed that EXT1 was up-regulated and IER3 was down-regulated. Based on the deep excavation of public database, combined with machine learning algorithm and Mendelian randomization, this study identified EXT1 and IER3 as potential candidate biomarkers for DCM, providing a new theoretical foundation and hypotheses for future mechanistic and translational research.

Transposable elements (TEs), commonly known as "jumping genes," constitute nearly half of the human genome and are increasingly recognized as important regulators of gene expression, chromatin organization, and immune signaling. Although most TEs are epigenetically silenced under physiological conditions, aging, chronic inflammation, and cancer can induce TE reactivation, leading to genomic instability, innate immune activation, and transcriptional reprogramming. Emerging evidence demonstrates that TEs contribute to immune cell differentiation, enhancer landscape formation, interferon signaling, and inflammatory responses through diverse mechanisms, including the generation of regulatory non-coding RNAs, alternative splicing events, and TE-derived peptides presented by major histocompatibility complex molecules. In addition to their roles in cancer biology, dysregulated TE activities have also been implicated in aging-associated and inflammatory disorders. In this review, we summarize the classification and regulatory functions of TEs, discuss their roles in immune regulation, inflammation and cancer, and examine emerging therapeutic strategies targeting TE-associated pathways in cancer and inflammatory diseases.

Child well-being policies require quality data that takes children's perspectives into account, recorded through appropriate, accurate and reliable measurement instruments. This study evaluated the psychometric properties of two versions of the KINDL-R questionnaire used in the 2022 French National Study on Children's Well-being (Enabee) to assess Health-Related Quality of Life (HRQoL) in children: a self-report version for elementary school children aged 6-11 (n = 15,114), and a parent-report version for preschool and kindergarten children aged 3-6 (n = 3,785).

We examined the distributions of responses and the correlations between items. We performed confirmatory factor analysis (CFA) and exploratory structural equation modelling (ESEM) to assess the fit of first- and second-order factor models. Internal consistency was measured using McDonald's omega. We tested measurement invariance across child's gender, grade, type of school and whether or not they had a chronic illness. We also conducted a known-groups analysis via analysis of variance (ANOVA) based on child's chronic illness, mental health and parental educational attainment.

The parent-report version demonstrated satisfactory CFA model fit (CFI = 0.915, TLI = 0.901, RMSEA = 0.072, SRMR = 0.073), supporting dimensional scoring. The acceptable fit of the hierarchical model (CFI = 0.916, TLI = 0.905, RMSEA = 0.073, SRMR = 0.075) provides preliminary support for reporting an overall score. Invariance was confirmed for the child's gender, grade, type of school and chronic illness. This version effectively distinguished between children with chronic illnesses or at least one probable mental health difficulty and healthy peers. However, the self-report version lacked factorial validity and showed poor CFA model fit (CFI = 0.757, TLI = 0.717). The ESEM model provided a detailed assessment of the fitting issues, which were primarily related to the emotional well-being dimension.

The parent-report version of the Kiddy-KINDL-R can provide a valid measure of HRQoL for French children aged 3-6 with comparable mean scores across groups. However, the proposed factor structure of the self-report version of the Kid-KINDL-R was not supported, and most subscales showed insufficient internal consistency in elementary school children. Further refinement is thus required. This was the first study to evaluate the psychometric properties of the KINDL-R measure in the French general population. It provided critical, reliable, and unprecedented information about measuring children's HRQoL.

Identifying geographic clusters with distinct profiles may support evidence-based policy and planning. This study aimed to identify clusters based on suicide rates, proportion of people reporting a mental health condition, sociodemographic characteristics, and mental health workforce features.

Area-level data were obtained for 294 Statistical Area Level 3 (SA3) regions across Australia using routine administrative and census data. Hierarchical clustering of principal components identified clusters, and spatial join-count analysis assessed their spatial concentration.

Our analysis found three clusters. Cluster 1 (N = 136; 46.2%) was characterised by a higher suicide rate and a high proportion of people self-reporting a mental health condition. This cluster was mainly in regional and remote areas with an older population, lower household income and educational attainment, and lower mental health workforce density. Cluster 2 (N = 146; 49.7%) had the lowest suicide rates and the lowest proportion of people reporting a mental health condition; these areas were predominantly metropolitan and characterised by a younger population, fewer Indigenous people, higher income and educational attainment, and higher mental health workforce density. Cluster 3 (N = 12; 4.1%) had the highest suicide rate yet the lowest proportion of people reporting a mental health condition. This final cluster was entirely regional and remote, had the highest Indigenous population proportion, lowest educational attainment, and lowest mental health workforce density. All clusters exhibited significant spatial clustering.

This study highlights geographic disparities in mental health and suicide-related profiles across Australia. Prioritising community-level interventions that reduce socioeconomic disparities and improve access to mental health care is crucial in regional and remote areas.

Given rising rates of mental health difficulties among young people, early intervention is crucial to mitigate personal and societal costs. Interventions should be locally adapted to ensure acceptability and sustainability, particularly in low- and middle-income countries (LMICs), where health systems are often under-resourced. Vietnam and Cambodia are LMICs with young populations, recent histories of conflict and ongoing vulnerabilities, including poverty and urban-rural inequality. While many adolescents experience common mental disorders, access to care is limited by stigma, low mental health literacy and reliance on urban, medicalised services. Community-based interventions are therefore needed; however, evidence on adapting such interventions in LMICs remains limited. This article describes the co-adaptation of a school-based mental health literacy intervention in Vietnam and Cambodia.

The intervention, within the Mental health capacity Building and stRengthening In Global HealTh systems study, was adapted from the co-created Adolescent Mental Health Promotion intervention implemented in Vietnam and Tanzania. Adaptations to content and delivery were developed through workshops across four study sites (two in each country). Facilitated by local research teams, the workshops engaged adolescents alongside parents, teachers and other stakeholders. Activities included topic ranking, workbook exercises and group discussions. Adaptations were synthesised across sites using spreadsheets, and feedback from stakeholder advisory groups informed the final intervention design.

Key adaptations included delivery by two trained facilitators per session (one teacher, one external provider, with an additional back-up teacher in Cambodia), inclusion of peer-led co-facilitation of some sessions and the addition of new topics: 'the Internet', 'Eating disorders and body image' and 'Self-harm and suicide'.

Co-adaptation was strengthened by early and diverse stakeholder engagement and participatory workshops that enabled all stakeholders, including adolescents, to voice their views. Responsive adaptations will likely continue throughout delivery via participant input, research team discussions and consultations with stakeholder advisory groups.