Cardiopulmonary exercise testing (CPET) assesses physiological responses to incremental exercise and identifies potential causes of exercise limitation. There have been several population specific reference equations published, none that span the human age range. It would be advantageous to have all-age global reference ranges. This Task Force aimed to derive Global Lung Function Initiative (GLI) reference equations for peak oxygen uptake (VO_2peak) and peak work rate (W_peak) in healthy individuals.

CPET data were collected retrospectively. Generalised additive models of location, shape and scale (GAMLSS) were used to develop reference ranges, including age, sex, height, and weight as explanatory variables. The influence of geographic region, equipment, testing protocols and averaging methods for peak exercise data was also examined.

Data from 5956 healthy individuals between 6 and 83 years across 17 sites in Europe, North and South America, and Asia were analysed. There was substantial between-subject variability in both VO_2peak and W_peak, with wide confidence intervals across age groups. Heterogeneity in VO_2peak was related to geographic region, metabolic cart type, and averaging methods for peak exercise values. Controlling for these variables improved model fit but not sufficiently to be reliable predictors for reference ranges.

Significant heterogeneity in CPET testing methodology and outcomes between sites precluded the development of reference ranges for VO_2peak and W_peak. This Task Force has developed a framework for prospective data collection with strictly standardised protocols and centralised data analysis to reduce variability and establish robust, clinically meaningful reference ranges for CPET outcomes.

Myocarditis is a clinical condition characterized by inflammation of the myocardium. It commonly occurs in various heart disorders and, in extreme circumstances, can be fatal. However, the effective and safe dietary strategies for alleviating myocardial inflammatory injury are currently lacking. Here we investigated the potential of daidzein (DD), a natural isoflavone found in leguminous plants, in alleviating myocardial inflammatory injury. The lipopolysaccharides (LPS)-treated C57BL/6J mice and H9c2 cardiomyocytes were employed to investigate the protective effects and mechanisms of DD against myocardial inflammation. In animal studies, DD supplementation at 50 and 100 mg/kg/day significantly alleviated the myocardial injury induced by LPS. In cell experiments, 2.5 μM DD effectively decreased LPS-induced oxidative stress, cell death, and inflammatory responses. In addition, DD mitigated the LPS-induced calcium imbalance in cardiomyocytes. Mechanistically, DD inhibited the LPS-induced myocardial inflammatory injury by targeting estrogen receptor beta (ERβ), subsequently leading to a reduction in ER stress. Furthermore, the molecular docking and experimental validation revealed that the binding pocket of DD in ERβ was highly conserved, and that the H475 and R376 residues were essential for binding DD. In summary, our results suggest that dietary DD supplementation is a promising strategy for alleviating myocardial inflammatory injury.

Gastrointestinal bleeding (GIB) is common in patients with cardiovascular (CV) disease, but a complete understanding of subsequent outcomes is unknown. We assessed outcomes following GIB in patients with CV disease.

INTERBLEED is an international multi-center prospective study comparing adults with CV disease (coronary or peripheral arterial disease, heart failure, atrial fibrillation, cerebrovascular disease, or venous thromboembolic disease) with GIB to those without. Outcomes included major adverse cardiovascular events (MACE - myocardial infarction, stroke, or CV-related death), all-cause death, and recurrent GIB at 12 months. Multivariable regression modelling yielded odds ratios (ORs) with 95% confidence intervals (CIs), and reverse Kaplan Meier curves were created.

A total of 3,814 patients were enrolled: 1,612 patients with GIB and 2,202 without. On multivariable analyses, patients with CV disease experiencing GIB were more likely to die within 12 months (OR 2.29, 95%CI 1.24-4.19). GIB was associated with recurrent GIB (OR 4.28, 95%CI 2.80-6.53) but not MACE. However, resumption of antithrombotic therapy between 4-7 days (OR 0.37, 95%CI 0.17-0.83) or 8-30 days (OR 0.37, 95%CI 0.17-0.81) following GIB were associated with lower odds of MACE within 12 months compared to discontinuation or lack of resumption within 60 days. Any antithrombotic use following enrolment was associated with lower all-cause death (OR 0.45, 95%CI 0.28-0.71). Neither antithrombotic use nor early resumption was associated with higher odds of recurrent GIB.

GIB in patients with CV disease is independently associated with subsequent morbidity and mortality. Patterns in antithrombotic resumption were associated with outcomes. Further research into optimal antithrombotic management following GIB is essential.

With an aging population globally, prevention of frailty and sarcopenia will become a public health priority. Growth Differentiation Factor-15 (GDF-15), a stress-responsive cytokine of the TGF-β superfamily, has emerged as a promising biomarker linking mitochondrial dysfunction, cellular senescence, and systemic inflammation to biological and phenotypic aging.

This systematic literature review systematically synthesizes the clinical evidence on GDF-15 as a biomarker of frailty, sarcopenia, and physical function, highlighting patterns, gaps, and the biological plausibility of its role as a predictive marker and therapeutic target.

Following PRISMA guidelines, we searched CENTRAL, Embase, MEDLINE, and PubMed up to February 2026. Studies involving adult human participants with measured serum GDF-15 levels and assessments of frailty or sarcopenia were included. Data were extracted and grouped thematically by population type, study design, and outcome domains. Narrative synthesis was used to compare findings and explore heterogeneity.

From 1027 records, 35 studies were included, spanning community-dwelling adults, hospitalized patients, and individuals with cardiovascular, metabolic, gastrointestinal, and respiratory diseases. Elevated GDF-15 levels were consistently associated with poorer physical performance and greater frailty severity. Longitudinal studies suggested predictive value for future functional decline, although associations with sarcopenia were less consistent. Sex-specific variations and methodological heterogeneity, including assay techniques and diagnostic criteria, were key sources of variability. Interventional studies demonstrated limited modulation of GDF-15 levels through physical activity alone.

These findings support the integration of GDF-15 into precision geriatric care, though further longitudinal and interventional studies, including those evaluating the incremental value of adding GDF-15 to existing screening tools for frailty, sarcopenia, and functional status, are required to establish its clinical utility.

Self-amplifying RNA (saRNA) enables sustained protein expression from a single administration. In this study, we developed an intramuscular saRNA-lipid nanoparticle (saNppa-LNP) therapy encoding natriuretic peptide type A (Nppa) for cardioprotection. A single injection induced sustained pro-atrial natriuretic peptide (pro-ANP) secretion for 4 weeks; pro-ANP was subsequently cleaved by the cardiac protease corin into active ANP, producing robust cardioprotection in mouse and swine myocardial infarction models. At equivalent doses, saNppa achieved greater efficacy than conventional mRNA. Single-nucleus transcriptomics identified natriuretic peptide receptor 1-positive (Npr1⁺) endothelial and epicardial cells as primary effectors, with saNppa-LNPs reshaping their paracrine profile to promote cardiomyocyte regeneration and suppress fibrosis. Longitudinal biosafety assessments revealed no systemic toxicity. Together, these results demonstrate that one-shot saNppa-LNP therapy offers durable cardioprotection, supporting the broader potential of saRNA-LNP-based approaches for cardiac therapy.

Disorders of Sex Development (DSD) refer to a group of congenital conditions where chromosomal, gonadal, or anatomical sex development is atypical. Cardiovascular diseases (CVD) are a leading cause of illness and death worldwide, often resulting in serious conditions like heart attacks, strokes, and heart failure. Recent research suggests that shared mechanisms may link DSD and CVD. This study aims to investigate the shared genetic mechanisms between DSD and CVD, which could uncover common biological pathways involved in their development.

We performed a comprehensive analysis using a dataset of 169 genes associated with 46XY DSD and corresponding genes linked to CVD, gathered from published research. The overlapping genes between them were identified and grouped into four biological processes: transcription factors, signaling pathways, hormonal regulation, and developmental regulation.

In this review, we explored the potential link between recognized 46XY DSD genes and CVD. We found 25 genes that are shared between the 46 XY DSD and CVD, suggesting a genetic connection between the two conditions. These shared genes fall into categories such as transcription factors, signaling pathways, hormonal regulation, and developmental regulation. This gives us valuable insights into how these genetic factors might affect cardiovascular health in people with DSD. Each gene and its role in 46XY DSD and CVD will be discussed separately. We will also address challenges and provide suggestions for a better understanding of the genetics involved. Additionally, the review will outline future research directions crucial for advancing our understanding of the connection between 46XY DSD and CVD, with the goal of improving health outcomes for affected individuals.

Our findings suggest a genetic link between 46 XY DSD and CVD, indicating that shared molecular mechanisms may play a role in the development of both conditions. These insights into the connections could have important implications for personalized medicine, potentially allowing for treatments that target both 46 XY DSD and CVD.

Breastfeeding is one of the most important public health interventions that supports infant and young child survival in humanitarian crises. Yet, breastfeeding in these settings is often difficult and challenges are not always easy to address. The purpose of this study was to understand breastfeeding decisions and experiences among a population of internally displaced Yazidi women living in IDP camps across the Kurdistan Region of Iraq. This mixed-methods, multi-sited study was designed to document Yazidi women's breastfeeding experiences while living in an IDP camp in the KRI. Qualitative and quantitative data were collected November 2018-December 2019 in five IDP camps throughout Sulaymaniya Province to which Yazidi families had been resettled. Mental Health screening data were collected with 30 pregnant and postpartum women. Semi-structured interviews were conducted with these same 30 women as well as some spouses (n = 7) and aid workers (n = 5). Thematic narrative analysis was used to analyze the data and develop themes and interpretations. Breastfeeding decisions and practices are strongly circumscribed by living conditions in the camp, pregnancy and birth experiences, poverty, lack of mental health care, social support, and cultural beliefs regarding the importance of breastfeeding. There is a critical need for increased investment in delivering mental health support in camps, specifically for people experiencing pregnancy, childbirth, and breastfeeding and those who are supporting these populations, with an emphasis on culturally sensitive, trauma-informed care. Doing so has the potential to promote more humane, holistic, and human-rights-based approaches to perinatal and postpartum care for Yazidis and for IYCF-E programs globally.

Depression is common among adolescents, particularly in low- and middle-income countries, such as Ghana. Yet, access to mental health care in these settings remains limited. There is a need for research to focus on innovative strategies to improve access to care. The African Youth in Mind consortium, together with a group of young people with depression and relevant stakeholders have developed a novel six-session lay professional intervention (Y-MIND) to treat depression.

As part of the early phase of intervention development, we conducted a case series aimed at testing the feasibility, acceptability, and preliminary safety of Y-MIND when delivered by a trained clinical psychologist within Navrongo, Ghana. Four adolescents, aged 16-18 years, with a primary DSM-5 diagnosis of major depressive disorder were purposively recruited and received the intervention. The Patient Health Questionnaire-9 (PHQ-9) was administered at baseline and weekly, and each session audiotaped. In addition, semi-structured interviews were conducted after each session and at two weeks' follow-up. PHQ-9 data were analysed using Stata 17 to generate descriptive statistics. A deductive framework guided the analysis of semi-structured interview transcripts and participant evaluations using NVivo 12.

Three of four adolescents completed all six sessions. The mean session duration was 58 minutes (SD = 12.0). All four participants demonstrated a ≥50% reduction in PHQ-9 scores by end of treatment. Mean PHQ-9 scores decreased from 14.5 (SD = 0.6) at baseline to 2.3 (SD = 4.0) at endline. By the beginning of session five, two participants had PHQ-9 scores ≤5. No participant showed symptom deterioration during the intervention. Qualitative interviews indicated that participants found the intervention understandable and relevant to their context. The interventionist identified areas for refinement, including clarifying sections of the manual and worksheets, addressing variability in remission rates, and strengthening the emphasis on mutual respect within the therapeutic relationship.

The Y-MIND intervention appeared to be feasible, acceptable, and safe for treating depression among senior high students in Ghana. Planned piloting with non-specialists will include adaptations for training, supervision, and fidelity monitoring.

Clinical Trials.gov Trial registration number ID NCT06740084, Trial registration data, December 9, 2024.

The COVID-19 pandemic and associated public health orders did not impact all population groups equally. We examined perceived pandemic impacts on daily life by socio-demographic and psychological factors. Participants, quota sampled by region, age and sex, completed a cross-sectional online survey between Oct 21st and Nov 10th 2020. COVID-19 impact categories (negative/same/positive) were compared by age and sex with chi-square tests. Associations between COVID-19 impacts and socio-demographic and psychological characteristics were examined with hierarchical regressions. COVID-19 impacts differed by sex for 7/19 aspects: females reported negative impacts on mental health, loneliness, and sleep quality more frequently than males, whereas more males reported negative impacts on substance use, alcohol consumption, and time availability. Males reported both more negative and positive impacts on job security than women. Young adults reported more negative impacts across all daily life aspects except social connections, where those ≥ 60 years reported worse impacts. Negative impacts were also associated with poor health status, reduced work hours, lower satisfaction with government communication, higher intolerance of uncertainty, and some coping strategies, while several other coping strategies correlated with positive impacts. Overall, COVID-19 impacts differed by age, sex, and several other variables. These findings could guide targeted public health messaging and interventions to mitigate the impact of future pandemics.

Adolescents in Aotearoa New Zealand (NZ) face rising mental health challenges amidst strained school support systems. Digital mental health interventions (DMHIs) offer scalable and cost-effective support, yet little is known about their real-world implementation in school settings, particularly for culturally diverse populations.

This study explored qualitative considerations of implementing Whitu for Schools (WFS), a digital wellbeing app, within secondary schools in NZ. A qualitative design using semi-structured interviews was conducted with 12 high school staff across 12 schools from the North Island, guided by the Exploration, Preparation, Implementation, Sustainment (EPIS) framework.

Participants described escalating student mental health concerns and limited access to timely support. WFS was welcomed as a timely, low-barrier intervention with engaging and culturally affirming content. However, challenges emerged around digital access, policy constraints (eg phone bans), staff digital literacy, and concerns about sustaining engagement. Effective implementation was seen as contingent on flexible, embedded delivery within school routines, tailored training, and ongoing student feedback. Equity was a recurring theme, with concerns that digital divides may reinforce existing disparities.

WFS holds promise as a school-based digital wellbeing intervention, but successful implementation requires contextual responsiveness, strong staff and leadership buy-in, and equity-driven infrastructure. Findings highlight the importance of co-design, relational engagement, and sustained adaptation to ensure that digital tools meet the dynamic and diverse needs of rangatahi in NZ.