There is striking evidence that a high lipoprotein(a) [Lp(a)] concentration is a strong, independent, and causal cardiovascular risk factor. However, Lp(a) testing rates are very low (1 %-2 %) despite the fact that 1 in 5 individuals have elevated Lp(a) concentrations. The Brussels International Declaration on Lp(a) Testing and Management was co-created by the Lp(a) International Task Force and global leaders at the Lp(a) Global Summit, held in Brussels, Belgium, on March 24-25, 2025. The event, organized by FH Europe Foundation, brought together scientific experts, people with the lived experience of elevated Lp(a) and policy makers from the European Institutions and World Health Organization. The World Heart Federation, Global Heart Hub, and European Alliance for Cardiovascular Health and scientific organizations such as European Atherosclerosis Society, and International Atherosclerosis Society were formal partners. The Summit was hosted by a Member of the European Parliament, Romana Jerković, and held under the patronage of the Polish presidency of the Council of the European Union. The Declaration calls for 1) integration of Lp(a) testing and management into Global, European and National Cardiovascular Health Plans; 2) appropriate investment, policy and programmes in targeting Lp(a) testing and management based on a recent study demonstrating the substantial overall cost-saving to health systems across the globe; 3) political commitment to mandate systematic Lp(a) testing at least once during a person's lifetime, ideally at an early age, with full reimbursement; 4) incorporation of Lp(a) test results in the context of a person's cardiovascular risk assessment, with development of personalised cardiovascular health roadmaps as needed, without fear of dredit aiscrimination; 5) investment in public and healthcare professional education to increase awareness of Lp(a) and its impact on cardiovascular health.
- MeSH
- Biomarkers blood MeSH
- Risk Assessment MeSH
- Cardiovascular Diseases * blood diagnosis prevention & control epidemiology MeSH
- Consensus MeSH
- Humans MeSH
- Lipoprotein(a) * blood MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
BACKGROUND AND PURPOSE: The global burden of neurological diseases exceeds 43.1%, imposing a significant burden on patients, caregivers and society. This paper presents a roadmap to reduce this burden and improve brain health (BH) in Europe. METHODS: The roadmap is based on the European Academy of Neurology's (EAN) five-pillar BH strategy: advancing a global BH approach (P1), supporting policymaking (P2), fostering research (P3), promoting education (P4), and raising awareness of prevention and treatment (P5). It reviews current efforts, collaborations and future directions aligned with the WHO Intersectoral Global Action Plan (iGAP) for Neurological Disorders and suggests future initiatives and call for action. RESULTS: P1: Support WHO-iGAP through defined action points, international collaborations, in particular, the WHO BH Unit, and the EAN Brain Health Mission. P2: Collaborate with 48 national neurological societies to promote National Brain Plans (NBPs), addressing local needs, and improving access to care. P3: Advocate for more research funding; identify determinants of BH; develop preventive measures. P4: Provide educational opportunities for neurologists, public education programs, and advocacy training, including tools to educate the public. P5: Spearhead global awareness campaigns, organize public educational activities, and train BH advocates to contribute toward sustainable and long-term public health campaigns and policy engagement. CONCLUSIONS: The paper highlights the importance of a unified approach, integrating international collaborations and local initiatives, to improve BH outcomes based on the WHO-iGAP, and support sustainable development goals, in particular SDG 3: Good Health and Well-being and SDG 4: Quality Education.
OBJECTIVES: Illicit drug use presents a significant challenge to global health and public safety, requiring innovative and effective monitoring strategies. This study aimed to evaluate the current landscape of wastewater-based epidemiology (WBE) for monitoring illicit drugs in Europe, focusing on collaboration, current practices, and barriers, while identifying opportunities for improvement. STUDY DESIGN: Cross-sectional survey-based study. METHODS: Coordinated by the Sewage Analysis CORe Group Europe (SCORE) and the European Union Drugs Agency (EUDA), two surveys were conducted in 2023 targeting researchers and stakeholders using WBE for illicit drugs. Data were analysed to identify trends, gaps, and opportunities for improving WBE implementation. RESULTS: The findings indicate a robust research infrastructure and diverse analytical methods among European institutions. Two-thirds of the participating countries reported using WBE data to inform policy. However, challenges persist, particularly in securing funding and coordination, as well as generating national estimates from multiple locations and addressing specific local policy needs. CONCLUSIONS: WBE has proven to be a valuable tool for monitoring illicit drug trends and informing drug policies. To unlock its full potential, sustained funding, methodological standardization, and enhanced cooperation are essential. This study provides critical insights into the European WBE landscape, offering a roadmap for strengthening the integration of actionable WBE data into public health and policy frameworks.
- MeSH
- Wastewater-Based Epidemiological Monitoring MeSH
- Humans MeSH
- Wastewater * MeSH
- Substance-Related Disorders epidemiology MeSH
- Cross-Sectional Studies MeSH
- Surveys and Questionnaires MeSH
- Decision Making MeSH
- Illicit Drugs * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Europe MeSH
BACKGROUND AND PURPOSE: Neurological disorders constitute a significant portion of the global disease burden, affecting >30% of the world's population. This prevalence poses a substantial threat to global health in the foreseeable future. A lack of awareness regarding this high burden of neurological diseases has led to their underrecognition, underappreciation, and insufficient funding. Establishing a strategic and comprehensive research agenda for brain-related studies is a crucial step towards aligning research objectives among all pertinent stakeholders and fostering greater societal awareness. METHODS: A scoping literature review was undertaken by a working group from the European Academy of Neurology (EAN) to identify any existing research agendas relevant to neurology. Additionally, a specialized survey was conducted among all EAN scientific panels, including neurologists and patients, inquiring about their perspectives on the current research priorities and gaps in neurology. RESULTS: The review revealed the absence of a unified, overarching brain research agenda. Existing research agendas predominantly focus on specialized topics within neurology, resulting in an imbalance in the number of agendas across subspecialties. The survey indicated a prioritization of neurological disorders and research gaps. CONCLUSIONS: Building upon the findings from the review and survey, key components for a strategic and comprehensive neurological research agenda in Europe were delineated. This research agenda serves as a valuable prioritization tool for neuroscientific researchers, as well as for clinicians, donors, and funding agencies in the field of neurology. It offers essential guidance for creating a roadmap for research and clinical advancement, ultimately leading to heightened awareness and reduced burden of neurological disorders.
- MeSH
- Global Burden of Disease MeSH
- Humans MeSH
- Nervous System Diseases * epidemiology therapy MeSH
- Neurology * MeSH
- Research MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Europe MeSH
BACKGROUND: Micro- and nanoplastics (MNPs) are emerging pollutants of concern with ubiquitous presence in global ecosystems. MNPs pose potential implications for human health; however, the health impacts of MNP exposures are not yet understood. Recent evidence suggests that MNPs can cross the placental barrier, underlying the urgent need to understand their impact on reproductive health and development. OBJECTIVE: The Actionable eUropean ROadmap for early-life health Risk Assessment of micro- and nanoplastics (AURORA) project will investigate MNP exposures and their biological and health effects during pregnancy and early life, which are critical periods due to heightened vulnerability to environmental stressors. The AURORA project will enhance exposure assessment capabilities for measuring MNPs, MNP-associated chemicals, and plastic additives in human tissues, including placenta and blood. METHODS: In this interdisciplinary project, we will advance methods for in-depth characterization and scalable chemical analytical strategies, enabling high-resolution and large-scale toxicological, exposure assessment, and epidemiological studies. The AURORA project performs observational studies to investigate determinants and health impacts of MNPs by including 800 mother-child pairs from 2 existing birth cohorts and 110 women of reproductive age from a newly established cohort. This will be complemented by toxicological studies using a tiered-testing approach and epidemiological investigations to evaluate associations between maternal and prenatal MNP exposures and health perturbations, such as placental function, immune-inflammatory responses, oxidative stress, accelerated aging, endocrine disruption, and child growth and development. The ultimate goal of the AURORA project is to create an MNP risk assessment framework and identify the remaining knowledge gaps and priorities needed to comprehensively assess the impact of MNPs on early-life health. RESULTS: In the first 3 years of this 5-year project (2021-2026), progress was made toward all objectives. This includes completion of recruitment and data collection for new and existing cohorts, development of analytical methodological protocols, and initiation of the toxicological tiered assessments. As of September 2024, data analysis is ongoing and results are expected to be published starting in 2025. CONCLUSIONS: As plastic pollution increases globally, it is imperative to understand the impact of MNPs on human health, particularly during vulnerable developmental stages such as early life. The contributions of the AURORA project will inform future risk assessment. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/63176.
- MeSH
- Adult MeSH
- Risk Assessment MeSH
- Humans MeSH
- Maternal Exposure adverse effects MeSH
- Microplastics * adverse effects toxicity MeSH
- Nanoparticles adverse effects toxicity MeSH
- Pregnancy MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Progress in cytokine engineering is driving therapeutic translation by overcoming these proteins' limitations as drugs. The IL-2 cytokine is a promising immune stimulant for cancer treatment but is limited by its concurrent activation of both pro-inflammatory immune effector cells and antiinflammatory regulatory T cells, toxicity at high doses, and short serum half-life. One approach to improve the selectivity, safety, and longevity of IL-2 is complexing with anti-IL-2 antibodies that bias the cytokine toward immune effector cell activation. Although this strategy shows potential in preclinical models, clinical translation of a cytokine/antibody complex is complicated by challenges in formulating a multiprotein drug and concerns regarding complex stability. Here, we introduced a versatile approach to designing intramolecularly assembled single-agent fusion proteins (immunocytokines, ICs) comprising IL-2 and a biasing anti-IL-2 antibody that directs the cytokine toward immune effector cells. We optimized IC construction and engineered the cytokine/antibody affinity to improve immune bias. We demonstrated that our IC preferentially activates and expands immune effector cells, leading to superior antitumor activity compared with natural IL-2, both alone and combined with immune checkpoint inhibitors. Moreover, therapeutic efficacy was observed without inducing toxicity. This work presents a roadmap for the design and translation of cytokine/antibody fusion proteins.
- MeSH
- Cytokines metabolism MeSH
- Interleukin-2 * immunology MeSH
- Humans MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Cell Line, Tumor MeSH
- Neoplasms immunology therapy drug therapy MeSH
- Protein Engineering methods MeSH
- T-Lymphocytes, Regulatory immunology drug effects MeSH
- Recombinant Fusion Proteins * pharmacology immunology administration & dosage MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
PIWI-interacting RNAs (piRNAs) play a crucial role in safeguarding genome integrity by silencing mobile genetic elements. From flies to humans, piRNAs originate from long single-stranded precursors encoded by genomic piRNA clusters. How piRNA clusters form to adapt to genomic invaders and evolve to maintain protection remain key outstanding questions. Here, we generate a roadmap of piRNA clusters across seven species that highlights both similarities and variations. In mammals, we identify transcriptional readthrough as a mechanism to generate piRNAs from transposon insertions (piCs) downstream of genes (DoG). Together with the well-known stress-dependent DoG transcripts, our findings suggest a molecular mechanism for the formation of piRNA clusters in response to retroviral invasion. Finally, we identify a class of dynamic piRNA clusters in humans, underscoring unique features of human germ cell biology. Our results advance the understanding of conserved principles and species-specific variations in piRNA biology and provide tools for future studies.
- MeSH
- Species Specificity MeSH
- Humans MeSH
- RNA, Small Interfering * metabolism genetics MeSH
- Mice MeSH
- Piwi-Interacting RNA MeSH
- Dogs MeSH
- Mammals * genetics MeSH
- DNA Transposable Elements genetics MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Dogs MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Comparative Study MeSH
Pulmonary hypertension (PH) associated with left heart failure (LHF) (PH-LHF) is one of the most common causes of PH. It directly contributes to symptoms and reduced functional capacity and negatively affects right heart function, ultimately leading to a poor prognosis. There are no specific treatments for PH-LHF, despite the high number of drugs tested so far. This scientific document addresses the main knowledge gaps in PH-LHF with emphasis on pathophysiology and clinical trials. Key identified issues include better understanding of the role of pulmonary venous versus arteriolar remodelling, multidimensional phenotyping to recognize patient subgroups positioned to respond to different therapies, and conduct of rigorous pre-clinical studies combining small and large animal models. Advancements in these areas are expected to better inform the design of clinical trials and extend treatment options beyond those effective in pulmonary arterial hypertension. Enrichment strategies, endpoint assessments, and thorough haemodynamic studies, both at rest and during exercise, are proposed to play primary roles to optimize early-stage development of candidate therapies for PH-LHF.
Theoretical frameworks and models provide a roadmap for clinical practice and research by explaining and predicting the processes that influence intervention outcomes. They serve as the basis for understanding, conceptualizing, and designing nursing and social science intervention studies. Yet what is often not clearly understood is how theory actually guides intervention development and testing. What do we really mean when we describe an intervention as theoretically driven and how does a research scientist go about making this happen? The purpose of this article is to provide an exemplar of how theory guided the development of an evidence-based nursing intervention developed to reduce sexual risk behaviors (The Health Improvement Project for Teens). This approach can be used as a guide or framework applicable to other intervention programs in development. We also discuss the need in the Czech Republic for more rapid integration of broader theoretical approaches to guide intervention development and continued focus on the development and testing of nursing interventions. While still in its initial stages of development, nurse and social scientists in the Czech Republic can quickly build rigorous interventions by expanding the use of the broad array of useful theories that can guide intervention development.
- MeSH
- Role Playing MeSH
- Humans MeSH
- Adolescent MeSH
- Motivation MeSH
- Practice Patterns, Nurses' * MeSH
- Nursing methods organization & administration MeSH
- Psychodrama methods MeSH
- Psychometrics methods MeSH
- Psychosocial Intervention methods MeSH
- Unsafe Sex prevention & control MeSH
- Sexual Behavior psychology MeSH
- Models, Theoretical * MeSH
- Check Tag
- Humans MeSH
- Adolescent MeSH
Recent COVID-19 vaccines unleashed the potential of mRNA-based therapeutics. A common bottleneck across mRNA-based therapeutic approaches is the rapid design of mRNA sequences that are translationally efficient, long-lived and non-immunogenic. Currently, an accessible software tool to aid in the design of such high-quality mRNA is lacking. Here, we present mRNAid, an open-source platform for therapeutic mRNA optimization, design and visualization that offers a variety of optimization strategies for sequence and structural features, allowing one to customize desired properties into their mRNA sequence. We experimentally demonstrate that transcripts optimized by mRNAid have characteristics comparable with commercially available sequences. To encompass additional aspects of mRNA design, we experimentally show that incorporation of certain uridine analogs and untranslated regions can further enhance stability, boost protein output and mitigate undesired immunogenicity effects. Finally, this study provides a roadmap for rational design of therapeutic mRNA transcripts.
- Publication type
- Journal Article MeSH
