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Pancreatic ductal adenocarcinoma (PDAC) is one of the most challenging types of cancer with little or no response to immune checkpoint inhibitors (ICIs). Photodynamic therapy (PDT) has been shown to ablate tumors and induce an immune response. In our study, we investigated the effect of photodynamic therapy (PDT), using the photosensitizer Bremachlorin, in its ability to reduce tumor burden and to sensitize immunologically T-cell high and T-cell low murine PDAC tumors to the ICI that blocks programmed cell death-1 (PD-1) immune checkpoint. In addition, we monitored the effect on survival and investigated if there was a response in PDT-treated and non PDT-treated distant tumors. Our results showed that Bremachlorin PDT induces direct tumor killing which increased survival in both 'hot' T-cell high and 'cold' T-cell low PDAC tumors and that it can make the T-cell high tumors more sensitive to ICI blocking PD-1. We found that T-cell high tumor bearing mice had an overall greater response to therapy than T-cell low tumor bearing mice. One mouse with T-cell high tumors exhibited complete tumor regression in both the treated and non-treated distant tumor 90 days after treatment. These results indicate that combining immune checkpoint inhibitors (ICIs) with Bremachlorin PDT could be a promising therapeutic intervention for enhancing PDAC's response to therapy.

Aims: The Fick principle states that oxygen uptake (V̇O2) is cardiac output (Qc) * arterial-venous O2 content difference [ΔC(a-v)O2]. Blood flow distribution is hidden in Fick principle, and its relevance during exercise in heart failure (HF) is undefined. To highlight the role of blood flow distribution, we evaluated peak exercise V̇O2, Qc, and ΔC(a-v)O2, before and after HF therapeutic interventions., Methods and Results: Symptom-limited cardiopulmonary exercise tests with Qc measurement (inert gas rebreathing) was performed in 234 HF patients before and 6 months after successful exercise training, cardiac resynchronization therapy, or percutaneous edge-to-edge mitral valve repair. Considering all tests (n = 468), a direct correlation between peakV̇O2 and peakQc (R2 = 0.47) and workload (R2 = 0.70) was observed. Patients were grouped according to treatment efficacy in Group 1 (peakV̇O2 increase >10%, n = 93), Group 2 (peakV̇O2 change between 0 and 10%, n = 60), and Group 3 (reduction in peakV̇O2, n = 81). Post-treatment peakV̇O2 changes poorly correlated with peakQc and peakΔC(a-v)O2 changes. Differently, post-procedure peakQc vs. peakΔC(a-v)O2 changes showed a close negative correlation (R2 = 0.46), becoming stronger grouping patients according to peakV̇O2 improvement (R2 = 0.64, 0.79, and 0.58 in Groups 1, 2, and 3, respectively). In 76% of patients, peakQc and ΔC(a-v)O2 changes diverged regardless of treatment., Conclusion: The bulk of these data suggests that blood flow distribution plays a pivotal role on peakV̇O2 determination regardless of HF treatment strategies. Accordingly, for assessing HF treatment efficacy on exercise performance, the sole peakV̇O2 may be deceptive and the combination of V̇O2, Qc and ΔC(a-v)O2, must be considered., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background/Objectives : Vaccination is one of the most effective public health interventions, preventing millions of deaths globally each year. However, vaccine hesitancy, driven by misinformation and reduced disease risk perception, has led to declining vaccination rates and the resurgence of vaccine-preventable diseases (VPDs) in Europe. In response to this, countries have implemented various strategies, including mandatory and recommended vaccination programs. The objective of this study is to map the current European landscape of pediatric vaccination policies, and the variations that have occurred in the last decade. Methods : This rapid review was conducted on PubMed, Google, and the European Centre for Disease Prevention and Control website, to collect all vaccination schedules in EU/EEA countries in 2024 and all documents focusing on the introduction of mandatory vaccines during the last decade. Results : As of 2024, 13 countries had at least one mandatory pediatric vaccination, with France, Hungary, and Latvia requiring all but one vaccine. In contrast, 17 countries had no mandatory vaccinations, relying only on recommendations. Between 2014 and 2024, six countries (Croatia, France, Germany, Hungary, Italy, and Poland) introduced or extended mandatory vaccinations. Conclusions : European vaccination policies show significant variation. Effective programs depend on robust healthcare systems, public trust, and adaptable strategies to address vaccine hesitancy and the resurgence of VPDs.

Despite growing recognition of nature's impact on mental health, its specific effects on adolescents remain unclear. This gap hinders effective strategies for youth well-being in a world facing increasing environmental pressures. This study directly investigates the connections between coastal environments and subjective well-being in adolescents. We explore how interactions with coastal landscapes and associated cultural ecosystem services contribute to both personal and social dimensions of well-being in a sample of 202 adolescents (16 and 17 years old) from Sardinia, Italy. Our findings reveal a beneficial impact of coastal experiences, promoting positive affect, social integration, and physiological well-being. However, human pressures on these environments can lead to negative affect, while fostering a sense of social contribution. This research highlights the complex interplay between coastal environments, human impacts, and teenagers' well-being. Understanding these links empowers planners to craft coastal management strategies that balance adolescents' well-being with the long-term sustainability of coastal regions., (© 2024. The Author(s).)

When an increased nuchal translucency (>3.00 mm) is observed during the echographic examination of a foetus in the first trimester of pregnancy, an increased risk of chromosomopathy is considered, and the pregnant woman is offered the possibility of an invasive investigation. Here, we focused our attention on prenatal diagnosis issues in cases of foetuses with cytogenetically balanced reciprocal translocations. We report the finding of a cytogenetically balanced, de facto genomically unbalanced translocation that poses a challenge in a case of prenatal diagnosis, changing the risk of Down syndrome in a Zellweger syndromic spectrum risk ( PEX3 deletion). At term, a healthy baby was born. This case teaches that prenatal diagnosis in cases of foetuses at increased risk of chromosomal abnormality imperatively requires molecular investigation in addition to a morphological karyotype.

Background: Cardiovascular diseases (CVDs) pose a significant global health challenge, necessitating innovative approaches for primary prevention. Personalized prevention, based on genetic risk scores (PRS) and digital technologies, holds promise in revolutionizing CVD preventive strategies. However, the clinical efficacy of these interventions requires further investigation. This study presents the protocol of the INNOPREV randomized controlled trial, aiming to evaluate the clinical efficacy of PRS and digital technologies in personalized cardiovascular disease prevention., Methods: The INNOPREV trial is a four-arm RCT conducted in Italy. A total of 1,020 participants, aged 40-69 with high 10-year CVD risk based on SCORE 2 charts, will be randomly assigned to traditional CVD risk assessment, genetic testing (CVD PRS), digital intervention (app and smart band), or a combination of genetic testing and digital intervention. The primary objective is to evaluate the efficacy of providing CVD PRS information, measured at baseline, either alone or in combination with the use of an app and a smart band, on two endpoints: changes in lifestyle patterns, and modification in CVD risk profiles. Participants will undergo a comprehensive assessment and cardiovascular evaluation at baseline, with follow-up visits at one, five, and 12 months. Lifestyle changes and CVD risk profiles will be assessed at different time points beyond the initial assessment, using the Life's Essential 8 and SCORE 2, respectively. Blood samples will be collected at baseline and at study completion to evaluate changes in lipid profiles. The analysis will employ adjusted mixed-effect models for repeated measures to assess significant differences in the data collected over time. Additionally, potential moderators and mediators will be examined to understand the underlying mechanisms of behavior change., Discussion: As the largest trial in this context, the INNOPREV trial will contribute to the advancement of personalized cardiovascular disease prevention, with the potential to positively impact public health and reduce the burden of CVDs on healthcare systems. By systematically examining the clinical efficacy of PRS and digital interventions, this trial aims to provide valuable evidence to guide future preventive strategies and enhance population health outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Pastorino, Pezzullo, Agodi, de Waure, Mazzucco, Russo, Bianchi, Maio, Farina, Porcelli, Tona, Di Pumpo, Amore, Wachocka, Pasciuto, Barchitta, Magnano San Lio, Favara, Tuttolomondo, Tramuto, Morello, De Bella, Fruscione, Severino, Liuzzo and Boccia.)

The etiopathology of Parkinson's disease has been associated with mitochondrial defects at genetic, laboratory, epidemiological, and clinical levels. These converging lines of evidence suggest that mitochondrial defects are systemic and causative factors in the pathophysiology of PD, rather than being mere correlates. Understanding mitochondrial biology in PD at a granular level is therefore crucial from both basic science and translational perspectives. In a recent study, we investigated mitochondrial alterations in fibroblasts obtained from PD patients assessing mitochondrial function in relation to clinical measures. Our findings demonstrated that the magnitude of mitochondrial alterations parallels disease severity. In this study, we extend these investigations to blood cells and dopamine neurons derived from induced pluripotent stem cells reprogrammed from PD patients. To overcome the inherent metabolic heterogeneity of blood cells, we focused our analyses on metabolically homogeneous, accessible, and expandable erythroblasts. Our results confirm the presence of mitochondrial anomalies in erythroblasts and induced dopamine neurons. Consistent with our previous findings in fibroblasts, we observed that mitochondrial alterations are reversible, as evidenced by enhanced mitochondrial respiration when PD erythroblasts were cultured in a galactose medium that restricts glycolysis. This observation indicates that suppression of mitochondrial respiration may constitute a protective, adaptive response in PD pathogenesis. Notably, this effect was not observed in induced dopamine neurons, suggesting their distinct bioenergetic behavior. In summary, we provide additional evidence for the involvement of mitochondria in the disease process by demonstrating mitochondrial abnormalities in additional cell types relevant to PD. These findings contribute to our understanding of PD pathophysiology and may have implications for the development of novel biomarkers and therapeutic strategies., (© 2024. The Author(s).)

Introduction: Over the last decade, the emergence and spread of personalized medicine (PM) have defined a substantial revolution in healthcare. In principle, healthcare system sustainability is challenged by the investments required for research and development, as well as the adoption of PM techniques in routine clinical care. The "Integrating China in the International Consortium for Personalized Medicine" (IC2PerMed) EU-funded project aims to integrate China into the "International Consortium for Personalized Medicine" (ICPerMed). IC2PerMed aims to align the EU and China's research agendas in this field to enable a swift development of approaches in the EU and China with strong leverage upon EU-Chinese collaborations., Methods: Within this project, we first mapped relevant policies on PM in both the EU and China, and then we involved European and Chinese experts in PM in workshops and Delphi surveys in order to identify relevant priorities for the implementation of PM in sustainable healthcare., Results: As a result of this process, we identified nine overarching priorities, each addressing specific aspects of the sustainability of healthcare systems and PM implementation, with the main goal of supporting policymakers in integrating PM approaches in the EU and China., Discussion/conclusion: The implementation of PM in health systems is appealing in terms of improved accuracy in diagnostics, treatment, and prevention of disease, as well as reduction of the side effects resulting from inefficient use of drugs. Research, development, and implementation of needed techniques require time and resources that can slow the adoption of PM in healthcare systems. The nine priorities we identified address some of the most critical points, trying to lay the foundations for a comprehensive approach., (© 2023 The Author(s). Published by S. Karger AG, Basel.)