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Background: Atrial fibrillation (AF) is the most common arrhythmia diagnosed at an older age. AF is associated with frailty, a condition possibly justifying the higher rate of complications and mortality in aged individuals. This study was aimed at describing the characteristics correlated to frailty in older AF subjects. Methods: After having excluded a

Societal Impact Statement Seagrass ecosystems are of fundamental importance to our planet and wellbeing. Seagrasses are marine flowering plants, which engineer ecosystems that provide a multitude of ecosystem services, for example, blue foods and carbon sequestration. Seagrass ecosystems have largely been degraded across much of their global range. There is now increasing interest in the conservation and restoration of these systems, particularly in the context of the climate emergency and the biodiversity crisis. The collation of 100 questions from experts across Europe could, if answered, improve our ability to conserve and restore these systems by facilitating a fundamental shift in the success of such work. Summary Seagrass meadows provide numerous ecosystem services including biodiversity, coastal protection, and carbon sequestration. In Europe, seagrasses can be found in shallow sheltered waters along coastlines, in estuaries & lagoons, and around islands, but their distribution has declined. Factors such as poor water quality, coastal modification, mechanical damage, overfishing, land‐sea interactions, climate change and disease have reduced the coverage of Europe’s seagrasses necessitating their recovery. Research, monitoring and conservation efforts on seagrass ecosystems in Europe are mostly uncoordinated and biased towards certain species and regions, resulting in inadequate delivery of critical information for their management. Here, we aim to identify the 100 priority questions, that if addressed would strongly advance seagrass monitoring, research and conservation in Europe. Using a Delphi method, researchers, practitioners, and policymakers with seagrass experience from across Europe and with diverse seagrass expertise participated in the process that involved the formulation of research questions, a voting process and an online workshop to identify the final list of the 100 questions. The final list of questions covers areas across nine themes: Biodiversity & Ecology; Ecosystem services; Blue carbon; Fishery support; Drivers, Threats, Resilience & Response; Monitoring & Assessment; Conservation & Restoration; Governance, Policy & Management; and Communication. Answering these questions will fill current knowledge gaps and place European seagrass onto a positive trajectory of recovery.

Introduction: In 2021, the European Medicines Agency supported the “Covid Vaccine Monitor (CVM),” an active surveillance project spanning 13 European countries aimed at monitoring the safety of COVID-19 vaccines in general and special populations (i.e., pregnant/breastfeeding women, children/adolescents, immunocompromised people, and people with a history of allergies or previous SARS-CoV-2 infection). Italy participated in this project as a large multidisciplinary network called the “ilmiovaccinoCOVID19 collaborating group.”Methods: The study aimed to describe the experience of the Italian network “ilmiovaccinoCOVID19 collaborating group” in the CVM context from June 2021 to February 2023. Comprising about 30 partners, the network aimed to facilitate vaccinee recruitment. Participants completed baseline and follow-up questionnaires within 48 h from vaccination over a 6-month period. Analyses focused on those who completed both the baseline and the first follow-up questionnaire (Q1), exploring temporal trends, vaccination campaign correlation, and loss to follow-up. Characteristics of recruited vaccinees and vaccinee-reported adverse drug reactions (ADRs) were compared with passive surveillance data in Italy.Results: From June 2021 to November 2022, 22,384,663 first doses and 38,207,452 booster doses of COVID-19 vaccines were administered in Italy. Simultaneously, the study enrolled 1,229 and 2,707 participants for the first and booster doses, respectively. Of these, 829 and 1,879 vaccinees, respectively, completed both baseline and at least Q1 and were included in the analyses, with a significant proportion of them (57.8%/34.3%) belonging to special cohorts. Most vaccinees included in the analyses were women. Comirnaty® (69%) and Spikevax® (29%) were the most frequently administered vaccines. ADR rates following Comirnaty® and Spikevax® were higher after the second dose, particularly following Spikevax®. Serious ADRs were infrequent. Differences were observed in ADR characteristics between CVM and Italian passive surveillance.Conclusion: This study confirmed the favorable safety profile of COVID-19 vaccines, with findings consistent with pivotal clinical trials of COVID-19 vaccines, although different proportions of serious ADRs compared to spontaneous reporting were observed. Continuous evaluation through cohort event monitoring studies provides real-time insights crucial for regulatory responses. Strengthening infrastructure and implementing early monitoring strategies are essential to enhance vaccine safety assessment and prepare for future pandemics.

Abstract Multiple sclerosis is a debilitating autoimmune disease, characterized by chronic inflammation of the central nervous system. While the significance of the gut microbiome on multiple sclerosis pathogenesis is established, the underlining mechanisms are unknown. We found that serum levels of the microbial postbiotic tryptophan metabolite indole-3-carboxaldehyde (3-IAld) inversely correlated with disease duration in multiple sclerosis patients. Much like the host-derived tryptophan derivative l-Kynurenine, 3-IAld would bind and activate the Aryl hydrocarbon Receptor (AhR), which, in turn, controls endogenous tryptophan catabolic pathways. As a result, in peripheral lymph nodes, microbial 3-IAld, affected mast-cell tryptophan metabolism, forcing mast cells to produce serotonin via Tph1. We thus propose a protective role for AhR–mast-cell activation driven by the microbiome, whereby natural metabolites or postbiotics will have a physiological role in immune homeostasis and may act as therapeutic targets in autoimmune diseases.

Abstract In the last one-hundred years, the exponential expansion of wine making has artificialized the agricultural landscape as well as its microbial diversity, spreading human selected Saccharomyces cerevisiae strains. Evidence showed that social wasps can harbor a significant fraction of the yeast phenotypic diversity of a given area of wine production, allowing different strains to overwinter and mate in their gut. The integrity of the wasp-yeast ecological interaction is of paramount importance to maintain the resilience of microbial populations associated to wine aromatic profiles. In a field experiment, we verified whether Polistes dominula wasps, reared in laboratory and fed with a traceable S. cerevisiae strain, could be a useful tool to drive the controlled yeast dispersion directly on grapes. The demonstration of the biotechnological potential of social insects in organic wine farming lays the foundations for multiple applications including maintenance of microbial biodiversity and rewilding vineyards through the introduction of wasp associated microbiomes.

CCDC78 was identified as a novel candidate gene for autosomal dominant centronuclear myopathy-4 (CNM4) approximately ten years ago. However, to date, only one family has been described, and the function of CCDC78 remains unclear. Here, we analyze for the first time a family harboring a CCDC78 nonsense mutation to better understand the role of CCDC78 in muscle. Methods: We conducted a comprehensive histopathological analysis on muscle biopsies, including immunofluorescent assays to detect multiple sarcoplasmic proteins. We examined CCDC78 transcripts and protein using WB in CCDC78-mutated muscle tissue; these analyses were also performed on muscle, lymphocytes, and fibroblasts from healthy subjects. Subsequently, we conducted RT-qPCR and transcriptome profiling through RNA-seq to evaluate changes in gene expression associated with CCDC78 dysfunction in muscle. Lastly, coimmunoprecipitation (Co-Ip) assays and mass spectrometry (LC-MS/MS) studies were carried out on extracted muscle proteins from both healthy and mutated subjects. Results: The histopathological features in muscle showed novel histological hallmarks, which included areas of dilated and swollen sarcoplasmic reticulum (SR). We provided evidence of nonsense-mediated mRNA decay (NMD), identified the presence of novel CCDC78 transcripts in muscle and lymphocytes, and identified 1035 muscular differentially expressed genes, including several involved in the SR. Through the Co-Ip assays and LC-MS/MS studies, we demonstrated that CCDC78 interacts with two key SR proteins: SERCA1 and CASQ1. We also observed interactions with MYH1, ACTN2, and ACTA1. Conclusions: Our findings provide insight, for the first time, into the interactors and possible role of CCDC78 in skeletal muscle, locating the protein in the SR. Furthermore, our data expand on the phenotype previously associated with CCDC78 mutations, indicating potential histopathological hallmarks of the disease in human muscle. Based on our data, we can consider CCDC78 as the causative gene for CNM4.

Interferometric radars are widely used sensors for structural health monitoring. They are able to perform dynamic measurements of displacement with sub-millimeter precision. Today, the Ku-band is the most common, due to the spread of commercial systems operating in this band. At the same time, the W-band sensors are gaining ever more interest. Other popular systems work in the X-band. Since the characteristics of the measurements dramatically depend on the operative frequency, it is essential to highlight their differences. For instance, higher frequency allows for high displacement resolution, but it is more subject to phase wrapping and decorrelation effects. In this paper, a direct comparison between radars operating in X, Ku, and W-band for bridge monitoring is carried out. The radars provide frequency-modulated continuous-wave signals. Experimental campaigns were performed both in controlled and realistic scenarios (a stayed bridge). The results of the experiments demonstrate that all the three sensors are suitable for performing dynamic structure monitoring despite their differences. It is worth noting that this comparative analysis has highlighted the role of amplitude variation in phase/displacement measurement. Regarding this point, the three different bands exhibit significant differences.

Abstract Background Aggregation of α-synuclein (α-syn) is a prominent feature of Parkinson’s disease (PD) and other synucleinopathies. Currently, α-syn seed amplification assays (SAAs) using cerebrospinal fluid (CSF) represent the most promising diagnostic tools for synucleinopathies. However, CSF itself contains several compounds that can modulate the aggregation of α-syn in a patient-dependent manner, potentially undermining unoptimized α-syn SAAs and preventing seed quantification. Methods In this study, we characterized the inhibitory effect of CSF milieu on detection of α-syn aggregates by means of CSF fractionation, mass spectrometry, immunoassays, transmission electron microscopy, solution nuclear magnetic resonance spectroscopy, a highly accurate and standardized diagnostic SAA, and different in vitro aggregation conditions to evaluate spontaneous aggregation of α-syn. Results We found the high-molecular weight fraction of CSF (> 100,000 Da) to be highly inhibitory on α-syn aggregation and identified lipoproteins to be the main drivers of this effect. Direct interaction between lipoproteins and monomeric α-syn was not detected by solution nuclear magnetic resonance spectroscopy, on the other hand we observed lipoprotein-α-syn complexes by transmission electron microscopy. These observations are compatible with hypothesizing an interaction between lipoproteins and oligomeric/proto-fibrillary α-syn intermediates. We observed significantly slower amplification of α-syn seeds in PD CSF when lipoproteins were added to the reaction mix of diagnostic SAA. Additionally, we observed a decreased inhibition capacity of CSF on α-syn aggregation after immunodepleting ApoA1 and ApoE. Finally, we observed that CSF ApoA1 and ApoE levels significantly correlated with SAA kinetic parameters in n = 31 SAA-negative control CSF samples spiked with preformed α-syn aggregates. Conclusions Our results describe a novel interaction between lipoproteins and α-syn aggregates that inhibits the formation of α-syn fibrils and could have relevant implications. Indeed, the donor-specific inhibition of CSF on α-syn aggregation explains the lack of quantitative results from analysis of SAA-derived kinetic parameters to date. Furthermore, our data show that lipoproteins are the main inhibitory components of CSF, suggesting that lipoprotein concentration measurements could be incorporated into data analysis models to eliminate the confounding effects of CSF milieu on α-syn quantification efforts.