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We are currently developing a tunable high-repetition rate femtosecond UV laser system for external seeding superconducting soft X-ray Free Electron Laser FLASH. Initial results show excellent power and wavelength stability of the Optical Parametric Chirped Pulse Amplification system.

This paper provides insights into the indirect effect of subject matter knowledge on the pre-service teachers’ mitigation action of willingness to include climate change in their future teaching practices. Mediation analysis was conducted to assess the mediating role of emotions and attitudes on direct and indirect mitigation actions with a nationally representative sample of 889 pre-service teachers from Spain. The results show that subject matter knowledge has an indirect effect on pre-service teachers’ willingness to teach and is mediated by emotions and attitudes. Mediation analysis also revealed a relationship between emotional engagement and mitigation actions: students who experience stronger emotions are more likely to take direct and indirect mitigation action, but a more environmentally friendly lifestyle (direct mitigation) is not associated with willingness to engage in climate change education (indirect mitigation). We conclude that educators should consider emotions and attitudes when implementing climate change education. [ABSTRACT FROM AUTHOR]

Background: The appropriate duration of treatment with beta-blocker drugs after a myocardial infarction is unknown. Data are needed on the safety and efficacy of the interruption of long-term beta-blocker treatment to reduce side effects and improve quality of life in patients with a history of uncomplicated myocardial infarction. Methods: In a multicenter, open label, randomized, noninferiority trial conducted at 49 sites in France, we randomly assigned patients with a history of myocardial infarction, in a 1:1 ratio, to interruption or continuation of beta-blocker treatment. All the patients had a left ventricular ejection fraction of at least 40% while receiving long-term beta-blocker treatment and had no history of a cardiovascular event in the previous 6 months. The primary end point was a composite of death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for cardiovascular reasons at the longest follow-up (minimum, 1 year), according to an analysis of noninferiority (defined as a between-group difference of <3 percentage points for the upper boundary of the two-sided 95% confidence interval). The main secondary end point was the change in quality of life as measured by the European Quality of Life-5 Dimensions questionnaire. Results: A total of 3698 patients underwent randomization: 1846 to the interruption group and 1852 to the continuation group. The median time between the last myocardial infarction and randomization was 2.9 years (interquartile range, 1.2 to 6.4), and the median follow-up was 3.0 years (interquartile range, 2.0 to 4.0). A primary-outcome event occurred in 432 of 1812 patients (23.8%) in the interruption group and in 384 of 1821 patients (21.1%) in the continuation group (risk difference, 2.8 percentage points; 95% confidence interval [CI], <0.1 to 5.5), for a hazard ratio of 1.16 (95% CI, 1.01 to 1.33; P = 0.44 for noninferiority). Beta-blocker interruption did not seem to improve the patients' quality of life. Conclusions: In patients with a history of myocardial infarction, interruption of long-term beta-blocker treatment was not found to be noninferior to a strategy of beta-blocker continuation. (Funded by the French Ministry of Health and ACTION Study Group; ABYSS ClinicalTrials.gov number, NCT03498066; EudraCT number, 2017-003903-23.). [ABSTRACT FROM AUTHOR]

Myotonic dystrophy type 1 (DM1) patients often present with cognitive impairment and gait abnormalities mostly related to distal muscle weakness, including increased dynamic instability and gait variability. Since an influence of cognitive function on gait has been suggested in several neurological conditions, the aim of this study was to evaluate the mobility changes using mobile health technology (MHT) and their relationship with cognition in DM1. Eight DM1 patients (49 yrs, mean) underwent MHT-based gait analysis (Rehagait, Hasomed) during the six-minute walking test [6MWT] and a one-minute dual-task walking ("check boxes" [CB] and "serial subtraction" [SS]). The dual-task cost (i.e. the difference between the values obtained during the dual task and the values obtained during normal-pace walking, divided by these seconds) was calculated for each parameter. Data were compared with twenty healthy controls (57 years, mean) using an adjusted ANCOVA. Patients underwent an extended neuropsychological battery and a standard neurological assessment. In comparison to HC, DM1 patients showed greater double limb support variability (p = 0.005), step time variability (p = 0.005), and number of steps (p<0.001) in 6MWT. Looking at changes in gait parameters between the three different tasks within the DM1 cohort, patients took longer steps on the 6MWT than on the CB-1MWT (p = 0.030, 0.64 vs. 0.58 mt). In the DM1 cohort, MoCA scores correlated negatively with the number of steps in the 6MWT (r = -0.997, p = 0.003). MoCA scores and Clock's drawing correlated negatively with dual-task cost related to step length variability in both CB- and SS-1MWT. DM1 patients showed greater variability and number of steps in regular walking compared to HC. Our findings suggest that cognitive performance, namely poorer visuo-constructive skills, in DM1 patients might contribute to the observed gait abnormalities and deserve to be validated in larger studies. [ABSTRACT FROM AUTHOR]

In the upcoming decades, the incidence and mortality rates of cancer are expected to rise globally, with colorectal and prostate cancers among the most prevalent types. Despite advancements in molecular targeted therapy, platinum-based chemotherapies remain the cornerstone of treatment, especially for colorectal and prostate cancer, with oxaliplatin and cisplatin being extremely effective due to their DNA-targeting capabilities. In our pursuit of new platinum-based chemotherapeutics that are potentially less toxic and more effective, we have explored the combination of the Pt-binding groups of the diaminocyclohexane ring used in oxaliplatin, with the stable amino-pyrimidine hemicurcumin moiety. This new derivative exhibit improved stability in physiological conditions and increased solubility in aqueous media, demonstrating promising effects on cell proliferation of both colorectal and prostate cells. We report herein the complete synthesis and chemical characterization in solution of the new derivative [(1R,2R)-N1-(3-(4-((E)-2-(2-Amino-6-methylpyrimidin-4-yl)vinyl)-2-methoxyphenoxy) propyl) cyclohexane-1,2-diamine] (MPYD). Our analysis includes an examination of its acid-base equilibria, speciation and stability in physiological conditions. The synthesis and in situ formation of Pt(II) complexes were investigated by nuclear magnetic resonance spectroscopy, while density functional theory calculations were employed to elucidate the chemical structure in solution. Results on the biological activity were obtained through cell viability assays on different colorectal and prostate cell lines (HCT116, HT29, PC3 and LNCaP)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Paracetamol and ibuprofen are the most commonly used drugs for pain treatment in children and their combination has shown improved analgesic effect compared to treatment with either drug alone. Current literature lacks specific guidelines regarding the settings in which this combination should be adopted., Methods: The survey, conducted with Delphi methodology, involved 75 hospital and outpatient pediatricians with clinical experience in the management of pain in children. Pediatricians involved were asked to validate or not the results of the previous NominalGroup Tecnique (NGT) consensus and thus specify the optimal clinical settings in which the paracetamol/ibuprofen fixed-dose combination could be adopted., Results: The results confirm the importance of the fixed-dose paracetamol and ibuprofen combination for the control of mild-to-moderate acute pain in children. Particularly, this association seems to be appropriate in case of headache, earache, odontalgia and musculoskeletal pain, and in specific settings such as post-operative and post-procedural pain. The broadening of the panel brought to slight variations in clinical management practices between hospital and outpatient specialists. Nonetheless, overall consensus supports the notion that the fixed dose combination is more efficacious than monotherapies and it is well tolerated. Moreover, experts unanimously agree on the usefulness of the combination for caregivers, leading to improved adherence and effectiveness., Conclusions: Both the NGT consensus and the broader Delphi consensus confirm the usefulness of the paracetamol-ibuprofen fixed-dose combination in pediatric pain. This is attributed to its superior effectiveness compared to monotherapies, a good tolerability profile, and improved compliance and ease of use. Some pain settings related to chronic, inflammatory and rheumatological pathologies remain to be investigated to evaluate the use of this combination., (© 2024. The Author(s).)

The dysregulation of the immune system plays a crucial role in the pathogenesis of manyfold diseases, among which we find rheumatoid arthritis (RA), an autoimmune disease characterized by chronic inflammation in synovial joints, leading to pain and disability. Immune cells such as pro-inflammatory macrophages and T helper 1 (Th1) cells drive the inflammatory cascade. Thus, including immune system in in vitro models is pivotal to recapitulate and better understand the complex interactions between these immune cell subsets and their secreted mediators. Here, a compartmentalized microfluidic platform is presented, for precise confinement of circulating immune cells in organs-on-chip. The integration of innovative normally-closed sieving valves allows, through minimal waste of biological material, to co-culture different immune cell types (e.g. macrophages and Th1). Moreover, the platform allows to stimulate cell subsets separately, and to assess their cross-talk at desired time points. Functional validation of the platform demonstrates its ability to create stable chemotactic gradients, allowing for induction and evaluation of Th1 cells migration. In a proof-of-concept study, the platform allowed to assess Th1 T cells migration towards pro-inflammatory macrophages, thus replicating a characteristic interaction among immune cells triggered during RA onset. These results thus support the suitability of the platform to study immune cells cross-talk and migration phenomena, being potentially applicable to a manyfold immune cell mechanisms, both involved in RA progression and in different immune-mediated pathologies., (Creative Commons Attribution license.)

Background: COVID-19 patients may exhibit neurological symptoms due to direct viral damage, systemic inflammatory syndrome, or treatment side effects. Mechanical ventilation in patients with severe respiratory failure often requires sedation and neuromuscular blockade, hindering thorough clinical examinations. This study aimed to investigate neurological involvement through clinical and noninvasive techniques and to detect signs of intracranial hypertension in these patients., Method: We conducted a prospective observational study on mechanically ventilated COVID-19 adult patients admitted to our ICU, following standard of care protocols for ventilation and permissive hypercapnia. Data were collected at three time points: admission day (T1), day seven (T7), and day fourteen (T14). At each time point, patients underwent multimodal noninvasive neurological monitoring, including clinical examination, pupillary reactivity, transcranial color doppler of the middle cerebral artery (MCA), and optic nerve sheath diameter (ONSD) assessed via ultrasound (US). Head computer tomography (CT) was performed at T1 and T14. A limited subset of patients had a follow-up examination six months after ICU discharge., Results: Seventy-nine patients were recruited; most were under deep sedation and neuromuscular blockade at T1. Pupillary size, symmetry, and reactivity were normal, as was the MCA mean velocity. However, ONSD, assessed by both US and CT, appeared enlarged, suggesting raised intracranial pressure (ICP). In a subgroup of 12 patients, increased minute ventilation was associated with a significant decrease in US-ONSD, corresponding to a drop in paCO2. At follow-up, twelve patients showed no long-term neurological sequelae, and US-ONSD was decreased in all of them., Discussion and Conclusions: In this cohort, enlarged ONSD was detected during non-invasive neurological monitoring, suggesting a raised ICP, with hypercapnia playing a prominent role. Further studies are needed to explore ONSD behavior in other samples of mechanically ventilated, hypercapnic patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Carbonara et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Although cardiovascular surgery societies in Europe and the USA constantly strive for the exchange of knowledge and best practices in coronary artery bypass grafting (CABG), the available evidence on whether such efforts result in similar patient outcomes is limited. Therefore, in the present analysis, we sought to compare patient profiles and overall survival outcomes for up to 3 years between large European and US patient cohorts who underwent isolated CABG., Methods: Patients from the European DuraGraft Registry ( n  = 2,522) who underwent isolated CABG at 45 sites in eight different European countries between 2016 and 2019 were compared to randomly selected patients from the US STS database who were operated during the same period ( n  = 294,725). Free conduits (venous and arterial grafts) from the DuraGraft Registry patients were intraoperatively stored in DuraGraft, an endothelial damage inhibitor, before anastomosis, whereas grafts from the STS Registry patients in standard-of-care solutions (e.g., saline). Propensity score matching (PSM) models were used to account for differences in patient baseline and surgical characteristics, using a primary PSM with 35 variables (2,400 patients matched) and a secondary PSM with 25 variables (2,522 patients matched, sensitivity analysis). The overall survival for up to 3 years after CABG was assessed as the primary endpoint., Results: The comparison of patient profiles showed significant differences between the European and US cohorts. The European patients had more left main disease, underwent more off-pump CABG, and received more arterial grafts together with more complete arterial grafting procedures. In contrast, the US patients received more distal anastomoses with more saphenous vein grafts (SVGs) that were mainly harvested endoscopically. Such differences, however, were well balanced after PSM for the mortality comparison. Mortality comparison at 30 days, 12 months, and 24 months between the European and US patients was 2.38% vs. 1.96%, 4.32% vs. 4.79%, and 5.38% vs. 6.96%, respectively. At 36 months, the mortality was significantly lower in the European patients than that of their US counterparts (7.37% vs. 9.65%; p -value = 0.016). The estimated hazard ratio (HR) was 1.29 (95% CI 1.05-1.59)., Conclusion: This large-scale transatlantic comparative analysis shows that there are some significant differences in patient profiles between large cohorts of European and US patients. These differences were adjusted by using PSM for the mortality analysis. No significant difference in mortality was detected between groups through 2 years, but survival was significantly better in the European DuraGraft Registry patients at 3 years post-CABG., Competing Interests: EC, MM, JA, SS, Y-HC, and AB are members of the registry advisory committee (RAC). LP is a member of the RAC and is a consultant for Marizyme. ME is the principal investigator of the registry, the chair of the RAC, and a consultant for Marizyme. EF received research grants from Somalution, a Marizyme company. Other authors have nothing to disclose. The remaining 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., (© 2024 Caliskan, Misfeld, Sandner, Böning, Aramendi, Salzberg, Choi, Perrault, Tekin, Cuerpo, Lopez-Menendez, Weltert, Böhm, Krane, González-Santos, Tellez, Holubec, Ferrari, Doros and Emmert.)

The ability to freely control the polarization of X-rays enables measurement techniques relying on circular or linear dichroism, which have become indispensable tools for characterizing the properties of chiral molecules or magnetic structures. Therefore, the demand for polarization control in X-ray free-electron lasers is increasing to enable polarization-sensitive dynamical studies on ultrafast time scales. The soft X-ray branch Athos of SwissFEL was designed with the aim of providing freely adjustable and arbitrary polarization by building its undulator solely from modules of the novel Apple X type. In this paper, the magnetic model of the linear inclined and circular Apple X polarization schemes are studied. The polarization is characterized by measuring the angular electron emission distributions of helium for various polarizations using cold target recoil ion momentum spectroscopy. The generation of fully linear polarized light of arbitrary angle, as well as elliptical polarizations of varying degree, are demonstrated., (open access.)

Background: Red blood cell transfusion can cause fluid overload. We evaluated the interaction between heart failure (HF) at baseline and transfusion strategy on outcomes in acute myocardial infarction (AMI)., Methods: We used data from the randomized REALITY trial. HF was defined as history of HF or Killip class > 1 at randomization. Primary outcome was major adverse cardiovascular events (MACE): composite of all-cause death, nonrecurrent AMI, stroke, or emergency revascularization prompted by ischemia at 30 days., Results: Among 658 randomized patients, 311 (47.3%) had HF. Patients with HF had higher rates of MACE at 30 days and 1 year and higher rates of nonfatal new-onset HF. There was no interaction between HF and effect of randomized assignment on the primary outcome or nonfatal new-onset HF. A liberal transfusion strategy was associated with increased all-cause death at 30 days and at 1 year in patients with HF (P interaction  = 0.009 and P = 0.049, respectively). The main numerical difference in cause of death between restrictive and liberal strategies was death by HF at 30 days (4 vs 11)., Conclusions: HF is frequent in patients with AMI and anemia and is associated with higher risk of MACE (including all-cause death) and nonfatal new-onset HF. Although there was no interaction of HF with effect of transfusion strategy on MACE, a liberal transfusion strategy was associated with higher all-cause death that appears driven by a higher risk of early death caused by HF., Clinical Trial Registration: NCT02648113., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: This study aimed to assess the proportions of type 2 diabetes (T2D) subjects meeting cardiovascular outcome trials (CVOTs) criteria for sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and estimate SGLT2i utilization, along with associated demographic and clinical characteristics, in a primary care setting., Methods: T2D patients in Italy were selected between January 1, 2021, and December 31, 2022, from The Health Improvement Network (THIN ® ) database. Representativeness was determined by dividing patients meeting key inclusion criteria for four CVOTs (CANVAS, DECLARE-TIMI 58, EMPA-REG OUTCOME, VERTIS-CV) to the total T2D population. Demographic and clinical characteristics of eligible T2D subjects and SGLT2i users were compared, and logistic regression models assessed the likelihood of receiving SGLT2i., Results: Out of 17,102 T2D patients, 8,828 met eligibility criteria for at least one CVOT. DECLARE-TIMI 58 exhibited the highest representativeness (51.1%), compared to CANVAS (21.1%), EMPA-REG OUTCOME (5.5%), and VERTIS-CV (4.9%) trials. Eligible CVOTs patients were older (74.6 vs. 68.3 years), with a longer disease duration (10.2 vs. 9.7 years), and higher established cardiovascular disease (CVD) prevalence (36.0 vs. 27.3%) compared to SGLT2i users. Less than 10% of eligible T2D patients received SGLT2i. Males (OR: 1.43; 95%CI: 1.24-1.66) were more likely to be prescribed SGLT2i than other antidiabetic drugs, while the elderly (80 + vs. 40-64 years, OR: 0.17; 95% CI: 0.14-0.22) were less likely. Eligible T2D patients with CVD reported an increased likelihood of receiving SGLT2is compared to other antidiabetics., Conclusion: This study highlights significant variability in the proportion of T2D subjects meeting SGLT2i CVOT inclusion criteria, with DECLARE-TIMI-58 being the most represented. Low SGLT2i prescription rates in the Italian primary care setting, along with substantial demographic and clinical differences between SGLT-2i users and T2D eligible patients, emphasize the need for targeted interventions to optimize the use of these medications in primary care settings., (© 2024. The Author(s).)

Aim: In 2022, in Italy, general practitioners (GPs) have been allowed to prescribe SGLT2i in Type 2 Diabetes (T2D) under National Health Service (NHS) reimbursement. In the pivotal clinical trial named DECLARE-TIMI 58, dapagliflozin reduced the risk of hospitalization for heart failure, CV death and kidney disease progression compared to placebo in a population of T2D patients. This study evaluated the health and economic impact of dapagliflozin for T2D patients who had or were at risk for atherosclerotic cardiovascular disease in the Italian GPs setting., Methods: A budget impact model was developed to assess the health and economic impact of introducing dapagliflozin in GPs setting. The analysis was conducted by adopting the Italian NHS perspective and a 3-year time horizon. The model estimated and compared the health outcomes and direct medical costs associated with a scenario with dapagliflozin and other antidiabetic therapies available for GPs prescription (scenario B) and a scenario where only other antidiabetic therapies are available (scenario A). Rates of occurrence of cardiovascular and renal complications as well as adverse events were captured from DECLARE-TIMI 58 trial and the literature, while cost data were retrieved from the Italian tariff and the literature. One-way sensitivity analyses were conducted to test the impact of model parameters on the budget impact., Results: The model estimated around 442.000 patients eligible for the treatment with dapagliflozin in the GPs setting for each simulated year. The scenario B compared to scenario A was associated with a reduction in the occurrence of cardiovascular and renal complication (-1.83%) over the 3 years simulated. Furthermore, the scenario A allowed for an overall cost saving of 102,692,305€: 14,521,464€ in the first year, 33,007,064€ in the second and 55,163,777€ in the third. The cost of cost of drug acquisition, the probability of cardiovascular events and the percentage of patients potentially eligible to the treatment were the factor with largest impact on the results., Conclusions: The use of dapagliflozin in GPs setting reduce the number of CVD events, kidney disease progression and healthcare costs in Italy. These data should be considered to optimize the value produced for the T2D patients who had or were at risk for atherosclerotic cardiovascular disease., (© 2024. The Author(s).)

Survival from UV-induced DNA lesions relies on nucleotide excision repair (NER) and the Mec1 ATR DNA damage response (DDR). We study DDR and NER in aging cells and find that old cells struggle to repair DNA and activate Mec1 ATR . We employ pharmacological and genetic approaches to rescue DDR and NER during aging. Conditions activating Snf1 AMPK rescue DDR functionality, but not NER, while inhibition of the TORC1-Sch9 S6K axis restores NER and enhances DDR by tuning PP2A activity, specifically in aging cells. Age-related repair deficiency depends on Snf1 AMPK -mediated phosphorylation of Sch9 S6K on Ser160 and Ser163. PP2A activity in old cells is detrimental for DDR and influences NER by modulating Snf1 AMPK and Sch9 S6K . Hence, the DDR and repair pathways in aging cells are influenced by the metabolic tuning of opposing AMPK and TORC1 networks and by PP2A activity. Specific Sch9 S6K phospho-isoforms control DDR and NER efficiency, specifically during aging., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: In the context of Infections Prevention and Control activities, the training of healthcare-associated infection control figures is crucial; the COVID-19 pandemic further emphasized the necessity of ensuring a widespread and stable level of skills over time for such professionals. The present work aims to identify the number and training needs of the personnel working in the Emilia-Romagna Region's healthcare facilities as "healthcare-associated infection control figures"., Methods: Data were collected through a survey created by experts from the Regional Group "Training in the prevention and control of antibiotic resistance". The questionnaire explored the number, professional and educational background, and training requirements of Healthcare-associated infections control figures in Emilia-Romagna., Results: With 73 figures dedicated to Healthcare-associated infections control, the Emilia-Romagna Region appears to be in line with the European standard ratio (1 professional every 125 beds). Professionals with a nursing background, over 50 years old and of female sex prevail in the group, while the training needs expressed include both theoretical and practical aspects., Conclusions: Healthcare assistants and nursing staff represent a fundamental resource for the implementation of infection prevention and control programs in our healthcare facilities; continuous, multidisciplinary and targeted training of these professionals is confirmed as necessary.

Capitalizing on the widespread adoption of smartphones among farmers and the application of artificial intelligence in computer vision, a variety of mobile applications have recently emerged in the agricultural domain. This paper introduces GranoScan, a freely available mobile app accessible on major online platforms, specifically designed for the real-time detection and identification of over 80 threats affecting wheat in the Mediterranean region. Developed through a co-design methodology involving direct collaboration with Italian farmers, this participatory approach resulted in an app featuring: (i) a graphical interface optimized for diverse in-field lighting conditions, (ii) a user-friendly interface allowing swift selection from a predefined menu, (iii) operability even in low or no connectivity, (iv) a straightforward operational guide, and (v) the ability to specify an area of interest in the photo for targeted threat identification. Underpinning GranoScan is a deep learning architecture named efficient minimal adaptive ensembling that was used to obtain accurate and robust artificial intelligence models. The method is based on an ensembling strategy that uses as core models two instances of the EfficientNet-b0 architecture, selected through the weighted F1-score. In this phase a very good precision is reached with peaks of 100% for pests, as well as in leaf damage and root disease tasks, and in some classes of spike and stem disease tasks. For weeds in the post-germination phase, the precision values range between 80% and 100%, while 100% is reached in all the classes for pre-flowering weeds, except one. Regarding recognition accuracy towards end-users in-field photos, GranoScan achieved good performances, with a mean accuracy of 77% and 95% for leaf diseases and for spike, stem and root diseases, respectively. Pests gained an accuracy of up to 94%, while for weeds the app shows a great ability (100% accuracy) in recognizing whether the target weed is a dicot or monocot and 60% accuracy for distinguishing species in both the post-germination and pre-flowering stage. Our precision and accuracy results conform to or outperform those of other studies deploying artificial intelligence models on mobile devices, confirming that GranoScan is a valuable tool also in challenging outdoor conditions., Competing Interests: SM, EF, MS, SA and PL were employed by Barilla G. e R. Fratelli S.p.A. The remaining 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 Dainelli, Bruno, Martinelli, Moroni, Rocchi, Morelli, Ferrari, Silvestri, Agostinelli, La Cava and Toscano.)

Background: Despite major advances in prevention and treatment, cardiovascular diseases - particularly acute myocardial infarction - remain a leading cause of death worldwide and in France. Collecting contemporary data about the characteristics, management and outcomes of patients with acute myocardial infarction in France is important., Aims: The main objectives are to describe baseline characteristics, contemporary management, in-hospital and long-term outcomes of patients with acute myocardial infarction hospitalized in tertiary care centres in France; secondary objectives are to investigate determinants of prognosis (including periodontal disease and sleep-disordered breathing), to identify gaps between evidence-based recommendations and management and to assess medical care costs for the index hospitalization and during the follow-up period., Methods: FRENCHIE (FRENch CoHort of myocardial Infarction Evaluation) is an ongoing prospective multicentre observational study (ClinicalTrials.gov Identifier: NCT04050956) enrolling more than 19,000 patients hospitalized for acute myocardial infarction with onset of symptoms within 48hours in 35 participating centres in France since March 2019. Main exclusion criteria are age<18 years, lack of health coverage and procedure-related myocardial infarction (types 4a and 5). Detailed information was collected prospectively, starting at admission, including demographic data, risk factors, medical history and treatments, initial management, with prehospital care pathways and medication doses, and outcomes until hospital discharge. The follow-up period (up to 20 years for each patient) is ensured by linking with the French national health database (Système national des données de santé), and includes information on death, hospital admissions, major clinical events, healthcare consumption (including drug reimbursement) and total healthcare costs. FRENCHIE is also used as a platform for cohort-nested studies - currently three randomized trials and two observational studies., Conclusions: This nationwide large contemporary cohort with very long-term follow-up will improve knowledge about acute myocardial infarction management and outcomes in France, and provide a useful platform for nested studies and trials., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Periodontal diseases, including gingivitis and periodontitis, are among the most prevalent diseases in humans. Gingivitis is the mildest form of periodontal disease, characterized by inflammation of the gingiva caused by the accumulation of dental plaque. Salivary diagnostics are becoming increasingly popular due to the variation in saliva composition in response to pathological processes. We used a metabolomics approach to investigate whether a specific saliva metabolic composition could indicate preclinical stage of gingivitis. 1 H-NMR spectroscopy was used to obtain the salivary metabolite profiles of 20 healthy subjects. Univariate/multivariate statistical analysis evaluated the whole saliva metabolite composition, and the Full-Mouth Bleeding Score (FMBS) was employed as a classification parameter. Identifying a signature of specific salivary metabolites could distinguish the subjects with high FMBS scores but still within the normal range. This set of metabolites may be due to the enzymatic activities of oral bacteria and be associated with the early stages of gingival inflammation. Although this analysis is to be considered exploratory, it seems feasible to establish an FMBS threshold that distinguishes between the absence and presence of early inflammatory alterations at the salivary level.

Introduction: Some evidence suggests that surgical minimally invasive (MIDCAB) and hybrid coronary revascularization (HCR) are safe and potentially effective at short-term follow-up. Data on long-term outcomes are more limited and inconclusive., Methods: Between February 2013 and December 2023, a total of 1997 patients underwent surgical coronary artery revascularization at our institution, of whom, 92 (4.7%) received left anterior mini-thoracotomy access (MIDCAB), either isolated (N = 78) or in combination with percutaneous coronary intervention (N = 14, HCR group)., Results: After a median follow-up of 75 months (range 3.1: 149 months), cardiac mortality was 0% while overall mortality was 3%, with one in-hospital mortality and two additional late deaths. Conversion to sternotomy happened in two patients (2.1%), and surgical re-explorations occurred in five patients (4.6%), of whom three for bleeding and two for graft failure. All patients received left internal mammary (LIMA) to left anterior descending artery (LAD) grafting (100%). In the HCR group, 10 patients (72%) showed percutaneous revascularization (PCI) after MIDCAB, showing PCI on a mean of 1.6 ± 0.6 vessels and implanting 2.1 ± 0.9 drug-eluting stents., Conclusions: MIDCAB, in isolation or in association with hybrid coronary revascularization, is associated with encouraging short- and long-term results in selected patients discussed within a dedicated heart-team.

Objectives: To estimate the incidence and prevalence of SLE in Italy, and to describe the demographic and clinical characteristics of patients with newly diagnosed SLE., Methods: A retrospective cohort study was conducted using The Health Improvement Network general practice database in Italy, encompassing data from 634 753 people. SLE cases were identified over the period 2017-2022, employing three alternative definitions to provide a more detailed understanding of SLE characteristics. Incidence rates were expressed as cases per 100 000 person-years and prevalence as cases per 100 000 people. Demographic and clinical characteristics of incident SLE cases were also studied., Results: From 2017 to 2022, a total of 191 incident and 1385 prevalent cases were identified under our first definition. In 2022, the incidence rate was 6.51 cases (95% CI 6.29 to 6.74) per 100 000 person-years, and the prevalence 60.57 (95% CI 59.89 to 61.25) per 100 000 people, being the prevalence five times higher in women compared with men. Both estimates have trended upwards since 2017. A geographical variation across the country was also seen. The demographic and clinical characteristics of incident SLE cases were described, while the potential associations of SLE incidence with some pre-existing conditions were observed, such as chronic kidney disease, chronic hepatic disease, rheumatoid arthritis and Sjogren's syndrome., Conclusions: The results of this nationwide study, the first conducted in Italy, showed that the incidence of SLE has increased in Italy in recent years. Age, sex, and area of residence strongly correlate with the epidemiology of this condition., Competing Interests: Competing interests: PF, ICA, MZ, CF, AB, IM and GE declare no conflicts of interest. EZF and PP are employees of Cegedim Srl, which is a private company that performs financially supported studies for several pharmaceutical companies.CB are SB are employees of AstraZeneca Italy. LGM reports receiving grants from Bayer, Daiiki-Sankyo, and Boehringer Ingelheim and speaker fees from Pfizer and Bayer, outside this work. GM reports receiving grants from CSL Behring for consultancy outside this work., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This work is focused on performing a quantitative assessment of the environmental impacts associated with an organic synthesis reaction, optimized using an experimental design approach. A nucleophilic substitution reaction was selected, employing vanillin as the substrate, a phenolic compound widely used in the food industry and of pharmaceutical interest, considering its antioxidant and antitumoral potential. To carry out the reaction, three different solvents have been chosen, namely acetonitrile (ACN), acetone (Ace), and dimethylformamide (DMF). The syntheses were planned with the aid of a multivariate experimental design to estimate the best reaction conditions, which simultaneously allow a high product yield and a reduced environmental impact as computed by Life Cycle Assessment (LCA) methodology. The experimental results highlighted that the reactions carried out in DMF resulted in higher yields with respect to ACN and Ace; these reactions were also the ones with lower environmental impacts. The multilinear regression models allowed us to identify the optimal experimental conditions able to guarantee the highest reaction yields and lowest environmental impacts for the studied reaction. The identified optimal experimental conditions were also validated by experimentally conducting the reaction in those conditions, which indeed led to the highest yield (i.e., 93%) and the lowest environmental impacts among the performed experiments. This work proposes, for the first time, an integrated approach of DoE and LCA applied to an organic reaction with the aim of considering both conventional metrics, such as reaction yield, and unconventional ones, such as environmental impacts, during its lab-scale optimization.

The activity of dental caries, combined with its multifactorial etiology, alters salivary molecule composition. The present systematic review was developed to answer the following question: "Are salivary biomarkers reliable for diagnosis of dental caries?". Following the "Preferred Reporting Item for Systematic Reviews and Meta-analysis" (PRISMA) guidelines, the review was conducted using multiple database research (Medline, Web of Science, and Scopus). Studies performed on healthy subjects with and without dental caries and providing detailed information concerning the clinical diagnosis of caries (Decayed, Missing, Filled Teeth-DMFT and International Caries Detection and Assessment System-ICDAS criteria) were included. The quality assessment was performed following a modified version of the Joanna Briggs Institute Prevalence Critical Appraisal Checklist. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO, ID: CRD42022304505). Sixteen papers were included in the review. All studies reported statistically significant differences in the concentration of salivary molecules between subjects with and without caries ( p < 0.05). Proteins were the most investigated molecules, in particular alpha-amylase and mucins. Some studies present a risk of bias, such as identifying confounding factors and clearly defining the source population. Nevertheless, the 16 papers were judged to be of moderate to high quality. There is evidence that some salivary compounds studied in this review could play an important diagnostic role for dental caries, such as salivary mucins, glycoproteins (sCD14), interleukins (IL-2RA, 4,-13), urease, carbonic anhydrase VI, and urea.

Soluble di-iron monooxygenases (SDIMOs) are multi-component enzymes catalysing the oxidation of various substrates. These enzymes are characterized by high sequence and functional diversity that is still not well understood despite their key role in biotechnological processes including contaminant biodegradation. In this study, we analysed a mutant of Rhodoccocus aetherivorans BCP1 (BCP1-2.10) characterized by a transposon insertion in the gene smoA encoding the alpha subunit of the plasmid-located SDIMO SmoABCD. The mutant BCP1-2.10 showed a reduced capacity to grow on propane, lost the ability to grow on butane, pentane and n-hexane and was heavily impaired in the capacity to degrade chloroform and trichloroethane. The expression of the additional SDIMO prmABCD in BCP1-2.10 probably allowed the mutant to partially grow on propane and to degrade it, to some extent, together with the other short-chain n-alkanes. The complementation of the mutant, conducted by introducing smoABCD in the genome as a single copy under a constitutive promoter or within a plasmid under a thiostreptone-inducible promoter, allowed the recovery of the alkanotrophic phenotype as well as the capacity to degrade chlorinated n-alkanes. The heterologous expression of smoABCD allowed a non-alkanotrophic Rhodococcus strain to grow on pentane and n-hexane when the gene cluster was introduced together with the downstream genes encoding alcohol and aldehyde dehydrogenases and a GroEL chaperon. BCP1 smoA gene was shown to belong to the group 6 SDIMOs, which is a rare group of monooxygenases mostly present in Mycobacterium genus and in a few Rhodococcus strains. SmoABCD originally evolved in Mycobacterium and was then acquired by Rhodococcus through horizontal gene transfer events. This work extends the knowledge of the biotechnologically relevant SDIMOs by providing functional and evolutionary insights into a group 6 SDIMO in Rhodococcus and demonstrating its key role in the metabolism of short-chain alkanes and degradation of chlorinated n-alkanes., (© 2024 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd.)

Background: Blood glucose level variability has been associated with increased risk of complication in the postoperative setting of cardiovascular surgery. Although interesting for optimization of blood glucose management in this context, continuous blood glucose (CBG) devices can have a limited reliability in this context, in particular because of the use of paracetamol. The aim of this study was to evaluate the reliability of Dexcom G6®, a recently developed continuous glucose monitoring device., Methods: We performed a prospective, observational, non-randomized, single-centre study comparing Dexcom G6® CBG level monitoring with the standard methods routinely used in this context. The standard blood glucose values were paired to the time corresponding values measured with Dexcom G6®. Agreement between the two methods and potential correlation in case of paracetamol use were calculated., Results: From May 2020 to August 2021, 36 out of 206 patients operated for isolated coronary artery bypass grafting were enrolled; 673 paired blood glucose level were analyzed. Global agreement (ρc) was 0.85 (95% C.I.: 0.84-0.86), intensive care unit agreement was 0.78 (95%C.I.: 0.74-0.82) and ward agreement was 0.91 (95%C.I.: 0.89-0.93). In the diabetic population, it was 0.87 (95%C.I.: 0.85-0.90). When paracetamol was used, the difference was 0.02 mmol/l (95%C.I.: 0.29-0.33)., Conclusions: Dexcom G6 ® provides good blood glucose level accuracy in the postoperative context of cardiac surgery compared to the standard methods of measurements. The results are particularly reliable in the ward where the need for repeated capillary glucose measurements implies patient discomfort and time-consuming manipulations for the nursing staff., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Autoantibodies directed against the GluA3 subunit (anti-GluA3 hIgGs) of AMPA receptors have been identified in 20%-25% of patients with frontotemporal lobar degeneration (FTLD). Data from patients and in vitro/ex vivo pre-clinical studies indicate that anti-GluA3 hIgGs negatively affect glutamatergic neurotransmission. However, whether and how the chronic presence of anti-GluA3 hIgGs triggers synaptic dysfunctions and the appearance of FTLD-related neuropathological and behavioural signature has not been clarified yet. To address this question, we developed and characterized a pre-clinical mouse model of passive immunization with anti-GluA3 hIgGs purified from patients. In parallel, we clinically compared FTLD patients who were positive for anti-GluA3 hIgGs to negative ones. Clinical data showed that the presence of anti-GluA3 hIgGs defined a subgroup of patients with distinct clinical features. In the preclinical model, anti-GluA3 hIgGs administration led to accumulation of phospho-tau in the postsynaptic fraction and dendritic spine loss in the prefrontal cortex. Remarkably, the preclinical model exhibited behavioural disturbances that mostly reflected the deficits proper of patients positive for anti-GluA3 hIgGs. Of note, anti-GluA3 hIgGs-mediated alterations were rescued in the animal model by enhancing glutamatergic neurotransmission with a positive allosteric modulator of AMPA receptors. Overall, our study clarified the contribution of anti-GluA3 autoantibodies to central nervous system symptoms and pathology and identified a specific subgroup of FTLD patients. Our findings will be instrumental in the development of a therapeutic personalised medicine strategy for patients positive for anti-GluA3 hIgGs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The neuropsychological characteristics of the cerebellar cognitive affective syndrome (CCAS) in congenital, non-progressive malformations of the cerebellum have been scarcely investigated, and even less is known for Joubert syndrome (JS), an inherited, non-progressive cerebellar ataxia characterized by the so-called molar tooth sign. The few studies on this topic reported inconsistent results about intellectual functioning and specific neuropsychological impairments. The aim of this research is to examine the neuropsychological profile of JS compared to other congenital cerebellar malformations (CM), considering individual variability of intellectual quotient (IQ) in the two groups. Fourteen patients with JS and 15 patients with CM aged 6-25 years were tested through a comprehensive, standardized neuropsychological battery. Their scores in the neuropsychological domains were inspected through descriptive analysis and compared by mean of MANOVA and ANOVA models, then replicated inserting IQ as covariate. The two groups showed a largely overlapping neuropsychological profile, consistent with CCAS. However, the JS group showed worse performance in visual-spatial memory compared to CM patients, although this difference was mitigated when considering IQ. These findings highlight a divergence between JS and other CM in visual-spatial memory, which might suggest a critical role of the cerebellum in recalling task-relevant memories and might inform rehabilitative interventions., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Chronic kidney disease (CKD) is one of the leading causes of death worldwide, closely interrelated with cardiovascular diseases, ultimately leading to the failure of both organs - the so-called "cardiorenal syndrome". Despite this burden, data related to cardiogenic shock outcomes in CKD patients are scarce., Methods: FRENSHOCK (NCT02703038) was a prospective registry involving 772 patients with cardiogenic shock from 49 centres. One-year outcomes (rehospitalization, death, heart transplantation, ventricular assist device) were analysed according to history of CKD at admission and were adjusted on independent predictive factors., Results: CKD was present in 164 of 771 patients (21.3%) with cardiogenic shock; these patients were older (72.7 vs. 63.9years) and had more comorbidities than those without CKD. CKD was associated with a higher rate of all-cause mortality at 1month (36.6% vs. 23.2%; hazard ratio 1.39, 95% confidence interval 1.01-1.9; P=0.04) and 1year (62.8% vs. 40.5%, hazard ratio 1.39, 95% confidence interval 1.09-1.77; P<0.01). Patients with CKD were less likely to be treated with norepinephrine/epinephrine or undergo invasive ventilation or receive mechanical circulatory support, but were more likely to receive renal replacement therapy (RRT). RRT was associated with a higher risk of all-cause death at 1month and 1year regardless of baseline CKD status., Conclusions: Cardiogenic shock and CKD are frequent "cross-talking" conditions with limited therapeutic options, resulting in higher rates of death at 1month and 1year. RRT is a strong predictor of death, regardless of preexisting CKD. Multidisciplinary teams involving cardiac and kidney physicians are required to provide integrated care for patients with failure of both organs., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Background: There has been a growing interest in pathologic spine-hip relations (PSHR) in current literature, with the aim of reducing the risk of prosthetic impingement, dislocation, and edge loading in total hip arthroplasty (THA). The primary objective of this review is to determine the effect of different PSHR on primary THA outcomes and complication profile. The secondary objective is to stratify the risk of different subgroups of PSHR patients., Methods: A systematic review of the literature was performed in accordance with PRISMA guidelines. Randomised controlled trials, comparative cohort studies and case-control studies comparing outcomes and complication rates of primary THA in patients with and without a PSHR (spinal fusion; degenerative spinal conditions determining stiff spine and/or spinal misalignment) were included. The quality of the included studies and the risk of bias were assessed. The revision rate, complications, and clinical and radiological data were analysed. Complications included: aseptic loosening (AL), periprosthetic joint infections (PJI), hip dislocations and periprosthetic fractures (PF)., Results: Fifteen articles were included with 3.306.342 THAs. The mean follow-up (FU) was 31.4 ± 21.7 months. The population was divided into three subgroups: spinal fusion patients (48.315 THAs); non-fused patients with spinal stiffness (106.110 THAs); non-fused patients with normal spines (3.151.917 THAs). A statistically significant risk stratification was observed about dislocation rate (5.98 ± 6.9% SF, 3.0 ± 1.9% non-SF Stiff and 2.26 ± 1.4% non-SF; p = 0.028). Similarly, about THA revision rate, a statistically significant risk stratification was also observed (7.3 ± 6.8% SF, 6.4 ± 3.1% non-SF Stiff and 2.7 ± 1.7% non-SF; p = 0.020). No statistically significant difference was observed when analysing AL, PJI and PF., Conclusion: A statistically significant risk stratification of dislocation and revision rate was observed in the different PHSR, as theorised by the Bordeaux classification. Fused patients present a higher risk, degenerated and/or stiff spine an intermediate risk and mobile spines a lower risk profile. A standardised approach to THA candidate patients must consider the possible PSHR to improve clinical outcomes and reduce adverse events of THA., (© 2023. The Author(s) under exclusive licence to SICOT aisbl.)

InAs quantum wells (QWs) are promising material systems due to their small effective mass, narrow bandgap, strong spin-orbit coupling, large g-factor, and transparent interface to superconductors. Therefore, they are promising candidates for the implementation of topological superconducting states. Despite this potential, the growth of InAs QWs with high crystal quality and well-controlled morphology remains challenging. Adding an overshoot layer at the end of the metamorphic buffer layer, i.e., a layer with a slightly larger lattice constant than the active region of the device, helps to overcome the residual strain and provides optimally relaxed lattice parameters for the QW. In this work, we systematically investigated the influence of overshoot layer thickness on the morphological, structural, strain, and transport properties of undoped InAs QWs on GaAs(100) substrates. Transmission electron microscopy reveals that the metamorphic buffer layer, which includes the overshoot layer, provides a misfit dislocation-free InAs QW active region. Moreover, the residual strain in the active region is compressive in the sample with a 200 nm-thick overshoot layer but tensile in samples with an overshoot layer thicker than 200 nm, and it saturates to a constant value for overshoot layer thicknesses above 350 nm. We found that electron mobility does not depend on the crystallographic directions. A maximum electron mobility of 6.07 × 10 5 cm 2 /Vs at 2.6 K with a carrier concentration of 2.31 × 10 11 cm -2 in the sample with a 400 nm-thick overshoot layer has been obtained.

Purpose: Both scaphoid non-union advanced collapse wrist (SNAC) and scapho-lunate advanced collapse wrist (SLAC) at stage II-III are common indications for limited wrist fusions including four-corners fusion (4CF) and three-corners fusion (3CF). The aim of this study was to assess the clinical and radiological outcomes in patients undergoing 3CF vs. 4CF. A new radiological index called Lunate Shift Index (LSI) was devised to evaluate the importance of the lunate displacement relative to the radiolunate joint., Materials and Methods: Twenty-eight patients undergoing 3CF and 40 patients undergoing 4CF were clinically evaluated. The radiolunate angle, the carpal height, and the LSI were recorded radiographically. The LSI corresponds to the ratio between the distance from the lunate centre to the middle of the intermediate column and the length of the intermediate column of the distal radius., Results: A statistically significant correlation was observed between LSI and clinical outcomes. The lunate displacement was associated with an increased incidence of wrist ulnar pain. No statistically significant differences were observed between 3 and 4CF in all parameters compared., Conclusions: The osteoarthritis of piso-triquetral joint has been identified as the cause of wrist ulnar pain in patients undergoing 4CF. The lunate correct positioning allows to maintain the carpal height and to increase the contact area at the level of the radiolunate joint. A good reduction of the lunate could be obtained with the 3CF compared to 4CF. This study showed how proper realignment of the lunate following midcarpal arthrodesis correlates with a better clinical outcome., Level of Evidence: Level III, Retrospective comparative study., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Indian Orthopaedics Association 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

The study aimed to evaluate the effects of monoclonal antibodies (mAbs) acting on the calcitonin gene-related peptide (CGRP) or its receptor (anti-CGRP/R mAbs) on migraine comorbidities of depression, anxiety, and fatigue in patients resistant to traditional therapies. The issue addressed in this study is pivotal to unveiling the role of this neurotransmitter beyond pain processing. We conducted an open-label prospective study assessing comorbidities in patients with high frequency (HFEM) and chronic migraine (CM), medication overuse headache (MOH), and resistance to traditional prophylaxis. All patients were treated with anti-CGRP/R mAbs for 3 months. Seventy-seven patients were enrolled with either HFEM (21%) or CM (79%) with or without MOH (56% and 44%, respectively). We identified 21 non-responders (27%) and 56 responders (73%), defined on the reduction ≥50% of headache frequency. The two groups were highly homogeneous for the investigated comorbidities. Disease severity in terms of headache frequency, migraine-related disability, and affective comorbid symptoms was reduced in both groups with different thresholds; allodynia and fatigue were ameliorated only in responders. We found that anti-CGRP/R antibodies improved pain together with affection, fatigue, and sensory sensitization in a cohort of migraine patients resistant to traditional prophylaxis. Our results offer novel perspectives on the early efficacy of anti-CGRP/R mAbs in difficult-to-treat patients focusing on clinical features other than pain relief.

Background: An unexplained condition that follows transcatheter aortic valve implantation (TAVI) is platelet count reduction (PR). According to published research, patients with balloon-expandable valves (BEVs) had a greater PR than those with self-expandable valves (SEVs). Objectives: The purpose of this study was to investigate the incidence and clinical effects of PR following TAVI. Methods: In total, 1.122 adult TAVI patients were enrolled. Propensity score matching was carried out in a 1:1 ratio between patients with BEVs and those with SEVs. The analysis included changes in platelet count, in-hospital mortality, and early postoperative adverse events. Results: Notably, 632 patients were matched (BEV:316; SEV:316). All patients' post-procedural platelet counts changed according to a parabolic curve, using a mixed regression model for repeated analyses (estimate = -0.931; standard error = 0.421; p = 0.027). The platelet count varied comparably in patients with BEVs and SEVs (estimate = -4.276, standard error = 4.760, p = 0.369). The average time for obtaining the nadir platelet count value was three days after implantation (BEV: 146 (108-181) vs. SEV: 149 (120-186); p = 0.142). Overall, 14.6% of patients (92/632) had post-procedural platelet count <100,000/µL. There was no difference between the two prosthesis types (BEV:51/316; SEV:41/316; p = 0.266). Thrombocytopenia was found to be significantly linked to blood product transfusions, lengthier stays in the intensive care unit and hospital, and in-hospital mortality. Conclusions: TAVI, irrespective of the type of implanted valve, is linked to a significant but temporary PR. Thrombocytopenia increases the risk of serious complications and in-hospital death in TAVI patients. To explore and clarify the causes and associated effects, further prospective research is necessary.

Competing Interests: Competing interests: GA reports consulting fees from Metadeq and GHP Scientific. IB reports consulting fees from Apollo, Endosurgery, AndoTools, Nitinotes, Erbe Elektromedizin, Boston Scientific, Cook Medical and Pentax Medical. MGN reports consulting fees from Apollo EndoSurgery, USGI and Keyron. He is also a Scientific Advisor of Keyron and Morphic Medical. VB reports consulting fees from Apollo EndoSurgery. GM reports consulting fees from Novo Nordisk, Fractyl, Recor. She is also Scientific Advisor of Keyron, Metadeq, GHP Scientific, and Jemyll. All other authors declare no competing interests.

Background: The Virtual Reality Headset (VRH) is a device aiming at improving patient's comfort by reducing pain and anxiety during medical interventions. Its interest during cardiac implantable electronic devices (CIED) implant procedures has not been studied., Methods: We randomized consecutive patients admitted for pacemaker or Implantable Cardioverter Defibrillator (ICD) at our center to either standard analgesia care (STD-Group), or to VRH (VRH-Group). Patients in the STD-Group received intra-venous paracetamol (1 g) 60 min before the procedure, and local anesthesia was performed with lidocaine. For patients of the VRH-Group, VRH was used on top of standard care. We monitored patients' pain and anxiety using numeric rating scales (from 0 to 10) at the time of sub-cutaneous pocket creation, and during deep axillary vein puncture. Patient comfort during the procedure was assessed using a detailed questionnaire. Morphine consumption was also assessed., Results: We randomized 61 patients to STD-Group (n = 31) or VRH-Group (n = 30). Pain and anxiety were lower in the VRH-Group during deep venous puncture (3.0 ± 2.0 vs. 4.8 ± 2.2, p = 0.002 and 2.4 ± 2.2 vs. 4.1 ± 2.4, p = 0.006) but not during pocket creation (p = 0.58 and p = 0.5). Morphine consumption was lower in the VRH-Group (1.6 ± 0.7 vs. 2.1 ± 1.1 mg; p = 0.041). Patients' overall comfort during procedure was similar in both groups., Conclusion: VRH use improved pain and anxiety control during deep venous puncture compared to standard analgesia care, and allowed morphine consumption reduction. However, pain and anxiety were similar at the time of sub-cutaneous pocket creation., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The cerebellum causally supports social processing by generating internal models of social events based on statistical learning of behavioral regularities. However, whether the cerebellum is only involved in forming or also in using internal models for the prediction of forthcoming actions is still unclear. We used cerebellar transcranial Direct Current Stimulation (ctDCS) to modulate the performance of healthy adults in using previously learned expectations in an action prediction task. In a first learning phase of this task, participants were exposed to different levels of associations between specific actions and contextual elements, to induce the formation of either strongly or moderately informative expectations. In a following testing phase, which assessed the use of these expectations for predicting ambiguous (i.e. temporally occluded) actions, we delivered ctDCS. Results showed that anodic, compared to sham, ctDCS boosted the prediction of actions embedded in moderately, but not strongly, informative contexts. Since ctDCS was delivered during the testing phase, that is after expectations were established, our findings suggest that the cerebellum is causally involved in using internal models (and not just in generating them). This encourages the exploration of the clinical effects of ctDCS to compensate poor use of predictive internal models for social perception., (© The Author(s) 2024. Published by Oxford University Press.)

Considering the increase in patients who suffer from osteoporosis and the bone defects that occur in these patients, bone tissue regeneration is a promising option to solve this problem. To achieve a synergistic effect between the synthesis of a proper structure and bioactive/pharmaceutical activity, ions with a physiological effect can be added to silica structures, such as Ca 2+ , thanks to its bioactive behavior, and Ga 3+ for its antibacterial and anticancer action. In this work, the synthesis of large pore mesoporous silica (LPMS), potential bioactive glasses containing Ca 2+ and Ga 3+ , has been studied. Corresponding structures, in terms of composition, have been synthesized following the Sol-Gel EISA (Evaporation Induced Self-Assembly) process (obtaining Classical Mesoporous Silica, MS). Pore structure characterization of LPMSs and MSs has been performed using N 2 adsorption/desorption and Hg-porosimetry, showing the presence of pores for LPMSs in the range of 20-60 and 200-600 nm. Nisin, a polycyclic antibacterial peptide, has been used for load tests. The load and release tests performed highlight a higher loading and releasing, doubled for LPMSs if compared to MSs. To confirm the maintenance of the structure of LPMSs and their mechanical strength and resistance, scanning electron microscopy images were acquired before and after release tests. Ca and Ga release in SBF has been studied through inductively coupled plasma-optical emission spectroscopy (ICP-OES), showing a particularly high release of these ions performed with LPMSs. The bioactive behavior of Ca-containing structures has been confirmed using FT-IR (Fourier-transform infrared spectroscopy), SEM-EDS (Scanning Electron Microscope-Energy Dispersive Spectroscopy), and X-ray powder diffraction (XRDP). In conclusion, LPMSs showed better loading and releasing properties compared with classical MS and better release in terms of active ions. In addition, it has also been demonstrated that LPMSs have bioactive behavior (a well-known characteristic of MSs).

The intracellular ATP-ribosyltransferases PARP1 and PARP2, contribute to DNA base excision repair (BER) and DNA demethylation and have been implicated in epigenetic programming in early mammalian development. Recently, proteomic analyses identified BER proteins to be covalently poly-ADP-ribosylated by PARPs. The role of this posttranslational modification in the BER process is unknown. Here, we show that PARP1 senses AP-sites and SSBs generated during TET-TDG mediated active DNA demethylation and covalently attaches PAR to each BER protein engaged. Covalent PARylation dissociates BER proteins from DNA, which accelerates the completion of the repair process. Consistently, inhibition of PARylation in mESC resulted both in reduced locus-specific TET-TDG-targeted DNA demethylation, and in reduced general repair of random DNA damage. Our findings establish a critical function of covalent protein PARylation in coordinating molecular processes associated with dynamic DNA methylation., (© 2024. The Author(s).)

Background: Converging evidence points to impairments of the predictive function exerted by the cerebellum as one of the causes of the social cognition deficits observed in patients with cerebellar disorders., Objective: We tested the neurorestorative effects of cerebellar transcranial direct current stimulation (ctDCS) on the use of contextual expectations to interpret actions occurring in ambiguous sensory sceneries in a sample of adolescents and young adults with congenital, non-progressive cerebellar malformation (CM)., Methods: We administered an action prediction task in which, in an implicit-learning phase, the probability of co-occurrence between actions and contextual elements was manipulated to form either strongly or moderately informative expectations. Subsequently, in a testing phase, we probed the use of these contextual expectations for predicting ambiguous (i.e., temporally occluded) actions. In a sham-controlled, within-subject design, participants received anodic or sham ctDCS during the task., Results: Anodic ctDCS, compared to sham, improved patients' ability to use contextual expectations to predict the unfolding of actions embedded in moderately, but not strongly, informative contexts., Conclusions: These findings corroborate the role of the cerebellum in using previously learned contextual associations to predict social events and document the efficacy of ctDCS to boost social prediction in patients with congenital cerebellar malformation. The study encourages the further exploration of ctDCS as a neurorestorative tool for the neurorehabilitation of social cognition abilities in neurological, neuropsychiatric, and neurodevelopmental disorders featured by macro- or micro-structural alterations of the cerebellum., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Transfusions are extremely frequent after cardiac surgery, and they have a considerable economic burden and impact on outcomes. Optimal patient blood management could play a fundamental role in reducing the rate of transfusion and Jehovah's Witnesses (JW) represent the ideal surrogate study population. This meta-analysis compares outcomes of JWs and non-JWs' patients undergoing cardiac surgery, assessing the safety of a bloodless cardiac surgery. A scoping review was conducted using a search strategy for studies assessing outcomes of JW undergoing cardiac surgery. The primary outcome was perioperative mortality, and a random-effects meta-analysis was performed. Ten studies were included in our meta-analysis, involving 780 JW patients refusing any type of transfusion ("JW") and 1182 patients accepting transfusion if needed ("non-JW"). 86% of non-JW patients received at least 1 transfusion. There was no significant difference in terms of perioperative mortality (OR 0.91; 95% CI 0.55-1.52; p = 0.72). The volume blood loss was significantly less in the JW (p = 0.001), while the rate of reoperation for bleeding was also lower, but not statistically significative, in the JW (p = 0.16). Both preoperative and postoperative hemoglobin and hematocrit were significantly higher in the JW. Therefore, we concluded that bloodless cardiac surgery is safe and early outcomes are similar between JW and non-JW patients: optimal patient blood management is fundamental in guarantying these results. Further studies are needed to assess if a limitation of transfusion could have a positive long-term impact on outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)