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The springtime atmosphere over the southeast Atlantic Ocean (SEA) is subjected to a consistent layer of biomass burning (BB) smoke from widespread fires on the African continent. An elevated humidity signal is coincident with this layer, consistently proportional to the amount of smoke present. The combined humidity and BB aerosol has potentially significant radiative and dynamic impacts. Here, we use aircraft-based observations from the NASA ORACLES (ObseRvations of Aerosols above CLouds and their intEractionS) deployments in conjunction with reanalyses to characterize covariations in humidity and BB smoke across the SEA. The observed plume–vapor relationship, and its agreement with the European Centre for Medium-Range Weather Forecasts (ECMWF) Reanalysis version 5 (ERA5) and Copernicus Atmosphere Monitoring Service (CAMS) reanalysis, persists across all observations, although the magnitude of the relationship varies as the season progresses. Water vapor is well represented by the reanalyses, while CAMS tends to underestimate carbon monoxide especially under high BB. While CAMS aerosol optical depth (AOD) is generally overestimated relative to ORACLES AOD, the observations show a consistent relationship between carbon monoxide (CO) and aerosol extinction, demonstrating the utility of the CO tracer to understanding vertical aerosol distribution. We next use k-means clustering of the reanalyses to examine multi-year seasonal patterns and distributions. We identify canonical profile types of humidity and of CO, allowing us to characterize changes in vapor and BB atmospheric structures, and their impacts as they covary. While the humidity profiles show a range in both total water vapor concentration and in vertical structure, the CO profiles primarily vary in terms of maximum concentration, with similar vertical structures in each. The distribution of profile types varies spatiotemporally across the SEA region and through the season, ranging from largely one type in the northeast and southwest to more evenly distributed between multiple types where air masses meet in the middle of the SEA. These distributions follow patterns of transport from the humid, smoky source region (greatest influence in the northeast of the SEA) and the seasonal changes in both humidity and smoke (increasing and decreasing through the season, respectively). With this work, we establish a framework for a more complete analysis of the broader radiative and dynamical effects of humid aerosols over the SEA.

Digital twins of physical and human systems informed by real-time data are becoming ubiquitous across weather forecasting, disaster preparedness, and urban planning, but researchers lack the tools to run these models effectively and efficiently, limiting progress. One of the current challenges is to assimilate observations in highly non-linear dynamical systems, as the practical need is often to detect abrupt changes. We have developed a software platform to improve the use of real-time data in non-linear system representations where non-Gaussianity limits the applicability of data assimilation algorithms such as the ensemble Kalman filter and variational methods. Particle-filter-based data assimilation algorithms have been implemented within a user-friendly open-source software platform in Julia – ParticleDA.jl. To ensure the applicability of the developed platform in realistic scenarios, emphasis has been placed on numerical efficiency and scalability on high-performance computing systems. Furthermore, the platform has been developed to be forward-model agnostic, ensuring that it is applicable to a wide range of modelling settings, for instance unstructured and non-uniform meshes in the spatial domain or even state spaces that are not spatially organized. Applications to tsunami and numerical weather prediction demonstrate the computational benefits and ease of using the high-level Julia interface with the package to perform filtering in a variety of complex models.

Abstract Nanophononic materials are characterized by a periodic nanostructuration, which may lead to coherent scattering of phonons, enabling interference and resulting in modified phonon dispersions. We have used the extreme ultraviolet transient grating technique to measure phonon frequencies and lifetimes in a low-roughness nanoporous phononic membrane of SiN at wavelengths between 50 and 100 nm, comparable to the nanostructure lengthscale. Surprisingly, phonon frequencies are only slightly modified upon nanostructuration, while phonon lifetime is strongly reduced. Finite element calculations indicate that this is due to coherent phonon interference, which becomes dominant for wavelengths between ~ half and twice the inter-pores distance. Despite this, vibrational energy transport is ensured through an energy flow among the coherent modes created by reflections. This interference of phonon echos from periodic interfaces is likely another aspect of the mutual coherence effects recently highlighted in amorphous and complex crystalline materials and, in this context, could be used to tailor transport properties of nanostructured materials.

IntroductionIn this study we assessed the contribution of psychopathology, including the two domains of negative symptoms (motivational deficit and expressive deficit), processing speed as an index of neurocognition, and emotion recognition, as an index of social cognition, to poor functional outcomes in people with schizophrenia.MethodsThe Positive and Negative Syndrome Scale was used to evaluate positive symptoms and disorganization and the Brief Negative Symptom Scale to assess negative symptoms. The Symbol Coding and the Trail Making Test A and B were used to rate processing speed and the Facial Emotion Identification Test to assess emotion recognition. Functional outcome was assessed with the Personal and Social Performance Scale (PSP). Regression analyses were performed to identify predictors of functional outcome. Mediation analyses was used to investigate whether social cognition and negative symptom domains fully or partially mediated the impact of processing speed on functional outcome.ResultsOne hundred and fifty subjects from 8 different European centers were recruited. Our data showed that the expressive deficit predicted global functioning and together with motivational deficit fully mediated the effects of neurocognition on it. Motivational deficit was a predictor of personal and social functioning and fully mediated neurocognitive impairment effects on the same outcome. Both motivational deficit and neurocognitive impairment predicted socially useful activities, and the emotion recognition domain of social cognition partially mediated the impact of neurocognitive deficits on this outcome.ConclusionsOur results indicate that pathways to functional outcomes are specific for different domains of real-life functioning and that negative symptoms and social cognition mediate the impact of neurocognitive deficits on different domains of functioning. Our results suggest that both negative symptoms and social cognition should be targeted by psychosocial interventions to enhance the functional impact of neurocognitive remediation.

Abstract Background The conceptualization of negative symptoms (NS) in schizophrenia is still controversial. Recent confirmatory factor-analytic studies suggested that the bi-dimensional model (motivational deficit [MAP] and expressive deficit [EXP]) may not capture the complexity of NS structure, which could be better defined by a five-factor (five NS domains) or a hierarchical model (five NS domains as first-order factors, and MAP and EXP, as second-order factors). A validation of these models is needed to define the structure of NS. To evaluate the validity and temporal stability of the five-factor or the hierarchical structure of the brief negative symptom scale (BNSS) in individuals with schizophrenia (SCZ), exploring associations between these models with cognition, social cognition, functional capacity, and functioning at baseline and at 4 years follow-up. Methods Clinical variables were assessed using state-of-the-art tools in 612 SCZ at two-time points. The validity of the five-factor and the hierarchical models was analyzed through structural equation models. Results The two models had both a good fit and showed a similar pattern of associations with external validators at the two-time points, with minor variations. The five-factor solution had a slightly better fit. The associations with external validators favored the five-factor structure. Conclusions Our findings suggest that both five-factor and hierarchical models provide a valid conceptualization of NS in relation to external variables and that five-factor solution provides the best balance between parsimony and granularity to summarize the BNSS structure. This finding has important implications for the study of pathophysiological mechanisms and the development of new treatments.

Introduction: Reactivation of thymopoiesis in adult patients with autoimmune disorders treated with autologous haematopoietic stem cell transplantation (AHSCT) is supported by studies exploring immunoreconstitution. Radiological evidence of thymic hyperplasia after AHSCT was previously reported in patients with systemic sclerosis, but, to our knowledge, it has not been described in multiple sclerosis (MS), where premature thymic involution has been observed and immunosenescence might be accelerated by disease-modifying treatments (DMTs)., Participants and Methods: monocentric case series including MS patients who performed a chest CT scan for clinical purposes after having received AHSCT (BEAM/ATG regimen) for aggressive MS failing DMTs. Chest CT exams were reviewed by a thoracic radiologist: thymic hyperplasia was defined as a rounded mass in the thymic loggia with a density around 40 Hounsfield Units (HU) and thickness >1.3 cm., Results: Fifteen MS patients were included; the median time interval between AHSCT and chest CT scan was 2 (range 1-18) months. All the patients were free from new inflammatory events and DMTs over a median follow-up of 36 months (range 12-84) after AHSCT. Thymic hyperplasia was detected in 3/15 (20%) cases in an exam taken 1 to 3 months after AHSCT; all these patients were females, and aged 30 to 40 years. Lung infections and secondary autoimmunity were diagnosed in 5 and 1 cases, respectively, none of which showed thymic hyperplasia. No associations between thymic hyperplasia and clinical-demographic characteristics or post-AHSCT outcomes were observed., Conclusions: Thymic hyperplasia was detected in 20% of MS patients recently treated with AHSCT. These results are consistent with previous immunological studies showing that AHSCT promotes thymus reactivation in MS patients, further supporting de-novo thymopoiesis as a cornerstone of immune reconstitution after AHSCT in this population., 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. Author Contributions The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Mariottini, Boncompagni, Cozzi, Simonetti, Repice, Damato, Giordano, Miele, Nozzoli and Massacesi.)

NK cells offer a promising alternative to T cell therapies in cancer. We evaluated IPH6501, a clinical-stage, tetraspecific NK cell engager (NKCE) armed with a non-alpha IL-2 variant (IL-2v), which targets CD20 and was developed for treating B cell non-Hodgkin lymphoma (B-NHL). CD20-NKCE-IL2v boosts NK cell proliferation and cytotoxicity, showing activity against a range of B-NHL cell lines, including those with low CD20 density. Whereas it presented reduced toxicities compared with those commonly associated with T cell therapies, CD20-NKCE-IL2v showed greater killing efficacy over a T cell engager targeting CD20 in in vitro preclinical models. CD20-NKCE-IL2v also increased the cell surface expression of NK cell-activating receptors, leading to activity against CD20-negative tumor cells. In vivo studies in nonhuman primates and tumor mouse models further validated its efficacy and revealed that CD20-NKCE-IL2v induces peripheral NK cell homing at the tumor site. CD20-NKCE-IL2v emerges as a potential alternative in the treatment landscape of B-NHL.

Background: In all health-care systems, decisions need to be made regarding allocation of available resources. Evidence is needed for these decisions, especially in low-income countries. We aimed to estimate how health-care resources provided by the public sector were used in Malawi during 2015-19 and to estimate the effects of strengthening health-care services., Methods: For this modelling study, we used the Thanzi La Onse model, an individual-based simulation model. The scope of the model was health care provided by the public sector in Malawi during 2015-19. Health-care services were delivered during health-care system interaction (HSI) events, which we characterised as occurring at a particular facility level and requiring a particular number of appointments. We developed mechanistic models for the causes of death and disability that were estimated to account for approximately 81% of deaths and approximately 72% of disability-adjusted life-years (DALYs) in Malawi during 2015-19, according to the Global Burden of Disease (GBD) estimates; we computed DALYs incurred in the population as the sum of years of life lost and years lived with disability. The disease models could interact with one another and with the underlying properties of each person. Each person in the Thanzi La Onse model had specific properties (eg, sex, district of residence, wealth percentile, smoking status, and BMI, among others), for which we measured distribution and evolution over time using demographic and health survey data. We also estimated the effect of different types of health-care system improvement., Findings: We estimated that the public-sector health-care system in Malawi averted 41·2 million DALYs (95% UI 38·6-43·8) during 2015-19, approximately half of the 84·3 million DALYs (81·5-86·9) that the population would otherwise have incurred. DALYs averted were heavily skewed to children aged 0-4 years due to services averting DALYs that would be caused by acute lower respiratory tract infection, HIV or AIDS, malaria, or neonatal disorders. DALYs averted among adults were mostly attributed to HIV or AIDS and tuberculosis. Under a scenario whereby each appointment took the time expected and health-care workers did not work for longer than contracted, the health-care system in Malawi during 2015-19 would have averted only 19·1 million DALYs (95% UI 17·1-22·4), suggesting that approximately 21·3 million DALYS (20·0-23·6) of total effect were derived through overwork of health-care workers. If people becoming ill immediately accessed care, all referrals were successfully completed, diagnostic accuracy of health-care workers was as good as possible, and consumables (ie, medicines) were always available, 28·2% (95% UI 25·7-30·9) more DALYS (ie, 12·2 million DALYs [95% UI 10·9-13·8]) could be averted., Interpretation: The health-care system in Malawi provides substantial health gains with scarce resources. Strengthening interventions could potentially increase these gains, so should be a priority for investigation and investment. An individual-based simulation model of health-care service delivery is valuable for health-care system planning and strengthening., Funding: The Wellcome Trust, UK Research and Innovation, the UK Medical Research Council, and Community Jameel., Competing Interests: Declaration of interests TBH receives research funding from the UK Medical Research Council, UK Research and Innovation, and The Wellcome Trust, paid to their institution. NA receives research funding from the UK Medical Research Council and the Bill & Melinda Gates Foundation, paid to their institution. VC receives research funding from the UK Medical Research Council and UK Research and Innovation, paid to their institution, and consulting fees from Source Market Access. MC receives research funding from The Wellcome Trust, paid to their institution. JHC receives research funding from UK Research and Innovation and The Wellcome Trust, paid to their institution. JC receives research funding from UK Research and Innovation and The Wellcome Trust, paid to their institution. EJ receives research funding from UK Research and Innovation and The Wellcome Trust, paid to their institution. BLJ receives research funding from the UK Medical Research Council and the UK Department for International Development, paid to their institution. SM receives research funding from UK Research and Innovation and The Wellcome Trust, paid to their institution, and consulting fees from The Global Fund to Fight AIDS, Tuberculosis and Malaria. MM receives research funding from UK Research and Innovation and The Wellcome Trust, paid to their institution. TC receives research funding from UK Research and Innovation and The Wellcome Trust, paid to their institution; receives consulting fees from the UN Economic Commission for Africa; and is on a data safety monitoring board for a trial of adolescent mental health in Nepal. ANP receives research funding from The Wellcome Trust, paid to their institution; receives research funding from the Bill & Melinda Gates Foundation, The Wellcome Trust, the US National Institutes of Health, the UK National Institute for Health and Care Research, and the EU, paid to their institution; and receives consulting fees from WHO. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

This review investigated the effectiveness of robotic-assisted gait training (RAGT) in improving gait and balance performance in adults with multiple sclerosis (MS). Databases and registers were searched from inception to December 2023 to identify randomized controlled trials (RCTs) that analyzed the effects of RAGT on gait speed, function, balance, fatigue, and adverse events. Three reviewers screened studies for eligibility and extracted key information such as participants and intervention characteristics, as well as outcomes of interest. The reviewers assessed the risk of bias of included studies using Cochrane Risk of Bias tool. From the 948 records identified, 8 RCTs were included, involving 335 participants. The studies have demonstrated significant heterogeneity in patient characteristics, intervention protocols, and outcomes measured. The risk of bias assessment revealed concerns, mainly in terms of performance and detection bias. The evidence is uncertain on the effectiveness of RAGT on balance and gait in people with MS, but a multimodal rehabilitation approach, including RAGT, should be encouraged. No serious adverse events seem to be associated with RAGT, suggesting that these interventions are generally safe for use in people with MS. Further studies of higher methodological quality should be led to confirm these positive results., Competing Interests: Declarations Conflicts of interest The authors declare that there are no conflicts of interest. Informed consent Not applicable. Institutional review board statement Not applicable., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Nearly 58% of very low birth weight (VLBW) infants receive at least one red blood cell transfusion, which is not without risk. Reticulocyte fluorescence (RF) indicates the degree of cell maturation. The greater the fluorescence, the greater the immaturity of the reticulocytes., Aim: To evaluate RF as a marker of reticulocyte maturity and to investigate its predictive value for transfusion requirement in VLBW infants., Methods: Complete blood count was performed at 1, 7, 14, 21, and 28 d of age in 104 VLBW infants at the University Hospital of Parma. Iron supplementation was started at 15 d of life. The infants were divided into two groups: those who required transfusion after 28 d of life. (Tr) and those who did not (NTr)., Results: Twenty-seven of 104 newborns required a red blood cell transfusion after 28 d of life (Tr group). At 14 d of life, the percentage of high fluorescence reticulocyte (HFR) was significantly higher in the r group than in infants who did not receive any transfusion (NTr groups): 18.5 vs. 5%, p = 0.002. The ROC curve (AUC 74%) revealed an HFR cut-off value of 16.5% as a predictor of the need for red blood cell (RBC) transfusion., Conclusions: Reticulocyte maturation at 14 d of life is clinically useful for estimating the qualitative impairment of erythropoiesis and predicts the risk of RBC transfusion in VLBW infants. The data suggest the need for tailored iron integration in VLBW infants to improve the quality of hematopoiesis and reduce the risk of blood transfusion., (Copyright © 2024. Published by Elsevier Inc.)

Critical congenital heart diseases are life-threatening, with a high morbidity rate and mortality among newborns; in fact, a newborn discharged from the hospital with undiagnosed heart disease may experience severe complications during the initial days or weeks of their life, necessitating emergency care and even death. Among all kinds of critical congenital heart disease, coarctation of the aorta is one of the most difficult to diagnose because it only becomes noticeable a few days after birth, when patients have already been discharged from the hospital. This underlines the importance of having a reliable diagnostic tool to discover these diseases. The identification of some of these patients can be achieved through newborn screening with pulse oximetry, but only a small number are diagnosed. Hence, the objective of this review was to determine the value of pulse oximetry screening for the early detection of congenital heart defects in newborns, with a focus on coarctation of the aorta. A literature search was conducted between December 2023 and February 2024 using four electronic databases: Pubmed, Google Scholar, Embase, and Scopus to identify studies that evaluated the efficacy of pre- and post-discharge neonatal ductal saturation monitoring for the diagnosis of critical congenital heart defects before discharge. Twenty research studies with a large number of patients, demonstrating moderate sensitivity and high specificity of pulse oximetry test in detecting critical heart defects, especially coarctation of the aorta, were selected and analyzed. Many confirmations have been found of how good the specificity of screening is, reaching an average value of 99.9% in each study analyzed. The problem still lies in the sensitivity of the screening, which is not as good as the specificity, never reaching 90% in any of the studies analysed. So, it is crucial to keep up with efforts to improve the efficacy of the pulse oximetry screening method., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Experiences related to pediatric oncology diagnosis cause great imbalances within the family structure. Assessing the frailties and needs of families and children with cancer from a psychosocial perspective is an important step in providing appropriate pediatric psychology care., Methods: The aim of this study was to develop an Italian translation of the last version of the Psychosocial Assessment Tool questionnaire (PAT 3.1) and to pilot-test it among pediatric oncological families. The guidelines for cross-cultural adaptation of health-related quality of life measures were followed. Specifically, two independent forward translations were produced, followed by a reconciliation step by a multidisciplinary expert committee and back-translation. Revision of the original text and all translations were performed by the expert committee leading to a final version, which was pilot-tested by cognitive debriefing on five families. Subsequently, the final Italian PAT 3.1 version was approved., Results: The Italian version of the PAT 3.1 generated in the present study is a useful instrument to examine the psychosocial risk of the families with a child with cancer., Conclusions: This instrument will be a valuable tool for future clinical trials and it will help clinicians to target specific pediatric psychology support intervention. The questionnaire will be further validated through a multicenter Italian study on psychosocial screening of pediatric oncology and pediatric general diseases., 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.

Purpose: Although younger age has been negatively associated with persistence to adjuvant endocrine therapy (ET), factors contributing to non-persistence remain poorly understood. We assessed factors associated with non-persistence to ET and described the 5-year trajectories of quality of life (QoL) and symptoms in young women (≤40 years) with hormone receptor-positive breast cancer (BC)., Methods: We retrieved data on clinical characteristics and non-persistence from the medical annual records in the European cohort of the "Helping Ourselves, Helping Others: The Young Women's BC Study" (IBCSG 43-09 HOHO). Women completed surveys at baseline, biannually for three years, and annually for another seven years. Data collection included sociodemographic information, QoL aspects assessed by the Cancer Rehabilitation Evaluation System-Short Form and symptoms assessed by the Breast Cancer Prevention Trial symptom scales. Cox regression models were applied to identify factors associated with non-persistence., Results: The cumulative risk of interrupting ET within 5 years was 27.7 % (95 % CI, 21.5-35.2). The QoL subscale scores remained stable over 5 years, with slight improvements in the physical subscale. Hot flashes decreased (p < 0.001), while vaginal problems intensified (p < 0.001) over time. Being married without children and having difficulties interacting and communicating with the medical team were significantly associated with non-persistence., Conclusions: Discussing the desire to conceive with partnered childless women and establishing a good relationship with the medical team may be important in addressing the non-persistence in young BC survivors. As recent data suggests the safety of pausing ET to conceive, this approach may be a reasonable future option to limit non-persistence., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Eraldo Oreste Bucci reports a relationship with AstraZeneca R&D that includes: consulting or advisory and travel reimbursement. Eraldo Oreste Bucci reports a relationship with Astellas Pharma Europe Ltd that includes: travel reimbursement. Eraldo Oreste Bucci reports a relationship with Bristol Myers Squibb Co that includes: travel reimbursement. Eraldo Oreste Bucci reports a relationship with Eli Lilly and Company that includes: travel reimbursement. Eraldo Oreste Bucci reports a relationship with Merck Serono that includes: travel reimbursement. Eraldo Oreste Bucci reports a relationship with Roche that includes: travel reimbursement. Eraldo Oreste Bucci reports a relationship with Takeda Oncology that includes: travel reimbursement. Lorenzo Gianni reports a relationship with AstraZeneca that includes: consulting or advisory. Lorenzo Gianni reports a relationship with Seagen Inc that includes: consulting or advisory. Lorenzo Gianni reports a relationship with Pfizer and Novartis that includes: travel reimbursement. Alberto Farolfi reports a relationship with from Janssen Oncology, GSK-Tesaro, Astrazeneca, Clovis that includes: paid expert testimony. Rossana Berardi reports a relationship with AZ, BI, Novartis, MSD, Otsuka, Lilly, Roche, Amgen, GSK, EISAI, Seage that includes: consulting or advisory. Anne Patridge reports a relationship with Wolters Kluwer, Novartis that includes: equity or stocks and funding grants. If there are other authors, they 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 Ltd.. All rights reserved.)

Machine learning-based approaches are particularly suitable for identifying essential genes as they allow the generation of predictive models trained on features from multi-source data. Gene essentiality is neither binary nor static but determined by the context. The databases for essential gene annotation do not permit the personalisation of the context, and their update can be slower than the publication of new experimental data. We propose HELP (Human Gene Essentiality Labelling & Prediction), a computational framework for labelling and predicting essential genes. Its double scope allows for identifying genes based on dependency or not on experimental data. The effectiveness of the labelling method was demonstrated by comparing it with other approaches in overlapping the reference sets of essential gene annotations, where HELP demonstrated the best compromise between false and true positive rates. The gene attributes, including multi-omics and network embedding features, lead to high-performance prediction of essential genes while confirming the existence of essentiality nuances., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Granata 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.)

This perspective reviews the definition and current understanding of necrotizing enterocolitis and evaluates a future prevention approach to this multifactorial disease. An overview of the prevention approach in general is presented, where key aspects and emerging criticisms are identified. In addition, key elements of early diagnosis and treatment are presented, together with some of their challenges and ambiguities. Moreover, it concludes with emerging questions from the global community to reach a consensus on the definition, diagnosis, and management of necrotizing enterocolitis disease., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Group B Streptococcus (GBS) is a major cause of sepsis and meningitis in newborns. The Centers for Disease Control and Prevention (CDC) recommends to pregnant women, between 35 and 37 weeks of gestation, universal vaginal-rectal screening for GBS colonization, aimed at intrapartum antibiotic prophylaxis (IAP). The latter is the only currently available and highly effective method against early onset GBS neonatal infections. Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, the preventive measures implemented to mitigate the effects of SARS-CoV-2 infection led to the reduction in the access to many health facilities and services, including the obstetric and perinatal ones. The purpose of the present study was to evaluate the prevalence of maternal GBS colonization, as well as use of IAP and incidence of episodes of neonatal GBS infection when antibiotic prophylaxis has not been carried out in colonized and/or at risk subjects, in a population of pregnant women during (years 2020-2021) and after (year 2022) the COVID-19 pandemic, also with the aim to establish possible epidemiological and clinical differences in the two subjects' groups., Methods: We retrospectively analyzed the clinical data of pregnant women admitted to, and delivering, at the Gynaecology and Obstetrics Unit, Department of Sciences for Health Promotion and Mother and Child Care, of the University Hospital of Palermo, Italy, from 01.01.2020 to 31.12.2022. For each of them, we recorded pertinent socio-demographic information, clinical data related to pregnancy, delivery and peripartum, and specifically execution and status of vaginal and rectal swab test for GBS detection, along with eventual administration and modality of IAP. The neonatal outcome was investigated in all cases at risk (positive maternal swabs status for GBS, either vaginal or rectal, with or without/incomplete IAP, preterm labor and/or delivery, premature rupture of membranes ≥ 18 h, previous pregnancy ended with neonatal early onset GBS disease [EOD], urine culture positive for GBS in any trimester of current gestation, intrapartum temperature ≥ 38 °C and/or any clinical/laboratory signs of suspected chorioamnionitis). The data concerning mothers and neonates at risk, observed during the pandemic (years 2020-2021), were compared with those of both subjects' groups with overlapping risk factors recorded in the following period (year 2022). The chi squared test has been applied in order to find out the relationship between pregnant women with GBS colonization receiving IAP and outcome of their neonates., Results: The total source population of the study consisted of 2109 pregnant women, in addition to their 2144 newborns. Our analysis, however, focused on women and neonates with risk factors. The vaginal-rectal swab for GBS was performed in 1559 (73.92%) individuals. The test resulted positive in 178 cases overall (11.42% of those undergoing the screening). Amongst our whole sample of 2109 subjects, 298 women had an indication for IAP (vaginal and/or rectal GBS colonization, previous pregnancy ended with neonatal GBS EOD, urine culture positive for GBS in any trimester of current gestation, and unknown GBS status at labor onset with at least any among delivery at < 37 weeks' gestation, amniotic membranes rupture ≥ 18 h and/or intrapartum temperature ≥ 38.0 °C), and 64 (21.48%) received adequate treatment; for 23 (7.72%) it was inadequate/incomplete, while 211 (70.8%) did not receive IAP despite maternal GBS colonization and/or the presence of any of the above mentioned risk factors. Comparing the frequency of performing vaginal-rectal swabs in the women admitted in the two time periods, the quote of those screened out of the total in the pandemic period (years 2020-2021) was higher than that of those undergoing GBS screening out of the total admitted in the year 2022 (75.65% vs. 70.38%, p = 0.009), while a greater number (not statistically significant, p = 0.12) of adequate and complete IAP was conducted in 2022, than in the previous biennium (26.36 vs. 18.62%). During the whole 3 years study period, as expected, none of the newborns of mothers with GBS colonization and/or risk factors receiving IAP developed EOD. Conversely, 13 neonates with EOD, out of 179 (7.3%) born to mothers with risk factors, were observed: 3 among these patients' mothers performed incomplete IAP, while the other 10 did not receive IAP. Neither cases of neonatal meningitis, nor deaths were observed. The incidence rate in the full triennium under investigation, estimated as the ratio between the number of babies developing the disease out of the total of 2144 newborns, was 6.06‰; among those born to mothers with risk factors, if comparing the two time periods, the incidence was 8.06% in the pandemic biennium, while 5.45% in the following year, evidencing thus no statistical significance (p = 0.53)., Conclusions: The present study revealed in our Department an increased prevalence of pregnant women screened for, and colonized by GBS, in the last decade. However, an overall still low frequency of vaginal-rectal swabs performed for GBS, and low number of adequate and complete IAP despite the presence of risk factors have been found, which did not notably change during the two time periods. Moreover, significant EOD incidence rates have been reported among children of mothers carrying risk factors, although also in this case no statistically significant differences have been observed during and after the pandemic. Such data seem to be in contrast to those reported during the COVID-19, showing a decrease in the access to health facilities and increased mortality/morbidity rates also due to the restrictive measures adopted to mitigate the effects of the pandemic. These findings might be explained by the presence within the same metropolitan area of our Department of a COVID hospital and birthing center, which all the patients with SARS-CoV-2 infection referred to, and likely leading to a weaker concern of getting sick perceived by our patients. Although IAP is an easy procedure to implement, however adherence and uniformity in the management protocols are still not optimal. Therefore, the prophylactic measures adopted to date cannot be considered fully satisfactory, and should be improved. Better skills integration and obstetrical-neonatological collaboration, in addition to new effective preventive tools, like vaccines able to prevent invasive disease, may allow further reduction in morbidity and mortality rates related to GBS perinatal infection., (© 2024. The Author(s).)

The omphalocele is an abdominal wall defect at the base of the umbilical cord, with the worldwide prevalence of 2.6 per 10,000 births. Omphalocele contains herniated abdominal organs and is classified in small and giant based on the size of the defect. Omphalocele is associated with several syndromes or structural anomalies. We reported a case of giant omphalocele of 6 cm with right lung agenesis with tracheal and right bronchial hypoplasia. Laryngeal mask stabilized the newborn allowing endotracheal intubation. Due to serious malformations, the newborn died after few hours of life for cardio-respiratory arrest. Early and accurate prenatal diagnosis allows a better intervention strategies in delivery room, improving the chances of survival and reducing complications for infants with omphalocele., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

The cornerstone of treatment for respiratory distress syndrome in preterm infants is surfactant administration, traditionally performed through an invasive procedure involving tracheal intubation and mechanical ventilation. Consequently, there has been a growing interest in exploring less invasive methods of surfactant delivery to mitigate the associated risks. Currently, several techniques are under evaluation, including intratracheal instillation using a thin catheter, aerosolized or nebulized administration, and guided administration by supraglottic airway devices. One such method is surfactant administration through laryngeal or supraglottic airway, which involves placing a laryngeal mask without the need for laryngoscopy and administering surfactant through the device. The simplicity of laryngeal mask insertion could potentially streamline the surfactant delivery process, eliminating the necessity for advanced skills. This narrative review aimed to assess the current evidence in the literature regarding the benefits and risks associated with surfactant administration through a laryngeal supraglottic airway., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Supraventricular tachyarrhythmias pose a significant challenge in neonates and infants, particularly within the first year of life, where prompt and effective management is crucial. By synthesizing available evidence and clinical experience, this review aims to provide a comprehensive overview of antiarrhythmic therapy in this vulnerable population, with a focus on narrow QRS supraventricular tachyarrhythmias. This review examines the current understanding of supraventricular tachyarrhythmia management and discusses the challenges associated with antiarrhythmic therapy in newborns and infants during the critical first year of life, evaluating the efficacy and safety of various antiarrhythmic agents commonly utilized in this population, including dosing considerations, adverse effects, and strategies for acute management and prophylactic long-term antiarrhythmic treatment., 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 Indian Heart Rhythm Society. Published by Elsevier B.V. All rights reserved.)

Background: Several factors contribute to ischemia/reperfusion injury (IRI), including activation of the NLRP3 inflammasome and its byproducts, such as interleukin-1β (IL-1β) and caspase-1. However, NLRP3 may paradoxically exhibit cardioprotective properties. This study aimed to assess the protective effects of the novel NLRP3 inhibitor, INF195, both in vitro and ex vivo., Methods: To investigate the relationship between NLRP3 and myocardial IRI, we synthetized a series of novel NLRP3 inhibitors, and investigated their putative binding mode via docking studies. Through in vitro studies we identified INF195 as optimal for NLRP3 inhibition. We measured infarct-size in isolated mouse hearts subjected to 30-min global ischemia/one-hour reperfusion in the presence of three different doses of INF195 (5, 10, or 20-μM). We analyzed caspase-1 and IL-1β concentration in cardiac tissue homogenates by ELISA. Statistical significance was determined using one-way ANOVA followed by Tukey's test., Results and Conclusion: INF195 reduces NLRP3-induced pyroptosis in human macrophages. Heart pre-treatment with 5 and 10-μM INF195 significantly reduces both infarct size and IL-1β levels. Data suggest that intracardiac NLRP3 activation contributes to IRI and that low doses of INF195 exert cardioprotective effects by reducing infarct size. However, at 20-μM, INF195 efficacy declines, leading to a lack of cardioprotection. Research is required to determine if high doses of INF195 have off-target effects or dual roles, potentially eliminating both harmful and cardioprotective functions of NLRP3. Our findings highlight the potential of a new chemical scaffold, amenable to further optimization, to provide NLRP3 inhibition and cardioprotection in the ischemia/reperfusion setting., 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. Published by Elsevier Inc.)

Small-cell lung cancer (SCLC), accounting for 10-20 % of all lung tumors, represents the most aggressive high-grade neuroendocrine carcinoma. Most patients are diagnosed with extensive-stage SCLC (ES-SCLC), with brian metastases identified in ∼ 80 % of cases during the disease cours, and the prognosis is dismal, with a 5-year survival rate of less than 5 %. Current available treatments in the second-line setting are limited, and topotecan has long been the only FDA-approved drug in relapsed or refractory ES-SCLC, until the recent approval of lurbinectedin, a selective inhibitor of RNA polymerase II. Temozolomide (TMZ) is an oral alkylating agent, which showed single-agent activity in SCLC, particularly among patients with O 6 -methylguanine-DNA methyltransferase (MGMT) promoter methylation. Several studies have revealed the synergistic activity of temozolomide with poly-ADP-ribose polymerase (PARP) inhibitors, that prevent repair of TMZ-induced DNA damage. This review focuses on the rationale for the use of TMZ in ES-SCLC and provides an overview of the main trials that have evaluated and are currently investigating its role, both as a single-agent and in combinations, in relapse or refractory disease., 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 Elsevier Ltd. All rights reserved.)

Thermal camouflage is a highly coveted technology aimed at enhancing the survivability of military equipment against infrared (IR) detectors. Recently, two-dimensional (2D) nanomaterials have shown low IR emissivity, widely tunable opto-electronic properties, and compatibility with stealth applications. Among these, graphene and graphene-like materials are the most appealing 2D materials for thermal camouflage applications. In multilayer graphene (MLG), charge density can be effectively tuned through sufficiently intense electric fields or through electrolytic gating. Therefore, MLG's optical properties, like infrared emissivity and absorbance, can be controlled in a wide range by voltage bias. The large emissivity modulation achievable with this material makes it suitable in the design of thermal dynamic camouflage devices. Generally, the emissivity modulation in the multilayered graphene medium is governed by an intercalation process of non-volatile ionic liquids under a voltage bias. The electrically driven reduction of emissivity lowers the apparent temperature of a surface, aligning it with the background temperature to achieve thermal camouflage. This characteristic is shared by other graphene-based materials. In this review, we focus on recent advancements in the thermal camouflage properties of graphene in composite films and aerogel structures. We provide a summary of the current understanding of how thermal camouflage materials work, their present limitations, and future opportunities for development.

Arthrospira platensis holds promise for biotechnological applications due to its rapid growth and ability to produce valuable bioactive compounds like phycocyanin (PC). This study explores the impact of salinity and brewery wastewater (BWW) on the mixotrophic cultivation of A. platensis . Utilizing BWW as an organic carbon source and seawater (SW) for salt stress, we aim to optimize PC production and biomass composition. Under mixotrophic conditions with 2% BWW and SW, A. platensis showed enhanced biomass productivity, reaching a maximum of 3.70 g L -1 and significant increases in PC concentration. This study also observed changes in biochemical composition, with elevated protein and carbohydrate levels under salt stress that mimics the use of seawater. Mixotrophic cultivation with BWW and SW also influenced the FAME profile, enhancing the content of C16:0 and C18:1 FAMES. The purity (EP of 1.15) and yield (100 mg g -1 ) of PC were notably higher in mixotrophic cultures, indicating the potential for commercial applications in food, cosmetics, and pharmaceuticals. This research underscores the benefits of integrating the use of saline water with waste valorization in microalgae cultivation, promoting sustainability and economic efficiency in biotechnological processes.

Congenital absence of the pericardium (CAP) is an unusual condition discovered, in most cases, incidentally but can potentially lead to fatal complications, including severe arrhythmias and sudden death. Recently, the use of modern imaging technologies has increased the diagnosis of CAP, providing important findings for risk stratification. Nevertheless, there is not yet consensus regarding therapeutic decisions, and the management of patients with CAP remains challenging. In this paper, we discuss the pathophysiological implication of CAP, review the current literature and explain the role of multimodality imaging tools for its diagnosis, management and treatment.

Context: In the last decade the Sanger method of DNA sequencing has been replaced by next-generation sequencing (NGS). NGS is valuable in conditions characterized by high genetic heterogeneity such as neonatal diabetes mellitus (NDM)., Objective: To compare results of genetic analysis of patients with NDM and congenital severe insulin resistance (c.SIR) identified in Italy in 2003-2012 (Sanger) vs 2013-2022 (NGS)., Methods: We reviewed clinical and genetic records of 104 cases with diabetes onset before 6 months of age (NDM + c.SIR) of the Italian dataset., Results: Fifty-five patients (50 NDM + 5 c.SIR) were identified during 2003-2012 and 49 (46 NDM + 3 c.SIR) in 2013-2022. Twenty-year incidence was 1:103 340 (NDM) and 1:1 240 082 (c.SIR) live births. Frequent NDM/c.SIR genetic defects (KCNJ11, INS, ABCC8, 6q24, INSR) were detected in 41 and 34 probands during 2003-2012 and 2013-2022, respectively. We identified a pathogenic variant in rare genes in a single proband (GATA4) (1/42 or 2.4%) during 2003-2012 and in 8 infants (RFX6, PDX1, GATA6, HNF1B, FOXP3, IL2RA, LRBA, BSCL2) during 2013-2022 (8/42 or 19%, P = .034 vs 2003-2012). Notably, among rare genes 5 were recessive. Swift and accurate genetic diagnosis led to appropriate treatment: patients with autoimmune NDM (FOXP3, IL2RA, LRBA) were subjected to bone marrow transplant; patients with pancreas agenesis/hypoplasia (RFX6, PDX1) were supplemented with pancreatic enzymes, and the individual with lipodystrophy caused by BSCL2 was started on metreleptin., Conclusion: NGS substantially improved diagnosis and precision therapy of monogenic forms of neonatal diabetes and c.SIR in Italy., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

The herbicide atrazine (ATR) has been one of the most widely used herbicides worldwide. However, due to its indiscriminate use, it has been considered an environmental contaminant. Several studies have classified ATR as an endocrine disruptor, and it has been found to have neurotoxic effects on behavior, along with alterations in the dopaminergic, GABAergic, and glutamatergic systems in the basal ganglia of male rodents. These findings suggest that these neurotransmitter systems are targets of this herbicide. However, there are no studies evaluating the neurotoxicity of ATR in female rodents. Our study aimed to assess the effects of repeated IP injections of 100 mg ATR/kg or a vehicle every other day for 2 weeks (six injections) on the locomotor activity, content of monoamines, GABA, glutamate, and glutamine in the striatum, nucleus accumbens, ventral midbrain, and prefrontal cortex, and tyrosine hydroxylase (TH) protein levels in striatum and nucleus accumbens of female rats. Repeated 100 mg ATR/kg injections immediately decreased all the locomotor activity parameters evaluated, and such hypoactivity persisted for at least 48 h after the last ATR administration. The ATR administration increased dopamine and DOPAC content in the nucleus accumbens and the dopamine and DOPAC and serotonin and 5-HIAA content in the ventral midbrain. In contrast, the TH protein levels in the striatum and nucleus accumbens were similar between groups. Meanwhile, GABA, glutamine, and glutamate levels remained unaltered in all brain regions evaluated. The observed behavioral alterations could be associated with the monoamine changes presented by the rats. These data reveal that the nucleus accumbens and ventral midbrain are susceptible to repeated ATR exposure in female rats., 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 Acevedo-Huergo, Sánchez-Yépez, Mendoza-Trejo, Hernández-Plata, Giordano, Rodríguez.)

Background: This is a multicentre, single-arm, phase II study aimed at further exploring the activity of trabectedin as second-/further-line treatment in retroperitoneal leiomyosarcoma (LMS) and well-differentiated/dedifferentiated liposarcoma (LPS)., Materials and Methods: The primary endpoint was the growth modulation index (GMI) defined as the ratio between PFS under trabectedin (PFS) and during previous chemotherapy treatment: time to progression (TTP-1). Secondary endpoints were objective response rate (ORR) and PFS. As per protocol, patients were considered responders if the GMI was >1.33, non-responders if <0.75 and neither if 0.76-1.32., Results: Overall 91 patients were assessable for the primary endpoint (32 patients with LMS and 59 patients with LPS): the median number of cycles received was 6.0 (Q1-Q3 3.0-12.0), and the main reason for treatment discontinuation was disease progression in 72% of patients. The median PFS was 6.0 months, while the median TTP1 was 7.5 months (8.1 and 6.4 months for LMS and LPS, respectively). Thirty-three patients [52%, 95% confidence interval (CI) 36% to 58%, P = 0.674, odds of response 1.1] had a GMI >1.33 (LMS 46%, 95% CI 26% to 67%, odds of response 0.85; LPS 56%, 95% CI 40% to 72%, odds of response 1.3). Overall, in LPS we observed 15/47 patients with a GMI <0.5 and 15/47 patients with a GMI >2. Among LMS patients, 9/26 had a GMI <0.5 and 10/26 had a GMI >2. Overall, ORR (complete response + partial response) was 16% (24% for LMS and 12% for LPS)., Conclusions: While the primary endpoint of the study was not met, we noticed a subgroup of patients with a markedly discrepant TTP with trabectedin in comparison to previous therapy (GMI <0.5 or >2, the latter including some patients with a long TTP with trabectedin). A mismatch between PFS and overall survival was observed, possibly due to the natural history of the two different histologies and the availability of further lines in LMS., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: A recent trend of looking for health-related conditions on the Internet has been described, with up 70% of searchers stating that online sources have affected their medical decision-making. Patients with vestibular schwannomas (VS) use online sources, including videos, to seek information about treatment alternatives and outcomes and surgeons experience. Our study investigates the reliability and quality of VS-related online videos., Methods: In April 2020, a search was launched on YouTube for the key terms 'vestibular schwannoma,' 'acoustic neuroma,' 'eighth cranial nerve schwannoma,' and 'eighth cranial nerve neuroma.' Results were screened for possible inclusion. Three authors independently used the DISCERN instrument to evaluate the reliability and quality of the included videos. Factors possibly influencing popularity were investigated., Results: The initial search yielded 6416 videos. 38 videos were included in the final analysis. The average DISCERN score was 2.76, indicating overall poor quality and reliability of information. Only 5% scored 4.0 or more (unbiased videos that offer evidence-supported information); 31% scored between 3.0 and 3.99, and 63% scored 2.99 or less. Videos describing symptoms or the patient's clinical presentation were slightly more popular than videos without these characteristics. Surgical videos (videos containing clips of surgical procedures) were significantly more popular than non-surgical videos ( p  = .024) despite being of similarly poor quality (DISCERN score 2.85 vs. 2.74, respectively)., Conclusions: Available patient educational videos for VS are of mixed quality and reliability: the authors describe the strengths and pitfalls of existing YouTube videos. Considering that VS is a pathology with multiple available management modalities, and that patients' decision-making is affected by the information available on the Internet, it is of great importance that good-quality informative material be released by medical, academic, or educational institutions.

Background: Heel pain in children is a common condition. The aetiology can be ascribed to fractures, osteochondrosis, tendinitis, calcaneal-navicular or talo-calcaneal coalition, osteomyelitis, rheumatic diseases, anatomic variants, malignant tumours (osteosarcoma, Ewing's sarcoma), and benign lesions (bone cyst, aneurismal bone cyst, osteoid osteoma, or exostosis). In particular, this manuscript focuses on a case of calcaneal exostosis in the paediatric age, aiming to highlight its rarity. Osteochondromas are benign tumours of the surface of the bone and the overlying cartilage. They grow until skeletal maturity and can cause stiffness, pain, cosmetic alterations, tendinitis, and neuro-vascular compression. The calcaneus is an extremely rare site for these tumours. Only two case reports of paediatric exostosis of the calcaneus bone are available., Methods: We describe a case of a girl of 16 years of age, affected by multiple cartilaginous exostosis, who presented with a painful mass on the inferior margin of the foot in the calcaneal region, which was diagnosed as an exostosis. The neoformation was excised, and the girl underwent clinical follow-up., Results: The patient was promptly discharged in good condition, and on the 25th postoperative day, she was completely pain-free and allowed weight bearing., Conclusions: In the case of heel pain resistant to conservative treatment, the presence of an osteochondroma should be considered after excluding more common causes. If symptomatic, calcaneal osteochondromas could require surgical excision.

The use of 3D printing technology for manufacturing new products based on sustainable materials enables one to take advantage of secondary raw materials derived from recycling. This work investigates the structural performances of 3D printing composite filaments based on polylactic acid (PLA), as a matrix, reinforced by recycled carbon fiber (rCF). Carbon fibers were recovered from industrial scraps by a patented thermal process and used to produce thermoplastic composite filaments for additive manufacturing without any additional treatment and additives. The influence of the recovered carbon fiber (rCF) content on the thermal properties, mechanical properties and microstructure of the composites was studied in the range of 3-20 wt%. The recorded TGA curves exhibited a one-stage weight loss within the temperature range 290-380 °C for all samples and the residual rCF content was in good agreement with the theoretical fiber loading. The Young modulus of the extruded filaments strongly increased below a critical content (5 wt%), while at higher content the improvement was reduced. An increase in the storage modulus of 54% compared to neat PLA 3D printed sample resulted in a printed specimen with a higher rCF content. SEM images highlighted a strong rCF prevailing alignment in the direction of the extrusion flow, creating almost unidirectional reinforcement inside the filament. These findings suggest that homogeneous composite filaments reinforced with well-dispersed recycled CF without additional chemical modification and additives are suitable materials for additive manufacturing. The effect of rCF topological distribution within the material on the mechanical performances has been discussed, highlighting that the isolated fibers could efficiently transfer loads with respect to the percolated 3D network and have been correlated with the microstructure.

Introduction: This study examined the efficacy of eye movement desensitisation and reprocessing (EMDR) therapy compared with standard psychotherapy (SP) in treating post-traumatic stress disorder (PTSD) in paediatric oncology patients and their families in the early stage of cancer treatment. The secondary aim of this study was to assess whether EMDR therapy has a different impact on post-traumatic growth compared to SP., Methods: Forty patients were randomly assigned to EMDR or SP groups. The Impact of Event Scale - Revised (IES-R) and the Distress Thermometer (DT) were used to assess PTSD symptoms at pre-treatment (at cancer diagnosis) and in the post-treatment stages (after 8 sessions). The Post-traumatic Growth Inventory-PTGI was administered in the post-treatment stage in order to evaluate positive changes., Results: Both EMDR and SP are effective in reducing PTSD, but EMDR was significantly more effective than the SP in reducing scores on the IES-R, especially regarding the intrusive symptom subscale. Also, in the EMDR group there were higher scores of PTGI than in the standard group., Conclusion: EMDR thus represents a promising treatment in the paediatric psycho-oncology setting., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Zucchetti, Ciappina, Roccia, Concas, Giordano, Battaglini, Geuna, Peirolo, Faretta, Fernandez, Quarello and Fagioli.)

Aims: This study evaluated the feasibility of the intermittent use of direct oral anticoagulants (DOACs) guided by continuous rhythm monitoring via a clinically validated wearable smart device in high-bleeding risk (HBR) patients with symptomatic paroxysmal atrial fibrillation (AF) otherwise subjected to chronic anticoagulation after percutaneous coronary intervention (PCI)., Methods and Results: The INTERMITTENT registry was a 3-year prospective observational study at eight Italian centres. Inclusion criteria were elective or urgent PCI, Academic Research Consortium HBR criteria, history of symptomatic 12-lead ECG detected paroxysmal AF episodes, indication to DOACs, and use of a wearable smart device (Apple Watch™). Thirty days after PCI, patients free of AF episodes discontinued DOAC. However, if an AF episode lasting >6 min or a total AF burden > 6 h over 24 h was detected, DOAC was initiated for 30 consecutive days, and withdrawn afterwards if no further AF episodes occurred. At the discretion of the referring physician, intermittent anticoagulation was offered to 89 patients, whereas continuous treatment with DOACs was prescribed to 151 patients. During a follow-up of 298 ± 87 days, the average duration of oral anticoagulation was significantly shorter in the intermittent anticoagulation group (176 ± 43 days, P = 0.0001), representing a 40% reduction in anticoagulation time compared to the continuous group. Ischaemic and bleeding endpoints were not significantly different between the two groups. Propensity score-matching resulted in a total of 69 matched patients with intermittent vs. continuous anticoagulation, respectively. During a follow-up of 291 ± 63 days, there was a significant 46% reduction in anticoagulation time in the intermittent compared to the continuous group ( P = 0.0001)., Conclusion: In HBR patients with a history of paroxysmal AF episodes who underwent PCI, intermittent anticoagulation guided by continuous rhythm monitoring with a wearable device was feasible and decreased significantly the duration of anticoagulation., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Physiology and behavior are structured temporally to anticipate daily cycles of light and dark, ensuring fitness and survival. Neuromodulatory systems in the brain-including those involving serotonin and dopamine-exhibit daily oscillations in neural activity and help shape circadian rhythms. Disrupted neuromodulation can cause circadian abnormalities that are thought to underlie several neuropsychiatric disorders, including bipolar mania and schizophrenia, for which a mechanistic understanding is still lacking. Here, we show that genetically depleting serotonin in Tph2 knockout mice promotes manic-like behaviors and disrupts daily oscillations of the dopamine biosynthetic enzyme tyrosine hydroxylase (TH) in midbrain dopaminergic nuclei. Specifically, while TH mRNA and protein levels in the Substantia Nigra (SN) and Ventral Tegmental Area (VTA) of wild-type mice doubled between the light and dark phase, TH levels were high throughout the day in Tph2 knockout mice, suggesting a hyperdopaminergic state. Analysis of TH expression in striatal terminal fields also showed blunted rhythms. Additionally, we found low abundance and blunted rhythmicity of the neuropeptide cholecystokinin (Cck) in the VTA of knockout mice, a neuropeptide whose downregulation has been implicated in manic-like states in both rodents and humans. Altogether, our results point to a previously unappreciated serotonergic control of circadian dopamine signaling and propose serotonergic dysfunction as an upstream mechanism underlying dopaminergic deregulation and ultimately maladaptive behaviors.

Background and Objectives: Children with chronic neuromuscular conditions (CCNMC) have many coexisting conditions and often require musculoskeletal surgery for progressive neuromuscular scoliosis or hip dysplasia. Adequate perioperative optimization may decrease adverse perioperative outcomes. The purpose of this scoping review was to allow us to assess associations of perioperative health interventions (POHI) with perioperative outcomes in CCNMC., Methods: Eligible articles included those published from January 1, 2000 through March 1, 2022 in which the authors evaluated the impact of POHI on perioperative outcomes in CCNMC undergoing major musculoskeletal surgery. Multiple databases, including PubMed, Embase, Cumulative Index of Nursing and Allied Health Literature, Web of Science, the Cochrane Library, Google Scholar, and ClinicalTrials.gov, were searched by using controlled vocabulary terms and relevant natural language keywords. Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines were used to perform the review. A risk of bias assessment for included studies was performed by using the Risk of Bias in Non-randomized Studies of Interventions tool., Results: A total of 7013 unique articles were initially identified, of which 6286 (89.6%) were excluded after abstract review. The remaining 727 articles' full texts were then reviewed for eligibility, resulting in the exclusion of 709 (97.5%) articles. Ultimately, 18 articles were retained for final analysis. The authors of these studies reported various impacts of POHI on perioperative outcomes, including postoperative complications, hospital length of stay, and hospitalization costs. Because of the heterogeneity of interventions and outcome measures, meta-analyses with pooled data were not feasible., Conclusions: The findings reveal various impacts of POHI in CCNMC undergoing major musculoskeletal surgery. Multicenter prospective studies are needed to better address the overall impact of specific interventions on perioperative outcomes in CCNMC., (Copyright © 2024 by the American Academy of Pediatrics.)

Background: The gastrointestinal (GI) tract represents one of the main targets of typical hemolytic uremic syndrome (HUS) in children. In this observational study, we tried to establish (1) the main features of GI complications during STEC-HUS and (2) the relationship between Escherichia coli serotypes and Shiga toxin (Stx) variants with hepatopancreatic involvement., Methods: A total of 79 STEC-HUS patients were admitted to our pediatric nephrology department between January 2012 and June 2021. Evidence of intestinal, hepatobiliary, and pancreatic involvements was reported for each patient, alongside demographic, clinical, and laboratory features. Frequency of gastrointestinal complications across groups of patients infected by specific E. coli serotypes and Stx gene variants was evaluated., Results: Six patients developed a bowel complication: two developed rectal prolapse, and four developed bowel perforation which resulted in death for three of them and in bowel stenosis in one patient. Acute pancreatitis was diagnosed in 13 patients. An isolated increase in pancreatic enzymes and/or liver transaminases was observed in 41 and 15 patients, respectively. Biliary sludge was detected in three, cholelithiasis in one. Forty-seven patients developed direct hyperbilirubinemia. Neither E. coli serotypes nor Shiga toxin variants correlated with hepatic or pancreatic involvement., Conclusions: During STEC-HUS, GI complications are common, ranging from self-limited elevation of laboratory markers to bowel perforation, a severe complication with a relevant impact on morbidity and mortality. Hepatopancreatic involvement is frequent, but usually short-lasting and self-limiting., (© 2024. The Author(s).)

Gas-loaded nanocarriers (G-LN) show promise in improving heart transplantation (HTx) outcomes. Given their success in reducing cell death during normothermic hypoxia/reoxygenation (H/R) in vitro, we tested their integration into cardioplegic solutions and static cold storage (SCS) during simulated HTx. Wistar rat hearts underwent four hours of SCS with four G-LN variants: O 2 - or N 2 -cyclic-nigerosyl-nigerose-nanomonomers (CNN), and O 2 - or N 2 -cyclic-nigerosyl-nigerose-nanosponges (CNN-NS). We monitored physiological-hemodynamic parameters and molecular markers during reperfusion to assess cell damage/protection. Hearts treated with nanomonomers (N 2 -CNN or O 2 -CNN) showed improvements in left ventricular developed pressure (LVDP) and a trend towards faster recovery of the rate pressure product (RPP) compared to controls. However, nanosponges (N 2 -CNN-NS or O 2 -CNN-NS) did not show similar improvements. None of the groups exhibited an increase in diastolic left ventricular pressure (contracture index) during reperfusion. Redox markers and apoptosis/autophagy pathways indicated an increase in Beclin 1 for O 2 -CNN and in p22phox for N 2 -CNN, suggesting alterations in autophagy and the redox environment during late reperfusion, which might explain the gradual decline in heart performance. The study highlights the potential of nanomonomers to improve early cardiac performance and mitigate cold/H/R-induced stunning in HTx. These early improvements suggest a promising avenue for increasing HTx success. Nevertheless, further research and optimization are needed before clinical application.

Background: Ministerial Decrete 77 (DM 77) promotes dehospitalization for chronic patients and defines out-of-hospital health facilities at this purpose. It has never been investigated how much patients with cancer know and judge this decree law., Material and Methods: The Collegio italiano dei primari oncologi medici ospedalieri (Cipomo) carried out a survey with a dedicated questionnaire on oncological patients attending public hospital to investigate the liking of DM 77., Results: Anonymous responses were obtained from 1.443 patients. Median age 64ys, 42% males, 21% live alone, 70% have a companion. 19% thinks that oral chemotherapy could be managed outside the hospital, 26.68% carried out follow-up (FU),19.15% parenteral therapy, 32.16% basic examinations. Home is preferred by 21.8%, a health facility close to home by 36.3%, hospital by 37.54%. 59.67% would like FU in hospital by their personal oncologist, 5.47% by GP, 35.41% by both together and 9.45% by oncologist outside the hospital. Asked what they might feel about being followed out of the hospital, 29.94% say of not being treated at its best, 12.68% of not being able to be visited in hospital anymore, 5.27% of being abandoned, 30.7% of being freer and 10.88% of feeling less sick. Regarding the use of new technical tools to favor dehospitalisation, 44.15% answered yes, 15.88% no and 30.07% did not know. About the distance or traveling time from home to the therapy administration side, 20.26% answered this should be no more than 15 km or 30 mins, 9.91% no more than 30 km or 45 mins, 5.47% no more than 50 km or 60 mins but 39.5% say that the distance does not matter to them but only the continuity of care. The question related to the inconveniences with going to hospital for therapy: 40.81% waiting time, 20.47% lack of parking, 17.02% rotation of doctors,12.76% travel time and 5.62% bureaucracy., Conclusions: The patients' answers suggest that dehospitalization could improve their quality of life, but at the condition of being able to maintain a close relationship with the personal oncologist.

Evidence about feeding practices' consequences in small for gestational age newborns is not well established because they are less likely to initiate and continue breastfeeding than other newborns. Our aim was to study current knowledge about the benefits of exclusive human milk diet after 2 years of age in small for gestational age newborns. A systematic review of the literature was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline criteria. Pubmed and Scopus were searched for studies published from databases inception until June 2, 2023. Included articles were analysed and synthesised. Risk of bias and level of evidence assessments were performed. They were enrolled small for gestational age newborns fed by breastfeeding, breast milk or donor milk. The systematic review included 9 articles which were related to 4 health domains: neurodevelopment, cardiovascular, somatic growth and bone mineralization and atopy. Extracted data support a beneficial effect of breastfeeding on these outcomes. Better quality of evidence and longer follow-up are needed., (© 2024. The Author(s).)

Prader-Willi syndrome (PWS) is a complex genetic disorder caused by three different types of molecular genetic abnormalities. The most common defect is a deletion on the paternal 15q11-q13 chromosome, which is seen in about 60% of individuals. The next most common abnormality is maternal disomy 15, found in around 35% of cases, and a defect in the imprinting center that controls the activity of certain genes on chromosome 15, seen in 1-3% of cases. Individuals with PWS typically experience issues with the hypothalamic-pituitary axis, leading to excessive hunger (hyperphagia), severe obesity, various endocrine disorders, and intellectual disability. Differences in physical and behavioral characteristics between patients with PWS due to deletion versus those with maternal disomy are discussed in literature. Patients with maternal disomy tend to have more frequent neurodevelopmental problems, such as autistic traits and behavioral issues, and generally have higher IQ levels compared to those with deletion of the critical PWS region. This has led us to review the pertinent literature to investigate the possibility of establishing connections between the genetic abnormalities and the endocrine disorders experienced by PWS patients, in order to develop more targeted diagnostic and treatment protocols. In this review, we will review the current state of clinical studies focusing on endocrine disorders in individuals with PWS patients, with a specific focus on the various genetic causes. We will look at topics such as neonatal anthropometry, thyroid issues, adrenal problems, hypogonadism, bone metabolism abnormalities, metabolic syndrome resulting from severe obesity caused by hyperphagia, deficiencies in the GH/IGF-1 axis, and the corresponding responses to treatment., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Madeo, Zagaroli, Vandelli, Calcaterra, Crinò, De Sanctis, Faienza, Fintini, Guazzarotti, Licenziati, Mozzillo, Pajno, Scarano, Street, Wasniewska, Bocchini, Bucolo, Buganza, Chiarito, Corica, Di Candia, Francavilla, Fratangeli, Improda, Morabito, Mozzato, Rossi, Schiavariello, Farello, Iughetti, Salpietro, Salvatoni, Giordano, Grugni and Delvecchio.)

Background : Dabigatran etexilate is a pro-drug hydrolyzed into dabigatran by carboxylesterases (CES) and is a substrate of the P-Glycoprotein encoded by the adenosine-triphosphate-binding cassette sub-family B member (ABCB)1 genes. We evaluated the functional response to dabigatran according to different CES1 and ABCB1 single-nucleotide polymorphisms (SNPs) in patients with atrial fibrillation (AF). Methods : A total of 100 consecutive patients with AF taking dabigatran were enrolled by two Italian centers. A venous blood sample was drawn for genetic determinations, as well as a measurement of the diluted thrombin time (dTT) and drug plasma concentrations, at the trough and peak. The main objective was the relationship between the dTT values and CES1 rs2244613 , CES1 rs8192935 and ABCB1 rs4148738 SNP while on two different dabigatran doses (110 and 150 mg BID). Results : A total of 43 patients were on a 110 mg dabigatran dose and 57 on 150 mg. The DTT values at the trough and at peak were not different among patients with different CES1 rs2244613 and CES1 rs8192935 genotypes, regardless of the dabigatran dose. In patients on 150 mg dabigatran, the dTT values at the trough were 77 (44-111) ng/mL in patients with the ABCB1 rs4148738 heterozygous CT genotype vs. 127 (85-147) ng/mL in the wild-type CC genotype vs. 110 (47-159) ng/mL in the mutant trait TT genotype ( p = 0.048). In patients with the ABCB1 rs4148738 CT genotype, OR for having dTT values at a trough below the median was 3.21, 95% CI 1.04-9.88 ( p = 0.042). Conclusions : ABCB1 rs4148738 CT heterozygous is associated with the reduced anticoagulant activity of dabigatran at the trough in patients receiving the higher dose regimen.

Objective: Chronic subdural hematoma (CSDH) is frequently met in neurosurgical practice and often need urgent surgical treatment in case of neurological deterioration. Different surgical approaches to evacuate CSDH are described in the literature. In our experience, an external drainage system is crucial in order to avoid recurrences. We recently encountered a case of subcutaneous CSF collection after drainage removal. Thus, we developed a simple surgical technique to prevent postoperative CSF leak after subdural drainage system removal., Method: We have developed a technique in which the periosteum is harvested during the surgery prior to the evacuation of the hemorrhage and fixed with sutures on the uncut dura mater opposite and laterally to the exit of the catheter exiting the dural hole caused by the passage of the Jackson-Pratt subdural drainage system. When the drainage catheter is removed, the flap, partially held by the sutures, falls over the hole avoiding CSF leakage. By using this technique, the small dural hole will be covered with the periosteum allowing for natural closure and wound healing hence preventing CSF leakage., Results: This technique was successfully employed in 21 patients who didn't develop postoperative CSF leakage following CSDH evacuation and removal of subdural drainage system., Conclusion: In this technical note, we describe a safe dura closure technique that we developed to help reduce the risk of postoperative CSF leakage following subdural drainage removal, which can, however, also be applied in all surgeries in which a catheter is placed in the subdural space., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background/aim: Late vitamin K deficiency bleeding (VKDB) during early infancy is a serious problem worldwide. Vitamin K (VK) deficiency commonly occurs in newborns who are exclusively breastfed. Protein Induced by VK Absence (PIVKA-II) has been identified as an early indicator of subclinical VK deficiency in neonates, surpassing prothrombin time. To assess PIVKA-II levels at 48 h, 1 and 3 months of age in full-term newborns who were exclusively breastfed and received varying VKDB prophylaxis regimens., Methods: A prospective observational study was conducted in four hospitals, enrolling 105 newborns. PIVKA-II levels were measured using a sandwich-type enzyme-linked immunosorbent assay., Results: At 48 h of age, there was no significant difference in PIVKA-II concentrations between newborns who received intramuscular administration of 1 mg of phylloquinone (VK1) and those who received oral administration of 2 mg of VK1 at birth. At 1 and 3 months of life, infants who received any supplementation regimen between 2 and 14 weeks exhibited significantly lower PIVKA-II concentrations compared to infants who received only 1 mg of intramuscular VK1 at birth. The prophylaxis involving a dose of 1 mg of intramuscular VK1 at birth followed by oral administration of 150 μg/day of VK1 from the 2nd to the 14th week of life showed the lowest PIVKA-II blood concentrations., Conclusions: Oral supplementation of VK1 after discharge significantly reduced PIVKA-II concentrations in exclusively breastfed term infants. These findings suggest the importance of oral VK1 supplementation in exclusively breastfed infants during their first 3 months of life to avoid the risk of VK insufficiency., (© 2023 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Background: Diagnosis of pericarditis may be challenging because not all patients meet the conventional criteria. An overlooked diagnosis implies a longer course of symptoms and an increased risk of recurrences. C-reactive protein (CRP), widely used as an inflammation marker, has some limitations. This study aimed to assess the usefulness and prognostic value of INFLA-score, a validated index assessing low-grade inflammation, in the definite diagnosis of pericarditis., Methods: Patients with suspected pericarditis were included. The INFLA-score was computed based on white blood cells and platelet count, neutrophil-to-lymphocyte ratio, and CRP, ranging from -16 to +16. An INFLA-score > 0 was considered positive for the presence of pericardial inflammation. The primary end point was the association of INFLA-score with diagnosis of pericarditis according to conventional criteria. The recurrence of pericarditis at 6 months was the secondary end point., Results: A total of 202 patients were included, aged 47 ± 17 years, and 57% were females. Among 72 (36%) patients with a diagnosis of pericarditis, an INFLA-score > 0 was observed in 86% (vs. 36%, p < 0.001), abnormal CRP in 42% (vs. 10%, p < 0.001), pericardial effusion in 44% (vs. 19%, p < 0.001), abnormal electrocardiogram in 56% (vs. 24%, p < 0.001), and rubs in 5% (vs. 0.1%, p = 0.072). INFLA-score > 0 had the strongest predictive value for the diagnosis of pericarditis (hazard ratio 8.48, 95% confidence interval [CI] 3.39-21.21), with 86% sensitivity and 64% specificity, as opposed to CRP (hazard ratio 1.72, non-significant 95% CI 0.69-4.29). Recurrent pericarditis at 6 months was more frequent in patients with a positive INFLA-score (37% vs. 8%, p < 0.001, rate ratio 4.15, 95% CI 2.81-6.12). In patients with normal CRP, INFLA-score-confirmed ongoing inflammation in 78% of the cases. Compared with the conventional criteria, the INFLA-score had the highest accuracy (area under the curve = 0.82). Different cutoffs were valuable to rule out (INFLA-score > 0, sensitivity 86%, and negative likelihood ratio 0.22) or rule in (INFLA-score ≥ 10, specificity 97%, and positive likelihood ratio 13) the diagnosis., Conclusions: The INFLA-score is a useful diagnostic tool to assess the probability of pericarditis, with a strong prognostic value for further recurrences, outperforming CRP., Competing Interests: Declarations of interest None., (Copyright © 2024 Hellenic Society of Cardiology. Published by Elsevier Inc. All rights reserved.)

Introduction: Biomarker testing is mandatory for the clinical management of patients with advanced non-small cell lung cancer (NSCLC). Myriads of technical platforms are now available for biomarker analysis with differences in terms of multiplexing capability, analytical sensitivity, and turnaround time (TAT). We evaluated the technical performance of the diagnostic workflows of 24 representative Italian institutions performing molecular tests on a series of artificial reference specimens built to mimic routine diagnostic samples., Methods: Sample sets of eight slides from cell blocks of artificial reference specimens harboring exon 19 EGFR (epidermal growth factor receptor) p.E746&#95;AT50del, exon 2 KRAS (Kirsten rat sarcoma viral oncogene homologue) p.G12C, ROS1 (c-ros oncogene 1)-unknown gene fusion, and MET (MET proto-oncogene, receptor tyrosine kinase) Δ exon 14 skipping were distributed to each participating institution. Two independent cell block specimens were validated by the University of Naples Federico II before shipment. Methodological and molecular data from reference specimens were annotated., Results: Overall, a median DNA concentration of 3.3 ng/µL (range 0.1-10.0 ng/µL) and 13.4 ng/µL (range 2.0-45.8 ng/µL) were obtained with automated and manual technical procedures, respectively. RNA concentrations of 5.7 ng/µL (range 0.2-11.9 ng/µL) and 9.3 ng/µL (range 0.5-18.0 ng/µL) were also detected. KRAS exon 2 p.G12C, EGFR exon 19 p.E736&#95;A750del hotspot mutations, and ROS1 aberrant transcripts were identified in all tested cases, whereas 15 out of 16 (93.7%) centers detected MET exon 14 skipping mutation., Conclusions: Optimized technical workflows are crucial in the decision-making strategy of patients with NSCLC. Artificial reference specimens enable optimization of diagnostic workflows for predictive molecular analysis in routine clinical practice., (© 2024. The Author(s).)

Several studies have shown that chronic exposure to the herbicide atrazine (ATR) causes alterations in locomotor activity and markers of the dopaminergic systems of male rats. However, few studies have evaluated the sex-dependent effects of atrazine exposure. The aim of the present study was to evaluate whether chronic ATR exposure causes alterations in behavioral performance and dopaminergic systems of female rats. At weaning, two groups of rats were exposed to 1 or 10 mg ATR/kg body weight daily thorough the food, while the control group received food without ATR for 14 months. Spontaneous locomotor activity was evaluated monthly for 12 months, while anxiety, egocentric and spatial memory, motor coordination, and olfactory function tasks were evaluated between 13 and 14 months of ATR exposure. Tyrosine hydroxylase (TH) and monoamine content in brain tissue were assessed at the end of ATR treatment. Female rats treated with 1 or 10 mg ATR showed vertical hypoactivity compared to the control group only in the first month of ATR exposure. Impairments in olfactory functions were found due to ATR exposure. Nevertheless, no alterations in anxiety, spatial and egocentric memory, or motor coordination tasks were observed, while the levels of TH and dopamine and its metabolites in brain tissue were similar among groups. These results suggest that female rats could present greater sensitivity to the neurotoxic effects of ATR on spontaneous locomotor activity in the early stages of development. However, they are unaffected by chronic ATR exposure later in life compared to male rats. More studies are necessary to unravel the sex-related differences observed after chronic ATR exposure., 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 Elsevier B.V. All rights reserved.)