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Abstract Background Effective pain management during labor induction for pregnancy termination is essential. However, to date, no effective treatment has been identified. The primary aim of this study was to measure the analgesic efficacy of a sufentanil sublingual tablet system during pregnancy termination and patient satisfaction by comparing nulliparous and multiparous women. The secondary aims were to characterize the safety profile by reporting any side effects or adverse events and to determine the need for rescue therapy. Methods We conducted an observational, retrospective, single-center study involving 48 women. The data retrieved for analysis included the total and hourly doses of sublingual sufentanil, evaluations of pain management satisfaction using a 5-point rating scale (ranging from 1, indicating “not satisfied” to 5, denoting “completely satisfied”), occurrence of side effects and adverse events, and the rate of rescue analgesic use. Categorical and numerical variables were compared between the two groups, and a correlation analysis was performed. Results The median total dose of sufentanil required was 60 mcg. Nulliparous women required a higher dose of sufentanil compared with multiparous women (105 mcg vs. 45 mcg; P = 0.01). Additionally, they underwent a longer labor, indirectly measured by the time of device usage (625 min vs. 165 min; P = 0.05). Regarding satisfaction, 40 patients (83.4%) were satisfied or completely satisfied, whereas only 8 patients (16.6%) reported dissatisfaction. Multiparous women exhibited higher satisfaction levels than did nulliparous women (P = 0.03). No adverse events were reported, and the most common side effects were nausea and vomiting (31.2%). Four patients (12%) required acetaminophen due to insufficient analgesia, with only one patient necessitating a switch to intravenous morphine. Conclusions Sublingual sufentanil was effective in both nulliparous and multiparous women with minimal side effects. Therefore, sublingual sufentanil can be considered a valid strategy for analgesia during labor induction for pregnancy termination.

Abstract Arctic amplification (AA), the greater Arctic surface warming compared to the global average, has been widely attributed to increasing concentrations of greenhouse gases (GHG). However, less is known about the impacts of other forcings - notably, anthropogenic aerosols (AER) - and how they may compare to the impacts of GHG. Here we analyze sets of climate model simulations, specifically designed to isolate the AER and GHG effects on global climate. Surprisingly, we find stronger AA produced by AER than by GHG during the 1955–1984 period, when the strongest global AER increase. This stronger AER-induced AA is due to a greater sensitivity of Arctic sea ice, and associated changes in ocean-to-atmosphere heat exchange, to AER forcing. Our findings highlight the asymmetric Arctic climate response to GHG and AER forcings, and show that clean air policies which have reduced aerosol emissions may have exacerbated the Arctic warming over the past few decades.

ABSTRACT Objective: To describe cases of acute kidney injury (AKI) in children diagnosed with COVID-19, associated risk factors, clinical aspects and outcome of cases. Methods: Retrospective study, carried out in a pediatric hospital between March 2020 and September 2021, with patients with COVID-19 who were diagnosed with AKI, studying information present in medical records such as comorbidities, age, gender and use of nephrotoxic medications. Results: We studied 40 cases, and male individuals were significantly more affected (62.5%; p=0.025). AKI was a severe complication of COVID-19 infection, with 100% of the sample requiring admission to the Intensive Care Unit and 22.5% dying. The most prevalent comorbidities analyzed in this study were epilepsy, cerebral palsy and heart disease. Most patients were classified according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria as KDIGO 1 (42.5%), and required orotracheal intubation (67.5%). The frequency of use of nephrotoxic medications and need for dialysis was low, with percentages of 35 and 17.5%, respectively. Among the children who died, 70.4% had some comorbidity and 88.8% received invasive ventilation. Conclusions: AKI in children with COVID-19 infection is associated with severe conditions. Despite the severity, most patients were discharged alive from the hospital.

RESUMO Nesta pesquisa, foram produzidas em laboratório, chapas de madeira aglomerada de Eucalyptus saligna, E. citriodora e E. pilularis e misturas destas espécies. As partículas de madeira foram obtidas a partir de costaneiras provenientes de desdobro de toras em serraria. A quantidade de resina aplicada foi de 8 e 12%. Foram avaliadas as seguintes propriedades: absorção de água e inchamento em espessura após 2 e 24 horas de imersão em água, módulos de elasticidade e de ruptura em flexão estática e ligação interna. As chapas demonstraram boa estabilidade dimensional e as propriedades de módulo de ruptura e ligação interna apresentaram valores médios bem acima do mínimo exigido pela norma CS 236-66. Com base nos resultados obtidos, pode-se recomendar a utilização destas espécies de eucalipto para produção industrial de chapas de madeira aglomerada.

Barotrauma occurs in a significant number of patients with COVID-19 interstitial pneumonia undergoing mechanical ventilation. The aim of the current study was to investigate whether the Brixia score (BS) calculated on chest-X-rays acquired at the Emergency Room was associated with barotrauma. We retrospectively evaluated 117 SARS-CoV-2 patients presented to the Emergency Department (ED) and then admitted to the intensive care unit (ICU) for mechanical ventilation between February and April 2020. Subjects were divided into two groups according to the occurrence of barotrauma during their hospitalization. CXRs performed at ED admittance were assessed using the Brixia score. Distribution of barotrauma (pneumomediastinum, pneumothorax, subcutaneous emphysema) was identified in chest CT scans. Thirty-eight subjects (32.5%) developed barotrauma (25 pneumomediastinum, 24 pneumothorax, 24 subcutaneous emphysema). In the barotrauma group we observed higher Brixia score values compared to the non-barotrauma group (mean value 12.18 vs. 9.28), and logistic regression analysis confirmed that Brixia score is associated with the risk of barotrauma. In this work, we also evaluated the relationship between barotrauma and clinical and ventilatory parameters: SOFA score calculated at ICU admittance and number of days of non-invasive ventilation (NIV) prior to intubation emerged as other potential predictors of barotrauma.

Wine is a relevant part of the diet in many countries, showing significant nutritional properties, providing health benefits to consumers, and having a significant weight in economy. Also, wine plays an important role in many cultures as a part of their social relationships, feasts, or religion where some of them may become a sign of luxury and distinction. For those reasons, objective and subjective quality of wines is an important issue in their production and marketing. To improve wine excellence, some production methods try to relate its physicochemical properties to the quality as it is perceived by humans. Then, modern data prescriptive analysis can be applied to measure the importance (the influence) of each wine attribute. This paper examines and compare several metrics of the attribute importance and its application to the quality-aware design and production of wines. Moreover, for the cases where the perceived quality is characterized using a discrete value, a novel importance metric, based on the Jensen-Shannon Divergence (JSD) is introduced and compared to the existing ones. The results show that JSD clearly overperforms other metrics previously proposed in the literature. Also, it can be asserted that JSD properly reflects the importance of discrete multivalued functions. The results, using this metric in an importance performance analysis of a public wine dataset, show that the main physicochemical attributes of a red wine are citric acidity, alcohol, sulphates and fixed acidity. As for the white wine case, the main attributes are alcohol, free sulfure dioxide and pH.

Abstract The cell/microenvironment interface is the starting point of integrin-mediated mechanotransduction, but many details of mechanotransductive signal integration remain elusive due to the complexity of the involved (extra)cellular structures, such as the glycocalyx. We used nano-bio-interfaces reproducing the complex nanotopographical features of the extracellular matrix to analyse the glycocalyx impact on PC12 cell mechanosensing at the nanoscale (e.g., by force spectroscopy with functionalised probes). Our data demonstrates that the glycocalyx configuration affects spatio-temporal nanotopography-sensitive mechanotransductive events at the cell/microenvironment interface. Opposing effects of major glycocalyx removal were observed, when comparing flat and specific nanotopographical conditions. The excessive retrograde actin flow speed and force loading are strongly reduced on certain nanotopographies upon strong reduction of the native glycocalyx, while on the flat substrate we observe the opposite trend. Our results highlight the importance of the glycocalyx configuration in a molecular clutch force loading-dependent cellular mechanism for mechanosensing of microenvironmental nanotopographical features. Graphical Abstract

Abstract Background Coronavirus disease 2019-associated acute respiratory distress syndrome (COVID-19 ARDS) seems to differ from the “classic ARDS”, showing initial significant hypoxemia in the face of relatively preserved compliance and evolving later in a scenario of poorly compliant lungs. We tested the hypothesis that in patients with COVID-19 ARDS, the initial value of static compliance of respiratory system (Crs) (1) depends on the previous duration of the disease (i.e., the fewer days of illness, the higher the Crs and vice versa) and (2) identifies different lung patterns of time evolution and response to prone positioning. Methods This was a single-center prospective observational study. We enrolled consecutive mechanically ventilated patients with a diagnosis of COVID-19 who met ARDS criteria, admitted to intensive care unit (ICU). Patients were divided in four groups based on quartiles of initial Crs. Relationship between Crs and the previous duration of the disease was evaluated. Respiratory parameters collected once a day and during prone positioning were compared between groups. Results We evaluated 110 mechanically ventilated patients with a diagnosis of COVID-19 who met ARDS criteria admitted to our ICUs. Patients were divided in groups based on quartiles of initial Crs. The median initial Crs was 41 (32–47) ml/cmH2O. No association was found between the previous duration of the disease and the initial Crs. The Crs did not change significantly over time within each quartile. Positive end-expiratory pressure (PEEP) and driving pressure were respectively lower and greater in patients with lower Crs. Prone positioning significantly improved PaO2/FiO2 in the 4 groups, however it increased the Crs significantly only in patients in lower quartile of Crs. Conclusions In our cohort, the initial Crs is not dependent on the previous duration of COVID-19 disease. Prone positioning improves oxygenation irrespective to initial Crs, but it ameliorates respiratory mechanics only in patients with lower Crs.

Abstract Arctic Amplification (AA) exhibits a distinct seasonal dependence; it is weakest in boreal summer and strongest in winter. Here, we analyze simulations from single‐model initial‐condition large ensembles and Coupled Model Intercomparison Project Phase 5 to decipher the seasonal evolution of Arctic climate change. Models agree that the annual maximum AA shifts from autumn into winter over the 21st century, accompanied by similar shifts in sea‐ice loss and surface turbulent heat fluxes, whereas the maximum precipitation shifts only into late autumn. However, the exact seasonal timing and magnitude of these shifts are highly uncertain. Decomposing the uncertainty into model structural differences, emission scenarios, and internal variability reveals that model differences dominate the total uncertainty, which also undergo autumn‐to‐winter shifts. We also find that the scenario uncertainty is unimportant for projections of AA. These results highlight that understanding model differences is critical to reducing uncertainty in projected Arctic climate change.

BackgroundThe PROTECT Center is a multi-project initiative that studies the relationship between exposure to environmental contaminants and preterm births during the prenatal and postnatal period among women living in Puerto Rico. PROTECT's Community Engagement Core and Research Translation Coordinator (CEC/RTC) play a key role in building trust and capacity by approaching the cohort as an engaged community that provides feedback about processes, including how personalized results of their exposure to chemicals should be reported back. The goal of the Mi PROTECT platform was to create a mobile-based application of DERBI (Digital Exposure Report-Back Interface) for our cohort that provides tailored, culturally appropriate information about individual contaminant exposures as well as education on chemical substances and approaches to exposure reduction.MethodsParticipants (N = 61) were presented with commonly used terms in environmental health research related to collected samples and biomarkers, followed by a guided training on accessing and exploring the Mi PROTECT platform. Participants evaluated the guided training and Mi PROTECT platform answering a Likert scale in separated surveys that included 13 and 8 questions, respectively.ResultsParticipants provided overwhelmingly positive feedback on the clarity and fluency of presenters in the report-back training. Most participants reported that the mobile phone platform was both accessible and easy to navigate (83% and 80%, respectively) and that images included in the platform facilitated comprehension of the information. Overall, most participants (83%) reported that language, images, and examples in Mi PROTECT strongly represented them as Puerto Ricans.ConclusionsFindings from the Mi PROTECT pilot test informed investigators, community partners and stakeholders by demonstrating a new way to promote stakeholder participation and foster the "research right-to-know."

Understanding which patients will respond to FOLFIRINOX therapy is important for clinical outcome. Here, the authors show that the MIR1307 is increased pancreatic cancer cell lines and inhibition of the microRNA sensitises cells to treatment.’ stratifying patients to achieve the best clinical outcome. Here, the authors show that the MIR1307 is increased in a subgroup of human pancreatic cancers and inhibition of the microRNA in in vitro and in vivo models of pancreatic cancer sensitises cells to treatment.

ABSTRACT Objective: The aim of this study was to evaluate the coronavirus disease 2019 (COVID-19) cutaneous manifestations described in pediatric patients and discuss their relevance for early diagnosis. Data source: The study consisted of a systematic review of original articles indexed in PubMed and Embase databases, as well as gray literature articles found through Google Scholar. A search strategy, based on PICO (Patient, Intervention, Comparison, Outcome) Tool, with the terms “child,” “infant,” “childhood,” “adolescents,” “teenagers,” “COVID-19,” “SARS-CoV-2,” and “skin manifestations,” was performed to optimize the findings. The study did not restrict any article regarding language. Data synthesis: Out of the 310 articles that initially met the inclusion criteria, 35 were selected for review, totalizing 369 patients. The most common COVID-19 cutaneous manifestations in children and adolescents were Chilblain-like lesions, presented in 67.5% of the cases, followed by erythema multiforme-like (31.7%) and varicella-like lesions (0.8%). The Chilblain-like lesions appeared 7.6 days (95%CI 7.4–7.8) after the viral infection and lasted for 17.5 days (95%CI 16.5–18.5), erythema multiforme-like lesions appeared in 9.5 days (95%CI 9–10) and lasted for 10.3 days (95%CI 9.1–11.5), and varicella-like lesions appeared in 12.3 days (95%CI 4–20.6) and lasted for 7 days. Conclusions: Knowledge of the different skin manifestations in children and adolescents with COVID-19 is essential for an early diagnosis and, consequently, the possibility of promptly care adoption as well as to interrupt the new coronavirus transmission chains in the current pandemic context.

The Antarctic surface mass balance (SMB) has global climatic impacts through its effects on global sea-level rise. The forced increase in Antarctic SMB over the second half of the 20th century was argued to stem from multiple forcing agents, including ozone and ozone-depleting substances (ODSs). Here we use ensembles of fixed-forcing model simulations to quantify and contrast the contributions of stratospheric ozone, tropospheric ozone and ODSs to increases in the Antarctic SMB. We show that ODSs and stratospheric ozone make comparable contributions and together account for 44 % of the increase in the annual mean Antarctic SMB over the second half of the 20th century. In contrast, tropospheric ozone has an insignificant impact on the SMB increase. A large portion of the annual mean SMB increase occurs during austral summer, when stratospheric ozone is found to account for 63 % of the increase. Furthermore, we demonstrate that stratospheric ozone increases the SMB by enhancing the meridional mean and eddy flows towards the continent, thus converging more water vapor over the Antarctic.

The climatic implications of regional aerosol and precursor emissions reductions implemented to protect human health are poorly understood. We investigate the mean and extreme temperature response to regional changes in aerosol emissions using three coupled chemistry–climate models: NOAA GFDL CM3, NCAR CESM1, and NASA GISS-E2. Our approach contrasts a long present-day control simulation from each model (up to 400 years with perpetual year 2000 or 2005 emissions) with 14 individual aerosol emissions perturbation simulations (160–240 years each). We perturb emissions of sulfur dioxide (SO2) and/or carbonaceous aerosol within six world regions and assess the statistical significance of mean and extreme temperature responses relative to internal variability determined by the control simulation and across the models. In all models, the global mean surface temperature response (perturbation minus control) to SO2 and/or carbonaceous aerosol is mostly positive (warming) and statistically significant and ranges from +0.17 K (Europe SO2) to −0.06 K (US BC). The warming response to SO2 reductions is strongest in the US and Europe perturbation simulations, both globally and regionally, with Arctic warming up to 1 K due to a removal of European anthropogenic SO2 emissions alone; however, even emissions from regions remote to the Arctic, such as SO2 from India, significantly warm the Arctic by up to 0.5 K. Arctic warming is the most robust response across each model and several aerosol emissions perturbations. The temperature response in the Northern Hemisphere midlatitudes is most sensitive to emissions perturbations within that region. In the tropics, however, the temperature response to emissions perturbations is roughly the same in magnitude as emissions perturbations either within or outside of the tropics. We find that climate sensitivity to regional aerosol perturbations ranges from 0.5 to 1.0 K (W m−2)−1 depending on the region and aerosol composition and is larger than the climate sensitivity to a doubling of CO2 in two of three models. We update previous estimates of regional temperature potential (RTP), a metric for estimating the regional temperature responses to a regional emissions perturbation that can facilitate assessment of climate impacts with integrated assessment models without requiring computationally demanding coupled climate model simulations. These calculations indicate a robust regional response to aerosol forcing within the Northern Hemisphere midlatitudes, regardless of where the aerosol forcing is located longitudinally. We show that regional aerosol perturbations can significantly increase extreme temperatures on the regional scale. Except in the Arctic in the summer, extreme temperature responses largely mirror mean temperature responses to regional aerosol perturbations through a shift of the temperature distributions and are mostly dominated by local rather than remote aerosol forcing.

This study examines the Arctic surface air temperature response to regional aerosol emissions reductions using three fully coupled chemistry–climate models: National Center for Atmospheric Research-Community Earth System Model version 1, Geophysical Fluid Dynamics Laboratory-Coupled Climate Model version 3 (GFDL-CM3) and Goddard Institute for Space Studies-ModelE version 2. Each of these models was used to perform a series of aerosol perturbation experiments, in which emissions of different aerosol types (sulfate, black carbon (BC), and organic carbon) in different northern mid-latitude source regions, and of biomass burning aerosol over South America and Africa, were substantially reduced or eliminated. We find that the Arctic warms in nearly every experiment, the only exceptions being the U.S. and Europe BC experiments in GFDL-CM3 in which there is a weak and insignificant cooling. The Arctic warming is generally larger than the global mean warming (i.e. Arctic amplification occurs), particularly during non-summer months. The models agree that changes in the poleward atmospheric moisture transport are the most important factor explaining the spread in Arctic warming across experiments: the largest warming tends to coincide with the largest increases in moisture transport into the Arctic. In contrast, there is an inconsistent relationship (correlation) across experiments between the local radiative forcing over the Arctic and the simulated Arctic warming, with this relationship being positive in one model (GFDL-CM3) and negative in the other two. Our results thus highlight the prominent role of poleward energy transport in driving Arctic warming and amplification, and suggest that the relative importance of poleward energy transport and local forcing/feedbacks is likely to be model dependent.

Arctic amplification (AA), defined as the enhanced warming of the Arctic compared to the global average, is a robust feature of historical observations and simulations of future climate. Despite many studies investigating AA mechanisms, their relative importance remains contested. In this study, we examine the different timescales of these mechanisms to improve our understanding of AA’s fundamental causes. We use the Community Earth System Model v1, Large Ensemble configuration (CESM-LE), to generate large ensembles of 2 years simulations subjected to an instantaneous quadrupling of CO _2 . We show that AA emerges almost immediately (within days) following CO _2 increase and before any significant loss of Arctic sea ice has occurred. Through a detailed energy budget analysis of the atmospheric column, we determine the time-varying contributions of AA mechanisms over the simulation period. Additionally, we examine the dependence of these mechanisms on the season of CO _2 quadrupling. We find that the surface heat uptake resulting from the different latent heat flux anomalies between the Arctic and global average, driven by the CO _2 forcing, is the most important AA contributor on short (1 month) timescales. Our results confirm that AA is an inherently fast atmospheric response to radiative forcing and reveal a new AA mechanism.

Astrocytes’ organisation affects the functioning and the fine morphology of the brain, both in physiological and pathological contexts. Although many aspects of their role have been characterised, their complex functions remain, to a certain extent, unclear with respect to their contribution to brain cell communication. Here, we studied the effects of nanotopography and microconfinement on primary hippocampal rat astrocytes. For this purpose, we fabricated nanostructured zirconia surfaces as homogenous substrates and as micrometric patterns, the latter produced by a combination of an additive nanofabrication and micropatterning technique. These engineered substrates reproduce both nanotopographical features and microscale geometries that astrocytes encounter in their natural environment, such as basement membrane topography, as well as blood vessels and axonal fibre topology. The impact of restrictive adhesion manifests in the modulation of several cellular properties of single cells (morphological and actin cytoskeletal changes) and the network organisation and functioning. Calcium wave signalling was observed only in astrocytes grown in confined geometries, with an activity enhancement in cells forming elongated agglomerates with dimensions typical of blood vessels or axon fibres. Our results suggest that calcium oscillation and wave propagation are closely related to astrocytic morphology and actin cytoskeleton organisation.

This paper presents a health monitoring approach for Electro-Mechanical Actuators (EMA). We define four different indicators to continuously evaluate the health state of the system. The four indicators are computed by leveraging the output from a Statistical Process Monitoring (SPM) method based on multivariate statistics, such as the Hotelling's T2 statistic and the Q statistic. SPM approaches give a dichotomous answer, i.e. the presence/absence of a fault. In this work, we propose four ways to compute a continuous indicator starting from the discrete SPM output, that is better suited for health monitoring. We test the approach using a dataset collected from a large experimental campaign on a 1:1 scale EMA for primary flight controls of small aircrafts, that led to EMA failure. Results show the effectiveness of the method.

The PROTECT research Center funded by the NIH’s National Institute of Environmental Health Sciences (NIEHS) Superfund Research Program was launched in 2010 to explore the impact of exposure to pollutants on the high rate of premature births in Puerto Rico. In September 2017, Hurricanes Irma and María devastated the archipelago, which caused: collapse of the electrical system, collapse of the communication system, limited access to clean water, food, gas, and health services, destruction of public (e.g., hospitals) and private property (e.g., houses) and more than 4500 deaths. Pregnant and postpartum individuals are especially vulnerable to natural disasters. They face difficulty obtaining adequate pre- and post-natal care, are exposed to increased risk of miscarriage, premature delivery, and giving birth to low birth weight babies during and after disasters and are also more likely to suffer physical and mental health problems compared to the general population during and after disasters. A face-to-face questionnaire was administered to PROTECT participants who were pregnant during hurricanes Irma or Maria or who became pregnant shortly after in order to identify hurricane-related sources of stress and other adverse effects. This paper is based on the answers to the open-ended question at the end of the questionnaire where participants were asked to share their experiences during and after the hurricanes. Among the 375 participants who completed the survey, 76 answers to the open-ended question were considered due to data saturation. The answers to the open-ended question were transcribed into a document in order to facilitate the coding process. The transcribed text was analyzed first to identify emerging categories and then coded to identify common themes as well as divergence among participants. The following themes were identified: pregnancy and birth challenges, lack of access to basic services, housing conditions, stressful working conditions, concerns about health, concerns about their children, and positive or protective aspects. The results indicate how the disruption in access to basic services has a unique impact on the physical and mental health of pregnant and post-partum women in an emergency situation. These findings point to the potential benefit of developing specific protocols designed for emergency preparedness aimed at this population, which can inform healthcare providers and community organizations in case of future events.

This article describes the data acquired during the first test activity carried out in the Reliable Electromechanical actuator for PRImary SurfacE with health monitoring (REPRISE) H2020 project. The data consist of a set of measures from an Electro-Mechanical Actuator (EMA) employed in small aircrafts, such as phase currents, positions, temperature and loads. A test bench was developed to perform endurance sessions in various loads and working conditions. Specifically, two datasets are provided: (i) measurements used to monitor the EMA degradation through time; (ii) measurements that characterize the EMA closed-loop dynamic behaviour in healthy condition. The data are helpful to develop and test system identification methods and condition monitoring approaches. Keywords: Electro-mechanical actuators, Fault diagnosis, Condition monitoring, Predictive maintenance, Aerospace

Arctic amplification (AA)—the greater warming of the Arctic near-surface temperature relative to its global mean value—is a prominent feature of the climate response to increasing greenhouse gases. Recent work has revealed the importance of ozone-depleting substances (ODS) in contributing to Arctic warming and sea-ice loss. Here, using ensembles of climate model integrations, we expand on that work and directly contrast Arctic warming from ODS to that from carbon dioxide (CO _2 ), over the 1955–2005 period when ODS loading peaked. We find that the Arctic warming and sea-ice loss from ODS are slightly more than half (52%–59%) those from CO _2 . We further show that the strength of AA for ODS is 1.44 times larger than that for CO _2 , and that this mainly stems from more positive Planck, albedo, lapse-rate, and cloud feedbacks. Our results suggest that AA would be considerably stronger than presently observed had the Montreal Protocol not been signed.

Abstract Background A substantial increase in pulmonary and extra-pulmonary diseases due to non-tuberculous mycobacteria (NTM) has been documented worldwide, especially among subjects suffering from chronic respiratory diseases and immunocompromised patients. Many questions remain regarding the epidemiology of pulmonary disease due to NTM (NTM-PD) mainly because reporting of NTM-PD to health authorities is not mandated in several countries, including Italy. This manuscript describes the protocol of the first Italian registry of adult patients with respiratory infections caused by NTM (IRENE). Methods IRENE is an observational, multicenter, prospective, cohort study enrolling consecutive adult patients with either a NTM respiratory isolate or those with NTM-PD. A total of 41 centers, including mainly pulmonary and infectious disease departments, joined the registry so far. Adult patients with all of the following are included in the registry: 1) at least one positive culture for any NTM species from any respiratory sample; 2) at least one positive culture for NTM isolated in the year prior the enrolment and/or prescribed NTM treatment in the year prior the enrolment; 3) given consent to inclusion in the study. No exclusion criteria are applied to the study. Patients are managed according to standard operating procedures implemented in each IRENE clinical center. An online case report form has been developed to collect patients’ demographics, comorbidities, microbiological, laboratory, functional, radiological, clinical, treatment and outcome data at baseline and on an annual basis. An IRENE biobank has also been developed within the network and linked to the clinical data of the registry. Conclusions IRENE has been developed to inform the clinical and scientific community on the current management of adult patients with NTM respiratory infections in Italy and acts as a national network to increase the disease’s awareness. Trial registration Clinicaltrial.gov: NCT03339063.

The unintended climatic implications of aerosol and precursor emission reductions implemented to protect public health are poorly understood. We investigate the precipitation response to regional changes in aerosol emissions using three coupled chemistry–climate models: NOAA Geophysical Fluid Dynamics Laboratory Coupled Model 3 (GFDL-CM3), NCAR Community Earth System Model (CESM1), and NASA Goddard Institute for Space Studies ModelE2 (GISS-E2). Our approach contrasts a long present-day control simulation from each model (up to 400 years with perpetual year 2000 or 2005 emissions) with 14 individual aerosol emissions perturbation simulations (160–240 years each). We perturb emissions of sulfur dioxide and/or carbonaceous aerosol within six world regions and assess the significance of precipitation responses relative to internal variability determined by the control simulation and across the models. Global and regional precipitation mostly increases when we reduce regional aerosol emissions in the models, with the strongest responses occurring for sulfur dioxide emissions reductions from Europe and the United States. Precipitation responses to aerosol emissions reductions are largest in the tropics and project onto the El Niño–Southern Oscillation (ENSO). Regressing precipitation onto an Indo-Pacific zonal sea level pressure gradient index (a proxy for ENSO) indicates that the ENSO component of the precipitation response to regional aerosol removal can be as large as 20 % of the total simulated response. Precipitation increases in the Sahel in response to aerosol reductions in remote regions because an anomalous interhemispheric temperature gradient alters the position of the Intertropical Convergence Zone (ITCZ). This mechanism holds across multiple aerosol reduction simulations and models.

Abstract Background Argininosuccinate synthase (ASS)1 is a urea cycle enzyme that catalyzes the conversion of citrulline and aspartate to argininosuccinate. Mutations in the ASS1 gene cause citrullinemia type I, a rare autosomal recessive disorder characterized by neonatal hyperammonemia, elevated citrulline levels, and early neonatal death. Treatment for this disease is currently restricted to liver transplantation; however, due to limited organ availability, substitute therapies are required. Recently, extracellular vesicles (EVs) have been reported to act as intercellular transporters carrying genetic information responsible for cell reprogramming. In previous studies, we isolated a population of stem cell-like cells known as human liver stem cells (HLSCs) from healthy liver tissue. Moreover, EVs derived from HLSCs were reported to exhibit regenerative effects on the liver parenchyma in models of acute liver injury. The aim of this study was to evaluate whether EVs derived from normal HLSCs restored ASS1 enzymatic activity and urea production in hepatocytes differentiated from HLSCs derived from a patient with type I citrullinemia. Methods HLSCs were isolated from the liver of a patient with type I citrullinemia (ASS1-HLSCs) and characterized by fluorescence-activated cell sorting (FACS), immunofluorescence, and DNA sequencing analysis. Furthermore, their differentiation capabilities in vitro were also assessed. Hepatocytes differentiated from ASS1-HLSCs were evaluated by the production of urea and ASS enzymatic activity. EVs derived from normal HLSCs were purified by differential ultracentrifugation followed by floating density gradient. The EV content was analyzed to identify the presence of ASS1 protein, mRNA, and ASS1 gene. In order to obtain ASS1-depleted EVs, a knockdown of the ASS1 gene in HLSCs was performed followed by EV isolation from these cells. Results Treating ASS1-HLSCs with EVs from HLSCs restored both ASS1 activity and urea production mainly through the transfer of ASS1 enzyme and mRNA. In fact, EVs from ASS1-knockdown HLSCs contained low amounts of ASS1 mRNA and protein, and were unable to restore urea production in hepatocytes differentiated from ASS1-HLSCs. Conclusions Collectively, these results suggest that EVs derived from normal HLSCs may compensate the loss of ASS1 enzyme activity in hepatocytes differentiated from ASS1-HLSCs.

Arctic amplification (AA)—referring to the enhancement of near-surface air temperature change over the Arctic relative to lower latitudes—is a prominent feature of climate change with important impacts on human and natural systems. In this review, we synthesize current understanding of the underlying physical mechanisms that can give rise to AA. These mechanisms include both local feedbacks and changes in poleward energy transport. Temperature and sea ice-related feedbacks are especially important for AA, since they are significantly more positive over the Arctic than at lower latitudes. Changes in energy transport by the atmosphere and ocean can also contribute to AA. These energy transport changes are tightly coupled with local feedbacks, and thus their respective contributions to AA should not be considered in isolation. It is here emphasized that the feedbacks and energy transport changes that give rise to AA are sensitively dependent on the state of the climate system itself. This implies that changes in the climate state will lead to changes in the strength of AA, with implications for past and future climate change.

The fabrication of in vitro neuronal cell networks where cells are chemically or electrically connected to form functional circuits with useful properties is of great interest. Standard cell culture substrates provide ensembles of cells that scarcely reproduce physiological structures since their spatial organization and connectivity cannot be controlled. Supersonic Cluster Beam Deposition (SCBD) has been used as an effective additive method for the large-scale fabrication of interfaces with extracellular matrix-mimicking surface nanotopography and reproducible morphological properties for cell culture. Due to the high collimation of SCBD, it is possible to exploit stencil masks for the fabrication of patterned films and reproduce features as small as tens of micrometers. Here, we present a protocol to fabricate micropatterned cell culture substrates based on the deposition of nanostructured cluster-assembled zirconia films by stencil-assisted SCBD. The effectiveness of this approach is demonstrated by the fabrication of micrometric patterns able to confine primary astrocytes. Calcium waves propagating in the astrocyte networks are shown.