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A substantial increase in broad-spectrum antibiotics as empirical therapy in patients with community-acquired pneumonia (CAP) has occurred over the last 15 years. One of the driving factors leading to that has been some evidence showing an increased incidence of drug-resistant pathogens (DRP) in patients from a community with pneumonia, including methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. Research has been published attempting to identify DRP in CAP through the implementation of probabilistic approaches in clinical practice. However, recent epidemiological data showed that the incidence of DRP in CAP varies significantly according to local ecology, healthcare systems and countries where the studies were performed. Several studies also questioned whether broad-spectrum antibiotic coverage might improve outcomes in CAP, as it is widely documented that broad-spectrum antibiotics overuse is associated with increased costs, length of hospital stay, drug adverse events and resistance. The aim of this review is to analyze the different approaches used to identify DRP in CAP patients as well as the outcomes and adverse events in patients undergoing broad-spectrum antibiotics.

Kaum muda adalah generasi penerus Gereja dan Bangsa. Salah satu bentuk pembinaan kaum muda adalah kegiaatan katekese kaum muda,yang bertujuan membawa kaum muda pada pengenalan akan Yesus Kristus, agar kaum muda mampu menghayati dan mengaktualisasikan imannya dalam kehidupan mengereja maupun dalam kehidupan bermasyarakat. Stasi St. Fransiskus Asisi ini adalah salah satu stasi yang berada di Paroki Santa Maria Asumpta Keuskupan Tanjung Selor, Kalimantan utara. Berdasarkan wawancara secara langsung dan penulis turut terlibat aktif dalam kegiatan kaum muda yang sangat membantu pertumbuhan iman mereka namun dengan perkembangan zaman mengakibatkan perubahan terhadap kaum muda di Stasi St. Fransiskus Asisi, yang mana membawa budaya-budaya baru masuk, yang menyebabkan kaum muda tersebut terjerumus dalam perbuatan-perbuatan yang negatif. Situasi ini kini menjadi perhatian besar bagi orangtua, Pastor Paroki dan masyarakat setempat. Dari hasil uji coba penilaian produk dan bahan katekese yang telah diuji coba menunjukkan mayoritas adalah A, B dan dapat ditarik kesimpulan bahwa bahan yang diujikan baik. Adapun presentase pada nilai A pada setiap tema.

We aim to study the association between state child access prevention (CAP) and overall firearm laws with pediatric firearm-related mortality.The Centers for Disease Control and Prevention Web-based Injury Statistics Query and Reporting System was queried for pediatric (aged18 y) all-intent (accidental, suicide, and homicide) firearm-related crude death rates (CDRs) among the 50 states from 1999 to 2019. States were into three groups: Always CAP (throughout the 20-year period), Never CAP, and New CAP (enacted CAP during study period). We used the Giffords Law Center Annual Gun Law Scorecard (A, B, C, D, F) to group states into strict (A, B) and lenient (C, D, F) firearm laws. A scatter plot was constructed to display state CDR based on CAP laws by year. The top 10 states by CDR per year were tabulated based on CAP law status. Wilcoxon rank-sum was used to compare CDR between strict and lenient scorecard states in 2019.There were 12 Always CAP, 21 Never CAP, and 17 New CAP states from 1999 to 2019. No states changed from CAP laws to no CAP laws. Never CAP and New CAP states dominated the high outliers in CDR compared to Always CAP. The top 10 states with the highest CDR per year were most commonly Never CAP. Strict firearm laws states had lower median CDR in 2019 than lenient states (0.79 [0-1.67] versus 2.59 [1.66-3.53], P = 0.007).Stricter overall gun laws are associated with three-fold lower all-intent pediatric firearm-related deaths. For 2 decades, the 10 states with the highest CDR were almost universally those without CAP laws. Our findings support the RAND Gun Policy in America initiative's claims on the importance of CAP laws in reducing suicide, unintentional deaths, and violent crime among children, but more research is needed.

BackgroundAlthough interest in nontuberculous mycobacteria (NTM) infection has increased in the last decades, published data vary according to different geographical areas, diagnostic facilities and quality of study design. This study aims at assessing both prevalence and incidence of NTM infection and NTM pulmonary disease (NTM-PD) among adults with bronchiectasis, to describe patients’ characteristics, therapeutic options and clinical outcomes.MethodsBronchiectasis adults who had been tested for NTM were enrolled at the Bronchiectasis Program of the Policlinico Hospital in Milan, Italy, from 2016 to 2018.ResultsAmong the 373 patients enrolled, 26.1% had at least one respiratory sample positive for NTM and 12.6% reached a diagnosis of NTM-PD. Incidence rates for NTM infection and NTM-PD were 13 (95% CI 10–16) and 4 (95% CI 2–6) per 100 person-years, respectively. The most prevalent NTM species causing NTM-PD wereM. intracellulare(38.3%),M. avium(34.0%),M. abscessus(8.5%) andM. kansasii(8.5%). Once treatment for NTM-PD was initiated, a favourable outcome was documented in 52.2% of the patients, while a negative outcome was recorded in 32.6%, including recurrence (17.4%), treatment failure (10.9%), re-infection (2.2%) and relapse (2.2%). Treatment halted was experienced in 11 (23.9%) patients.ConclusionsNTM infection is frequent in bronchiectasis patients and the presence of NTM-PD is relevant. The low success rate of NTM-PD treatment in bronchiectasis patients requires a call to action to identify new treatment modalities and new drugs to improve patients’ outcomes.

Background and purpose: Clinical outcomes of multiple sclerosis (MS) patients affected by coronavirus disease 2019 (COVID-19) have been thoroughly investigated, but a further analysis on main signs and symptoms and their risk factors still needs attention. The objective of this study was to group together and describe based on similarity the most common signs and symptoms of COVID-19 in MS patients and identify all factors associated with their manifestation. Method: Logistic and linear regression models were run to recognize factors associated with each pooled group of symptoms and their total number. Results: From March 2020 to November 2021, data were collected from 1354 MS patients with confirmed infection of COVID-19. Ageusia and anosmia was less frequent in older people (odds ratio [OR] 0.98; p=0.005) and more in smoker patients (OR 1.39; p=0.049). Smoke was also associated with an incremental number of symptoms (OR 1.24; p=0.031), substance abuse (drugs or alcohol), conjunctivitis and rash (OR 5.20; p=0.042) and the presence of at least one comorbidity with shortness of breath, tachycardia or chest pain (OR 1.24; p=0.008). Some disease-modifying therapies were associated with greater frequencies of certain COVID-19 symptoms (association between anti-CD20 therapies and increment in the number of concomitant symptoms: OR 1.29; p=0.05). Differences in frequencies between the three waves were found for flu-like symptoms (G1, p=0.024), joint or muscle pain (G2, p=0.013) and ageusia and anosmia (G5, p < 0.001). All cases should be referred to variants up to Delta. Conclusion: Several factors along with the choice of specific therapeutic approaches might have a different impact on the occurrence of some COVID-19 symptoms.

The arrival of COVID-19 meant a drastic change in the way of teaching and research. This paper explores the effect that the measures taken to contain the COVID-19 spreads have had on the research activities of teachers about variables such as area of knowledge, educational level, and role in projects or gender. To this end, an online survey was designed to collect data, requesting information about time lost in research, the number of papers proposed for publication in scientific journals, difficulties in managing research projects, guarantees in project funding or the capacity to reformulate research activities. Two hundred seventy-one teachers and researchers were asked to participate. Among the main results, most respondents agree on the difficulties in managing their projects; they have been forced to reformulate their research, although they claim that the time lost in research has been limited. The results will help to make decisions on the measures to be taken to alleviate the low performance of research by teacher-researchers during this period and to prepare contingency plans to reduce the impact.

In natural ecosystems, brown-rot fungi are major biodegrading agents of standing trees and dead wood. Decay caused by basidiomycetes results in structural instability and therefore negatively affects the quality and quantity of the produced wood. Fungal attack can also trigger defense mechanisms within the tree aimed at delaying or halting the progress of infection. As these defense mechanisms can decrease the value of the wood, their identification and study are of foremost importance. In this work, healthy trees of Eucalyptus grandis W.Hill — a widely commercialized species in Uruguay — were inoculated with Laetiporus sulphureus and Gloeophyllum trabeum. The decay process was characterized in terms of chemical and anatomical changes, and the defense mechanisms elicited by the tree were identified. Three months after inoculation, no symptoms of infection could be detected with the naked eye; however, microscopic analysis revealed anatomical and chemical changes (weakening, delamination, and rupture of vascular and parenchymal cells) and decreased holocellulose and lignin contents. Compartmentalization and the production of kino were used by the tree as defense mechanisms.

Background and purpose Some studies have shown that air pollution, often assessed by thin particulate matter with diameter below 2.5 µg/m3 (PM2.5), may contribute to severe COVID‐19 courses, as well as play a role in the onset and evolution of multiple sclerosis (MS). However, the impact of air pollution on COVID‐19 has never been explored specifically amongst patients with MS (PwMS). This retrospective observational study aims to explore associations between PM2.5 and COVID‐19 severity amongst PwMS. Methods Data were retrieved from an Italian web‐based platform (MuSC‐19) which includes PwMS with COVID‐19. PM2.5 2016–2018 average concentrations were provided by the Copernicus Atmospheric Monitoring Service. Italian patients inserted in the platform from 15 January 2020 to 9 April 2021 with a COVID‐19 positive test were included. Ordered logistic regression models were used to study associations between PM2.5 and COVID‐19 severity. Results In all, 1087 patients, of whom 13% required hospitalization and 2% were admitted to an intensive care unit or died, were included. Based on the multivariate analysis, higher concentrations of PM2.5 increased the risk of worse COVID‐19 course (odds ratio 1.90; p = 0.009). Conclusions Even if several other factors explain the unfavourable course of COVID‐19 in PwMS, the role of air pollutants must be considered and further investigated., Air pollution, often assessed by particulate matter with diameter below 2.5 µg/m3, may contribute to severe COVID‐19 courses. 1087 patients were included, of whom 13% required hospitalization and 2% were admitted to an intensive care unit or died. Even if several other factors explain the unfavourable course of COVID‐19 in patients with multiple sclerosis, the role of air pollutants must be considered and further investigated.

En los últimos años la gastronomía se ha convertido para la sociedad en un atractivo que alude a la identidad de un territorio. La transversalidad de este patrimonio en el hecho turístico brinda posibilidades a cualquier tipo de destino. Esto implica que deban trabajar en la identificación de los atractivos gastronómicos del territorio para poder elaborar propuestas turísticas. Esta identificación habitualmente alude al concepto de cadena de valor. Los objetivos de este artículo son, por un lado, profundizar en el desarrollo conceptual de cadena de valor del turismo gastronómico. Por otro, proponer una metodología de análisis de los elementos de esta cadena de valor a partir de criterios de potencialidad y de funcionalidad turística. El primer resultado de la investigación se refleja en la definición, la identificación y la categorización de los elementos que conforman la estructura de la cadena de valor según los criterios mencionados. El segundo resultado de la investigación es la aportación de una propuesta metodológica que sirva para el análisis de dichos elementos. Su aplicación en el análisis de cualquier propuesta turística gastronómica contribuye a un mejor conocimiento sobre las relaciones entre elementos que configuran estas experiencias y su vinculación con los valores territoriales. In recent years, gastronomic tourism is a tourism product that has experienced a remarkable growth in tourism destinations of diverse nature. This is due to the fact that gastronomy has become an element of territorial identity that is highly valued by the demand in the development of tourism experiences that pursue knowledge of others through tourism. In addition, the transversality of gastronomy in tourism gives differentiation possibilities for any type of destination. For this reason, the consideration of gastronomy as a tourism resource implies that tourism destinations should identify the gastronomic attractions in the territory with the aim of propose tourism activities based on gastronomy. This identification usually refers to the concept of the value chain. Thus, the main objective of this article is to propose a methodology for analysing the elements of that value chain, going deeper into the concept itself, as well as into those of tourism potential and functionality, which are considered key aspects in the definition of the structure of the elements as a part of this chain. The methodological proposal can be used to analyze the structure of gastronomic tourism experiences and to identify the elements of the chain and the way they interrelate in the territory for the development of these experiences.

Developing mathematical competencies in future teachers requires particular attention to both cognitive and affective aspects. A positive attitude towards mathematics increases enjoyment, motivation, and confidence when working with the subject. It also reduces the anxiety of facing activities and problems and gives greater value to the academic and professional usefulness of mastering mathematical knowledge. These attitudes will also be reflected in their future teaching practice. For this reason, it is of great interest to study the attitudes of this critical group since, despite the numerous investigations carried out in this field, the influence of variables, such as place of origin or gender, on the attitudes and, in particular, on the attitudinal factor that best explains them, anxiety towards mathematics, has not yet been clarified. This work has analyzed the attitude and anxiety of 235 future teachers who study in rural and urban environments. The results show that gender is a differentiating factor in anxiety, with similar results in the schools of the two environments. However, the differences between men and women are more pronounced in the rural environment.

The Deliverable 6.1 of the MobiSpaces project “Use Cases Co-Creation & Design Activities v1” aims to deliver the co-creation activities and design for the different Use Case (UC) scenarios. This deliverable aims to provide an overview of co-creation and design activities for different UC scenarios and to analyse the requirements of the UCs involved to define the necessary implementation actions. The first part of the document describes the theoretical approach of co-creation and the role of User Interface (UI)/User Experience (UX) design, suggesting both the methodology and related guidelines to be applied according to the context, i.e., that of co-design, and associated tools, i.e., sketches, wireframes, and mock-ups. The document then proceeds to illustrate a description of each of the five UCs: from the goals and objectives and the relative scenarios to the dataset description, including the information concerning the current infrastructure. Furthermore, a timeline for the co-creation processes is given. Overall, this deliverable highlights the key points of the guidelines to make the application of the co-creation process constructive to the project UCs and related scenarios to maximise cooperation and smooth integration between the partners.

The organic nature of wood makes it susceptible to abiotic and biotic degradation. Impregnation with chemical products is the most common method of protection. Only inorganic borates combine the unique set of properties that make them well suited for wood protection: they are insecticidal, fungicidal and flame retardants. In this work, zinc borate is suspended in an ammonia solution and applied in depth to wood. Its resistance to leaching is evaluated. The product is tested against rot fungi (Gloeophyllum trabeum and Trametes versicolor) and a xylophagous insect (Anobium punctatum). The results verify its effectiveness as a wood protector, while leaching less than other borate-based products.

Applied nucleation (AN) is a nature-based solution alternative to traditional regular plantations. It is a cost-effective technique that integrates artificial seedlings and natural regeneration dynamics to enhance forest recovery, mimicking successional processes. Given the current shift of disturbance regimes caused by global change, this technique will likely be a valuable active restoration approach for many forest ecosystems affected by extreme disturbance events. Indeed, AN is suitable for ecological restoration after stand-replacing events, improving seed availability and microsite conditions supporting natural regeneration. AN has been mostly applied in tropical forests, but its use in Mediterranean forests should be increasingly considered since a higher occurrence of large and severe fires has been observed over the last decades and further increases are expected in the future. These changes are raising concerns about regeneration recruitment, particularly for obligate seeders in mountain ecosystems. In these ecosystems, it is crucial to reconsider current post-fire policies to identify strategies that promote and maintain the ecosystem services of degraded forests, particularly when natural regeneration is ineffective. The main aim of this study was to define the best methodology for implementing AN in a mountain area affected by a large stand-replacing fire that occurred in 2005 in the Aosta Valley Region (North-Western Italy). After the fire salvage logging was performed, increasing ecosystem degradation, and, 16 years later, natural regeneration is still scarce and struggling to settle. Hotspots for AN were identified based on post-fire natural regeneration response to a series of site characteristics, such as topography, fire severity, and distance from seed trees. We assessed the drivers of post-fire regeneration through a machine learning correlative model (Bayesian Regression Tree, BART). The probability of regeneration presence across the landscape was then predicted under the current situation and a set of AN scenarios. Starting from the current scenario, we reclassified the prediction raster into three levels, according to the probability of presence and uncertainty. Polygons with low uncertainty and probability (< 0.3) were included in level one and considered hotspots for AN. From these predictions, it was possible to assess the most efficient active management scenario to speed up the regeneration process. Our results showed that AN could be a promising post-fire management technique for promoting natural regeneration while limiting anthropic interventions and their related economic and ecological costs.

Background The Mediterranean basin is currently facing major changes in fire regimes as a result of climate and land-use changes. These alterations could affect the ability of forests to recover after a fire, hence triggering degradation processes and modifying the provision of fundamental ecosystem services. Examining patterns and drivers of post-fire forest recovery, particularly for obligate seeders without specific fire-adaptive traits, thus becomes a priority for researchers and land managers. We studied the post-fire dynamics of Scots pine (Pinus sylvestris L.) stands affected by a mixed-severity fire in North-Western Italy, aiming to understand the impact of fire on soil properties and assess drivers, spatial distribution, and characteristics of short-term post-fire recovery. Results We observed that fire did not significantly affect soil organic carbon (OC) content, while we detected significantly lower nitrogen (N) content in severely burnt sites. Regeneration density was particularly abundant in medium-severity areas, while it drastically decreased in high-severity patches. The most abundant tree species in the regeneration layer was Scots pine, followed by goat willow (Salix caprea L.), European aspen (Populus tremula L.), and, to a lesser extent, European larch (Larix decidua Mill.). Slope, fire severity, and distance from seed trees emerged as the most important drivers of post-fire forest regeneration patterns. Conclusions Our results highlight the importance of preserving seed trees from salvage logging, even if they are damaged and have a low survival probability. Active post-fire management, such as tree planting, should be limited to large and severely burnt patches, where natural forest regeneration struggles to settle, increasing the risk of ecosystem degradation. These findings could be useful for informing land managers, helping them to enhance potential mitigation strategies in similar ecosystems and plan appropriate restoration approaches.

Background and Aims The efficacy of current biologics may be limited by targeting only one pathway. Pentoxifylline [PTX] interferes with tumour necrosis factor [TNF] gene expression. We performed a randomised, placebo-controlled pilot study to determine if PTX plus vedolizumab [VDZ] in patients with Crohn’s disease [CD] is safe and improves response compared with VDZ monotherapy. Methods Thirty adult patients with active CD were randomised to VDZ/PTX or VDZ/placebo and followed for 24 weeks. Endoscopic activity and inflammatory cytokines were measured at baseline and Week 24. Descriptive statistics were used to determine estimates of effect. Results Demographics were similar but baseline disease activity was higher in the VDZ/PTX group. There was no difference in clinical remission at Week 14 (60.0% vs 66.67%, odds ratio [OR] 0.76, 95% confidence interval [CI] 0.16, 3.51) or steroid-free clinical remission at Week 24 in patients receiving VDZ/PTX. Improved clinical response was noted in the VDZ/PTX group at Weeks 6, 14, and 24 [Week 6: 20% vs 6.67%, Week 14: 26.67% vs 6.67%, Week 24: 40% vs 20%]. The rate of endoscopic remission was similar between the groups [40% vs 33.33%], with a greater mean decrease in Simple Endoscopic Score-CD [SES-CD] and C-reactive protein [CRP] with VDZ/PTX [SES-CD -3.17 vs -0.15, CRP -5.56 vs 0.46]. An increase in serum TNF-α concentration was observed with VDZ/placebo group; PTX mitigated this effect. No serious adverse events occurred. Conclusions VDZ/PTX did not provide benefit over VDZ monotherapy in clinical or endoscopic remission but appeared to improve clinical response and was safe. These data should inform a fully powered study.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in wastewater has been used to track community infections of coronavirus disease-2019 (COVID-19), providing critical information for public health interventions. Since levels in wastewater are dependent upon human inputs, we hypothesize that tracking infections can be improved by normalizing wastewater concentrations against indicators of human waste [Pepper Mild Mottle Virus (PMMoV), β-2 Microglobulin (B2M), and fecal coliform]. In this study, we analyzed SARS-CoV-2 and indicators of human waste in wastewater from two sewersheds of different scales: a University campus and a wastewater treatment plant. Wastewater data were combined with complementary COVID-19 case tracking to evaluate the efficiency of wastewater surveillance for forecasting new COVID-19 cases and, for the larger scale, hospitalizations. Results show that the normalization of SARS-CoV-2 levels by PMMoV and B2M resulted in improved correlations with COVID-19 cases for campus data using volcano second generation (V2G)-qPCR chemistry (

En los últimos años la igualdad efectiva entre hombres y mujeres se ha convertido en un objetivo del que toda la sociedad debe ser partícipe y eso incluye a la comunidad educativa. En este sentido, resulta relevante conocer si la formación de maestros se aborda o no desde la perspectiva de género. El objetivo de este trabajo es analizar desde esta perspectiva los planes de formación en matemáticas y educación matemática de los futuros maestros en Educación Infantil de las universidades andaluzas. Para ello se ha realizado una investigación exploratoria, basada en el análisis de contenido de los planes de igualdad de las universidades andaluzas y de las guías docentes de distintas asignaturas de matemáticas y educación matemática, utilizando entre otros el software ATLAS.ti. Los resultados muestran que, si bien se aprecia una preocupación por el profesorado por el uso de lenguaje inclusivo, no se identifica un criterio único a la hora de implementarlo. Con respecto al uso del masculino genérico, su uso es mayor en las guías de las asignaturas donde la totalidad del profesorado es femenino. Por otro lado, en la mayoría de las guías analizadas no se hallaron competencias ni contenidos centrados en la perspectiva de género.

Cirrhosis is a major cause of death and is associated with extensive health care use. Patients with cirrhosis have complex treatment choices due to risks of morbidity and mortality. To optimally counsel and treat patients with cirrhosis requires tools to predict their longer-term liver-related survival. We sought to develop and validate a risk score to predict longer-term survival of patients with cirrhosis.We conducted a retrospective cohort study of adults with cirrhosis with no major life-limiting comorbidities. Adults with cirrhosis within the Veterans Health Administration were used for model training and internal validation, and external validation used the OneFlorida Clinical Research Consortium. We used four model-building approaches including variables predictive of cirrhosis-related mortality, focused on discrimination at key time points (1, 3, 5, and 10 years). Among 30,263 patients with cirrhosis ≤75 years old without major life-limiting comorbidities and complete laboratory data during the baseline period, the boosted survival tree models had the highest discrimination, with 1-year, 3-year, 5-year, and 10-year survival rates of 0.77, 0.81, 0.84, and 0.88, respectively. The 1-year, 3-year, and 5-year discrimination was nearly identical in external validation. Secondary analyses with imputation of missing data and subgroups by etiology of liver disease had similar results to the primary model.We developed and validated (internally and externally) a risk score to predict longer-term survival of patients with cirrhosis. This score would transform management of patients with cirrhosis in terms of referral to specialty care and treatment decision-making for non-liver-related care.

The construction of concrete structures for radiological protection in sanitaryfacilities requires a series of constructive conditions that guarantee safety. Theinfluence of the correct bunkers design, wall thicknesses and the type of mate-rials used is essential to ensure effective protection. The use of barite aggregateconcrete is a common resource to improve the radiation attenuation capacityof concrete walls. The present study analyses the structure of a bunker duringa renovation work, studying the construction characteristics of the chamber,the state of its elements, the characterization of materials, the identification ofthe emissions of the possible isotopes present, beta radioactive contaminationand the measurement of equivalent dose rates at different points in the con-crete. The results made it possible to determine the use of conventional con-crete and barite concrete, the latter presenting a BaO content of around 40%and particularly low resistance values, not observing alteration processes inthe materials

Old mathematics books and textbooks have always been sources of relevant information for researchers working on the history of mathematics and mathematics education. However, helpful information about this field can also be found in journals, ministerial decrees, or notes. Consequently, this article analyzes the contents related to mathematics or mathematics education in an 18th-century weekly journal published in the Spanish city of Salamanca, Semanario de Salamanca. To this end, we conducted a qualitative and descriptive investigation using a content analysis technique, which is widely used in research in this related area. Our results show that despite the fact that the weekly publication under investigation was specialized neither in mathematics nor in science, it included mathematical problems and solutions, mathematical texts, job advertisements for mathematics teachers, mathematics book reviews, and opinions about mathematics. Therefore, the present work expands knowledge of the presence and dissemination of mathematics and mathematics education in 18th-century Spanish society.

This is an abstract accepted by theXI Annual Meeting of the Italian Chapter of the European Society of Biomechanics (ESB-ITA) which was held in Massa (Italy) on the 6thand 7thof October 2022.

Striatal projection neurons (SPNs), which progressively degenerate in human patients with Huntington’s disease (HD), are classified along two axes: the canonical direct-indirect pathway division and the striosome-matrix compartmentation. It is well established that the indirect-pathway SPNs are susceptible to neurodegeneration and transcriptomic disturbances, but less is known about how the striosome-matrix axis is compromised in HD in relation to the canonical axis. Here we show, using single-nucleus RNA-sequencing data from male Grade 1 HD patient post-mortem brain samples and male zQ175 and R6/2 mouse models, that the two axes are multiplexed and differentially compromised in HD. In human HD, striosomal indirect-pathway SPNs are the most depleted SPN population. In mouse HD models, the transcriptomic distinctiveness of striosome-matrix SPNs is diminished more than that of direct-indirect pathway SPNs. Furthermore, the loss of striosome-matrix distinction is more prominent within indirect-pathway SPNs. These results open the possibility that the canonical direct-indirect pathway and striosome-matrix compartments are differentially compromised in late and early stages of disease progression, respectively, differentially contributing to the symptoms, thus calling for distinct therapeutic strategies.

Wildfires play the role of ecosystem shapers in the majority of terrestrial biomes. Nowadays, their regimes are changing as a consequence of land abandonment and climate change. After-fire dynamics are widely studied in North America and Mediterranean environments. However, soils developed in different biomes might not unequivocally respond to fire-induced heating, and forests of the Western Italian Alps are not unfamiliar to fire occurrence.For these reasons, we conducted several experiments (at plot and lab scale) at environmentally realistic conditions to systematically assess the impacts of fire on the physico-chemical properties of soils belonging to the Italian Alpine ecological region.A homogenous pine forest (Pinus sylvestris L.) located in a mountain region near Torino experienced the passage of a severe and large wildfire in fall 2017. The field survey carried out in 2020 revealed that lower organic carbon (OC) contents and higher bulk density (BD) values were associated to a greater fire severity. Abundance of pyrogenic carbon was related to the steepness degree, as a consequence of erosion. In the superficial horizons, the naturally high WR expected from soils developed under a conifer stand was not present.To elucidate mechanisms regulating WR occurrence and evolution, the thermal transformations borne by Alpine soils were investigated at controlled laboratory conditions. Topsoil samples displayed extremely different wettable behaviors upon increasing temperatures (Ts), with or without WR build-up. This occurred mainly in relation to content and composition of organic matter (OM), particle size distribution and abundance of iron (Fe) oxides. Notwithstanding the initial sample hydrophobicity, WR was dramatically lost above 200 °C due to increasing pH values, inducing OM de-sorption from the negatively charged mineral surfaces.In the same T range, the thermal transformation of soil Fe oxides were found to be primarily directed towards oxidative processes (hematite formation). Ts up to 300 °C could have potentially promoted the stabilization of the remaining (non-combusted) OM, with the synthesis of defect-rich Fe oxides and enrichment in condensed and aromatic compounds, and yet OM was highly dispersible at the high pH values resulting from the thermal treatment, such that OC might be weakly retained on mineral phases in an after-fire scenario.

Microbiological surveillance of endoscopes is a safety measure for verifying the quality of reprocessing procedures and identifying contaminated devices, but duodenoscope-related outbreaks are still reported.To assess the effectiveness of duodenoscope reprocessing procedures in Italy.Between December 2019 and April 2020, data obtained from microbiological surveillance post-reprocessing in 15 Italian endoscopy units were collected. Sampling was carried out after reprocessing or during storage in a cabinet. In keeping with international guidelines and the Italian position paper, the micro-organisms were classified as high-concern organisms (HCOs) and low-concern organisms (LCOs).In total, 144 samples were collected from 51 duodenoscopes. Of these, 36.81% were contaminated: 22.92% were contaminated with HCOs and 13.89% were contaminated with LCOs [2.08% with an LCO load of 11-100 colony-forming units (CFU)/device and 0.69% with an LCO load of100 CFU/device]. The contamination rate was 27.5% in samples collected after reprocessing, 40% in samples collected during storage in a cabinet that was compliant with EN 16442:2015 (C-I), and 100% in samples collected during storage in a cabinet that was not compliant with EN 16442:2015 (NC-I). The respective HCO rates were 15.00%, 27.27% and 66.67%. Correlation between LCO contamination and storage time was demonstrated (Spearman's rho=0.3701; P=0.0026). The Olympus duodenoscope TJFQ180V demonstrated the lowest rate of contamination (29.82%), although the contamination rate was 100% for duodenoscopes stored in an NC-I cabinet.Microbiological surveillance, along with strict adherence to reprocessing protocols, may help to detect endoscope contamination at an early stage, and reduce the risk of duodenoscope-associated infections.

Developing mathematical competencies in future teachers requires particular attention to both cognitive and affective aspects. A positive attitude towards mathematics increases enjoyment, motivation, and confidence when working with the subject. It also reduces the anxiety of facing activities and problems and gives greater value to the academic and professional usefulness of mastering mathematical knowledge. These attitudes will also be reflected in their future teaching practice. For this reason, it is of great interest to study the attitudes of this critical group since, despite the numerous investigations carried out in this field, the influence of variables, such as place of origin or gender, on the attitudes and, in particular, on the attitudinal factor that best explains them, anxiety towards mathematics, has not yet been clarified. This work has analyzed the attitude and anxiety of 235 future teachers who study in rural and urban environments. The results show that gender is a differentiating factor in anxiety, with similar results in the schools of the two environments. However, the differences between men and women are more pronounced in the rural environment.

BackgroundThe reported prevalence of immunodeficiencies in bronchiectasis patients is variable depending on the frequency and extent of immunological tests performed. European Respiratory Society guidelines recommend a minimum bundle of tests. Broadening the spectrum of immunological tests could increase the number of patients diagnosed with an immunodeficiency and those who could receive specific therapy. The primary objective of the present study was to assess the performance of different sets of immunological tests in diagnosing any, primary, secondary or treatable immunodeficiencies in adults with bronchiectasis.MethodsAn observational, cross-sectional study was conducted at the Bronchiectasis Program of the Policlinico University Hospital in Milan, Italy, from September 2016 to June 2019. Adult outpatients with a clinical and radiological diagnosis of bronchiectasis underwent the same immunological screening during the first visit when clinically stable consisting of: complete blood count; immunoglobulin (Ig) subclass tests for IgA, IgG, IgM and IgG; total IgE; lymphocyte subsets; and HIV antibodies. The primary endpoint was the prevalence of patients with any immunodeficiencies using five different sets of immunological tests.ResultsA total of 401 bronchiectasis patients underwent the immunological screening. A significantly different prevalence of bronchiectasis patients diagnosed with any, primary or secondary immunodeficiencies was found across different bundles. 44.6% of bronchiectasis patients had a diagnosis of immunodeficiency when IgG subclasses and lymphocyte subsets were added to the minimum bundle suggested by the guidelines.ConclusionA four-fold increase in the diagnosis of immunodeficiencies can be found in adults with bronchiectasis when IgG subclasses and lymphocyte subsets are added to the bundle of tests recommended by guidelines.

Background Allosensitization has been reported after discontinuation of immunosuppression following graft failure in islet transplantation (ITx) recipients, though duration of its persistence is unknown. Methods We evaluated 35 patients with type 1 diabetes who received ITx, including 17 who developed graft failure (ITx alone, n=13; ITx plus bone marrow-derived hematopoietic stem cells, n=4) and 18 with persistent graft function. Panel reactive antibody (PRA) was measured yearly for the duration of graft function within 1 year after graft failure at enrollment and yearly thereafter. Results In ITx alone graft failure patients, 61% (8/13) were PRA-positive at 6 years postgraft failure, and 46% (6/13) developed donor-specific anti-HLA antibodies (DSA to 2 ± 1 donors) during follow up. The degree of sensitization was variable (cPRA ranging between 22% and 100% after graft failure). Allosensitization persisted for 7 to 15 years. Three subjects (3/13) were not allosensitized. In ITx plus bone marrow-derived hematopoietic stem cell recipients, cPRA-positivity (88% to 98%) and DSA-positivity persisted for 15 years in 75% (3/4) of subjects. Conclusions Allosensitization was minimal while subjects remained on immunosuppression but after discontinuation of immunosuppressive therapy the majority of subjects (77%) became allosensitized with persistence of PRA positivity for up to 15 years. Persistence of allosensitization in this patient population is of clinical importance as it may result in longer transplant waiting-list times for identification of a suitable donor in case of requiring a subsequent transplant.

The constantly increasing incidence of coronary artery disease worldwide makes necessary to set advanced therapies and tools such as tissue engineered vessel grafts (TEVGs) to surpass the autologous grafts [(i.e., mammary and internal thoracic arteries, saphenous vein (SV)] currently employed in coronary artery and vascular surgery. To this aim, in vitro cellularization of artificial tubular scaffolds still holds a good potential to overcome the unresolved problem of vessel conduits availability and the issues resulting from thrombosis, intima hyperplasia and matrix remodeling, occurring in autologous grafts especially with small caliber (in vivo biocompatibility. In the present work, we propose a method to optimize coverage of the luminal surface of silk electrospun tubular scaffold with endothelial cells. Our strategy is based on seeding endothelial cells (ECs) on the luminal surface of the scaffolds using a low-speed rolling. We show that this procedure allows the formation of a nearly complete EC monolayer suitable for flow-dependent studies and vascular maturation, as a step toward derivation of complete vascular constructs for transplantation and disease modeling.

ObjectiveOur knowledge on the long-term consequences of COVID-19 is still scarce despite the clinical relevance of persisting syndrome. The aim of this study was to analyze patient-reported outcomes, including assessment by specific questionnaires of health impairment and symptoms.MethodsThis is a prospective, observational and multicenter cohort study coordinated by Fondazione IRCSS Ca' Granda Ospedale Maggiore Policlinico di Milano and Istituto di Ricerche Farmacologiche Mario Negri IRCCS including eight hospitals located in North and Central Italy. A telephone interview to assess rehospitalization, access to health care resources, general health status subjective evaluation, and symptoms was performed at 12 months after the discharge in patients admitted to hospital because of COVID-19 from February 2020 to the end of May 2020.ResultsAmong the 776 patients discharged alive, 44 (5.7%) died, 456 subjects (58.8%) completed the questionnaire and 276 (35.6%) were not reachable or refused to join the telephone interview. The mean age of the study population was 59.4 years (SD 14.1), 69.8% of individuals needed oxygen support during hospitalization and 10.4% were admitted to ICU. Overall, 91.7% of participants reported at least one symptom/sequela at 12 months. Exertional dyspnea (71.7%), fatigue (54.6%), and gastrointestinal symptoms (32.8%) were the most reported ones. Health issues after discharge including hospitalization or access to emergency room were described by 19.4% of subjects. Female and presence of comorbidities were independent predictors of whealth impairment and presence of ≥2 symptoms/sequelae after 12 months from hospitalization for COVID-19.ConclusionsPatient-reported symptoms and sequelae, principally dyspnea and fatigue, are found in most individuals even 12 months from COVID-19 hospitalization. Long-term follow-up based on patient-centered outcome can contribute to plan tailored interventions.

Bone tissue features a complex microarchitecture and biomolecular composition, which determine biomechanical properties. In addition to state-of-the-art technologies, innovative optical approaches allowing the characterization of the bone in native, label-free conditions can provide new, multi-level insight into this inherently challenging tissue. Here, we exploited multimodal nonlinear optical (NLO) microscopy, including co-registered stimulated Raman scattering, two-photon excited fluorescence, and second-harmonic generation, to image entire vertebrae of murine spine sections. The quantitative nature of these nonlinear interactions allowed us to extract accurate biochemical, morphological, and topological information on the bone tissue and to highlight differences between normal and pathologic samples. Indeed, in a murine model showing bone loss, we observed increased collagen and lipid content as compared to the wild type, along with a decreased craniocaudal alignment of bone collagen fibres. We propose that NLO microscopy can be implemented in standard histopathological analysis of bone in preclinical studies, with the ambitious future perspective to introduce this technique in the clinical practice for the analysis of larger tissue sections.

We examined effects of exposing female and male mice for 33 weeks to 45% or 60% high fat diet (HFD). Males fed with either diet were more vulnerable than females, displaying higher and faster increase in body weight and more elevated cholesterol and liver enzymes levels. Higher glucose metabolism was revealed by PET in the olfactory bulbs of both sexes. However, males also displayed altered anterior cortex and cerebellum metabolism, accompanied by a more prominent brain inflammation relative to females. Although both sexes displayed reduced transcripts of neuronal and synaptic genes in anterior cortex, only males had decreased protein levels of AMPA and NMDA receptors. Oppositely, to anterior cortex, cerebellum of HFD-exposed mice displayed hypometabolism and transcriptional up-regulation of neuronal and synaptic genes. These results indicate that male brain is more susceptible to metabolic changes induced by HFD and that the anterior cortex versus cerebellum display inverse susceptibility to HFD.

Introduction Mutations of the skeletal muscle sodium channel gene SCN4A are associated with several neuromuscular disorders including hyper/hypokaliemic periodic paralysis, paramyotonia congenita and sodium channel myotonia. These disorders are distinguished from dystrophic myotonias by the absence of progressive weakness and extramuscular systemic involvement. Methods We present an Italian family with 2 subjects carrying a p.Asn1180Ile mutation in SCN4A gene showing a peculiar clinical picture characterized by the association of myopathic features and myotonia. Results The clinical, electromyographic and histological findings of these patients are reported. The possible pathogenicity of the mutation was tested by three different software, all giving positive results. Discussion This is the first report of a dominant, heterozygous mutation in SCN4A causing a complex phenotype of non-congenital myopathy and myotonic syndrome. We suggest that, in patients with myotonia and myopathy not related to dystrophic myotonias, the sequence analysis of SCN4A gene should be performed.

The aim of this work was to determine which parameters are sufficient to measure in order to describe the water quality of a pit lake and to identify patterns in the data among different kind of pit lakes. The data consisted of ambient dose equivalent rate, elemental and radionuclide concentration, pH, and specific conductance in surface water and sediment samples collected from different types of mines. Data were tested for normality and log-normality and used in principal component analysis (PCA) and hierarchical cluster analysis (HCA). The normality tests indicated that only 40K was normally distributed, while only the 234,238U isotopes were log-normally distributed. HCA performed on parameters measured in surface water provided clusters that in most cases separated the elements according to their chemical groups. However, when HCA was performed on pit lakes, the clustering seemed to indicate that surface water might not be the preferred sample to differentiate between different types of pit lakes. PCA of surface water data resulted in three components that explained 72% of the variance when pH, SC, concentration of the elements Mg, K, Ca, Cu, Zn, Sr, Pb, activity concentration of 234,238U and 210Po, and ambient dose equivalent rate were included. For surface sediment data, the PCA resulted in three components explaining 83% of the variance when the concentration of Na, Mg, Al, P, K, Ca, Rb, Sr, Y, Tl, activity concentration of 234Th, 226Ra, 210Pb, 232Th (series average), and 40K, and ambient dose equivalent rate were included.

This open-label phase II clinical trial evaluated the antitumor activity and safety of trabectedin in patients with advanced ovarian (OC) or uterine carcinosarcomas (UC).Eligible patients were adults (≥18 years) with histologically proven recurrent OC/UC not amenable to surgery or radiotherapy who received up to two prior chemotherapy lines. Trabectedin 1.3 mg/mForty-five patients with either OC (n = 32) or UC (n = 13) from seven MITO centers across Italy were enrolled. The ORR was 11.9% (90% CI: 6-23) and included two patients with a complete response and three with a partial response. Eight patients (19.0%) had disease stabilization for a disease control rate of 31.0% (90% CI: 20-44). Median progression-free survival was 2.01 months (95% CI: 1.78-2.30) and median overall survival was 4.64 months (95% CI: 3.19-8.29). Neutrophil count decreases (n = 8, 18.2%) and transaminase increases (n = 6, 13.6%) were the most common grade 3-5 adverse events related with trabectedin. Two patients died due to trabectedin-related grade 5 hematological toxicity.Although trabectedin did not meet the prespecified activity criteria, it confers modest but clinically meaningful benefit to patients with advanced OC/UC as being as effective as any other available treatment for this indication. The toxicity profile appears in line with that previously reported for the drug.

Objective: This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS). Methods: We retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results. Results: Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18–4.74, p = 0.015) with increased risk of severe COVID-19. Recent use (

We establish lower bounds for the Betti numbers of the conormal module for licci ideals in a regular local ring. In particular, for a licci Gorenstein ideal I, the i-th Betti number of I/I $$I/I^{2}$$ is at least $$5f_{2i-1}$$ , for $$i\ge 1$$ , where $$f_{n}$$ is the n-th Fibonacci number.

Patients are prioritized for liver transplantation (LT) under an "urgency-based" system using the Model for End-Stage Liver Disease score. This system focuses solely on waitlist mortality, without considerations of posttransplant morbidity, mortality, and health care use. We sought to develop and internally validate a continuous posttransplant risk score during 5-year and 10-year time horizons. This retrospective cohort study used national registry data of adult deceased donor LT (DDLT) recipients with ≥90 days of pretransplant waiting time from February 27, 2002 to December 31, 2018. We fit Cox regression models at 5 and 10 years to estimate beta coefficients for a risk score using manual variable selection and calculated the absolute predicted survival time. Among 21,103 adult DDLT recipients, 11 variables were selected for the final model. The area under the curves at 5 and 10 years were 0.63 (95% confidence interval [CI], 0.60-0.66) and 0.67 (95% CI, 0.64-0.70), respectively. The group with the highest ("best") scores had 5-year and 10-year survivals of 89.4% and 85.4%, respectively, compared with 45.9% and 22.2% for those with the lowest ("worst") scores. Our score was significantly better at predicting long-term survival compared with the existing scores. We developed and validated a risk score using nearly 17 years of data to prioritize patients with end-stage liver disease based on projected posttransplant survival. This score can serve as the building block by which the transplant field can change the entire approach to prioritizing patients to an approach that is based on considerations of maximizing benefits (ie, survival benefit-based allocation) rather than simply waitlist mortality.

Background & Aims Liver transplant priority in the US and Europe follows the ‘sickest-first’ principle. However, for patients with hepatocellular carcinoma (HCC), priority is based on binary tumor criteria to expedite transplant for patients with ‘acceptable’ post-transplant outcomes. Newer risk scores developed to overcome limitations of these binary criteria are insufficient to be used for waitlist priority as they focus solely on HCC-related pre-transplant variables. We sought to develop a risk score to predict post-transplant survival for patients using HCC- and non-HCC-related variables. Methods We performed a retrospective cohort study using national registry data on adult deceased-donor liver transplant (DDLT) recipients with HCC from 2/27/02-12/31/18. We fit Cox regression models focused on 5- and 10-year survival to estimate beta coefficients for a risk score using manual variable selection. We then calculated absolute predicted survival time and compared it to available risk scores. Results Among 6,502 adult DDLT recipients with HCC, 11 variables were selected in the final model. The AUCs at 5- and 10-years were: 0.62, 95% CI 0.57–0.67 and 0.65, 95% CI 0.58–0.72, which was not statistically significantly different to the Metroticket and HALT-HCC scores. The LiTES-HCC score was able to discriminate patients based on post-transplant survival among those meeting Milan and UCSF criteria. Conclusion We developed and validated a risk score to predict post-transplant survival for patients with HCC. By including HCC- and non-HCC-related variables (e.g., age, chronic kidney disease), this score could allow transplant professionals to prioritize patients with HCC in terms of predicted survival. In the future, this score could be integrated into survival benefit-based models to lead to meaningful improvements in life-years at the population level. Lay summary We created a risk score to predict how long patients with liver cancer will live if they get a liver transplant. In the future, this could be used to decide which waitlisted patients should get the next transplant.

The fifties were important in Spain for the creation of a modern architecture. The architects, who began working in previous years, created his artistic languages inspired in modern styles. Miguel Fisac was one of the most popular Spanish architects in the second half of the twentieth century. In 1954 he received a request from the Dominican Order to design a theological centre for the youngest members. In view of the particular circumstances surrounding this case, the architect had many preparatory documents (sketches, memories, plans ...) and currently housed in the Miguel Fisac’s documentary archives and Foundation. Everything was done following Fisac’s drawings. In February 1958, Fisac carried out some furniture projects for the building while directing its construction. He wrote some documents where he explicitly detailed the place of each piece of furniture in each space.