Search

Aims: Multiple sclerosis (MS) is a chronic neurological disease that currently lacks effective curative treatments. There is a need to find effective therapies, especially to reverse the progressive demyelination and neuronal damage. Oligodendrocytes form the myelin sheath around axons in the central nervous system (CNS) and oligodendrocyte precursor cells (OPCs) undergo mechanisms that enable spontaneously the partial repair of damaged lesions. The aim of this study was to discover small molecules with potential effects in demyelinating diseases, including (re)myelinating properties. Methods: Recently, it has been shown how LRRK2 inhibition promotes oligodendrogliogenesis and therefore an efficient repair or myelin damaged lesions. Here we explored small molecules inhibiting LRRK2 as potential enhancers of primary OPCs proliferation and differentiation, and their potential impact on the clinical score of experimental autoimmune encephalomyelitys (EAE) mice, a validated model of the most frequent clinical form of MS, relapsing–remitting MS. Results: One of the LRRK2 inhibitors presented in this study promoted the proliferation and differentiation of OPC primary cultures. When tested in the EAE murine model of MS, it exerted a statistically significant reduction of the clinical burden of the animals, and histological evidence revealed how the treated animals presented a reduced lesion area in the spinal cord. Conclusions: For the first time, a small molecule with LRRK2 inhibition properties presented (re)myelinating properties in primary OPCs cultures and potentially in the in vivo murine model. This study provides an in vivo proof of concept for a LRRK2 inhibitor, confirming its potential for the treatment of MS. [ABSTRACT FROM AUTHOR]

This article brings as its theme the literacy proposals of the Bolsonaro government present in the current National Literacy Plan (PNA) in dialogue with academic theorizations of the last decades and other documents that parameterize Education. We sought to answer the following question: Do the current literacy proposals of the Bolsonaro government represent innovations in the educational field or setbacks to old and outdated discussions? To this end, a qualitative study with a documentary approach was developed. The theoretical contribution permeates literacy studies, as well as contributions from education scholars about literacy. The results point to significant setbacks, such as, for example, the defense of the only "savior" literacy method; little consideration of the intersubjective dimension of reading and the social side of learning to write; and the erasure of academic theories about literacy. [ABSTRACT FROM AUTHOR]

The objective of this work was to assess the possibility of dyeing a substrate composed of non-textile industrial hemp using natural dyes from common madder (Rubia Tinctorum L.) and calendula (Calendula Officialis) and tannin and alum as mordants. The substrate used for the dyeing had a 25/75 hemp/cotton composition. The hemp raw material is an agricultural by-product that was subjected to mechanical and chemical treatments in order to cottonize the fibers, blend them with cotton, and thus obtain first 40-tex open-end yarns and then a knitted fabric. The latter was subjected to different dyeing conditions by varying the dye, mordant, and method for its application, type of water, and rinsing after dyeing. Measurements of the difference (ΔE) and intensity (K/S) of color and fastness to washing and rubbing were carried out. The results showed that dyeing of a non-textile residual hemp substrate is possible, and that calendula is a good option for dyeing it with tap water, tannin-alum set in a meta-mordanting process, and rinsing after 24 h. In this way, a contribution has been made to the circular economy of the textile industry through the use of more sustainable sources and products. [ABSTRACT FROM AUTHOR]

Patients with chronic obstructive pulmonary disease (COPD) accumulate low levels of physical activity. How environmental factors affect their physical activity in the short-term is uncertain. Aim: to assess the short-term effects of air pollution and weather on physical activity levels in COPD patients. This multi-center panel study assessed 408 COPD patients from Catalonia (Spain). Daily physical activity (i.e., steps, time in moderate-to-vigorous physical activity (MVPA), locomotion intensity, and sedentary time) was recorded in two 7-day periods, one year apart, using the Dynaport MoveMonitor. Air pollution (nitrogen dioxide (NO 2), particulate matter below 10 μm (PM 10) and a marker of black carbon (absorbance of PM 2.5 : PM 2.5ABS), and weather (average and maximum temperature, and rainfall) were estimated the same day (lag zero) and up to 5 days prior to each assessment (lags 1–5). Mixed-effect distributed lag linear regression models were adjusted for age, sex, weekday, public holidays, greenness, season, and social class, with patient and city as random effects. Patients (85% male) were on average (mean ± SD) 68 ± 9 years old with a post-bronchodilator forced expiratory volume in 1 s (FEV 1) of 57 ± 18% predicted. Higher NO 2 , PM 10 and PM 2.5ABS levels at lag four were associated with fewer steps, less time in MVPA, reduced locomotion intensity, and longer sedentary time (e.g., coefficient (95% CI) of −60 (−105, −15) steps per 10 μg/m3 increase in NO 2). Higher average and maximum temperatures at lag zero were related to more steps and time in MVPA, and less sedentary time (e.g., +85 (15, 154) steps per degree Celsius). Higher rainfall at lag zero was related to fewer steps and more sedentary time. Air pollution affects the amount and intensity of physical activity performed on the following days in COPD patients, whereas weather affects the amount of physical activity performed on the same day. • Higher air pollution relates to low physical activity in COPD up to four days later. • High temperature relates to high physical activity in COPD only on the same day. • Greater rainfall relates to low physical activity in COPD only on the same day. • Urban and transport planning policy should consider people with chronic conditions. • Research on physical activity in COPD should collect data on environmental factors. [ABSTRACT FROM AUTHOR]

This article focuses on the teaching of reading - and of readers - in primary and secondary education. It aims at promoting theoretical-epistemological propositions which could underpin the methodological practices developed by teachers of Portuguese Language. Starting from the conception of encounter (PONZIO, 2010), it is proposed to investigate reading in its two constitutive dimensions: the intrasubjective and the intersubjective. The theoretical basis for the present study is the culturalhistorical perspective, stemming from Lev Vygotsky's psychology of language and Bakhtin's philosophy of language. This qualitative study focuses on documentary analysis and the data includes the discussion of research excerpts from the Research Hub of Written Culture and Schooling, at the Universidade Federal of Santa Catarina (UFSC), as well as official documents that compose the national parameters for education in Brazil. The results compose theoretical-epistemological propositions materialized in the form of a diagram of Didactic Integration from which it is possible to develop reading activities that would cover both the sociocultural and the linguistic aspects of the text. [ABSTRACT FROM AUTHOR]

Over the last few years, several policies and new technological solutions have targeted the construction sector with the aim of reducing the sector's impacts on the environment. Among the different technological advances proposed, the reuse of materials in construction has been reported as a promising solution for an increase in sustainability and circularity. In particular, a type of cities' undergrounds assets for which materials' reuse is being explored are trenches for protecting services (i.e., water and gas transport pipelines, and optic fibre and other telecommunications services). Nonetheless, the economic and environmental benefits and impact of this type of system is still insufficiently quantified. In this research study, the economic and environmental impacts of four scenarios of trenches were assessed by using Life Cycle Costing (LCC) and Life Cycle Assessment (LCA). The four alternatives analysed consisted of: (1) the classical solution; (2) the classical solution with the reuse of soil; (3) the control low-strength material, and (4) the eco-trench. The results allowed concluding that in the eco-trench system, for which all material is reused, the environmental and economic impacts could be reduced by more than 80% and 50%, respectively. A parametric study for which the dimensions of the trenches were varied, permitted to reinforce these results and to quantify the impact's change along with the width and depth of the trench. Overall, this study provides a comprehensive view of the high-impact potential of reusing material for the construction of trenches in cities. The outcomes allow also remarking that the eco-trench system could be an attractive and advantageous solution for urban infrastructure stakeholders, both from an economic and environmental perspective. • Trenches following circular economy principles yield between 30 and 63% lower costs. • In general, the surface finish (e.g., milling) contributes the most to higher costs. • Circular trenches present lower impacts (up to 97,4% less) in all impact categories. • Material reuse and not using asphalt contributed the most to decrease impacts. [ABSTRACT FROM AUTHOR]

Protein SUMOylation regulates multiple processes involved in the differentiation and maturation of cells and tissues during development. Despite this, relatively little is known about the spatial and temporal regulation of proteins that mediate SUMOylation and deSUMOylation in the CNS. Here we monitor the expression of key SUMO pathway proteins and levels of substrate protein SUMOylation in the forebrain and cerebellum of Wistar rats during development. Overall, the SUMOylation machinery is more highly-expressed at E18 and decreases thereafter, as previously described. All of the proteins investigated are less abundant in adult than in embryonic brain. Furthermore, we show for first time that the profiles differ between cerebellum and cerebrum, indicating differential regional regulation of some of the proteins analysed. These data provide further basic observation that may open a new perspective of research about the role of SUMOylation in the development of different brain regions. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the social impacts of microalgae-based systems for wastewater treatment and bioproducts recovery by using the Social Life Cycle Assessment (S-LCA) tool. In particular, two systems were analysed: 1) a system treating urban wastewater, and 2) another system treating wastewater from the food industry. Moreover, these alternatives were compared to 3) a system for bioproducts production from microalgae grown in a standard growth medium. The recovered bioproducts in all the systems considered were: natural pigments, biogas and digestate, which can be reused as biofertilizer. Results showed that the scenario using standard growth medium was the one showing the best results in all impacts and stakeholder categories (up to 24-fold lower impacts depending on the impact category). This was mainly due to: i) the simplicity of the system, which consequently improves health and safety for workers; ii) the absence of contaminants which consequently improves health and safety, acceptability and olfactory impact for both consumers and the local community; iii) the presence of well-established legislation, regulatory frameworks, and full-scale deployment, which benefit value chain actors and society. Overall, this study also identified several social factors hindering a transition towards a circular bioeconomy in the microalgae-based systems for the wastewater treatment and resource recovery sector. [Display omitted] • Social Life Cycle Assessment of microalgae-based systems was carried out. • Microalgae-based systems recovered natural pigments, biofertilizer and biogas. • Microalgae-based systems using wastewater and standard growth medium were compared. • Scenario using standard growth medium showed up to 24-fold lower impact. • Bottlenecks for full-scale deployment of microalgae-based systems were identified. [ABSTRACT FROM AUTHOR]

Anomalous cross-peaks observed in the NOESY spectra of 2,4-disubstituted thiazolidines and oxazolidines that cannot be attributed to classical dipolar NOE or chemical exchange peaks have been investigated experimentally and computationally and have been shown to arise from scalar cross-relaxation of the first kind. This process is stimulated by the relatively slow modulation of scalar couplings and, for the systems studied, arises from slow on-off proton exchange of the amino nitrogen, a process influenced by solution temperature, acidity, and concentration. The mechanism is likely to be significant for many systems in which proton exchange occurs on the millisecond time scale, and misinterpretation of these cross-peaks may lead to erroneous conclusions should their true origins not be recognized. [ABSTRACT FROM AUTHOR]

Stacking interactions between substitutedbuckybowls (corannuleneand sumanene) with fullerenes (C60and C70)were studied at the B97-D2/TZVP level of theory. Corannulene and sumanenemonomers were substituted with five and six Br, Cl, CH3, C2H, or CN units, respectively. A comprehensive studywas conducted, analyzing the interaction of corannulenes and sumaneneswith several faces of both fullerenes. According to our results, inall cases substitution gave rise to larger interaction energies ifcompared with those of unsubstituted buckybowls. The increase of dispersionseems to be the main source of the enhanced binding, so an excellentcorrelation between the increase of interaction energy and the increaseof dispersion contribution takes place. One of the noteworthy phenomenathat appears is the so-called CH···π interaction,which is responsible for the strong interaction of sumanene complexes(if compared with that of corannulene complexes). This interactionalso causes the substitution with CH3groups (in whichone of the H atoms points directly to the π cloud of fullerene)to be the most favorable case. This fact can be easily visualizedby noncovalent interaction plots. [ABSTRACT FROM AUTHOR]

Highlights: [•] Bi-layer diaphragm wall: sprayed concrete with steel fibres, over a conventional diaphragm wall. [•] Different construction process parameters analyzed through thirty numeric simulations. [•] Main flexural strength provided by the RC layer. [•] Secondary flexural contribution of the sprayed SFRC layer. [•] Bending reinforcement for RC layer reduced up to 7.0% if SFRC layer considered. [Copyright &y& Elsevier]

Acute myeloid leukemia (AML) is the most aggressive type of blood cancer, and there is a continued need for new treatments that are well tolerated and improve long-term survival rates in patients. Induction of differentiation has emerged as a promising alternative to conventional cytotoxic chemotherapy, but known agents lack efficacy in genetically distinct patient populations. Previously, we established a phenotypic screen to identify small molecules that could stimulate differentiation in a range of AML cell lines. Utilising this strategy, a 1,5-dihydrobenzo[e][1,4]oxazepin-2(3H)-one hit compound was identified. Herein, we report the hit validation in vitro, structure-activity relationship (SAR) studies and the pharmacokinetic profiles for selected compounds. [ABSTRACT FROM AUTHOR]

The mechanism of the decomposition of ethyl and ethyl 3-phenyl glycidate in gas phase was studied by density functional theory (DFT) and MP2 methods. A proposed mechanism for the reaction indicates that the ethyl side of the ester is eliminated as ethylene through a concerted six-membered cyclic transition state, and the unstable intermediate glycidic acid decarboxylates rapidly to give the corresponding aldehyde. Two possible pathways for glycidic acid decarboxylation were studied: one via a five-membered cyclic transition state, and the other via a four-membered cyclic transition state. The results of the calculations indicate that the decarboxylation reaction occurs via a mechanism with five-membered cyclic transition state. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

The theme of this article is the Portuguese class, focusing on factors that compromise students' formation as written text-statements producers in different discursive genres. The data was generated through an action research, with an ethnographic anchor, carried out in the Portuguese classes of a 1st-year high school class, in a state school situated in São José, Santa Catarina. The chronical genre was the main focus of the research. The analysis of the texts produced was done according to two main theoretical axes: Vigotski's social-interactionist anchoring and Bakhtin's concept of discursive genres. The results show the lack of appropriation of the chronicle genre by these students as reflected in the texts produced by them. This may point to the fact that the school have not been preparing students to be producers of written texts-statements. [ABSTRACT FROM AUTHOR]

Background: Gas sterilization (eg, ethylene oxide [EtO] and gas plasma) was introduced for polyethylene to reduce oxidation due to free radicals occurring during radiation sterilization. Recently, oxidation has been observed in polyethylenes with undetectable levels of free radicals, which were expected to be oxidatively stable. It is unclear whether in vivo oxidation will occur in unirradiated inserts sterilized with EtO. Questions/purposes: We analyzed the oxidation, mechanical behavior, and surface damage mechanisms of tibial inserts of a single design sterilized using EtO. Methods: We collected 20 EtO-sterilized tibial inserts at revision surgeries. We assessed oxidative using Fourier transform infrared spectroscopy and mechanical properties using the small punch test. Surface damage was assessed using damage scoring techniques and micro-CT. Results: Oxidation indexes were low and uniform between the regions. The subtle changes did not affect the mechanical properties of the polymer. The dominant surface damage modes included burnishing, abrasion, and third-body wear. There was no evidence of delamination in the retrievals. Conclusions: The retrieved EtO-sterilized UHMWPE retrievals remained stable with respect to both oxidative and mechanical properties for up to 10 years in vivo. We did observe slight measurable amounts of oxidation in the inserts; however, it was far below levels that would be expected to compromise the strength of the polymer. Clinical Relevance: Due to the stable oxidative and mechanical properties, EtO-sterilized tibial components appear to be an effective alternative to gamma-sterilized inserts, at least in short-term implantations. [ABSTRACT FROM AUTHOR]

Abstract: Restoration works in opencast mining are mostly done with fast-growing herbaceous species to control the erosion of embankments during rainfall, especially immediately after their construction. Such species often exhibit a high demand for water and their survival is therefore associated to an adequate hydric supply. If this fails, these species can rapidly disappear when water is scarce. This paper shows the results of a restoration experiment where two stony mineral substrates were used in a quarry area (NE Spain). The experiment was carried out at lysimeter scale and the aim was to evaluate the short time vegetation response to common restoration practices in semiarid areas with two types of substrates and two types of irrigation practices. Lysimeter results were used to indirectly draw implications for the usual irrigation practices in the area. During periods of the first year after sowing, irrigated and non-irrigated lysimeters were monitored for substrate humidity, water leachates and plant development. The population cover of sown plants fluctuated according to the water availability in the substrate before drought. Density of total basal shoots decreased dramatically during the period of water stress, reaching negligible cover values on both types of substrates. Water content in the top substrate (0–20cm) was dramatically reduced in June, just after the maximum plant cover and water demand were reached (May). According with our results, it is not advisable to aim at a continuous and dense herbaceous cover composed of species that are not drought tolerant in restoration works, especially if embankments are constructed with spoil mine substrates. The restoration of opencast areas should include the use of water stress-resistant plants and careful irrigation plans. [Copyright &y& Elsevier]

comprehensive MP2/6-311 + G(d,p) and B3LYP/6-311 + G(d,p) study of the aromatic character of phospholes, P(CH)PH with n = 0-4 was conducted. For this purpose, the structures for these compounds were optimized at both theoretical levels and different magnetic properties (magnetic susceptibility anisotropy, χ, and the nucleus-independent chemical shifts, NICS) were evaluated. For comparison, these magnetic properties were also calculated in the optimized structures with planarity constraints. We have also applied the ACID (anisotropy of the current-induced density) method in this analysis. The main conclusions are the aromatic character of these compounds, the relationship between aromaticity and planarity and the importance of other factors in this aromaticity. [ABSTRACT FROM AUTHOR]

The causes of incomplete remyelination in progressive multiple sclerosis are unknown, as are the pathological correlates of the different clinical characteristics of patients with primary and secondary progressive disease. We analysed brains and spinal cords from 51 patients with progressive multiple sclerosis by planimetry. Thirteen patients with primary progressive disease were compared with 34 with secondary progressive disease. In patients with secondary progressive multiple sclerosis, we found larger brain plaques, more demyelination in total and higher brain loads of active demyelination compared with patients with primary progressive disease. In addition, the brain density of plaques with high-grade inflammation and active demyelination was highest in secondary progressive multiple sclerosis and remained ∼18% higher than in primary progressive multiple sclerosis after adjustments for other plaque types and plaque number (P < 0.05). Conversely, the proportion of remyelinated shadow plaques (P < 0.05) and the overall remyelination capacity (P < 0.01) per brain were higher in primary, compared with secondary, progressive multiple sclerosis. By contrast, there were no group differences in the brain load or frequency of low-grade inflammatory plaques with slowly expanding demyelination. Spinal cord lesion loads and remyelination capacity were also comparable in the two patient groups. Remyelinated areas were more vulnerable than the normal-appearing white matter to new demyelination, including active demyelination in secondary progressive multiple sclerosis. ‘Recurrent’ slowly expanding demyelination, affecting remyelinated areas, and the load of slowly expanding demyelination correlated with incomplete remyelination in both groups. In turn, incomplete remyelination in the spinal cord correlated with higher disease-related disability (determined retrospectively; r = −0.53; P < 0.05 for remyelination capacity versus disease severity). By contrast, such a correlation was not observed in the brain. We propose that regulatory and reparative properties could protect the white matter of the brain in patients with primary progressive multiple sclerosis. These patients may, thereby, be spared symptoms until the spinal cord is affected. By contrast, recurrent active demyelination of repaired myelin could explain why similar symptoms often develop in consecutive relapses in relapsing-remitting/secondary progressive multiple sclerosis. Our data also indicate that slowly expanding demyelination may irreparably destroy normal and repaired myelin, supporting the concept of slowly expanding demyelination as an important pathological correlate of clinical progression. [ABSTRACT FROM PUBLISHER]

Some recent studies suggest that in progressive multiple sclerosis, neurodegeneration may occur independently from inflammation. The aim of our study was to analyse the interdependence of inflammation, neurodegeneration and disease progression in various multiple sclerosis stages in relation to lesional activity and clinical course, with a particular focus on progressive multiple sclerosis. The study is based on detailed quantification of different inflammatory cells in relation to axonal injury in 67 multiple sclerosis autopsies from different disease stages and 28 controls without neurological disease or brain lesions. We found that pronounced inflammation in the brain is not only present in acute and relapsing multiple sclerosis but also in the secondary and primary progressive disease. T- and B-cell infiltrates correlated with the activity of demyelinating lesions, while plasma cell infiltrates were most pronounced in patients with secondary progressive multiple sclerosis (SPMS) and primary progressive multiple sclerosis (PPMS) and even persisted, when T- and B-cell infiltrates declined to levels seen in age matched controls. A highly significant association between inflammation and axonal injury was seen in the global multiple sclerosis population as well as in progressive multiple sclerosis alone. In older patients (median 76 years) with long-disease duration (median 372 months), inflammatory infiltrates declined to levels similar to those found in age-matched controls and the extent of axonal injury, too, was comparable with that in age-matched controls. Ongoing neurodegeneration in these patients, which exceeded the extent found in normal controls, could be attributed to confounding pathologies such as Alzheimers or vascular disease. Our study suggests a close association between inflammation and neurodegeneration in all lesions and disease stages of multiple sclerosis. It further indicates that the disease processes of multiple sclerosis may die out in aged patients with long-standing disease. [ABSTRACT FROM AUTHOR]

Apart from the importance of Social Sciences and Humanities (SSH) in and of themselves, the potential contribution that they can make to Science, Technology, Engineering and Mathematics (STEM) is huge. Even though some STEM fields have already incorporated SSH elements in their research and education, there are still other disciplines that have not yet approach the intersection between them and SSH. Among these is civil engineering (CE), which has traditionally been set as purely technological and has lacked the inclusion of SSH elements in it. Nonetheless, it is indispensable that engineers have knowledge in SSH to allow them to make decisions more perceptively, realistically and critically. Ultimately, this social understanding can lead them to design and plan solutions that are more socially sustainable. However, there are still no clear guidelines on how to include aspects from social sciences and humanities at the higher education level. This article analyses perceptions, the real status and possible barriers for the incorporation of SSH in the studies of CE. Besides, it analyses and discusses the different methodologies in which engineering students can be introduced to these topics. A triangulation method that combined the use of qualitative and quantitative data was used. Surveys to students, researchers, professors and practitioners were carried out (n=583). Besides, accreditation criteria and CE syllabuses of 100 faculties were reviewed. The analyses showed a dissent between individual perceptions, collective reality and legislative frameworks. Even though the survey responses showed a common agreement concerning the inclusion of SSH, only a minority of CE schools have introduced SSH in their curricula. Besides, accrediting bodies have not yet introduced this as a specific requirement in their criteria. The barriers detected in the incorporation of SSH in CE curricula were: (1) resistance to change, (2) external influences on the curricula, (3) lack of guidelines, (4) misconceptions on what SSH in relation to CE involves. It is necessary to gradually incorporate both hard social skills and soft skills from the beginning of the degree courses and to do so in a transversal way in most of the subjects if professionals and researchers that are capable of designing socially sustainable activities are needed. [ABSTRACT FROM AUTHOR]

The polymerase protein of all known double-stranded RNA (dsRNA) viruses is located within a complex subviral core particle that is responsible for transcription of the viral genome. For members of the family Reoviridae, this particle allows messenger sense RNA synthesis while sequestering the viral genome away from cellular dsRNA surveillance systems during infection of eukaryotic cells. The core particle of bluetongue virus (BTV) consists of the major structural proteins VP3 and VP7 and the minor enzymatic proteins VP1 (polymerase), VP4 (capping enzyme), and VP6 (helicase). In this report we have characterized fully processive dsRNA synthesis by VPI from a viral plus-strand RNA template in the absence of the other proteins of the BTV core. This replicase activity consists of de nova initiation of synthesis, followed by elongation of the minus strand. Purified VP1 exhibits little sequence specificity for BTV plus-strand template, suggesting that the choice of viral over nonviral RNA template comes from its association with other proteins within the viral core. [ABSTRACT FROM AUTHOR]

Attribute-based credentials (ABCs) provide an efficient way to transfer custody of personal and private data to the final user, while minimizing the risk of sensitive data revelation and thus granting anonymity. Nevertheless, this method cannot detect whether one attribute has been used more than once without compromising anonymity when the emitter and consumer collude with one another. The protocol proposed in this article deals with this issue by using a modification of ZSS pairing-based short signatures over elliptic curves and Verheul's self-blinded credentials scheme. Each user can generate an identifier (pseudonym) that is unique and verifiable by everyone in a given scope, without compromising anonymity. However, the identifier cannot be reused in the same scope, since such reuse would be detected. [ABSTRACT FROM AUTHOR]

There is some evidence that male gender could have a negative impact on the prognosis and severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The aim of the present study was to compare the characteristics of coronavirus disease 2019 (COVID-19) between hospitalized men and women with confirmed SARS-CoV-2 infection. This multicenter, retrospective, observational study is based on the SEMI-COVID-19 Registry. We analyzed the differences between men and women for a wide variety of demographic, clinical, and treatment variables, and the sex distribution of the reported COVID-19 deaths, as well as intensive care unit (ICU) admission by age subgroups. This work analyzed 12,063 patients (56.8% men). The women in our study were older than the men, on average (67.9 vs. 65.7 years; p < 001). Bilateral condensation was more frequent among men than women (31.8% vs. 29.9%; p = 0.007). The men needed non-invasive and invasive mechanical ventilation more frequently (5.6% vs. 3.6%, p < 0.001, and 7.9% vs. 4.8%, p < 0.001, respectively). The most prevalent complication was acute respiratory distress syndrome, with severe cases in 19.9% of men (p < 0.001). In men, intensive care unit admission was more frequent (10% vs. 6.1%; p < 0.001) and the mortality rate was higher (23.1% vs. 18.9%; p < 0.001). Regarding mortality, the differences by gender were statistically significant in the age groups from 55 years to 89 years of age. A multivariate analysis showed that female sex was significantly and independently associated with a lower risk of mortality in our study. Male sex appears to be related to worse progress in COVID-19 patients and is an independent prognostic factor for mortality. In order to fully understand its prognostic impact, other factors associated with sex must be considered. [ABSTRACT FROM AUTHOR]

There is an increasing number of studies showing that thrombocytosis—accompanying a variety of solid tumors including colorectal cancer (CRC)—is associated with shorter survival and earlier development of metastases. The mechanisms of cancer-associated thrombocytosis are not completely understood yet. The aim of our study was to evaluate the role of IL-6 in tumor development and thrombocytosis in mice with inflammation-induced CRC, using a CRISPR/cas9 IL-6 knockout (KO) strain. Adult male FB/Ant mice (n = 39) were divided into four groups: (1) IL-6 KO controls (n = 5); (2) IL-6 KO CRC model group (n = 18); (3) Wild-type (WT) controls (n = 6); and (4) WT CRC model group (n = 10). CRC model animals in (2) and (4) received azoxymethane (AOM)/dextran sodium sulfate (DSS) treatment to induce inflammation-related CRC. Plasma and liver tissues were obtained to determine platelet counts, IL-6 and thrombopoietin-1 (TPO) levels. In 1 WT and 2 IL-6 KO mice in vivo confocal endomicroscopy and 18F-fluorodeoxyglucose (FDG) PET/MRI examinations were performed to evaluate the inflammatory burden and neoplastic transformation. At the end of the study, tumorous foci could be observed macroscopically in both CRC model groups. Platelet counts were significantly elevated in the WT CRC group compared to the IL-6 KO CRC group. TPO levels moved parallelly with platelet counts. In vivo fluorescent microscopy showed signs of disordered and multi-nuclear crypt morphology with increased mucus production in a WT animal, while regular mucosal structure was prominent in the IL-6 KO animals. The WT animal presented more intense and larger colonic FDG uptake than IL-6 KO animals. Our study confirmed thrombocytosis accompanying inflammation-related CRC and the crucial role of IL-6 in this process. Significantly higher platelet counts were found in the WT CRC group compared to both the control group and the IL-6 KO group. Concomitantly, the tumor burden of WT mice was also greater than that of IL-6 KO mice. Our findings are in line with earlier paraneoplastic IL-6 effect suggestions. [ABSTRACT FROM AUTHOR]

The first, and probably the most determining, decision that engineering teams need to make when facing the structural design of any infrastructure is the choice of both an appropriate material and the suitable structural typology for its components. Each component is required to satisfy technical and functional aspects imposed by standards and stakeholder. Currently, the aspects that are most frequently considered in decision-making processes are economic. Nevertheless, environmental and social criteria are also required if one aims at making sustainability-based decisions. In this regard, to the best of the authors' knowledge, very few tools or studies exist that can support decision-makers. The few that do exist, are rather limited, either because they fail to incorporate many relevant factors in the sustainability assessment of a project or because they only evaluate environmental and social impacts of a project as a whole. Although a global assessment is useful to gain a holistic understanding of impacts of a project and to compare them to other projects, it does not necessarily help engineering teams understand the impact of fundamental decisions made when designing individual structural components. Therefore, the aim of the present research paper is to develop a new method for the sustainability analysis of building structural components which has been specifically oriented to beams and girders. This is done by means of the Integrated Value Model for the Evaluation of Sustainability method, which is known by its Spanish acronym, MIVES (Modelo Integrado de Valor para una Evaluación Sostenible). This method draws on multi-attribute utility theory and that allows building an integrated value model as an approach for multi-criteria decision-making. The developed model has been applied to assess the sustainability of different alternatives of beams and trusts to support the non-accessible roof of a sports hall in Vila-seca, Spain. Different material types and structural typologies are analysed. The findings show that the most sustainable alternatives are timber and reinforced concrete trusses, which are actually two options that are seldom used in practice. • A model to evaluate the sustainability of structural elements is developed. • MIVES is proved to be an adequate sustainability assessment tool in these cases. • Girders and trusses made of timber, concrete and steel are analysed. • Timber and concrete trusses achieve the highest global sustainability indexes. [ABSTRACT FROM AUTHOR]

While economic and environmental aspects of civil engineering have attracted the greatest attention among contemporary academy, its social side has frequently been set aside. However, the social impact that infrastructures have is huge and its analysis and understanding are fundamental. At the same time, social aspects such as culture or human behaviour can have significant effects during the different stages of the lifecycle of infrastructures. Therefore, a better understanding of the connections between civil engineering and society can help to better adapt infrastructures to their contexts, as well as minimise their negative impacts; as a result, this understanding can bring about infrastructures that are more socially sustainable. The scarce studies that have assessed the connection between society and civil engineering have considered this relationship as unidirectional. The real scenario is not so simple. The analysis of this relationship needs to be interdisciplinary, and it is in this context that this paper addresses the analysis of infrastructures and of social sciences from a sociotechnical point of view. We draw on the interrelationships found to propose a conceptual framework with the main objective of providing both practitioners and academics with tools to carry out more sustainable and context-adapted decisions. We classify the fields of civil engineering and social sciences into several different subfields, namely six for infrastructures (transport, water, energy, environment, urban planning and buildings) and twelve for social sciences (culture and history, behaviour and mind, communication and interaction, socioeconomics, juridical sciences, life and health, politics, social problems, social groups, ethics and philosophy, arts and education and innovation). Afterwards, we review the existing literature at the intersection between the various categories. We conclude proposing a framework that can support decisions and actions made at different levels and working areas. The framework includes guidelines for a more holistic consideration of the interaction between infrastructures and society in key activities whereby an improved understanding of the effect of this relationship is often required. The guidelines provide a description of different key areas and can be applied to a wide variety of actions ranging from the development of university curricula to the social impact assessment of projects. Image 1 • The dual relationship between civil engineering and social sciences is studied. • Politics and vulnerability are the most studied social areas in civil engineering. • Transport is the most studied civil engineering area from a social perspective. • Infrastructure projects should consider social aspects during all their lifecycles. • A framework and future research directions are proposed. [ABSTRACT FROM AUTHOR]

Background Early and adequate antibiotic treatment are the cornerstones to improve clinical outcomes in patients with Bloodstream infections (BSI). Delays in appropriate antimicrobial therapy have catastrophic consequences for patients with BSI. Microbiological characterization of multi-drug-resistant pathogens (MDRP) allow clinicians to provide appropriate treatments. Current available microbiologic techniques may take-up to 96 hours to identify causative pathogens and its resistant patterns. Therefore, there is an important need to develop rapid diagnostic strategies for MDRP. However, rapid detection techniques are costly and are not widely available. We tested a modified protocol designed to detect Gram-negative bacilli (GNB) resistant to oximinocephalosporins and carbapenems from positive blood cultures. Methods This is a prospective, cohort study of consecutive patients with bacteremia. We developed a modified protocol using HB&L® system to detect MDRP. We then attempted to determine accuracy, concordance and reduction of identification time of this novel method in a reference hospital. Descriptive statistics and logistical regressions were used. Results Ninety-six patients with BSI were included in the study. A total of 161 positive blood cultures were analyzed. Escherichia coli (50%, 81/161) was the most frequently identified pathogen followed by Klebsiella pneumoniae (15%, 24/161) and Pseudomonas aeruginosa (8%, 13/161). 32% of isolations had usual resistance patters. However, in 29/161 (18%) of identified pathogens were producer of carbapenemasases and 21/161 (13%) of extended-spectrum β-lactamases. Concordance among our HB&L® modified protocol and traditional method was 99% (159/161). Finally, identification times were significantly shorter using our HB&L® modified protocol than traditional methods (Mean, hours [SD], 20.8 [6.22] vs. 62.8 [6.22], P < 0.001). Conclusion Here we provided novel evidence that using our HB&L® modified protocol is an effective strategy to reduce the time to MDRP detection/identification; with a great concordance rate when compared with the gold standard. Further studies are needed to confirm these findings and to determine whether this method may improve clinical outcomes. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

This paper reports results of laboratory and 3D numerical modeled pull-out tests with steel ladders and polymeric strip reinforcements. These types of reinforcement are commonly used in reinforced soil walls constructed with concrete facing elements. Laboratory pull-out tests are required to determine accurate and realistic pull-out strength values considering the interaction of specific reinforcement and backfill materials under different confining pressures (i.e., trying to simulate the different reinforcement layer arrangements and load conditions in actual reinforced soil walls). International design Codes for reinforced soil walls provide default values for pull-out strength. However, in many cases, default values are too conservative and/or are not strictly specified for particular reinforcement types. Pull-out tests can be difficult and expensive to perform, thus not being common nor worth for the vast majority of reinforced soil wall projects. Consequently, calibrated numerical models can be useful to predict pull-out response under site-specific conditions, and provide further understanding of the mechanisms involved in the soil-reinforcement interaction. Details of the numerical approach, including relevant aspects of the soil-reinforcement interfaces, are described. Examples of calibrated numerical predictions for pull-out loads, displacements, and soil-dilatancy effects are presented. The influence of reinforcement, soil and interface stiffnesses is shown. Numerical results provide useful insight for future modelling works of the complex interaction between type-specific backfill materials and reinforcement element, relevant for investigation and/or practical design of reinforced soil walls. [ABSTRACT FROM AUTHOR]

Background: Congestion is an essential issue in patients with heart failure (HF). Standard treatments do not usually achieve decongestion, and various strategies have been proposed to guide treatment, such as determination of natriuresis. After starting treatment with loop diuretics, we postulate that initial natriuresis might help treatment titration, decongestion, and improve prognosis. Methods: It was a prospective and observational study. Patients admitted with the diagnosis of HF decompensation were eligible. An assessment of congestion was performed during the first 48 h. Results: A total of 113 patients were included. A poor diuretic response was observed in 39.8%. After the first 48 h, patients with a greater diuretic response on admission (NaU > 80 mmol/L) showed fewer pulmonary b lines (12 vs. 15; p = 0.084), a lower IVC diameter (18 mm vs. 22 mm; p = 0.009), and lower IAP figures (11 mmHg vs. 13 mmHg; p = 0.041). Survival analysis tests demonstrated significant differences showing a higher proportion of all-cause mortality (ACM) and HF rehospitalization in the poor-diuretic-response group (log-rank test = 0.020). Conclusions: Up to 40% of the patients presented a poorer diuretic response at baseline, translating into worse outcomes. Patients with an optimal diuretic response showed significantly higher abdominal decongestion at 48 h and a better prognosis regarding ACM and/or HF rehospitalizations. [ABSTRACT FROM AUTHOR]

Background: There is no strong evidence that any drug is beneficial either for the treatment of SARS-CoV-2 disease or for post-exposure prophylaxis. Therefore, clinical research is crucial to generate results and evaluate strategies against COVID-19. Primary care (PC) centers, the first level of care in the health system, are in a favorable position to carry out clinical trials (CD), as they work with a large volume of patients with varied profiles (from acute to chronic pathologies). During the COVID-19 pandemic, the need for hospital admission and mortality is higher in people > 60 years. Therefore, this is a target population to try to reduce the serious complications and lethality of COVID pneumonia and to avoid overloading the hospital system. Given the pharmacological properties of colchicine (anti-inflammatory and anti-fibrotic, possible inhibition of viral replication, and inhibitory effect on coagulation activation), early treatment with colchicine may reduce the rate of death and serious pulmonary complications from COVID-19 in vulnerable patients.Methods: The COLCHICOVID study is a randomized, multicenter, controlled, open-label parallel group (2:1 ratio), phase III clinical trial to investigate the efficacy of early administration of colchicine in reducing the development of severe pulmonary complications associated with COVID-19 infection in patients over 60 years of age with at-risk comorbidities.Discussion: This is a pragmatic clinical trial, adapted to usual clinical practice. The demonstration that early administration of colchicine has clinical effectiveness in reducing the complications of SARS-CoV-2 infection in a population highly susceptible may mitigate the health crisis and prevent the collapse of the health system in the successive waves of the coronavirus pandemic. In addition, colchicine is a well-known medicine, simple to use in the primary care setting and with a low cost for the health system.Trial Registration: ClinicalTrials.gov NCT04416334 . Registered on 4 June 2020. Protocol version: v 3.0, dated 22 September 2020. [ABSTRACT FROM AUTHOR]

Redox reactions catalyzed by highly selective nicotinamide-dependent oxidoreductases are rising to prominence in industry. The cost of nicotinamide adenine dinucleotide coenzymes has led to the use of well-established elaborate regeneration systems and more recently alternative synthetic biomimetic cofactors. These biomimetics are highly attractive to use with ketoreductases for asymmetric catalysis. In this work, we show that the commonly studied cofactor analogue 1-benzyl-1,4-dihydronicotinamide (BNAH) can be used with alcohol dehydrogenases (ADHs) under certain conditions. First, we carried out the rhodium-catalyzed recycling of BNAH with horse liver ADH (HLADH), observing enantioenriched product only with unpurified enzyme. Then, a series of cell-free extracts and purified ketoreductases were screened with BNAH. The use of unpurified enzyme led to product formation, whereas upon dialysis or further purification no product was observed. Several other biomimetics were screened with various ADHs and showed no or very low activity, but also no inhibition. BNAH as a hydride source was shown to directly reduce nicotinamide adenine dinucleotide (NAD) to NADH. A formate dehydrogenase could also mediate the reduction of NAD from BNAH. BNAH was established to show no or very low activity with ADHs and could be used as a hydride donor to recycle NADH. [ABSTRACT FROM AUTHOR]

Background: So far, only limited studies exist that evaluate patients with brain metastases (BM) from GI cancer and associated primary cancers who were treated by Gamma Knife Radiosurgery (GKRS) and concomitant immunotherapy (IT) or targeted therapy (TT). Methods: Survival after GKRS was compared to the general and specific Graded Prognostic Assessment (GPA) and Score Index for Radiosurgery (SIR). Further, the influence of age, sex, Karnofsky Performance Status Scale (KPS), extracranial metastases (ECM) status at BM diagnosis, number of BM, the Recursive Partitioning Analysis (RPA) classes, GKRS1 treatment mode and concomitant treatment with IT or TT on the survival after GKRS was analyzed. Moreover, complication rates after concomitant GKRS and mainly TT treatment are reported. Results: Multivariate Cox regression analysis revealed IT or TT at or after the first Gamma Knife Radiosurgery (GKRS1) treatment as the only significant predictor for overall survival after GKRS1, even after adjusting for sex, KPS group, age group, number of BM at GKRS1, RPA class, ECM status at BM diagnosis and GKRS treatment mode. Concomitant treatment with IT or TT did not increase the rate of adverse radiation effects. There was no significant difference in local BM progression after GKRS between patients who received IT or TT and patients without IT or TT. Conclusion: Good local tumor control rates and low rates of side effects demonstrate the safety and efficacy of GKRS in patients with BM from GI cancers. The concomitant radiosurgical and targeted oncological treatment significantly improves the survival after GKRS without increasing the rate of adverse radiation effects. To provide local tumor control, radiosurgery remains of utmost importance in modern GI BM management. [ABSTRACT FROM AUTHOR]

Simple Summary: Medulloblastoma is one of the most common malignant brain tumor types and comprises the molecular groups WNT-MB, SHH-MB TP53-wildtype, SHH-MB TP53-mutant and non-WNT/non-SHH MB. Developmental gene expression data suggest that these molecular groups arise from different sites of origin in the developing brain. Therefore, we hypothesized that intraoperative observation could enable the neurosurgeon to predict the molecular group during surgery and opt for a less aggressive resection in molecular groups with favorable prognosis to preserve neurological function. We reviewed the intraoperative reports, surgical videos and information on the molecular group of 58 patients who were operated at our institution from 1996 to 2020. Our data demonstrate that the correct prediction of the molecular group based on the intraoperatively observed site of origin was limited. Based on our results, we conclude that maximal safe resection should remain the aim of surgery irrespective of the observed site of origin. Developmental gene expression data from medulloblastoma (MB) suggest that WNT-MB originates from the region of the embryonic lower rhombic lip (LRL), whereas SHH-MB and non-WNT/non-SHH MB arise from cerebellar precursor matrix regions. This study aimed to analyze detailed intraoperative data with regard to the site of origin (STO) and compare these findings with the hypothesized regions of origin associated with the molecular group. A review of the institutional database identified 58 out of 72 pediatric patients who were operated for an MB at our department between 1996 and 2020 that had a detailed operative report and a surgical video as well as clinical and genetic classification data available for analysis. The STO was assessed based on intraoperative findings. Using the intraoperatively defined STO, "correct" prediction of molecular groups was feasible in 20% of WNT-MB, 60% of SHH-MB and 71% of non-WNT/non-SHH MB. The positive predictive values of the neurosurgical inspection to detect the molecular group were 0.21 (95% CI 0.08–0.48) for WNT-MB, 0.86 (95% CI 0.49–0.97) for SHH-MB and 0.73 (95% CI 0.57–0.85) for non-WNT/non-SHH MB. The present study demonstrated a limited predictive value of the intraoperatively observed STO for the prediction of the molecular group of MB. [ABSTRACT FROM AUTHOR]

The chimeric EWSR1::FLI1 transcription factor is the main oncogenic event in Ewing sarcoma. Recently, it has been proposed that EWSR1::FLI1 levels can fluctuate in Ewing sarcoma cells, giving rise to two cell populations. EWSR1::FLI1low cells present a migratory and invasive phenotype, while EWSR1::FLI1high cells are more proliferative. In this work, we described how the CD44 standard isoform (CD44s), a transmembrane protein involved in cell adhesion and migration, is overexpressed in the EWSR1::FLI1low phenotype. The functional characterization of CD44s (proliferation, clonogenicity, migration, and invasion ability) was performed in three doxycycline-inducible Ewing sarcoma cell models (A673, MHH-ES1, and CADO-ES1). As a result, CD44s expression reduced cell proliferation in all the cell lines tested without affecting clonogenicity. Additionally, CD44s increased cell migration in A673 and MHH-ES1, without effects in CADO-ES1. As hyaluronan is the main ligand of CD44s, its effect on migration ability was also assessed, showing that high molecular weight hyaluronic acid (HMW-HA) blocked cell migration while low molecular weight hyaluronic acid (LMW-HA) increased it. Invasion ability was correlated with CD44 expression in A673 and MHH-ES1 cell lines. CD44s, upregulated upon EWSR1::FLI1 knockdown, regulates cell migration and invasion in Ewing sarcoma cells. [ABSTRACT FROM AUTHOR]

The design of building foundations has usually been based on tradition, local practice, experience, and structural design codes. Safety is invariably considered the main factor and environmental criteria (or, in general, sustainability) is seldom given due consideration. However, similar safety indicators can be achieved with different variables and a minimum safety factor must always be ensured. The main objective of this study is, from an environmental perspective, to assess the influence of the construction system (cast-in-situ or precast), foundation type (rigid or flexible), and structural code (EC-2 or EHE-08) in the case of a concrete shallow foundation (CSF), using Life Cycle Assessment (LCA). Applying this methodology, the materials (concrete and steel) yielded the highest impacts in all categories, at around 95% for cast-in-situ CSFs and at around 85% for precast CSFs, both in relation to global warming. Consequently, optimization of the amount of these materials is crucial when considering the particular variables selected in this study. The results showed that cast-in-situ and flexible CSFs at moderately shallow depths (and therefore with less steel reinforcement) and precast CSFs with considerable reductions in concrete volumes (due to sloped shapes) had lower environmental impacts. In addition, cast-in-situ CSFs constructed in accordance with the EHE-08 structural code showed lower impacts, while precast CSFs complying with the EC-2 code were environmentally preferable. However, a specific study might be required for specific factors in each case (loads, soil type, structural settlement, among others). Relevant environmental effects associated with the three variables should therefore be given specific consideration in the development of structural design codes and future constructions. [ABSTRACT FROM AUTHOR]

Paclitaxel (Taxol) is a taxane and a chemotherapeutic drug that stabilizes microtubules. While the interaction of paclitaxel with microtubules is well described, the lack of high-resolution structural information on a tubulin-taxane complex precludes a comprehensive description of the binding determinants that affect its mechanism of action. Here, we solved the crystal structure of baccatin III the core moiety of paclitaxel-tubulin complex at 1.9 Å resolution. Based on this information, we engineered taxanes with modified C13 side chains, solved their crystal structures in complex with tubulin, and analyzed their effects on microtubules (X-ray fiber diffraction), along with those of paclitaxel, docetaxel, and baccatin III. Further comparison of high-resolution structures and microtubules' diffractions with the apo forms and molecular dynamics approaches allowed us to understand the consequences of taxane binding to tubulin in solution and under assembled conditions. The results sheds light on three main mechanistic questions: (1) taxanes bind better to microtubules than to tubulin because tubulin assembly is linked to a βM-loopconformational reorganization (otherwise occludes the access to the taxane site) and, bulky C13 side chains preferentially recognize the assembled conformational state; (2) the occupancy of the taxane site has no influence on the straightness of tubulin protofilaments and; (3) longitudinal expansion of the microtubule lattices arises from the accommodation of the taxane core within the site, a process that is no related to the microtubule stabilization (baccatin III is biochemically inactive). In conclusion, our combined experimental and computational approach allowed us to describe the tubulin-taxane interaction in atomic detail and assess the structural determinants for binding. [ABSTRACT FROM AUTHOR]

This paper focuses on the sustainability analysis of different constituent materials for sewerage pipes by using a specific multi - criteria decision making (MCDM) method based on the value analysis and the multi-attribute utility theory. The scientific added value of this research consists of developing a method that minimizes the subjectivity involved in the process of quantification and comparison of different alternatives of materials to construct sewerage pipelines. In this context, a requirements tree is defined to derive a non-dimensional sustainability index for each alternative. The method is also supported by use of value functions and weights assigned to each criteria and indicator part of this requirements tree. These value functions were established during seminars and questionnaires solved by specialists and senior managers from the Spanish public sector. Besides, the weights were derived from the use of an Analytical Hierarchical Process. The model is used to assess the sustainability of 8 alternatives including rigid reinforced and non-reinforced concrete pipes as well as flexible polypropylene, polyethylene, polyvinyl chloride and glass-fibre reinforced polyester pipes. Nominal diameters of 400, 800, 1200 and 2000 were chosen as those representatives for urban and rural sewerage networks. The conclusions obtained from the research confirm that the sustainability indexes are similar for diameters of 400 mm and below, independently of the material. In addition, it has been also concluded that concrete solutions are clearly better in terms of sustainability for wider diameters with respect to the other alternative materials. [ABSTRACT FROM AUTHOR]

Myelin is the self-stacked membrane surrounding axons; it is also the target of several pathological and/or neurodegenerative processes like multiple sclerosis. These processes involve, among others, the hydrolytic attack by phospholipases. In this work we describe the changes in isolated myelin structure after treatment with several secreted PLA 2 (sPLA 2 ), by using small angle x-ray scattering (SAXS) measurements. It was observed that myelin treated with all the tested sPLA 2 s (from cobra and bee venoms and from pig pancreas) preserved the lamellar structure but displayed an enlarged separation between membranes in certain zones. Additionally, the peak due to membrane asymmetry was clearly enhanced. The coherence length was also lower than the non-treated myelin, indicating increased disorder. These SAXS results were complemented by Langmuir film experiments to follow myelin monolayer hydrolysis at the air/water interface by a decrease in electric surface potential at different surface pressures. All enzymes produced hydrolysis with no major qualitative difference between the isoforms tested. [ABSTRACT FROM AUTHOR]

Introduction: There are studies that evaluate the association between chronic obstructive pulmonary disease (COPD) and heart failure (HF) but there is little evidence regarding the prognosis of this comorbidity in older patients admitted for acute HF. In addition, little attention has been given to the extracardiac and extrapulmonary symptoms presented by patients with HF and COPD in more advanced stages. The aim of this study was to evaluate the prognostic impact of COPD on mortality in elderly patients with acute and advanced HF and the clinical manifestations and management from a palliative point of view. Methods: The EPICTER study ("Epidemiological survey of advanced heart failure") is a cross-sectional, multicenter project that consecutively collected patients admitted for HF in 74 Spanish hospitals. Demographic, clinical, treatment, organ-dependent terminal criteria (NYHA III-IV, LVEF <20%, intractable angina, HF despite optimal treatment), and general terminal criteria (estimated survival <6 months, patient/family acceptance of palliative approach, and one of the following: evidence of HF progression, multiple Emergency Room visits or admissions in the last six months, 10% weight loss in the last six months, and functional impairment) were collected. Terminal HF was considered if the patient met at least one organ-dependent criterion and all the general criteria. Both groups (HF with COPD and without COPD) were compared. A Kaplan–Meier survival analysis was performed to evaluate the presence of COPD on the vital prognosis of patients with HF. Results: A total of 3100 patients were included of which 812 had COPD. In the COPD group, dyspnea and anxiety were more frequently observed (86.2% vs. 75.3%, p = 0.001 and 35.4% vs. 31.2%, p = 0.043, respectively). In patients with a history of COPD, presentation of HF was in the form of acute pulmonary edema (21% vs. 14.4% in patients without COPD, p = 0.0001). Patients with COPD more frequently suffered from advanced HF (28.9% vs. 19.4%; p < 0.001). Consultation with the hospital palliative care service during admission was more frequent when patients with HF presented with associated COPD (94% vs. 6.8%; p = 0.036). In-hospital and six-month follow-up mortality was 36.5% in patients with COPD vs. 30.7% in patients without COPD, p = 0.005. The mean number of hospital admissions during follow-up was higher in patients with HF and COPD than in those with isolated HF (0.63 ± 0.98 vs. 0.51 ± 0.84; p < 0.002). Survival analysis showed that patients with a history of COPD had fewer survival days during follow-up than those without COPD (log Rank chi-squared 4.895 and p = 0.027). Conclusions: patients with HF and COPD had more severe symptoms (dyspnea and anxiety) and also a worse prognosis than patients without COPD. However, the prognosis of patients admitted to our setting is poor and many patients with HF and COPD may not receive the assessment and palliative care support they need. Palliative care is necessary in chronic non-oncologic diseases, especially in multipathologic and symptom-intensive patients. This is a clinical care aspect to be improved and evaluated in future research studies. [ABSTRACT FROM AUTHOR]

The purpose of our study is to quantify the extent to which Virchow-Robin spaces (VRS) detected on in vivo MRI are reproducible by post-mortem MRI. Double Echo Steady State 3T MRIs were acquired post-mortem in 49 double- and 32 single-hemispheric formalin-fixed brain sections from 12 patients, who underwent conventional diagnostic 1.5 or 3T MRI in median 22 days prior to death (25% to 75%: 12 to 134 days). The overlap of in vivo and post-mortem VRS segmentations was determined accounting for potential confounding factors. The reproducibility of VRS found on in vivo MRI by post-mortem MRI, in the supratentorial white matter was in median 80% (25% to 75%: 60 to 100). A lower reproducibility was present in the basal ganglia, with a median of 47% (25% to 75%: 30 to 50). VRS segmentations were histologically confirmed in one double hemispheric section. Overall, the majority of VRS found on in vivo MRI was stable throughout death and formalin fixation, emphasizing the translational potential of post-mortem VRS studies. [ABSTRACT FROM AUTHOR]

(1) Background: This work aims to analyze clinical outcomes according to ethnic groups in patients hospitalized for COVID-19 in Spain. (2) Methods: This nationwide, retrospective, multicenter, observational study analyzed hospitalized patients with confirmed COVID-19 in 150 Spanish hospitals (SEMI-COVID-19 Registry) from 1 March 2020 to 31 December 2021. Clinical outcomes were assessed according to ethnicity (Latin Americans, Sub-Saharan Africans, Asians, North Africans, Europeans). The outcomes were in-hospital mortality (IHM), intensive care unit (ICU) admission, and the use of invasive mechanical ventilation (IMV). Associations between ethnic groups and clinical outcomes adjusted for patient characteristics and baseline Charlson Comorbidity Index values and wave were evaluated using logistic regression. (3) Results: Of 23,953 patients (median age 69.5 years, 42.9% women), 7.0% were Latin American, 1.2% were North African, 0.5% were Asian, 0.5% were Sub-Saharan African, and 89.7% were European. Ethnic minority patients were significantly younger than European patients (median (IQR) age 49.1 (40.5–58.9) to 57.1 (44.1–67.1) vs. 71.5 (59.5–81.4) years, p < 0.001). The unadjusted IHM was higher in European (21.6%) versus North African (11.4%), Asian (10.9%), Latin American (7.1%), and Sub-Saharan African (3.2%) patients. After further adjustment, the IHM was lower in Sub-Saharan African (OR 0.28 (0.10–0.79), p = 0.017) versus European patients, while ICU admission rates were higher in Latin American and North African versus European patients (OR (95%CI) 1.37 (1.17–1.60), p < 0.001) and (OR (95%CI) 1.74 (1.26–2.41), p < 0.001). Moreover, Latin American patients were 39% more likely than European patients to use IMV (OR (95%CI) 1.43 (1.21–1.71), p < 0.001). (4) Conclusion: The adjusted IHM was similar in all groups except for Sub-Saharan Africans, who had lower IHM. Latin American patients were admitted to the ICU and required IMV more often. [ABSTRACT FROM AUTHOR]

Highlights: [•] Bi-layer diaphragm wall: sprayed concrete with steel fibres, over a conventional diaphragm wall. [•] Second layer with waterproofing and structural role. [•] A viable structural type validated through a full-scale test campaign. [•] Good agreement between numerical model and experimental results. [•] The contribution of the second layer allows for reduced reinforcement of the first layer. [Copyright &y& Elsevier]

Background: Previous studies regarding modular head-neck taper corrosion were largely based on cobalt chrome (CoCr) alloy femoral heads. Less is known about head-neck taper corrosion with ceramic femoral heads. Questions/purposes: We asked (1) whether ceramic heads resulted in less taper corrosion than CoCr heads; (2) what device and patient factors influence taper fretting corrosion; and (3) whether the mechanism of taper fretting corrosion in ceramic heads differs from that in CoCr heads. Methods: One hundred femoral head-stem pairs were analyzed for evidence of fretting and corrosion using a visual scoring technique based on the severity and extent of fretting and corrosion damage observed at the taper. A matched cohort design was used in which 50 ceramic head-stem pairs were matched with 50 CoCr head-stem pairs based on implantation time, lateral offset, stem design, and flexural rigidity. Results: Fretting and corrosion scores were lower for the stems in the ceramic head cohort (p = 0.03). Stem alloy (p = 0.004) and lower stem flexural rigidity (Spearman's rho = −0.32, p = 0.02) predicted stem fretting and corrosion damage in the ceramic head cohort but not in the metal head cohort. The mechanism of mechanically assisted crevice corrosion was similar in both cohorts although in the case of ceramic femoral heads, only one of the two surfaces (the male metal taper) engaged in the oxide abrasion and repassivation process. Conclusions: The results suggest that by using a ceramic femoral head, CoCr fretting and corrosion from the modular head-neck taper may be mitigated but not eliminated. Clinical Relevance: The findings of this study support further study of the role of ceramic heads in potentially reducing femoral taper corrosion. [ABSTRACT FROM AUTHOR]

The paper investigates the influence of backfill soil, foundation soil, and horizontal joint vertical compressibility on the magnitude of vertical loads developed in steel-reinforced soil concrete panel retaining walls at the end of construction. Measurements of toe loads recorded from instrumented field walls are reviewed and demonstrate that vertical toe loads can be much larger than the self-weight of the facing. In extreme cases, these loads can result in panel-to-panel contact leading to concrete spalling at the front of the wall. Vertical loads in excess of panel self-weight have been ascribed to relative movement between the backfill soil and the panels that can develop panel-soil interface shear and downdrag loads at the connections between the panels and the steel-reinforcement elements. A two-dimensional finite-element model is developed to systematically investigate the influence of backfill soil, foundation soil, bearing pad stiffness, and panel-soil interaction on vertical loads in the panel facing. The results show that an appropriately selected number and type of compressible bearing pads can be effective in reducing vertical compression loads in these structures and at the same time ensure an acceptable vertical gap between concrete panels. The parametric analyses have been restricted to a single wall height (16.7 m) and embedment depth of 1.5 m, matching a well-documented field case. However, the observations reported in the paper are applicable to other similar structures. The general numerical approach can be used by engineers to optimize the design of the bearing pads for similar steel-reinforced soil wall structures using available commercial finite-element model packages together with simple constitutive models. [ABSTRACT FROM AUTHOR]

This article focuses on the design of analytical methodological path for studies in the field of literacy and mother tongue teaching and learning practices. We aim to propose this design from a conceptual symposium between ideas of cultural and historical basis. We work with vigotskian, bakhtinian and literacies studies concepts, and we propose an interaction diagram, resignifying Hamilton (2000) analytical referrals. This diagram serves for analytical processes in research on the written culture. We are searching analytical paths to studies based on these three theories, which in their constructs don't contain this kind of information due to their particularities that constitute them as science or as literature. [ABSTRACT FROM AUTHOR]

Multiple sclerosis is a chronic inflammatory disease of the central nervous system, associated with demyelination and neurodegeneration. The mechanisms of tissue injury are currently poorly understood, but recent data suggest that mitochondrial injury may play an important role in this process. Since mitochondrial injury can be triggered by reactive oxygen and nitric oxide species, we analysed by immunocytochemistry the presence and cellular location of oxidized lipids and oxidized DNA in lesions and in normal-appearing white matter of 30 patients with multiple sclerosis and 24 control patients without neurological disease or brain lesions. As reported before in biochemical studies, oxidized lipids and DNA were highly enriched in active multiple sclerosis plaques, predominantly in areas that are defined as initial or ‘prephagocytic’ lesions. Oxidized DNA was mainly seen in oligodendrocyte nuclei, which in part showed signs of apoptosis. In addition, a small number of reactive astrocytes revealed nuclear expression of 8-hydroxy-d-guanosine. Similarly, lipid peroxidation-derived structures (malondialdehyde and oxidized phospholipid epitopes) were seen in the cytoplasm of oligodendrocytes and some astrocytes. In addition, oxidized phospholipids were massively accumulated in a fraction of axonal spheroids with disturbed fast axonal transport as well as in neurons within grey matter lesions. Neurons stained for oxidized phospholipids frequently revealed signs of degeneration with fragmentation of their dendritic processes. The extent of lipid and DNA oxidation correlated significantly with inflammation, determined by the number of CD3 positive T cells and human leucocyte antigen-D expressing macrophages and microglia in the lesions. Our data suggest profound oxidative injury of oligodendrocytes and neurons to be associated with active demyelination and axonal or neuronal injury in multiple sclerosis. [ABSTRACT FROM AUTHOR]

Besides giving rise to oligodendrocytes (the only myelin-forming cell in the Central Nervous System (CNS) in physiological conditions), Oligodendrocyte Precursor Cells (OPCs) are responsible for spontaneous remyelination after a demyelinating lesion. They are present along the mouse and human CNS, both during development and in adulthood, yet how OPC physiological behavior is modified throughout life is not fully understood. The activity of adult human OPCs is still particularly unexplored. Significantly, most of the molecules involved in OPC-mediated remyelination are also involved in their development, a phenomenon that may be clinically relevant. In the present article, we have compared the intrinsic properties of OPCs isolated from the cerebral cortex of neonatal, postnatal and adult mice, as well as those recovered from neurosurgical adult human cerebral cortex tissue. By analyzing intact OPCs for the first time with 1H High Resolution Magic Angle Spinning Nuclear Magnetic Resonance (1H HR-MAS NMR) spectroscopy, we show that these cells behave distinctly and that they have different metabolic patterns in function for their stage of maturity. Moreover, their response to Fibroblast Growth Gactor-2 (FGF-2) and anosmin-1 (two molecules that have known effects on OPC biology during development and that are overexpressed in individuals with Multiple Sclerosis (MS)) differs in relation to their developmental stage and in the function of the species. Our data reveal that the behavior of adult human and mouse OPCs differs in a very dynamic way that should be very relevant when testing drugs and for the proper design of effective pharmacological and/or cell therapies for MS. [ABSTRACT FROM AUTHOR]

Background: Few safety data of concurrent stereotactic radiosurgery and targeted therapy (TT) or immunotherapy (IT) are available. The aim of the study was to evaluate the outcome of melanoma patients with brain metastases (MBM) after Gamma Knife Radiosurgery (GKRS) in relation to IT/TT. Methods: We evaluated 182 MBM patients, who were treated with GKRS in the modern radiosurgical and oncological era. Results: The median time between the initial melanoma diagnosis and occurrence of MBM was 2.4 years. The median overall survival time was 5.4 years after melanoma diagnosis. The estimated median survival after the initial diagnosis of MBM was 1.0 year (95% CI = 0.7‐1.2 years). Patients treated with anti‐PD‐1 or a combination of anti‐CTLA‐4/PD‐1 showed a significantly longer survival after first GKRS compared to all other forms of treatment. In addition, patients treated with anti‐PD‐1, anti‐CTLA‐4, or a combination of anti‐CTLA‐4/PD‐1 showed a significantly longer time to new MBM after GKRS1 compared to patients treated with other forms and combinations of the oncological therapy. The occurrence of hemorrhage or radiation reaction/necrosis after GKRS did not show any statistically significant differences in relation to IT/TT. Conclusion: In MBM patients, complications after GKRS are not significantly increased if IT/TT treatment is performed at the time of or after radiosurgery. Further, a clear benefit in distant control and survival is seen in MBM patients treated with GKRS and checkpoint inhibitors. Thus, concomitant treatment of MBM with GKRS and IT/TT seems to be a safe and powerful treatment option although further prospective studies should be conducted. [ABSTRACT FROM AUTHOR]

Establishing causal links between bacterial metabolites and human intestinal disease is a significant challenge. This study reveals the molecular basis of antibiotic-associated hemorrhagic colitis (AAHC) caused by intestinal resident Klebsiella oxytoca. Colitogenic strains produce the nonribosomal peptides tilivalline and tilimycin. Here, we verify that these enterotoxins are present in the human intestine during active colitis and determine their concentrations in a murine disease model. Although both toxins share a pyrrolobenzodiazepine structure, they have distinct molecular targets. Tilimycin acts as a genotoxin. Its interaction with DNA activates damage repair mechanisms in cultured cells and causes DNA strand breakage and an increased lesion burden in cecal enterocytes of colonized mice. In contrast, tilivalline binds tubulin and stabilizes microtubules leading to mitotic arrest. To our knowledge, this activity is unique for microbiota-derived metabolites of the human intestine. The capacity of both toxins to induce apoptosis in intestinal epithelial cells--a hallmark feature of AAHC--by independent modes of action, strengthens our proposal that these metabolites act collectively in the pathogenicity of colitis. [ABSTRACT FROM AUTHOR]

Abstract Assuming specific behavior models, the variety of design codes currently used for the design of concrete beams inevitably results in different solutions, ensuring service during the whole expected lifetime with a maximum functional quality and safety. However, from a sustainable design perspective, such differences may have remarkable environmental impacts. This paper analyses if the approach of the newest design code, i.e., the Model Code, leads to a reduction in resource consumption and greenhouse gas emissions (GHG) over the life-cycle of concrete beams. To do so, a comparative analysis of the environmental impact of concrete beams was carried out depending on the reference code used for its design (i.e., EHE-08 or Model Code). The results show that the reduction of reinforcing steel is a basic objective to minimize the life cycle environmental impacts of concrete beams. Every country may have its own design codes and, thus, the reinforcing steel use can vary for structures subjected to the same loads and with equivalent structural reliability. Hence, regulations play a key role in the sustainability of construction assets. Conclusions depend on the beam length (L) and height (h) and characteristic compressive strength (f ck). For short beams (4 m), the greater the h , the greater the reinforcement difference between the two codes. With regard to beams of 8 m, these differences can lead to varying steel and GHG savings, e.g., up to 5.0% with MC-2010 (h = 0.6 m and f ck ≤ 35 MPa), almost 40% with EHE – 08 (h = 1.0 m and 35 MPa < f ck ≤ 50 MPa) and more than 30% with EHE–08 (h = 0.6 m and 35 MPa < f ck ≤ 50 MPa). For long beams (L = 12.0 m), steel consumption is 0.3–19% lower when the beam is designed with EHE-08, and this difference decreases as f ck increases. [ABSTRACT FROM AUTHOR]