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This article introduces the possibility of studying graffiti using a colorimeter developed with Arduino hardware technology according to the Do It Yourself (DIY) philosophy. Through the obtained Red Green Blue (RGB) data it is intended to study and compare the information extracted from each of the graffiti present on different walls. The same color can be found in different parts of a single graffiti, but also in other graffiti that could a priori be of different authorship. Nevertheless, graffiti may be related, and it may be possible to group graffiti artists and "gangs" that work together. The methodology followed for the construction of the colorimeter and its real application in a practical case are described in four case studies. The case studies describe how graffiti were identified and recognized and they provide a comparison of the collected color samples. The results show the added value of the colorimeter in the graffiti recognition process, demonstrating its usefulness on a functional level. Finally, the contributions of this research are outlined, and an analysis is carried out of the changes to be made to the proposed method in the future, for improved graffiti color identification.

HIV-1 infection cannot be cured due to long-lived viral reservoirs formed by latently infected CD4+ T cells. “Shock and Kill” strategy has been considered to eliminate the viral reservoir and achieve a functional cure but the stimulation of cytotoxic immunity is necessary. Ponatinib is a tyrosine kinase inhibitor (TKI) clinically used against chronic myeloid leukemia (CML) that has demonstrated to be effective against HIV-1 infection in vitro. Several TKIs may induce a potent cytotoxic response against cancer cells that makes possible to discontinue treatment in people with CML who present long-term deep molecular response. In this longitudinal study, we analyzed the capacity of ponatinib to induce an antiviral response against HIV-1 infection in peripheral blood mononuclear cells (PBMCs) obtained from people with CML previously treated with imatinib for a median of 10 years who changed to ponatinib for 12 months to boost the anticancer response before discontinuing any TKI as part of the clinical trial NCT04043676. Participants were followed-up for an additional 12 months in the absence of treatment. PBMCs were obtained at different time points and then infected in vitro with HIV-1. The rate of infection was determined by quantifying the intracellular levels of p24-gag in CD4+ T cells. The levels of p24-gag+ CD4+ T−cells were lower when these cells were obtained during and after treatment with ponatinib in comparison with those obtained during treatment with imatinib. Cytotoxicity of PBMCs against HIV-infected target cells was significantly higher during treatment with ponatinib than during treatment with imatinib, and it was maintained at least 12 months after discontinuation. There was a significant negative correlation between the lower levels of p24-gag+ CD4+ T−cells and the higher cytotoxicity induced by PBMCs when cells were obtained during and after treatment with ponatinib. This cytotoxic immunity was mostly based on higher levels of Natural Killer and Tγδ cells seemingly boosted by ponatinib. In conclusion, transient treatment with immunomodulators like ponatinib along with ART could be explored to boost the antiviral activity of cytotoxic cells and contribute to the elimination of HIV-1 reservoir.

In Spain, dual vocational training has recently become a fundamental pillar to train the working population. This article focuses on two objectives: to evaluate the quality of two models of dual VET in Spain and to identify their differences in terms of the following dimensions: Teaching Team, Process, Evaluation and Synergies. To achieve these objectives, a quantitative methodology and a cross-sectional design were used to collect data using an ad hoc questionnaire (37 items) developed based on a literature review and the 14 European quality criteria. The sample consisted of 263 educational institutions. Regarding the results for the first objective, Model B implemented EQAVET with higher quality. With regards to the second, researchers observed that all dimensions received a high or very high compliance of 70%. However, discrepancies were primarily found in the training of tutors in training centres, quality certification of dual VET and links, and support and cooperation between training centres and companies. This study provides empirical evidence regarding the factors that lead to higher quality dual VET in schools, based on the manner in which the criteria of the European Framework for Quality and Effective Vocational Education and Training (EQAVET) are implemented.

Introducción: La fluoxetina es un fármaco utilizado para la depresión especialmente en deportistas ya que parece no alterar el rendimiento deportivo. Algunos atletas combinan este fármaco con cafeína, sin embargo, el efecto combinado de ambas drogas se desconoce. Este estudio tuvo por objetivo explorar el efecto combinado de fluoxetina y cafeína sobre el rendimiento de fuerza, potencia y resistencia muscular. Metodología: En este estudio de caso, una mujer entrenada en fuerza realizó cuatro condiciones experimentales: a) placebo (PLA); b) placebo y fluoxetina (PLA+FLU); c) cafeina (CAF); d) cafeína y fluoxetina (CAF+FLU). La participante ingirió 20 mg/día de fluoxetina y 3 g/kg de masa corporal de cafeína o placebo (maltodextrina), 60 minutos antes de realizar los test. La participante realizó un test de fuerza y potencia muscular al 25%, 50%, 75% y 90% de 1-repetición-máxima (1RM), seguido de un test de resistencia muscular al 65% y 85% de 1RM, en ambos casos para los ejercicios de press de banca y sentadilla. Resultados: CAF+FLU redujo la velocidad y potencia media en press de banca y sentadilla al 75% y 90% de 1RM en el test de fuerza y potencia muscular, y al 85% en el test de resistencia muscular. Mientras que la administración de PLA+FLU y CAF+FLU redujo el pico de velocidad y potencia al 25% de 1RM en fuerza y potencia muscular y al 65% de 1RM en resistencia muscular. Conclusiones: La fluoxetina contrarresta el efecto ergogénico de la cafeína sobre la fuerza, potencia y resistencia muscular. Por tanto, aunque más estudios son necesarios, los atletas diagnosticados con depresión bajo tratamiento de fluoxetina debería reconsiderar el uso de cafeína como suplemento nutricional para mejorar el rendimiento.

Physical aggression is a serious and widespread problem in society, affecting people worldwide. It impacts nearly every aspect of life. While some studies explore the root causes of violent behavior, others focus on urban planning in high-crime areas. Real-time violence detection, powered by artificial intelligence, offers a direct and efficient solution, reducing the need for extensive human supervision and saving lives. This paper is a continuation of a systematic mapping study and its objective is to provide a comprehensive and up-to-date review of AI-based video violence detection, specifically in physical assaults. Regarding violence detection, the following have been grouped and categorized from the review of the selected papers: 21 challenges that remain to be solved, 28 datasets that have been created in recent years, 21 keyframe extraction methods, 16 types of algorithm inputs, as well as a wide variety of algorithm combinations and their corresponding accuracy results. Given the lack of recent reviews dealing with the detection of violence in video, this study is considered necessary and relevant.

En el presente trabajo se procede al estudio, desde su vertiente artística, de la cabalgata de Reyes Magos de Granada, entre 1912, cuando salió por primera vez, hasta 1936. La idea surgió del Centro Artístico, Literario y Científico, entidad cultural granadina con gran relevancia en el ámbito local durante este periodo, cuyo objetivo principal era llevar juguetes a los niños pobres y enfermos de la ciudad. Siendo este su fundamento, no se descuidaba ningún detalle del desfile: la iluminación y música que acompañaban al cortejo, el vestuario de la comitiva, elementos de atrezo destacando palanquines o carrozas, la presencia de animales como caballos o acémilas y otros más exóticos como camellos. Con ello, se conformaba una obra de arte total, provocando un gran impacto visual en los siempre numerosos asistentes.

El estudio de los incendios forestales del pasado ha permitido poner de relieve la importancia del fuego en la configuración de los paisajes de las zonas de montaña desde el inicio del Holoceno. Las formaciones vegetales asociadas a las quemas regulares y las perturbaciones provocadas en el paisaje han evolucionado a la vez que las actividades humanas se transformaban y se adaptaban a los cambios ambientales. En los últimos años, distintas técnicas paleobotánicas enmarcadas en la geohistoria ambiental han resaltado la importancia de los trabajos pluridisciplinarios. Concretamente, se ha visto la necesidad de complementar y contrastar los indicadores relativos a las plantas leñosas, tales como el polen y los palinomorfos no polínicos. Por ejemplo, las condiciones sedimentarias de los lagos y las turberas han permitido el estudio de macrocarbones (> 150 μm) y microcarbones sedimentarios (< 150 μm) interpretados a escala de cada valle. En los suelos, la pedoantracología (> 400 μm) ha aportado información espacial local y relativa a la composición de especies leñosas. Asimismo, las marcas de fuego en los anillos de crecimiento de los árboles son una opción para ajustar algunas cronologías. Este trabajo tiene como objetivo valorar qué aportaciones se pueden realizar desde la geografía histórica ambiental que sean útiles para la arqueología del paisaje de montaña. Para ello se han revisado las principales técnicas paleobotánicas para el estudio de los incendios del pasado en las zonas de montaña, se debate acerca de la precisión espacial y temporal de los carbones según su tamaño y la técnica de muestreo empleada y se discute cómo distinguir las señales climáticas y humanas en los incendios forestales. Los principales resultados apuntan a que los incendios naturales han quemado todo tipo de paisajes con independencia de la formación vegetal. La cantidad de biomasa disponible en cada momento se ha demostrado que ha sido un factor determinante de la intensidad de los incendios. Finalmente, la combinación de carbones sedimentarios e indicadores polínicos sugieren que han existido fuegos provocados por la acción humana desde el inicio del Neolítico, mientras que aún no queda claro si los incendios que hubo en tiempos pretéritos tuvieron influencia antrópica o no.

A comprehensive understanding of gut microbiota in a clearly defined group of healthy individuals is essential when making meaningful comparisons with various diseases. The Mediterranean diet (MD), renowned for its potential health benefits, and the influence of adherence thereto on gut microbiota have become a focus of research. Our aim was to elucidate the impact of adherence to the MD on gut microbiota composition in a well-defined cohort. In this prospective study, healthy volunteers completed a questionnaire to provide demographic data, medical history, and dietary intake. Adherence was evaluated using the Med-DQI. The V4 region of the 16S rRNA gene was sequenced. Analysis of sequencing data and statistical analysis were performed using MOTHUR software and R. The study included 60 patients (51.7% females). Adherence correlated with alpha diversity, and higher values were recorded in good adherers. Good adherers had a higher abundance of Paraprevotella and Bacteroides (p < 0.001). Alpha diversity correlated inversely with fat intake and positively with non-starch polysaccharides (NSPs). Evenness correlated inversely with red meat intake and positively with NSPs. Predicted functional analysis highlighted metabolic pathway differences based on adherence to the MD. In conclusion, our study adds useful information on the relationship between the MD and the gut microbiome.

Abstract Amyotrophic lateral sclerosis (ALS), a devastating progressive neurodegenerative disease, has no effective treatment. Recent evidence supports a strong metabolic component in ALS pathogenesis. Indeed, metabolic abnormalities in ALS correlate to disease susceptibility and progression, raising additional therapeutic targets against ALS. Ozone (O3), a natural bioactive molecule, has been shown to elicit beneficial effects to reduce metabolic disturbances and improved motor behavior in TDP-43A315T mice. However, it is fundamental to determine the mechanism through which O3 acts in ALS. To characterize the association between O3 exposure and disease-associated weight loss in ALS, we assessed the mRNA and protein expression profile of molecular pathways with a main role in the regulation of the metabolic homeostasis on the hypothalamus and the brown adipose tissue (BAT) at the disease end-stage, in TDP-43A315T mice compared to age-matched WT littermates. In addition, the impact of O3 exposure on the faecal bacterial community diversity, by Illumina sequencing, and on the neuromuscular junctions (NMJs), by confocal imaging, were analysed. Our findings suggest the effectiveness of O3 exposure to induce metabolic effects in the hypothalamus and BAT of TDP-43A315T mice and could be a new complementary non-pharmacological approach for ALS therapy.

The 2030 Agenda is a clear development milestone for humanity in its ambition to care for our future generations. Smart Cities play an essential role in this development, the development direction of which is based, among others factors, on the fulfilment of the criteria set by the various Sustainable Development Goals (SDGs). The purpose of the current research is to verify the current state of science concerning the development of the SDGs in Smart Cities to establish a theoretical framework for the development and integration of data specific to a Smart City to participate in homogeneous monitoring of these indicators and to compare with other Smart Cities. Once a robust bibliographic study has been carried out, we proceed to establish a theoretical study, the application methodology of which follows a process developed in various phases to obtain an integrated system for monitoring and linking of the development of Smart Cities according to the criteria set out in the applicable SDGs. The clear implication is establishing an objective and efficient process that covers collection to integrate and compare the obtained data. One of the limitations of this process is overcoming the technological barrier in specific less developed environments that may not have sufficient funding. With respect to future lines of research, the current study opens the door to studying the implications of this type of process on the management and elaboration of specific public policies, for example, concerning the time taken to establish and resolve them.

Background: Bisphosphonates have been reported to increase the risk of atrial fibrillation. Therefore, it is conceivable that they may increase the risk of cardioembolic ischemic stroke (IS). However, most epidemiological studies carried out thus far have not shown an increased risk of IS, though none separated by the main pathophysiologic IS subtype (cardioembolic and non-cardioembolic) which may be crucial. In this study, we tested the hypothesis that the use of oral bisphosphonates increases specifically the risk of cardioembolic IS, and explored the effect of treatment duration, as well as the potential interaction between oral bisphosphonates and calcium supplements and anticoagulants.Methods: We performed a case-control study nested in a cohort of patients aged 40–99 years, using the Spanish primary healthcare database BIFAP, over the period 2002-2015. Incident cases of IS were identified and classified as cardioembolic or non-cardioembolic. Five controls per case were randomly selected, matched for age, sex, and index date (first recording of IS) using an incidence-density sampling. The association of IS (overall and by subtype) with the use of oral bisphosphonates within the last year before index date was assessed by computing the adjusted odds ratios (AOR) and their 95% CI using a conditional logistic regression. Only initiators of oral bisphosphonates were considered.Results: A total of 13,781 incident cases of IS and 65,909 controls were included. The mean age was 74.5 (SD ± 12.4) years and 51.6% were male. Among cases, 3.15% were current users of oral bisphosphonates, while among controls they were 2.62%, yielding an AOR of 1.15 (95% CI:1.01–1.30). Of all cases, 4,568 (33.1%) were classified as cardioembolic IS (matched with 21,697 controls) and 9,213 (66.9%) as non-cardioembolic IS (matched with 44,212 controls) yielding an AOR of 1.35 (95% CI:1.10–1.66) and 1.03 (95% CI: 0.88–1.21), respectively. The association with cardioembolic IS was clearly duration-dependent (AOR≤1 year = 1.10; 95% CI:0.82–1.49; AOR>1–3 years = 1.41; 95% CI:1.01–1.97; AOR>3 years = 1.81; 95% CI:1.25–2.62; p for trend = 0.001) and completely blunted by anticoagulants, even in long-term users (AOR>1 year = 0.59; 0.30–1.16). An interaction between oral bisphosphonates and calcium supplements was suggested.Conclusion: The use of oral bisphosphonates increases specifically the odds of cardioembolic IS, in a duration-dependent manner, while leaves materially unaffected the odds of non-cardioembolic IS.

Individuals with chronic myeloid leukemia (CML) constitute a unique group within individuals with oncohematological disease (OHD). They receive treatment with tyrosine kinase inhibitors (TKIs) that present immunomodulatory properties, and they may eventually be candidates for treatment discontinuation under certain conditions despite the chronic nature of the disease. In addition, these individuals present a lower risk of infection than other immunocompromised patients. For this study, we recruited a cohort of 29 individuals with CML in deep molecular response who were on treatment with TKIs (n = 23) or were on treatment-free remission (TFR) (n = 6), and compared both humoral and cellular immune responses with 20 healthy donors after receiving the complete vaccination schedule against SARS-CoV-2. All participants were followed up for 17 months to record the development of COVID-19 due to breakthrough infections. All CML individuals developed an increased humoral response, with similar seroconversion rates and neutralizing titers to healthy donors, despite the presence of high levels of immature B cells. On the whole, the cellular immune response was also comparable to that of healthy donors, although the antibody dependent cytotoxic activity (ADCC) was significantly reduced. Similar rates of mild breakthrough infections were observed between groups, although the proportion was higher in the CML individuals on TFR, most likely due to the immunomodulatory effect of these drugs. In conclusion, as with the healthy donors, the vaccination did not impede breakthrough infections completely in individuals with CML, although it prevented the development of severe or critical illness in this special population of individuals with OHD.

Wie kann neu erlerntes Vokabular auf eine spielerische Art trainiert werden? Ich präsentiere hier eine Alternative zu den bekannten Spielen wie Tabu, Montagsmaler oder Pantomime: All for one. Hier arbeitet die ganze Klasse kooperativ als Team zusammen, und es braucht eine gehörige Portion Strategie, Cleverness und Kreativität. Denn die Schülerinnen und Schüler geben einander Hinweise auf einen Suchbegriff. Aber Achtung: Jedes Hinweiswort darf nur einmal vorkommen, sonst fliegt es raus. Ausser, es kommt in zwei verschiedenen Sprachen vor.

Background Interferon-y Release Assays (IGRA) reversions have been reported in different clinical scenarios for the diagnosis of tuberculosis (TB) infection. This study aimed to determine the rate of QuantiFERON-TB Gold Plus (QFT-Plus) reversions during contact investigation as a potential strategy to reduce the number of preventive treatments. Methods Prospective, multicentre cohort study of immunocompetent adult contacts of patients with pulmonary TB tested with QFT-Plus. Contacts with an initial positive QFT-Plus (QFT-i) underwent a second test within 4 weeks (QFT-1), and if negative, underwent a repeat test 4 weeks later (QFT-2). Based on the QFT-2 result, we classified cases as sustained reversion if they remained negative and as temporary reversion if they turned positive. Results We included 415 contacts, of whom 96 (23.1%) had an initial positive test (QFT-i). Following this, 10 had negative QFT-1 results and 4 (4.2%) of these persisted with a negative result in the QFT-2 (sustained reversions). All four sustained reversions occurred in contacts with IFN-γ concentrations between ≥0.35 and ≤0.99 IU•mL-1 in one or both QFT-i tubes. Conclusion In this study, TB contact investigations rarely reveal QFT-Plus reversion. These results do not support retesting cases with an initial positive result to reduce the number of preventive treatments.

Background: Migration is a present and pressing global phenomenon, as climate change and political instability continue to rise, more populations will be forced to relocate. Efficient strategies must be in place to aid the transition of vulnerable populations - such as children - and strategic interventions designed based on an understanding of their particular needs and risks. Aim of the review: This article reviewed recent research regarding the mental health of migrant children identifying a wide array of common characteristics to their emotional and behavioral responses following a migration, and compiled an extensive list of protective and risk factors. 48 studies were selected from Proquest, WOS, SCOPUS, and Pubpsych published between 2015 and 2022 covering studies of children around the world. Findings: The migration-related factors that most negatively impacted children's mental health were experiences such as discrimination, loss of access to governmental and educational resources, premigration trauma, loss of community, cultural distance and acculturation, the burden on the family unit, and socioeconomic difficulties. Thus, with the right interventions and policy changes, it is possible to make migration a non-traumatic experience in order to avoid the common emergence of depressive symptoms, PTSS (post-traumatic stress symptoms), anxiety, and other mental health issues. Supporting the family unit's transition, encouraging peer connections, and directing government aid to expedite resources upon arrival will serve as protective factors for children while they integrate into their new environment.

This work describes the development of analytical workflows based on pyrolysis coupled with gas chromatography-mass spectrometry (Pyr-GC/MS) for the qualitative and quantitative analysis of 12 of the most common plastic polymers in environmental samples. The most suitable characteristic pyrolyzate compounds and respective indicator ions were selected for each polymer in order to obtain the most appropriate response for analytical purposes. Additionally, commercial pyrolyzates and polymers libraries were used to confirm the identity of the detected microplastics. The method was validated, showing a good linearity for all the plastic polymers (R2 > 0.97) and limits of detection between 0.1 (polyurethane) to 9.1 µg (polyethylene). The developed methodology was successfully applied for the analysis of plastic polymers in environmental microplastic samples collected in three Mediterranean beaches (NE Spain). • Fast and reproducible Pyr-GC/MS method for the analysis of the 12 most common plastic polymers in a single GC/MS run • Straightforward analytical workflows using pyrolyzates and polymers libraries enable a fast identification and quantification of microplastics in environmental samples

In this work, we aim to highlight the increasing interest in semiconductors, particularly ZnO. A revision of the evolution of the scientific production on three selected topics has been conducted. As an indicator of scientific production, the number of publications indexed in the Web of Science Data Base has been used. The search terms selected range from the general to the particular: semiconductors, oxide semiconductors, and ZnO. The period considered is from 1 January 1900 to 6 June 2023. The importance of doping processes in tailoring the properties of these materials, and the relevance of the most recently derived applications are also revised. Since many of the most recent applications that have been developed or are under development refer to optoelecronic properties, doping with rare earth elements has a central role. This was the reason behind choosing the system ZnO doped with Rare Earth elements (Eu, Gd, and Ce) and codoped with Ru to illustrate the materials’ tuning potential of doping processes. Morphology, crystal structure, and luminescent properties have been investigated. Upon doping, both the Near Band Edge and the Deep Level emissions show a remarkable difference due to the change in the relative weight of the components constituting these bands. The spectra in all cases extend over the whole visible range, with a main emission in the violet-blue region corresponding to the Near Band Edge, and a broad band extending from the blue-green to orange-red region associated with the presence of different defects.

Research in Agents and Multiagent Systems has matured significantly in recent years, representing one of the main branches of Artificial Intelligence and currently there are numerous effective applications of these technologies combined with Deep Learning, Computer Vision or Natural Language Processing, including areas such as healthcare and Ambient Intelligence, smart cities and mobility, Industry 4.0, educational technology, and fintech, among many others. In this regard, the International Conference on Practical Applications of Agents and Multi-Agent System (PAAMS) provides an international forum to present and discuss the latest scientific advances and their effective applications in different sectors, evaluate the impact of the approach and facilitate technology transfer among different stakeholders. Currently, a series of co-located events specialized in different areas of research are held simultaneously with PAAMS, these being the International Congress on Blockchain and Applications (BLOCKCHAIN), the International Conference on Distributed Computing and Artificial Intelligence (DCAI), the International Conference on Decision Economics (DECON), the International Symposium on Ambient Intelligence (ISAmI), the International Conference on Methodologies and Intelligent Systems for Technology Enhanced Learning (MIS4TEL), and the International Conference on Practical Applications of Computational Biology & Bioinformatics (PACBB). In this regard, the present Special Issue includes a selection of extended papers presented at the 20th International Conference PAAMS 22 and its co-located events and held in L’Aquila (Italy), July 13-15, 2022.

Conflicting results about the association of calcium supplements (CS) with ischemic stroke (IS) have been reported. We tested this hypothesis by differentiating between CS alone (CaM) and CS with vitamin D (CaD) and between cardioembolic and non-cardioembolic IS. We examined the potential interaction with oral bisphosphonates (oBs). A nested case-control study was carried out. We identified incident IS cases aged 40–90 and randomly sampled five controls per case matched by age, sex, and index date. Current users were compared to non-users. An adjusted odds ratios (AOR) and 95% CI were computed through conditional logistic regression. Only new users were considered. We included 13,267 cases (4400 cardioembolic, 8867 non-cardioembolic) and 61,378 controls (20,147 and 41,231, respectively). CaM use was associated with an increased risk of cardioembolic IS (AOR = 1.88; 95% CI: 1.21–2.90) in a duration-dependent manner, while it showed no association with non-cardioembolic IS (AOR = 1.05; 95% CI: 0.74–1.50); its combination with oBs increased the risk of cardioembolic IS considerably (AOR = 2.54; 95% CI: 1.28–5.04), showing no effect on non-cardioembolic. CaD use was not associated with either cardioembolic (AOR = 1.08; 95% CI: 0.88–1.31) or non-cardioembolic IS (AOR = 0.98; 95% CI: 0.84–1.13) but showed a small association with cardioembolic IS when combined with oBs (AOR = 1.35; 95% CI: 1.03–1.76). The results support the hypothesis that CS increases the risk of cardioembolic IS, primarily when used concomitantly with oBs.

Endocrine-disrupting compounds (EDCs) constitute a wide variety of chemistries with diverse properties that may/can pose risks to both humans and the environment. Herein, a total of 26 compounds, including steroids, flame retardants, and plasticizers, were monitored in three major and heavily urbanized river catchments: the R. Liffey (Ireland), the R. Thames (UK), and the R. Ter (Spain), by using a single solid-phase extraction liquid chromatography-mass spectrometry (SPE-LC-MS/MS) method. Occurrence and frequency rates were investigated across all locations over a 10-week period, with the highest concentration obtained for the flame retardant tris(2-chloroethyl) phosphate (TCEP) at 4767 ng∙L−1 in the R. Thames in Central London. Geographical variations were observed between sites and were partially explained using principal component analysis (PCA) and hierarchical cluster analysis (HCA). In particular, discrimination between the R. Ter and the R. Thames was observed based on the presence and concentration of flame retardants, benzotriazole, and steroids. Environmental risk assessment (ERA) across sites showed that caffeine, a chemical marker, and bisphenol A (BPA), a plasticizer, were classified as high-risk for the R. Liffey and R. Thames, based on relative risk quotients (rRQs), and that caffeine was classified as high-risk for the R. Ter, based on RQs. The total risks at each location, namely ΣRQriver, and ΣrRQriver, were: 361, 455, and 723 for the rivers Liffey, Thames, and Ter, respectively. Caffeine, as expected, was ubiquitous in all 3 urban areas, though with the highest RQ observed in the R. Ter. High contributions of BPA were also observed across the three matrices. Therefore, these two compounds should be prioritized independently of location. This study represents a comprehensive EDC monitoring comparison between different European cities based on a single analytical method, which allowed for a geographically independent ERA prioritization to be performed.

DesignProspective, double-blind clinical trial comparing tetanus-diphtheria vaccine administration routes, intramuscular (IM) vs. subcutaneous (SC) injection, in patients with oral anticoagulants. ISRCTN69942081.Study populationPatients treated with oral anticoagulants, 15 health centers, Vigo (Spain). Sample size, 117 in each group.Outcome variablesSafety analysis: systemic reactions and, at the vaccine administration site, erythematic, swelling, hematoma, granuloma, pain.Effectiveness analysis: differences in tetanus toxoid antibody titers.Independent variables: route, sex, age, baseline serology, number of doses administered.AnalysisFollowing the CONSORT guidelines, we performed an intention-to-treat analysis. We conducted a descriptive study of the variables included in both groups (117 in each group) and a bivariate analysis. Fewer than 5% of missing values. Imputation in baseline and final serology with the median was performed. Lost values were assumed to be values missing at random. We conducted a descriptive study of the variables and compared routes. For safety, multivariate logistic regression was applied, with each safety criterion as outcome and the independent variables. Odds ratios (ORs) were calculated. For effectiveness, a generalized additive mixed model, with the difference between final and initial antibody titers as outcome. Due to the bimodal distribution of the outcome, the normal mixture fitting with gamlssMX was used. All statistical analyses were performed with the gamlss.mx and texreg packages of the R free software environment.ResultsA previously published protocol was used across the 6-year study period. The breakdown by sex and route showed: 102 women and 132 men; and 117 IM and 117 SC, with one dose administered in over 80% of participants. There were no differences between groups in any independent variable. The second and third doses administered were not analyzed, due to the low number of cases. In terms of safety, there were no severe general reactions. Locally, significant adjusted differences were observed: in pain, by sex (male, OR: 0.39) and route (SC, OR: 0.55); in erythema, by sex (male, OR: 0.34) and route (SC, OR: 5.21); and in swelling, by sex (male, OR: 0.37) and route (SC, OR: 2.75). In terms of effectiveness, the model selected was the one adjusted for baseline serology.

BackgroundIn recent years, different tools have been developed to facilitate analysis of social determinants of health (SDH) and apply this to health policy. The possibility of generating predictive models of health outcomes which combine a wide range of socioeconomic indicators with health problems is an approach that is receiving increasing attention. Our objectives are twofold: (1) to predict population health outcomes measured as hospital morbidity, taking primary care (PC) morbidity adjusted for SDH as predictors; and (2) to analyze the geographic variability of the impact of SDH-adjusted PC morbidity on hospital morbidity, by combining data sourced from electronic health records and selected operations of the National Statistics Institute (Instituto Nacional de Estadística/INE).MethodsThe following will be conducted: a qualitative study to select socio-health indicators using RAND methodology in accordance with SDH frameworks, based on indicators published by the INE in selected operations; and a quantitative study combining two large databases drawn from different Spain’s Autonomous Regions (ARs) to enable hospital morbidity to be ascertained, i.e., PC electronic health records and the minimum basic data set (MBDS) for hospital discharges. These will be linked to socioeconomic indicators, previously selected by geographic unit. The outcome variable will be hospital morbidity, and the independent variables will be age, sex, PC morbidity, geographic unit, and socioeconomic indicators.AnalysisTo achieve the first objective, predictive models will be used, with a test-and-training technique, fitting multiple logistic regression models. In the analysis of geographic variability, penalized mixed models will be used, with geographic units considered as random effects and independent predictors as fixed effects.DiscussionThis study seeks to show the relationship between SDH and population health, and the geographic differences determined by such determinants. The main limitations are posed by the collection of data for healthcare as opposed to research purposes, and the time lag between collection and publication of data, sampling errors and missing data in registries and surveys. The main strength lies in the project’s multidisciplinary nature (family medicine, pediatrics, public health, nursing, psychology, engineering, geography).

IntroductionSince the COVID-19 outbreak, specific mRNA-based anti-SARS-CoV-2 vaccines have been developed and distributed worldwide. Because this is the first time that mRNA vaccines have been used, there are several questions regarding their capacity to confer immunity and the durability of the specific anti-SARS-CoV-2 response. Therefore, the objective of this study was to recruit a large cohort of healthcare workers from the Gregorio Marañón Hospital vaccinated with the mRNA-1273 or BNT126b2 vaccines and to follow-up on IgG anti-RBD levels at 8 months post-vaccination.MethodsWe recruited 4,970 volunteers and measured IgG anti-RBD antibodies on days 30 and 240 post-vaccination.ResultsWe observed that both vaccines induced high levels of antibodies on day 30, while a drastic wane was observed on day 240, where mRNA-1273 vaccinated induced higher levels than BNT162b2. Stratifying by vaccine type, age, gender, and comorbidities, we identified that older mRNA-1273-vaccinated volunteers had higher antibody levels than the younger volunteers, contrary to what was observed in the BNT162b2-vaccinated volunteers.DiscussionIn conclusion, we observed that mRNA-1273 has a higher capacity to induce a humoral response than BNT162b2 and that age is a factor in the specific response.

Several biological processes related to cancer malignancy are regulated by 17-β estradiol (E2) in ER+-breast cancer. To establish the role of E2 on the atypical cancer energy metabolism, a systematic study analyzing transcription factors, proteins, and fluxes associated with energy metabolism was undertaken in multicellular tumor spheroids (MCTS) from human ER+ MCF-7 breast cancer cells. At E2 physiological concentrations (10 and 100 nM for 24 h), both ERα and ERβ receptors, and their protein target pS2, increased by 0.6-3.5 times vs. non-treated MCTS, revealing an activated E2/ER axis. E2 also increased by 30-470% the content of several transcription factors associated to mitochondrial biogenesis and oxidative phosphorylation (OxPhos) (p53, PGC1-α) and glycolytic pathways (HIF1-α, c-MYC). Several OxPhos and glycolytic proteins (36-257%) as well as pathway fluxes (48-156%) significantly increased being OxPhos the principal ATP cellular supplier (>75%). As result of energy metabolism stimulation by E2, cancer cell migration and invasion processes and related proteins (SNAIL, FN, MM-9) contents augmented by 24-189% vs. non-treated MCTS. Celecoxib at 10 nM blocked OxPhos (60%) as well as MCTS growth, cell migration and invasiveness (>40%); whereas the glycolytic inhibitor iodoacetate (0.5 µM) and doxorubicin (70 nM) were innocuous. Our results show for the first time using a more physiological tridimensional cancer model, resembling the initial stages of solid tumors, that anti-mitochondrial therapy may be useful to deter hormone-dependent breast carcinomas.

There is now sufficient evidence to support that vitamin D deficiency may predispose to SARS-CoV-2 infection and increase COVID-19 severity and mortality. It has been suggested that vitamin D3 supplementation may be used prophylactically as an affordable and safe strategy that could be added to the existing COVID-19 standard treatment. This multicenter, single-blinded, prospective randomized pilot clinical trial aimed to evaluate the safety, tolerability, and effectiveness of 10,000 IU/day in comparison with 2000 IU/day of cholecalciferol supplementation for 14 days to reduce the duration and severity of COVID-19 in 85 hospitalized individuals. The median age of the participants was 65 years (Interquartile range (IQR): 53–74), most of them (71%) were men and the mean baseline of 25-hydroxyvitamin D (25(OH)D) in serum was 15 ng/ml (standard deviation (SD):6). After 14 days of supplementation, serum 25(OH)D levels were significantly increased in the group who received 10,000IU/day (p < 0.0001) (n = 44) in comparison with the 2,000IU/day group (n = 41), especially in overweight and obese participants, and the higher dose was well tolerated. A fraction of the individuals in our cohort (10/85) developed acute respiratory distress syndrome (ARDS). The median length of hospital stay in these patients with ARDS was significantly different in the participants assigned to the 10,000IU/day group (n = 4; 7 days; IQR: 4–13) and the 2,000IU/day group (n = 6; 27 days; IQR: 12–45) (p = 0.04). Moreover, the inspired oxygen fraction was reduced 7.6-fold in the high dose group (p = 0.049). In terms of blood parameters, we did not identify overall significant improvements, although the platelet count showed a modest but significant difference in those patients who were supplemented with the higher dose (p = 0.0492). In conclusion, the administration of 10,000IU/day of vitamin D3 for 14 days in association with the standard clinical care during hospitalization for COVID-19 was safe, tolerable, and beneficial, thereby helping to improve the prognosis during the recovery process.

Background: Several studies have reported that the use of chondroitin sulphate (CS) and glucosamine may reduce the risk of acute myocardial infarction. Although it is thought that this potential benefit could be extended to ischaemic stroke (IS), the evidence is scarce. Objective: To test the hypothesis that the use of prescription glucosamine or CS reduces the risk of IS. Design: Case–control study nested in an open cohort. Methods: Patients aged 40–99 years registered in a Spanish primary healthcare database (BIFAP) during the 2002–2015 study period. From this cohort, we identified incident cases of IS, applying a case-finding algorithm and specific validation procedures, and randomly sampled five controls per case, individually matched with cases by exact age, gender and index date. Adjusted odds ratios (AORs) and 95% confidence interval (CI) were computed through a conditional logistic regression. Only new users of glucosamine or CS were considered. Results: A total of 13,952 incident cases of IS and 69,199 controls were included. Of them, 106 cases (0.76%) and 803 controls (1.16%) were current users of glucosamine or CS at index date, yielding an AOR of 0.66 (95% CI: 0.54–0.82) (for glucosamine, AOR: 0.55; 95% CI: 0.39–0.77; and for CS, AOR: 0.77; 95% CI: 0.60–0.99). The reduced risk among current users was observed in both sexes (men, AOR: 0.69; 95% CI: 0.49–0.98; women, AOR: 0.65; 95% CI: 0.50–0.85), in individuals above and below 70 years of age (AOR: 0.69; 95% CI: 0.53–0.89 and AOR: 0.59; 95% CI: 0.41–0.85, respectively), in individuals with vascular risk factors (AOR: 0.53; 95% CI: 0.39–0.74) and among current/recent users of nonsteroidal anti-inflammatory drugs (NSAIDs) (AOR: 0.71; 95% CI: 0.55–0.92). Regarding duration, the reduced risk was observed in short-term users (364 days AOR: 0.86; 95% CI: 0.57–1.31). Conclusions: Our results support a protective effect of prescription CS and glucosamine in IS, which was observed even in patients at vascular risk. Mini abstract Our aim was to analyse whether the use of glucosamine or chondroitin sulphate (CS) reduces the risk of ischaemic stroke (IS). We detected a significant decrease.

The high morbimortality due to SARS-CoV-2 infection in oncohematological diseases (OHD) and hematopoietic stem cell transplant (HSCT) recipients in the pre-vaccine era has made vaccination a priority in this group. After HSCT, the immune responses against common vaccines such as tetanus, varicella, rubella, and polio may be lost. However, the loss of immunity developed by COVID-19 vaccination after HSCT has not been completely defined. In this study, both humoral and cellular immunity against SARS-CoV-2 were analyzed in 29 individuals with OHD who were vaccinated before receiving allogeneic (n = 11) or autologous (n = 18) HSCT. All participants had low but protective levels of neutralizing IgGs against SARS-CoV-2 after HSCT despite B-cell lymphopenia and immaturity. Although antibody-dependent cellular cytotoxicity was impaired, direct cellular cytotoxicity was similar to healthy donors in participants with autologous-HSCT, in contrast to individuals with allogeneic–HSCT, which severely deteriorated. No significant changes were observed in the immune response before and after HSCT. During follow-up, all reported post-HSCT SARS-CoV-2 infections were mild. This data emphasizes that COVID-19 vaccination is effective, necessary, and safe for individuals with OHD and also supports the persistence of some degree of immune protection after HSCT, at least in the short term, when patients cannot yet be revaccinated.

Abstract Background In the first wave of the COVID-19 pandemic, the hypothesis that angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) increased the risk and/or severity of the disease was widely spread. Consequently, in many hospitals, these drugs were discontinued as a “precautionary measure”. We aimed to assess whether the in-hospital discontinuation of ARBs or ACEIs, in real-life conditions, was associated with a reduced risk of death as compared to their continuation and also to compare head-to-head the continuation of ARBs with the continuation of ACEIs. Methods Adult patients with a PCR-confirmed diagnosis of COVID-19 requiring admission during March 2020 were consecutively selected from 7 hospitals in Madrid, Spain. Among them, we identified outpatient users of ACEIs/ARBs and divided them in two cohorts depending on treatment discontinuation/continuation at admission. Then, they were followed-up until discharge or in-hospital death. An intention-to-treat survival analysis was carried out and hazard ratios (HRs), and their 95%CIs were computed through a Cox regression model adjusted for propensity scores of discontinuation and controlled by potential mediators. Results Out of 625 ACEI/ARB users, 340 (54.4%) discontinued treatment. The in-hospital mortality rates were 27.6% and 27.7% in discontinuation and continuation cohorts, respectively (HR=1.01; 95%CI 0.70–1.46). No difference in mortality was observed between ARB and ACEI discontinuation (28.6% vs. 27.1%, respectively), while a significantly lower mortality rate was found among patients who continued with ARBs (20.8%, N=125) as compared to those who continued with ACEIs (33.1%, N=136; p=0.03). The head-to-head comparison (ARB vs. ACEI continuation) yielded an adjusted HR of 0.52 (95%CI 0.29–0.93), being especially notorious among males (HR=0.34; 95%CI 0.12–0.93), subjects older than 74 years (HR=0.46; 95%CI 0.25–0.85), and patients with obesity (HR=0.22; 95%CI 0.05–0.94), diabetes (HR=0.36; 95%CI 0.13–0.97), and heart failure (HR=0.12; 95%CI 0.03–0.97). Conclusions The discontinuation of ACEIs/ARBs at admission did not improve the in-hospital survival. On the contrary, the continuation with ARBs was associated with a trend to a reduced mortality as compared to their discontinuation and to a significantly lower mortality risk as compared to the continuation with ACEIs, particularly in high-risk patients.

Main cause of severe illness and death in COVID-19 patients appears to be an excessive but ineffectual inflammatory immune response that may cause severe acute respiratory distress syndrome (ARDS). Vitamin D may favour an anti-inflammatory environment and improve cytotoxic response against some infectious diseases. A multicenter, single-blind, prospective, randomized clinical trial was approved in patients with COVID-19 pneumonia and levels of 25-hydroxyvitamin D (25(OH)D) of 14.8 ng/ml (SD: 6.18) to test antiviral efficacy, tolerance and safety of 10,000 IU/day of cholecalciferol (vitamin D3) for 14 days, in comparison with 2000 IU/day. After supplementation, mean serum 25(OH)D levels increased to 19 ng/ml on average in 2000 IU/day versus 29 ng/ml in 10,000 IU/day group (p

Introduction COVID-19 disease has caused a global health and economic crisis. The introduction of the different COVID-19 vaccines has resulted in a significant decrease in the morbidity and mortality associated with this disease. Adverse effects have been reported, including cardiological ones such as myocarditis or pericarditis after administration. Likewise, tyrosine kinase inhibitor drugs such as osimertinib used in lung cancer patients with epidermal growth factor receptor (EGFR) mutation are associated with heart failure or prolongation of the QT interval.Case report 62-year-old woman diagnosed in September 2019 of lung adenocarcinoma stage IV with bilateral lung and lymph node involvement, carrier of an EGFR mutation (Ex19Del) on treatment with osimertinib. She attended emergency department for fever and hypotension 24 h after administration of the third dose of Moderna® COVID-19 vaccine in the context of acute myocarditis with evidence of severe left ventricular (LV) dysfunction in cardiogenic shock. She required vasoactive support, non-invasive mechanical ventilation, corticotherapy, immunoglobulins and subsequent ventricular support with Impella, with improvement of the clinical picture after 3 days. Cardiac magnetic resonance imaging (MRI) showed evidence of global myocardial oedema compatible with acute myocarditis. Coronary CT showed a lesion in the anterior descending coronary artery requiring revascularization. A few days later, she presented febrile symptoms with isolation of Staphylococcus aureus in the central line catheter and antibiotherapy with cloxacillin was started, with subsequent resolution of the infectious symptoms.Conclusion This is an exceptional and controversial case of fulminant myocarditis probably related to the Modern COVID-19 vaccine in a patient diagnosed with metastatic lung adenocarcinoma on treatment with osimertinib. An increasing number of cases of myocarditis and pericarditis have been reported following vaccination with COVID-19 mRNA vaccines. In addition, retrospective data have shown an increased risk of QT prolongation and heart failure in patients treated with tyrosine kinase inhibitors. Hence, the need for close monitoring of cardiac function during treatment of these patients. Future studies will be necessary to evaluate unknown adverse reactions of these vaccines and their possible interaction with other antineoplastic drugs.

LGMDD2 is a rare form of muscular dystrophy characterized by one of the three heterozygous deletions described within the TNPO3 gene that result in the addition of a 15-amino acid tail in the C-terminus.TNPO3 is involved in the nuclear import of splicing factors and acts as a host cofactor for HIV-1 infection by mechanisms not yet deciphered. Further characterization of the crosstalk between HIV-1 infection and LGMDD2 disease may contribute to a better understanding of both the cellular alterations occurring in LGMDD2 patients and the role of TNPO3 in the HIV-1 cycle. To this regard, transcriptome profiling of PBMCs from LGMDD2 patients carrying the deletion c.2771delA in the TNPO3 gene was compared to healthy controls. A total of 545 differentially expressed genes were detected between LGMDD2 patients and healthy controls, with a high representation of G protein-coupled receptor binding chemokines and metallopeptidases among the most upregulated genes in LGMDD2 patients. Plasma levels of IFN-β and IFN-γ were 4.7- and 2.7-fold higher in LGMDD2 patients, respectively. An increase of 2.3-fold in the expression of the interferon-stimulated gene MxA was observed in activated PBMCs from LGMDD2 patients after ex vivo HIV-1 pseudovirus infection. Thus, the analysis suggests a pro-inflammatory state in LGMDD2 patients also described for other muscular dystrophies, that is characterized by the alteration of IL-17 signaling pathway and the consequent increase of metallopeptidases activity and TNF response. In summary, the increase in interferons and inflammatory mediators suggests an antiviral environment and resistance to HIV-1 infection but that could also impair muscular function in LGMDD2 patients, worsening disease evolution. Biomarkers of disease progression and therapeutic strategies based on these genes and mechanisms should be further investigated for this type of muscular dystrophy.

MoS2 nanoflowers (NFs) obtained through a hydrothermal approach were used as the substrate for the deposition of tiny spherical bimetallic AuAg or monometallic Au nanoparticles (NPs), leading to novel photothermal-assisted catalysts with different hybrid nanostructures and showing improved catalytic performance under NIR laser irradiation. The catalytic reduction of pollutant 4-nitrophenol (4-NF) to the valuable product 4-aminophenol (4-AF) was evaluated. The hydrothermal synthesis of MoS2 NFs provides a material with a broad absorption in the Vis-NIR region of the electromagnetic spectrum. The in situ grafting of alloyed AuAg and Au NPs of very small size (2.0–2.5 nm) was possible through the decomposition of organometallic complexes [Au2Ag2(C6F5)4(OEt2)2]n and [Au(C6F5)(tht)] (tht = tetrahydrothiophene) using triisopropilsilane as reducing agent, leading to nanohybrids 1–4. The new nanohybrid materials display photothermal properties arising from NIR light absorption of the MoS2 NFs component. The AuAg-MoS2 nanohybrid 2 showed excellent photothermal-assisted catalytic activity for the reduction of 4-NF, which is better than that of the monometallic Au-MoS2 nanohybrid 4. The obtained nanohybrids were characterised by transmission electron microscopy (TEM), High Angle Annular Dark Field—Scanning Transmission Electron Microscopy—Energy Dispersive X-ray Spectroscopy (HAADF-STEM-EDS), X-ray photoelectron spectroscopy and UV-Vis-NIR spectroscopy.

Real world applications using agent-based solutions can include many agents that needs communicate and interact each other in order to meet their objectives. In open multi-agent systems, the problems may include the organisation of a large number of agents that may be heterogeneous, of unpredictable provenance and where competitive behaviours or conflicting objectives may occur. An overview of the alternatives for dealing with these problems is presented, highlighting the way they try to solve or mitigate these problems.

Long-COVID is a new emerging syndrome worldwide that is characterized by the persistence of unresolved signs and symptoms of COVID-19 more than 4 weeks after the infection and even after more than 12 weeks. The underlying mechanisms for Long-COVID are still undefined, but a sustained inflammatory response caused by the persistence of SARS-CoV-2 in organ and tissue sanctuaries or resemblance with an autoimmune disease are within the most considered hypotheses. In this study, we analyzed the usefulness of several demographic, clinical, and immunological parameters as diagnostic biomarkers of Long-COVID in one cohort of Spanish individuals who presented signs and symptoms of this syndrome after 49 weeks post-infection, in comparison with individuals who recovered completely in the first 12 weeks after the infection. We determined that individuals with Long-COVID showed significantly increased levels of functional memory cells with high antiviral cytotoxic activity such as CD8+ TEMRA cells, CD8±TCRγδ+ cells, and NK cells with CD56+CD57+NKG2C+ phenotype. The persistence of these long-lasting cytotoxic populations was supported by enhanced levels of CD4+ Tregs and the expression of the exhaustion marker PD-1 on the surface of CD3+ T lymphocytes. With the use of these immune parameters and significant clinical features such as lethargy, pleuritic chest pain, and dermatological injuries, as well as demographic factors such as female gender and O+ blood type, a Random Forest algorithm predicted the assignment of the participants in the Long-COVID group with 100% accuracy. The definition of the most accurate diagnostic biomarkers could be helpful to detect the development of Long-COVID and to improve the clinical management of these patients.

Desmoplastic stroma (DS) and the epithelial-to-mesenchymal transition (EMT) play a key role in pancreatic ductal adenocarcinoma (PDAC) progression. To date, however, the combined expression of DS and EMT markers, and their association with variations in survival within each clinical stage and degree of tumor differentiation is unknown. The purpose of this study was to investigate the association between expression of DS and EMT markers and survival variability in patients diagnosed with PDAC. We examined the expression levels of DS markers alpha smooth muscle actin (α-SMA), fibronectin, and vimentin, and the EMT markers epithelial cell adhesion molecule (EPCAM), pan-cytokeratin, and vimentin, by immunohistochemistry using a tissue microarray of a retrospective cohort of 25 patients with PDAC. The results were examined for association with survival by clinical stage and by degree of tumor differentiation. High DS markers expression -α-SMA, fibronectin, and vimentin- was associated with decreased survival at intermediate and advanced clinical stages (p=0.006-0.03), as well as with both poorly and moderately differentiated tumor grades (p=0.01-0.02). Interestingly, the same pattern was observed for EMT markers, i.e., EPCAM, pan-cytokeratin, and vimentin (p=0.00008-0.03). High expression of DS and EMT markers within each clinical stage and degree of tumor differentiation was associated with lower PDAC survival. Evaluation of these markers may have a prognostic impact on survival time variation in patients with PDAC.

The clinical presentations of COVID-19 may range from an asymptomatic or mild infection to a critical or fatal disease. Several host factors such as elderly age, male gender, and previous comorbidities seem to be involved in the most severe outcomes, but also an impaired immune response that causes a hyperinflammatory state but is unable to clear the infection. In order to get further understanding about this impaired immune response, we aimed to determine the association of specific HLA alleles with different clinical presentations of COVID-19. Therefore, we analyzed HLA Class I and II, as well as KIR gene sequences, in 72 individuals with Spanish Mediterranean Caucasian ethnicity who presented mild, severe, or critical COVID-19, according to their clinical characteristics and management. This cohort was recruited in Madrid (Spain) during the first and second pandemic waves between April and October 2020. There were no significant differences in HLA-A or HLA-B alleles among groups. However, despite the small sample size, we found that HLA-C alleles from group C1 HLA-C*08:02, -C*12:03, or -C*16:01 were more frequently associated in individuals with mild COVID-19 (43.8%) than in individuals with severe (8.3%; p = 0.0030; pc = 0.033) and critical (16.1%; p = 0.0014; pc = 0.0154) disease. C1 alleles are supposed to be highly efficient to present peptides to T cells, and HLA-C*12:03 may present a high number of verified epitopes from abundant SARS-CoV-2 proteins M, N, and S, thereby being allegedly able to trigger an efficient antiviral response. On the contrary, C2 alleles are usually poorly expressed on the cell surface due to low association with β2-microglobulin (β2M) and peptides, which may impede the adequate formation of stable HLA-C/β2M/peptide heterotrimers. Consequently, this pilot study described significant differences in the presence of specific HLA-C1 alleles in individuals with different clinical presentations of COVID-19, thereby suggesting that HLA haplotyping could be valuable to get further understanding in the underlying mechanisms of the impaired immune response during critical COVID-19.

Abstract Background The aim of our study is to study the association between eye lesions in Hereditary Hemorrhagic Telangiectasia (HHT) and other signs of the disease, as well as to characterize its genetics. Methods A cross-sectional study was conducted of a cohort of 206 patients studied in the HHT Unit of Hospital de Sierrallana, a reference centre for Spanish patients with HHT. Odds ratios for several symptoms or characteristics of HHT and ocular lesions were estimated using logistic regression adjusting for age and sex. Results The ocular involvement was associated with being a carrier of a mutation for the ENG gene, that is, suffering from a type 1 HHT involvement (OR = 2.09; 95% CI [1.17–3.72]). p = 0.012). In contrast, patients with ocular lesions have less frequently mutated ACVRL1/ALK1 gene (OR = 0.52; 95% CI [0.30–3.88], p = 0.022). Conclusions In conclusion, half of the patients with HHT in our study have ocular involvement. These eye lesions are associated with mutations in the ENG gene and ACVRL1/ALK1 gene. Thus, the ENG gene increases the risk of ocular lesions, while being a carrier of the mutated ACVRL1/ALK1 gene decreases said risk.

The humoral immune response developed after receiving the full vaccination schedule against COVID-19 is impaired in individuals who received anti-CD20 therapy 6–9 months before vaccination. However, there is little information about the cellular immune responses elicited in these individuals. In this study, we analyzed the humoral and cellular immune responses in 18 individuals with hematological disease who received the last dose of rituximab 13.8 months (IQR 9.4–19) before the booster dose. One month after receiving the booster dose, the seroconversion rate in the rituximab-treated cohort increased from 83.3% to 88.9% and titers of specific IgGs against SARS-CoV-2 increased 1.53-fold (p = 0.0098), while the levels of neutralizing antibodies increased 3.03-fold (p = 0.0381). However, the cytotoxic activity of peripheral blood mononuclear cells (PBMCs) from rituximab-treated individuals remained unchanged, and both antibody-dependent cellular cytotoxicity (ADCC) and direct cellular cytotoxicity (CDD) were reduced 1.7-fold (p = 0.0047) and 2.0-fold (p = 0.0086), respectively, in comparison with healthy donors. Breakthrough infections rate was higher in our cohort of rituximab-treated individuals (33.33%), although most of the infected patients (83.4%) developed a mild form of COVID-19. In conclusion, our findings confirm a benefit in the humoral, but not in the cellular, immune response in rituximab-treated individuals after receiving a booster dose of an mRNA-based vaccine against COVID-19.

SARS-CoV-2 infection causes COVID-19, ranging from mild to critical disease in symptomatic subjects. It is essential to better understand the immunologic responses occurring in patients with the most severe outcomes. In this study, parameters related to the humoral immune response elicited against SARS-CoV-2 were analysed in 61 patients with different presentations of COVID-19 who were recruited in Hospitals and Primary Healthcare Centres in Madrid, Spain, during the first pandemic peak between April and June 2020. Subjects were allocated as mild patients without hospitalization, severe patients hospitalized or critical patients requiring ICU assistance. Critical patients showed significantly enhanced levels of B cells with memory and plasmablast phenotypes, as well as higher levels of antibodies against SARS-CoV-2 with neutralization ability, which were particularly increased in male gender. Despite all this, antibody-dependent cell-mediated cytotoxicity was defective in these individuals. Besides, patients with critical COVID-19 also showed increased IgG levels against herpesvirus such as CMV, EBV, HSV-1 and VZV, as well as detectable CMV and EBV viremia in plasma. Altogether, these results suggest an enhanced but ineffectual immune response in patients with critical COVID-19 that allowed latent herpesvirus reactivation. These findings should be considered during the clinical management of these patients due to the potential contribution to the most severe disease during SARS-CoV-2 infection.

Under dysbiosis, a gut metabolic disorder, short-chain carboxylic acids (SCCAs) are secreted to the lumen, affecting colorectal cancer (CRC) development. Butyrate and propionate act as CRC growth inhibitors, but they might also serve as carbon source. In turn, the roles of acetate as metabolic fuel and protein acetylation promoter have not been clearly elucidated. To assess whether acetate favors CRC growth through active mitochondrial catabolism, a systematic study evaluating acetate thiokinase (AcK), energy metabolism, cell proliferation, and invasiveness was performed in two CRC cell lines incubated with physiological SCCAs concentrations. In COLO 205, acetate (+glucose) increased the cell density (50%), mitochondrial protein content (3–10 times), 2-OGDH acetylation, and oxidative phosphorylation (OxPhos) flux (36%), whereas glycolysis remained unchanged vs. glucose-cultured cells; the acetate-induced OxPhos activation correlated with a high AcK activity, content, and acetylation (1.5–6-fold). In contrast, acetate showed no effect on HCT116 cell growth, OxPhos, AcK activity, protein content, and acetylation. However, a substantial increment in the HIF-1α content, HIF-1α-glycolytic protein targets (1–2.3 times), and glycolytic flux (64%) was observed. Butyrate and propionate decreased the growth of both CRC cells by impairing OxPhos flux through mitophagy and mitochondrial fragmentation activation. It is described, for the first time, the role of acetate as metabolic fuel for ATP supply in CRC COLO 205 cells to sustain proliferation, aside from its well-known role as protein epigenetic regulator. The level of AcK determined in COLO 205 cells was similar to that found in human CRC biopsies, showing its potential role as metabolic marker.

La muerte es un suceso natural al que todas las personas se enfrentan alguna vez en la vida. Por ello, resulta fundamental trabajar el duelo y la muerte desde las etapas más tempranas. La propuesta de intervención escolar presentada parte de una exhaustiva revisión del currículo oficial español de Educación Infantil y Educación Primaria, el cual no aborda el tema del duelo (De la Herrán, Rodríguez y De Miguel, 2019) y se sustenta en una amplia revisión bibliográfica. Esta propuesta de trabajo transversal a partir de la pedagogía de la muerte tiene como objetivo principal formar al alumnado de tres a doce años y a sus familias con relación al tema del duelo, la conciencia de finitud y las situaciones de pérdida. Se compone de distintas sesiones de trabajo cooperativo dirigidas por el profesorado: sesiones curriculares y extracurriculares de Educación Infantil y Educación Primaria, sesiones mixtas con alumnado de Infantil y Primaria y sesiones extraescolares con la participación de las familias. La temporalización abarcaría todo un año escolar, siendo óptima la prórroga del plan a lo largo de los cursos para garantizar la formación integral del alumnado a lo largo de toda su escolarización. La implantación de este plan de intervención, acompañado de la pertinente formación docente, resulta esencial para permitir al alumnado comprender y disfrutar la vida y aceptar la pérdida gracias a la pedagogía de la muerte en la escuela (De la Herrán y Cortina, 2006).

Our aim was to investigate the role of left atrial longitudinal strain (LALS) in the non-invasive diagnosis of acute cellular rejection (ACR) episodes in heart transplant (HTx) recipients. Methods: We performed successive echocardiographic exams in 18 consecutive adult HTx recipients in their first year after HTx within 3 h of the routine surveillance endomyocardial biopsies (EMB) in a single center. LALS parameters were analyzed with two different software. We investigated LALS association with ACR presence, as well as inter-vendor variability in comparable LALS values. Results: A total of 147 pairs of EMB and echo exams were carried out. Lower values of LALS were significantly associated with any grade of ACR presence. Peak atrial longitudinal strain (PALS) offered the best diagnostic value for any grade of ACR, with a C statistic of 0.77 using one software (95% CI 0.68–0.84, p < 0.0005) and 0.64 with the other (95% CI 0.54–0.73, p = 0.013) (p = 0.02 for comparison between both curves). Reproducibility between comparable LALS parameters was poor (intraclass correlation coefficients were 0.60 for PALS, 95% CI 0.42–0.73, p < 0.0005; and 0.42 for PALS rate, 95% CI −0.13–0.68, p < 0.0005). Conclusions: LALS variables might be a sensitive marker of ACR in HTx recipients, principally discriminating between those studies without rejection and those with any grade of ACR. Inter-vendor variability was significant.

Microplastics (MPs) have been recognized as an environmental threat due to their persistence, ubiquity, and toxicity potential. Due to their small size, MPs are endowed with a large specific surface area, having the ability to sorb and accumulate other contaminants that co-exist with them in the aquatic environment as it is the case of pharmaceuticals. In this way, MPs can act as vectors, facilitating the contact of pharmaceuticals with aquatic organisms. Once ingested, MPs may desorb pharmaceuticals, increasing their bioavailability, which could promote their bioaccumulation and biomagnification through the food web as well as modulate their toxic effects. Microplastics may differently impact the toxicity of pharmaceuticals by potentiating (synergism) or decreasing (antagonism) it. This review aims at highlighting the role of MPs as vectors of pharmaceuticals to aquatic organisms and how the interaction of these emerging contaminants may influence the bioaccumulation and toxicity of pharmaceuticals on biota. Examples of different scenarios resulting from the exposure of aquatic life to MPs and pharmaceuticals are presented. Future studies should cover a broader range of polymer types and environmental realistic concentrations to better understand the impact of MPs on the bioaccumulation and toxicity of pharmaceuticals.

Infection by novel coronavirus SARS-CoV-2 causes different presentations of COVID-19 and some patients may progress to a critical, fatal form of the disease that requires their admission to ICU and invasive mechanical ventilation. In order to predict in advance which patients could be more susceptible to develop a critical form of COVID-19, it is essential to define the most adequate biomarkers. In this study, we analyzed several parameters related to the cellular immune response in blood samples from 109 patients with different presentations of COVID-19 who were recruited in Hospitals and Primary Healthcare Centers in Madrid, Spain, during the first pandemic peak between April and June 2020. Hospitalized patients with the most severe forms of COVID-19 showed a potent inflammatory response that was not translated into an efficient immune response. Despite the high levels of effector cytotoxic cell populations such as NK, NKT and CD8+ T cells, they displayed immune exhaustion markers and poor cytotoxic functionality against target cells infected with pseudotyped SARS-CoV-2 or cells lacking MHC class I molecules. Moreover, patients with critical COVID-19 showed low levels of the highly cytotoxic TCRγδ+ CD8+ T cell subpopulation. Conversely, CD4 count was greatly reduced in association to high levels of Tregs, low plasma IL-2 and impaired Th1 differentiation. The relative importance of these immunological parameters to predict COVID-19 severity was analyzed by Random Forest algorithm and we concluded that the most important features were related to an efficient cytotoxic response. Therefore, efforts to fight against SARS-CoV-2 infection should be focused not only to decrease the disproportionate inflammatory response, but also to elicit an efficient cytotoxic response against the infected cells and to reduce viral replication.

Background Previous studies investigating the relationship of influenza with acute myocardial infarction (AMI) have not distinguished between AMI types 1 and 2. Influenza and cold temperature can explain the increased incidence of AMI during winter but, because they are closely related in temperate regions, their relative contribution is unknown. Methods and Results The temporal relationship between incidence rates of AMI with demonstrated culprit plaque (type 1 AMI) from the regional primary angioplasty network and influenza, adjusted for ambient temperature, was studied in Madrid region (Spain) during 5 influenza seasons (from June 2013 to June 2018). A time‐series analysis with quasi‐Poisson regression models and distributed lag‐nonlinear models was used. The incidence rate of type 1 AMI according to influenza vaccination status was also explored. A total of 8240 cases of confirmed type 1 AMI were recorded. The overall risk ratio (RR) of type 1 AMI during epidemic periods, adjusted for year, month, and temperature, was 1.23 (95% CI, 1.03–1.47). An increase of weekly influenza rate of 50 cases per 100 000 inhabitants resulted in an RR for type 1 AMI of 1.16 (95% CI, 1.09–1.23) during the same week, disappearing 1 week after. When adjusted for influenza, a decrease of 1ºC in the minimum temperature resulted in an increase of 2.5% type 1 AMI. Influenza vaccination was associated with a decreased risk of type 1 AMI in subjects aged 60 to 64 years (RR, 0.58; 95% CI, 0.47–0.71) and ≥65 years (RR, 0.53; 95% CI, 0.49–0.57). Conclusions Influenza and cold temperature were both independently associated with an increased risk of type 1 AMI, whereas vaccination was associated with a reduced risk among older patients.

El Internet de las Cosas ha venido incorporándose a nuestras vidas de forma progresiva, trayendo consigo grandes beneficios para la humanidad como lo es disponer de infraestructuras y servicios más interconectados y eficientes, generación de empleo, reducción de costos operativos e incremento de ganancias. En este sentido, el desarrollo e instalación de sensores avanzados para recolección de datos, las soluciones informáticas de conexión remota y otras tecnologías disruptivas están marcando un proceso de transformación en la industria; dando inicio a lo que diversos sectores han denominado cuarta revolución industrial o Industria 4.0. En este artículo se presenta un modelo predictivo para la extracción de patrones utilizando técnicas de fusión de datos que permitan el diseño de un modelo de mantenimiento predictivo, a través de un enfoque de entrenamiento supervisado, realizar la clasificación de datos y probabilísticamente valores predictivos.

Objetivo: Describir la percepción de enfermedad, características de personalidad y la dinámica familiar de niños y adolescentes afectados por VIH, teniendo en cuenta sus características sociodemográficas y la revelación o no del diagnóstico. Método: Es un estudio de tipo cualitativo, con diseño de teoría fundamentada. La muestra estuvo conformada por 14 niños y adolescentes afectados por VIH y diagnosticados desde su nacimiento, entre 6 y 15 años de edad. El muestreo fue no probabilístico intencional o con fines especiales. Se utilizó el test de Machover, el test de la familia y un cuestionario de preguntas abiertas y cerradas sobre percepción de enfermedad. Resultados: Se encontró que los participantes que no tienen conocimiento sobre su diagnóstico, a diferencia de los que han pasado por un proceso de revelación, poseen una autoimagen perturbada con tendencias a baja autoestima y autoconcepto pobre. A su vez, las conversaciones y los dibujos realizados por ellos sugieren sensación y tendencia a la soledad, inseguridad, deterioro a nivel de las relaciones familiares e interpersonales, evidenciando la existencia de una percepción de enfermedad negativa, que puede incidir en su desarrollo personal y social corroborando lo encontrado por Instone (2000), Trejos, Reyes, Bahamón y Alarcón (2014), Pérez Quiroz, et al. (2013) y Ehrenzweig (2005). Conclusiones: El presente estudio reconoce la importancia de llevar a cabo procesos adecuados de revelación del diagnóstico para el VIH en niños y adolescentes, permitiendo la mejora de su calidad de vida en pro de su desarrollo biopsicosocial teniendo en cuenta la normalización del ajuste psicológico y mantenimiento del cumplimiento terapéutico, atendiendo a las directrices internacionales sobre el tema de la revelación.