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Matters arising from: Mapping the human genetic architecture of COVID-19 Original Article published on 08 July 2021 https://www.nature.com/articles/s41586-021-03767-x The COVID-19 pandemic continues to pose a major public health threat, especially in countries with low vaccination rates. To better understand the biological underpinnings of SARS-CoV-2 infection and COVID-19 severity, we formed the COVID-19 Host Genetics Initiative1. Here we present a genome-wide association study meta-analysis of up to 125,584 cases and over 2.5 million control individuals across 60 studies from 25 countries, adding 11 genome-wide significant loci compared with those previously identified2. Genes at new loci, including SFTPD, MUC5B and ACE2, reveal compelling insights regarding disease susceptibility and severity. Here we present meta-analyses bringing together 60 studies from 25 countries (Fig. 1 and Supplementary Table 1) for three COVID-19-related phenotypes: (1) individuals critically ill with COVID-19 on the basis of requiring respiratory support in hospital or who died as a consequence of the disease (9,376 cases, of which 3,197 are new in this data release, and 1,776,645 control individuals); (2) individuals with moderate or severe COVID-19 defined as those hospitalized due to symptoms associated with the infection (25,027 cases, 11,386 new and 2,836,272 control individuals); and (3) all cases with reported SARS-CoV-2 infection regardless of symptoms (125,584 cases, 76,022 new and 2,575,347 control individuals). Most studies have reported results before the roll out of the COVID-19 vaccination campaign. An overview of the study design is provided in Supplementary Fig. 1. We found a total of 23 genome-wide significant loci (P

Dispersal is a key demographic process involving three stages: emigration, transience and settlement; each of which is influenced by individual, social and environmental determinants. An integrated understanding of species dispersal is essential for demographic modelling and conservation planning. Here, we review the dispersal patterns and determinants documented in the scientific literature for the grey wolf (Canis lupus) across its distribution range. We showed a surprisingly high variability within and among study areas on all dispersal parameters – dispersal rate, direction, distance, duration and success. We found that such large variability is due to multiple individual, social and environmental determinants, but also due to previously overlooked methodological research issues. We revealed a potential non-linear relationship between dispersal rate and population density, with dispersal rate higher at both ends of the gradient of population density. We found that human-caused mortality reduces distance, duration and success of dispersal events. Furthermore, dispersers avoid interaction with humans, and highly exposed areas like agricultural lands hamper population connectivity in many cases. We identified numerous methodological research problems that make it difficult to obtain robust estimates of dispersal parameters and robust inferences on dispersal patterns and their determinants. In particular, analyses where confounding factors were not accounted for led to substantial knowledge gaps on all aspects of dispersal in an otherwise much-studied species. Our understanding of wolf biology and management would significantly benefit if wolf dispersal studies reported the results and possible factors affecting wolf dispersal more transparently.

Out of the three core proteins in human adenovirus, protein V is believed to connect the inner capsid surface to the outer genome layer. Here, we explored mechanical properties and in vitro disassembly of particles lacking protein V (Ad5-ΔV). Ad5-ΔV particles were softer and less brittle than the wild-type ones (Ad5-wt), but they were more prone to release pentons under mechanical fatigue. In Ad5-ΔV, core components did not readily diffuse out of partially disrupted capsids, and the core appeared more condensed than in Ad5-wt. These observations suggest that instead of condensing the genome, protein V antagonizes the condensing action of the other core proteins. Protein V provides mechanical reinforcement and facilitates genome release by keeping DNA connected to capsid fragments that detach during disruption. This scenario is in line with the location of protein V in the virion and its role in Ad5 cell entry.

8 Pág. Centro de Investigación en Sanidad Animal (CISA), E/D163 polymorphism of dog prion protein (PrP) has been recently proposed as the variant responsible for canid prion resistance. To further investigate the protective role of this variant against prion replication, the transgenic mouse model OvPrP-Tg532 expressing sheep/goat PrP carrying the substitution D162 (equivalent to D163 position of dog PrP) was generated and intracranially inoculated with a broad collection of small ruminant prion strains. OvPrP-Tg532 mice showed resistance to classical bovine spongiform encephalopathy (BSE) from sheep and some classical scrapie isolates from sheep and goat but were susceptible to ovine atypical L-BSE and numerous classical scrapie isolates. Strikingly, some of these classical scrapie isolates showed a shift in their prion strain properties. These results suggest that other PrP residues apart from E/D163 variant of dog PrP or factors distinct than PrP may participate in prion resistance of canids and that different factors may be required for D162 sheep PrP to provide effective protection to sheep against ruminant prions., This work was supported by grants from the Spanish Ministerio de Ciencia PDI2019-105837RB-I00, Spanish Ministerio de Economía y Competitividad [AGL2016-78054-R (AEI/FEDER, UE) and AGL2009-11553-C02-02 and fellowship BES-2010-040922 to P.A.C.] and the Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (fellowship FPI-SGIT-2015-02 to A.M.M.).

Climate change is forcing the redistribution of life on Earth at an unprecedented velocity1,2. Migratory birds are thought to help plants to track climate change through long-distance seed dispersal3,4. However, seeds may be consistently dispersed towards cooler or warmer latitudes depending on whether the fruiting period of a plant species coincides with northward or southward migrations. Here we assess the potential of plant communities to keep pace with climate change through long-distance seed dispersal by migratory birds. To do so, we combine phenological and migration information with data on 949 seed-dispersal interactions between 46 bird and 81 plant species from 13 woodland communities across Europe. Most of the plant species (86%) in these communities are dispersed by birds migrating south, whereas only 35% are dispersed by birds migrating north; the latter subset is phylogenetically clustered in lineages that have fruiting periods that overlap with the spring migration. Moreover, the majority of this critical dispersal service northwards is provided by only a few Palaearctic migrant species. The potential of migratory birds to assist a small, non-random sample of plants to track climate change latitudinally is expected to strongly influence the formation of novel plant communities, and thus affect their ecosystem functions and community assembly at higher trophic levels., The ‘Molecular Ecology Laboratory’ (LEM–EBD–CSIC; ISO9001:2015 and ISO14001:2015 certifications) and the ‘Research Unit of Biodiversity’ (UO–CSIC–PA) provided logistical support for molecular analyses. We thank L. Viesca and E. Cires for laboratory assistance, and J. M. Varela for the bird illustrations. Barcoding data were obtained within an Individual Fellowship from the Marie Sklodowska-Curie Actions (H2020-MSCA-IF-2014-656572: MobileLinks) and supported by a GRUPIN grant from the Regional Government of Asturias (IDI/2018/000151). ‘King Jaume I’ awarded to A.T. supported data collation during two postdoctoral contracts. J.P.G.-V. is supported by a Spanish ‘Ramón y Cajal’ fellowship (RYC-2017-22095) and a grant from the Spanish MICINN (PID2019-104922GA-I00/AEI/10.13039/501100011033). B.R. is supported by a Spanish ‘Juan de la Cierva Incorporación’ fellowship (IJCI-2017-33475). R.H.H. is funded by the Portuguese Foundation for Science and Technology (UID/BIA/04004/2020). B.I.S. is supported by a Royal Commission for the Exhibition of 1851 Research Fellowship. W.J.S. is funded by Arcadia.

Telmatobius atacamensis, anuro microendémico de la Puna salteña, tiene hábitos exclusivamente acuáticos. Está categorizado como especie en peligro crítico a nivel global y como amenazada a nivel nacional. El conocimiento de la ecología trófica es útil para mejorar manejo y conservación de una especie y, debido a que esta información es escasa, el objetivo fue describir y analizar su dieta. Mediante la técnica de lavado estomacal se obtuvieron 37 contenidos de individuos recolectados en los ríos San Antonio y Los Patos durante un ciclo anual (2018), una vez al mes. Se registraron 724 presas, pertenecientes a diez órdenes; dípteros, coleópteros y hemípteros fueron los más importantes. No hubo correlación significativa entre el tamaño depredador-presa. Tampoco hubo diferencias significativas entre hembras, machos y juveniles y el número y volumen de presas consumidas. El índice de diversidad de la dieta fue de 1,05 y la amplitud del nicho trófico estandarizado fue de 0,09. La superposición de nicho entre las categorías fue de Ojk = 0,80. De acuerdo con el índice de similitud de Jaccard, las dietas de hembras y juveniles fueron más semejantes (71 %). Presentaron una predominancia al consumo de invertebrados de hábitos bentónicos y, si bien se encontraron presas de hábitos terrestres, podría deberse a un consumo accidental. Este consumo desproporcionado de fauna bentónica estaría directamente relacionado con los hábitos de vida de la especie. Por otro lado, la composición de la dieta no varía significativamente entre las categorías consideradas, sin registrar diferencias en la cantidad y volumen de presas.

Introduction Clostridioides difficile biofilms are believed to protect the pathogen from antibiotics, in addition to potentially contributing to recurrent infections. Methodology Biofilm production of 102 C. difficile isolates was determined using the crystal violet staining technique, and detachment assays were performed. The expression levels of cwp84 and slpA genes were evaluated by real-time PCR on selected isolates. Results More than 70% of isolates (75/102) were strong biofilm producers, and the highest detachment of biofilm was achieved with the proteinase K treatment (>90%). The overall mean expression of cwp84 was higher in RT027 than in RT001 (p = 0.003); among strong biofilm-producing strains, the slpA expression was lower in RT027 than in RT001 (p Conclusions Proteins seem to have an important role in the biofilm's initial adherence and maturation. slpA and cwp84 are differentially expressed by C. difficile ribotype and biofilm production level.

Resumen Introduccion En el mundo, alrededor de 50 millones de personas padecen demencia; la forma mas comun es la enfermedad de Alzheimer (EA), que representa el 60-70% de los casos. Dada su alta incidencia, se hace imperativo disenar estudios que permitan ampliar el conocimiento sobre su aparicion y desarrollo, para proponer diagnosticos tempranos y/o posibles tratamientos. Una de las estrategias metodologicas que se han desarrollado son los modelos transgenicos murinos para el estudio de los factores involucrados en su etiologia, y entre ellos, el estres oxidativo y la respuesta inmune. Desarrollo Se realizo una busqueda de articulos originales y revisiones en PubMed, Scopus y Google Scholar (2013-2019). En esta revision abordamos dos factores que han sido estudiados de forma independiente: el estres oxidativo y la respuesta inmune en modelos transgenicos para la EA, y se discute la relacion que existe entre ellos y que impacta en la perdida de la plasticidad sinaptica y estructural, produciendo como efecto final el deterioro cognitivo. Conclusion Esta revision describe posibles mecanismos en donde participan el estres oxidativo y la respuesta inmune sobre los efectos moleculares, celulares y conductuales en la EA, observando una estrecha relacion entre estos elementos que conducen hacia el deterioro cognitivo.

Background: A definition of myocardial infarction with non-obstructive coronary arteries (MINOCA) was published by European Society of Cardiology in 2016. The aim of this study is to analyze the clinical profile and prognosis of these patients in a prospective single-center study and compare it with the literature data. Methods: During a 3-year period, information from every consecutive MINOCA patient was gathered (n = 109). It was then compared with 412 contemporaneous patients with myocardial infarction and obstructive coronary arteries (MIOCA). Univariate and multivariate analyses were performed. Prognosis analysis was adjusted by age and cardiovascular risk factors (CVRF). Results: MINOCA represented 16.9% of the total of patients admitted for myocardial infarction. Compared with MIOCA, they had more psychosocial disorders (22.9% vs. 10.7%; p < 0.01) and more pro-inflammatory conditions (34.9% vs. 14.0%; p < 0.01). Atrial fibrillation was twice as frequent in MINOCA (14.7% vs. 7.3%; p = 0.016). Predictors of MINOCA were as follows: female gender, absence of diabetes, absence of tobacco use, tachycardia, troponin above 10 times the 99 th percentile, and pro-inflammatory conditions. Median follow-up was 17.3 ± 9.3 months. Major adverse cardiovascular events (MACE; a composite of a recurrence of acute myocardial infarction, transient ischemic attack/stroke, or death from cardiovascular cause and death from any cause) occurred in 10.8% of the MINOCA group as compared with 10.7% in the MIOCA group (hazard ratio [HR] 1.19, 95% confidence interval [CI] 0.58–2.45; p = 0.645). Cardiovascular re-admission rates were higher in the MINOCA group: 19.8% vs. 13.9% (HR 1.85; CI 1.06–3.21; p = 0.030). Conclusions: The frequency of MINOCA is high, with fewer CVRF, and it is linked to atrial fibrillation, psychosocial disorders, and pro-inflammatory conditions. Mid-term prognosis is worse than previously thought, with a similar proportion of MACE as compared to MIOCA, and even a higher rate of cardiovascular re-admissions.

To determinate the antimicrobial effect of chloramphenicol and aqueous extract against multidrug-resistant enterohemorrhagic Escherichia coli (EHEC) and Salmonella enterica serovar Typhimurium in C...

There are three different species of redfish (Sebastes spp.) in the waters of the Flemish Cap (Division 3M, NAFO Regulatory Area): S. fasciatus, S. mentella, and S. norvegicus. Historically, S. fasciatus and S. mentella have been managed together as a single stock because of similar biology and difficulty in species identification. Here we use multivariate autoregressive state-space models to examine the abundance trajectories of the three species and to determine whether they can be treated as a single stock for management purposes or whether they should be treaty separately. We also included covariates to evaluate relationships with climate, commercial catch, and the abundance of predators and (or) competitors and prey. We did two separate analyses: (i) a single-period analysis over the full time series and (ii) a blocked, two-period analysis over different regulatory periods. In both analyses, the best-fit model included separate trajectories for each species at each depth but one overall stock growth rate; both also included commercial catches as a covariate. These analyses suggest that a single assessment for the Sebastes complex is acceptable., Sí

To investigate a potential association between beta-blocker exposure and survival in patients with transthyretin amyloid cardiomyopathy (ATTR-CM).In this real-world prospective registry of 128 consecutive patients with ATTR-CM recruited in 7 institutions in Galicia (Spain), survival of 65 patients who received beta blockers on registry enrollment was compared with that of 63 untreated controls by means of both unweighted Cox regression and Cox regression with inverse probability of treatment weighting. Tolerance to and adverse effects of beta blockers were recorded. Median study follow-up was 520 days.Patients with ATTR-CM who received beta blockers showed statistically significant lower all-cause mortality than untreated controls as evaluated by either unweighted Cox regression (hazard ratio, 0.31; 95% CI, 0.12 to 0.79) or Cox regression with inverse probability of treatment weighting (hazard ratio, 0.18; 95% CI, 0.08 to 0.41; P.001). Several sensitivity analyses confirmed the internal validity of these results. The overall frequency of beta-blocker suspension due to adverse effects was 25% (95% CI, 15.5% to 34.5%).In this real-world, prospective, multi-institutional registry, patients with ATTR-CM who received beta blockers had lower all-cause mortality than untreated controls.

Catalonia; SARS-CoV-2; Molecular epidemiology Cataluña; SARS-CoV-2; Epidemiología molecular Catalunya; SARS-CoV-2; Epidemiologia molecular Herein, we describe the genetic diversity of circulating SARS-CoV-2 viruses by whole-genome sequencing (WGS) in Barcelona city (Catalonia, Spain) throughout the first four pandemic waves. From weeks 11/2020–24/2021, SARS-CoV-2-positive respiratory samples were randomly selected per clinical setting (80% from primary care or 20% from the hospital), age group, and week. WGS was performed following the ARTICv3 protocol on MiSeq or NextSeq2000 Illumina platforms. Nearly complete consensus sequences were used for genetic characterization based on GISAID and PANGOLIN nomenclatures. From 2475 samples, 2166 (87%) were fully sequenced (78% from primary care and 22% from hospital settings). Multiple genetic lineages were co-circulating, but four were predominant at different periods. While B.1.5 (50.68%) and B.1.1 (32.88%) were the major lineages during the first pandemic wave, B.1.177 (66.85%) and B.1.1.7 (83.80%) were predominant during the second, third, and fourth waves, respectively. Almost all (96.4%) were carrying D614G mutation in the S protein, with additional mutations that define lineages or variants. But some mutations of concern, such as E484K from B.1.351 and P.1 lineages are currently under monitoring, together with those observed in the receptor-binding domain or N-terminal domain, such as L452R and T478K from B.1.617.2 lineage. The fact that a predominant lineage was observed in each pandemic wave suggests advantageous properties over other contemporary co-circulating variants. This genetic variability should be monitored, especially when a massive vaccination campaign is ongoing because the potential selection and emergence of novel antigenic SARS-CoV-2 strains related to immunological escapement events. This work was supported by Spanish Network for the Research in Infectious Diseases: [Grant Number REIPI RD16/0016/0003]; Centro para el Desarrollo Tecnológico Industrial (CDTI) from the Spanish Ministry of Economy and Business [Grant Number IDI-20200297]; Direcció General de Recerca i Innovació en Salut (DGRIS); European Development Regional Fund (ERDF) “A way to achieve Europe” by Spanish Network for Research in Infectious Diseases [REIPI RD16/0016/0003].

Cystic fibrosis is characterized by abnormal mucous secretions in the lungs that favor the proliferation of colonizing bacteria, with Pseudomonas aeruginosa and Staphylococcus aureus being the most isolated, however, other less known species could also have an impact on the health of the patient. Here we demonstrate the isolation and antibiotic resistance profiles of Inquilinus limosus, a rarely reported multidrug resistant bacterium, and compare them to a co-infectant strain of Pseudomonas aeruginosa. Likewise, we found that co-infection with both bacteria promotes increased formation of neutrophil extracellular traps, which can have an impact on the disease severity and make treatment difficult.

One of the core challenges to achieve Land Degradation Neutrality (LDN) is to spatially identify, and strategically prioritise, the areas to implement actions to avoid, reduce and reverse land degradation. To achieve this, a tool for a participatory and data-driven assessment considering both the biophysical, and socio-economic dimensions of land degradation across scales was developed for Ecuador. In this paper, we present the methodology and results obtained, including the spatially explicit interactive tool developed to integrate indicators that support the scaling-up of sustainable land management (SLM). The process involved specialists from various national and international institutions, as well as decision makers from the public sector and other relevant stakeholders. Cloud computing allowed the integration of five main sources of data: (1) the results of a participatory land degradation assessment based on an expert knowledge questionnaire following the Land Degradation Assessment in Drylands (LADA) and World Overview of Conservation Approaches and Technologies (WOCAT) methodology; (2) the Hand-in-Hand Initiative Ecuador typology maps based on poverty maps and estimated agricultural potential and efficiency scores using household surveys on agricultural production; (3) National data sets on land cover and land use, soil properties, and hydro climatic indicators; (4) global satellite-derived LDN indicators, such as Land Productivity Dynamics; and (5) Documented SLM practices from WOCAT Global SLM Database. The tool is based on a Google Earth Engine application and allows decision makers to easily compare results and obtain statistics at different spatial scales and landscapes, including 647 Land Use Systems delimited by experts. It also includes a multi-criteria module to identify areas with specific characteristics to prioritise different types of interventions to achieve the country´s LDN targets. Convergence of local and global evidence allowed the identification of hotspots of degradation as well as areas of false positives/negatives - if only global or remote sensing indicators were considered. The participatory process contributed to strengthening multi-sector cooperation mechanisms and to guaranteeing ownership of the tool and the results. The system will support Ecuador’s efforts to monitor and report progress towards LDN to the United Nations Convention to Combat Desertification. The system´s code is shared as a repository at Earth Engine and can be adapted to and used by other countries and regions.

The Roman High- (RHA) and Low-(RLA) avoidance rat lines/strains were generated through bidirectional selective breeding for rapid (RHA) vs. extremely poor (RLA) two-way active avoidance acquisition. Compared with RLAs and other rat strains/stocks, RHAs are characterized by increased impulsivity, deficits in social behavior, novelty-induced hyper-locomotion, impaired attentional/cognitive abilities, vulnerability to psychostimulant sensitization and drug addiction. RHA rats also exhibit decreased function of the prefrontal cortex (PFC) and hippocampus, increased functional activity of the mesolimbic dopamine system and a dramatic deficit of central metabotropic glutamate-2 (mGlu2) receptors (due to a stop codon mutation at cysteine 407 in Grm2 -cys407*-), along with increased density of 5-HT2A receptors in the PFC, alterations of several synaptic markers and increased density of pyramidal "thin" (immature) dendrític spines in the PFC. These characteristics suggest an immature brain of RHA rats, and are reminiscent of schizophrenia features like hypofrontality and disruption of the excitation/inhibition cortical balance. RHA rats represent a promising heuristic model of neurodevelopmental schizophrenia-relevant features and comorbidity with drug addiction vulnerability.

17 Pág. Departamento de ​Mejora Genética Animal (INIA), Genomic relationship matrices are used to obtain genomic inbreeding coefficients. However, there are several methodologies to compute these matrices and there is still an unresolved debate on which one provides the best estimate of inbreeding. In this study, we investigated measures of inbreeding obtained from five genomic matrices, including the Nejati-Javaremi allelic relationship matrix (FNEJ), the Li and Horvitz matrix based on excess of homozygosity (FL&H), and the VanRaden (methods 1, FVR1, and 2, FVR2) and Yang (FYAN) genomic relationship matrices. We derived expectations for each inbreeding coefficient, assuming a single locus model, and used these expectations to explain the patterns of the coefficients that were computed from thousands of single nucleotide polymorphism genotypes in a population of Iberian pigs., This work was carried out with funding from the Ministerio de Ciencia e Innovación, Spain (CGL2016-75904-C2, PID2020-114426GB-C22), the European Commission Horizon 2020 (H2020) Framework Programme through grant agreement no 727315 MedAID project (Mediterranean Aquaculture Integrated Development), Xunta de Galicia (ED431C 2020-05) and Fondos FEDER.R. Pong-Wong is funded by the European Union’s Horizon 2020 research and innovation program under the Grant Agreement n°772787 (SMARTER) and the Biotechnology and Biological Sciences Research Council through Institute Strategic Programme Grant funding (BBS/E/D/30002275)

Departamento de Reproducción animal, Flea infestations of wild rabbits were examined monthly in central Spain in a meso-Mediterranean area for 5 yr. A total of 1,180 wild rabbits were trapped and 7,022 fleas were collected from them. Overall, the prevalence was 74.1% with a mean flea index of 5.95 fleas per rabbit. Four flea species were identified: Spilopsyllus cuniculi (Dale, 1878) was the most abundant species (accounting for 74.3% of fleas collected) followed by Xenopsylla cunicularis (Smit, 1957), Odontopsyllus quirosi (Gil Collado, 1934), and Nosopsyllus fasciatus (Bosc, 1800) (18.9, 6.7, and 0.1%, respectively). The highest prevalence was observed in S. cuniculi (48.6%) followed by X. cunicularis, O. quirosi, and N. fasciatus (34.3, 20.0, and 0.6%, respectively). Odontopsyllus quirosi and S. cuniculi were mainly collected from autumn to spring with the peak of infestation in winter, while X. cunicularis was mainly found from spring to autumn with maximum levels of infestation during the summer months. The relevance of these findings is discussed.

17 Pág. Departamento de Reproducción Animal​, Tick control is a priority in order to prevent the transmission of vector-borne diseases. Industrial chemical acaricides and repellents have been the most efficient tools against hard ticks for a long time. However, the appearance of resistances has meant the declining effectiveness of the chemicals available on the market. The trend today is to develop alternative control methods using natural products to replace nonefficient pesticides and to preserve the efficient ones, hoping to delay resistance development. Traditional in vitro evaluation of acaricidal activity or resistance to synthetic pesticides have been reviewed and they mainly focus on just one species, the one host tick (Rhipicephalus (Boophilus) microplus (Acari: Ixodidae)). Recent reports have called for the standardization of natural product components, extraction techniques, and experimental design to fully discover their acaricidal potential. This study reviews the main variables used in the bibliography about the efficiency of natural products against ticks, and it proposes a unification of variables relating to ticks, practical development of bioassays, and estimation of ixodicidal activity., This study was funded by Villamagna S.A.

Introduction: Cannabis plant uses are widespread across human cultures. The current tendency is to classify Cannabis varieties into chemovars upon their chemical fingerprint, mainly cannabinoids an...

It is crucial to assess the levels of protection generated by natural infection or SARS-CoV-2 vaccines, mainly in individuals professionally exposed and in vulnerable groups. Measuring T-cell responses may complement antibody tests currently in use as correlates of protection. Our aim was to assess the feasibility of a validated assay of T-cell responses.Twenty health-care-workers (HCW) were included. Antibody test to SARS-CoV-2 N and S-proteins in parallel with a commercially available whole-blood-interferon-gamma-release-assay (IGRA) to S-peptides and two detection methods, CLIA and ELISA were determined.IGRA test detected T-cell responses in naturally exposed and vaccinated HCW already after first vaccination dose. The correlation by the two detection methods was very high (Whole-blood-IGRA-tests amenable to automation and constitutes a promising additional tool for measuring the state of the immune response to SARS-CoV-2; they are applicable to large number of samples and may become a valuable correlate of protection to COVID-19, particularly for vulnerable groups at risk of being re-exposed to infection, as are health-care-workers.Es fundamental evaluar los niveles de protección inmune en infectados o tras la vacunación frente a SARS-CoV-2. La cuantificación de la respuesta inmune celular T puede complementar la determinación de anticuerpos. Evaluamos la viabilidad de un ensayo comercial validado de respuesta celular T específica frente a SARS-CoV-2.Se incluyeron veinte trabajadores sanitarios (TS). Medimos anticuerpos contra las proteínas N y S de SARS-CoV-2 y realizamos el ensayo de liberación de interferón-gamma (IFNγ) en sangre completa (IGRA) frente a péptidos de la proteína S. IFNγ se determinó mediante dos métodos de detección: CLIA y ELISA.IGRA detectó respuesta celular T en TS tanto infectados como vacunados. La correlación de los dos métodos de detección de IFNγ fue muy alta (R 0,8) y la sensibilidad y la especificidad variaron entre 100 y 86% y 100-73% respectivamente. Hubo una concordancia muy alta entre los niveles de anticuerpos específicos y el ensayo IGRA aunque la correlación cuantitativa fue relativamente baja. En el grupo de infectados, una dosis de vacuna fue suficiente para alcanzar el «plateau» de respuesta inmune. IGRA fue claramente positivo en un profesional vacunado inmunosuprimido que presentaba anticuerpos contra la proteína S negativos.IGRA frente a péptidos de la proteína-S es susceptible de automatización y constituye una herramienta prometedora para medir la respuesta inmune celular frente a SARS-CoV-2; es aplicable a un gran número de muestras y puede servir para valorar la protección, particularmente en los grupos vulnerables en riesgo de volver a exponerse a la infección, como los TS.

Background: The aim was to estimate the prevalence of tobacco and cannabis use and the relationship between these two substances in a cohort of young people from Central Catalonia in the period 2012-2020 according to sex and year of follow-up.Methods: Prospective longitudinal study with 828 students in 4th year of Compulsory Secondary Education (ESO) in Central Catalonia, who answered a survey on health behaviour in 2012 (828 young people), 2016 (342 young people) and in 2020 (271 young people). The dependent variables were traditional tobacco use, cannabis use in the last month and polydrug use of both substances. The independent variables were sex and year of follow-up. For the prevalence analysis, frequencies and percentages were analysed with their respective 95% confidence intervals. Chi-Square and Cochran's Q contrast were used to test the relationship between independent and paired qualitative variables. A significance level of 0.05 was set. Results: There are significant differences between the prevalence of smoking cannabis in the last month in boys and girls aged 19-20 years and 23-24 years. Girls who did not use traditional tobacco in 2012, 0.9% (0.1-6.5), 1.9% (0.4-7.5) and 7.5% (3.8-14.5) did use cannabis in 2012, 2016 and 2020 respectively, with a significant increase over the period analysed (p-value = 0.014). Boys who did not smoke traditional tobacco in 2012, 3.5% (1.1-10.6), 14.4% (8.3-23.9) and 14.3% (8.2-23.6) did smoke cannabis in 2012, 2016 and 2020 respectively, with a significant change between 2012 and 2020 (p-value = 0.006). Conclusions: There is a strong association between tobacco use and cannabis use, with those young people who smoke tobacco regularly having the highest prevalence of cannabis use. There is a significant percentage of young people where the gateway to smoked drugs is no longer tobacco but cannabis itself.

La flora del Santuario de Fauna y Flora de Iguaque, única área protegida de la provincia de Ricaurte, Boyacá, Colombia, representa la extraordinaria diversidad vegetal de la Cordillera Oriental colombiana. Nuestro primer objetivo consiste en reportar 88 novedades para esta flora regional, incluidas once especies de Lycophyta y Monilophyta y 77 especies de Angiospermae, con base en trabajo de herbario, de campo y reciente literatura. Sobresalen nuevos registros de Cactaceae, Cleomaceae, Cornaceae, Monimiaceae, Osmundaceae, Phrymaceae, Rosaceae, Woodsiaceae y Xyridaceae. Burmeistera glabrata (Campanulaceae), Cornus peruviana (Cornaceae) y Nothoscordum gracile (Amaryllidaceae) son nuevos reportes para el departamento de Boyacá. Los taxones endémicos Melpomene anazalea (Polypodiaceae), Piper daniel-gonzalezii var. moniquiranum (Piperaceae), Masdevallia aenigma y Stelis boyacensis (Orchidaceae), Espeletia cayetana y E. raquirensis (Asteraceae) presentan evidente grado de amenaza. Nuestro segundo objetivo consiste en actualizar la nomenclatura de 31 binomios, siete de ellos, de las familias Acanthaceae, Asteraceae, Crassulaceae, Euphorbiaceae, Poaceae y Rosaceae, con estatus taxonómico incierto. Nuestro trabajo permitirá actualizar los siguientes taxones en el Herbario Nacional Colombiano y en la catalogación de la Flora de Colombia: a nivel de género, Bartsia, Blechnum, Cheilanthes, Chenopodium, Cleome, Cordia, Diplostephium, Habracanthus, Hyptis, Lycopodium, Schefflera, Terpsichore y Vasquezia; y a nivel de especie, Melpomene anazalea, Opuntia soederstromiana, Rubus alutaceus, Spilotantha amanda, Stelis alleyoop, S. angustifolia, S. boyacensis y S. pleistantha.

Introduction and objectives Hereditary transthyretin amyloidosis (hATTR) is a disease caused by mutations in the transthyretin gene that frequently shows cardiac involvement due to amyloid deposition in the myocardium. Our objective was to identify cardiac involvement in a Spanish cohort. Methods Retrospective multicenter study of patients diagnosed with hATTR with cardiac involvement from Spanish centers. We collected demographic, clinical, and genetic data. Results A total of 181 patients from 26 centers were included (65.2% men, with a median age at diagnosis of 62 years). The most frequent mutations were Val50Met (67.7%) and Val142Ile (12.4%). The main reason for consultation was extracardiac symptoms (69%), mainly neurological. The mean N-terminal pro-B-type natriuretic peptide level was 2145±3586 pg/mL. The most characteristic electrocardiogram findings were a pseudoinfarct pattern (25.9%) and atrioventricular block (25.3%). Mean ventricular thickness was 15.4±4.1mm. Longitudinal strain was reduced in basal segments by 29.4%. Late diffuse subendocardial enhancement was observed in 58.8%. Perugini grade 2 or 3 uptake was observed in 75% of scintigraphy scans. During follow-up, 24.9% of the patients were admitted for heart failure, 34.3% required a pacemaker, and 31.6% required a liver transplant. One third (32.5%) died during follow-up, mainly due to heart failure (28.8%). The presence of non-Val50Met mutations was associated with a worse prognosis. Conclusions HATTR cardiac amyloidosis in Spain shows heterogeneous genetic and clinical involvement. The prognosis is poor, mainly due to cardiac complications. Consequently early diagnosis and treatment are vital.

21 p.-4 fig.-3 tab., Searching for improved indolesulfonamides with higher polarities, 45 new analogues with modifications on the sulfonamide nitrogen, the methoxyaniline, and/or the indole 3-position were synthesised. They show submicromolar to nanomolar antiproliferative IC50 values against four human tumour cell lines and they are not P-glycoprotein substrates as their potencies against HeLa cells did not improve upon cotreatment with multidrug resistance (MDR) inhibitors. The compounds inhibit tubulin polymerisation in vitro and in cells, thus causing a mitotic arrest followed by apoptosis as shown by cell cycle distribution studies. Molecular modelling studies indicate binding at the colchicine site. Methylated sulfonamides were more potent than those with large and polar substitutions. Amide, formyl, or nitrile groups at the indole 3-position provided drug-like properties for reduced toxicity, with Polar Surface Areas (PSA) above a desirable 75 Å2. Nitriles 15 and 16 are potent polar analogues and represent an interesting class of new antimitotics., This work was financially supported by the Consejería de Educacion de la Junta de Castilla y León [SA262P18 and SA116P20], co-funded by the EU’s European Regional Development Fund-FEDER, and the Spanish Ministry of Science,Innovation, and Universities [RTI2018-099474-B-I00 and SAF2017-89672-R].