Extracellular Protease ADAMTS1 Is Required at Early Stages of Human Uveal Melanoma Development by Inducing Stemness and Endothelial-Like Features on Tumor Cells

We would like to thank members of JCRM’s laboratory and GENYO’s support units for helping with animal handling, technical assistance, and further discussion. The results published here are in part based upon data generated by the TCGA Research Network (www.cancer.gov/tcga). This manuscript will be part of CPT PhD Thesis belonging to the Doctorate Program on Biomedicine, UGR, Spain.Extracellular matrix remodeling within the tumor microenvironment has been recognized as a relevant dynamic framework during tumor growth. However, research on proteases that trigger this remodeling keeps revealing a wide range of actions including both pro- and anti-tumorigenic. The extracellular protease ADAMTS1 exemplifies this dual role. In this work, we first confirmed a positive correlation of ADAMTS1 with endothelial-like phenotype of human melanoma cells together with the finding of associated signatures, including key genes such as endothelial CDH5. Using a CRISPR-Cas9 approach, we observed that the inhibition of ADAMTS1 in an aggressive uveal melanoma model compromised its endothelial-like properties, and more importantly, caused a robust blockade on the progression of tumor xenografts. Although vasculature emerged affected in ADAMTS1-deficient tumors, the most relevant action implied the downregulation of endothelial CDH5 in tumor cells, in association with stemness markers. Indeed, melanoma sphere assays also revealed a deficient commitment to form spheres in the absence of ADAMTS1, directly correlating with stemness markers and, remarkably, also with CDH5. Finally, taking advantage of advanced bioinformatics tools and available public data of uveal melanomas, we disclosed new prognosis factors, including endothelial elements and ADAMTS proteases. Our findings support the key role of ADAMTS proteases for uveal melanoma development since earlier stages, modulating the complex crosstalk between extracellular matrix and the induction of stemness and endothelial-like features. To our knowledge, this is the first report that supports the development of therapeutic targets on the extracellular matrix to overcome uveal melanoma.This research was supported by Ministerio de Economía y Competitividad and Instituto de Salud Carlos III from Spain, co-financed by FEDER (PI16/00345 to JCRM) and from Consejería de Salud de la Junta de Andalucía (OH-0028-2018, PE-0225-2018)

Wire Marking Results in a Small but Significant Reduction in Avian Mortality at Power Lines: A BACI Designed Study

10 paginas, 4 figuras y 4 tablesBackground: Collision with electric power lines is a conservation problem for many bird species. Although the implementation of flight diverters is rapidly increasing, few well-designed studies supporting the effectiveness of this costly conservation measure have been published. Methodology/Principal Findings: We provide information on the largest worldwide marking experiment to date, including carcass searches at 35 (15 experimental, 20 control) power lines totalling 72.5 km, at both transmission (220 kV) and distribution (15 kV-45 kV) lines. We found carcasses of 45 species, 19 of conservation concern. Numbers of carcasses found were corrected to account for carcass losses due to removal by scavengers or being overlooked by researchers, resulting in an estimated collision rate of 8.2 collisions per km per month. We observed a small (9.6%) but significant decrease in the number of casualties after line marking compared to before line marking in experimental lines. This was not observed in control lines. We found no influence of either marker size (large vs. small spirals, sample of distribution lines only) or power line type (transmission vs. distribution, sample of large spirals only) on the collision rate when we analyzed all species together. However, great bustard mortality was slightly lower when lines were marked with large spirals and in transmission lines after marking. Conclusions: Our results confirm the overall effectiveness of wire marking as a way to reduce, but not eliminate, bird collisions with power lines. If raw field data are not corrected by carcass losses due to scavengers and missed observations, findings may be biased. The high cost of this conservation measure suggests a need for more studies to improve its application, including wire marking with non-visual devices. Our findings suggest that different species may respond differently to marking, implying that species-specific patterns should be explored, at least for species of conservation concern.We thank A. Garcıa Fernandez and M. Carrasco for their assistance during the field work. We also thank J. Camaño and J. Velasco of HENARSA, and the electric companies Iberdrola, Union Fenosa and Red Electrica de España for their cooperation. S. Young reviewed the English. RB was contracted within the project CGL2008-02567 of the Direccion General de Investigacion, Spanish Ministry of Science and Innovation and later supported by a postdoctoral grant from Junta de Comunidades de Castilla-La Mancha. C. Ponce, C. Palacın, CM and BM were supported by contracts CSICHENARSA. This study was carried out within the Preventive, corrective and compensatory measures to balance the impact of the M-50 and R-2 highways on the population of great bustards and other steppe-land birds in the Important Bird Area Talamanca-Camarma and the Site of Community Importance Cuenca de los rıos Jarama y Henares, supported by a contract HENARSA-CSIC. Additional financial support was provided by project GL2008-02567 of the Direccion General de Investigacion, Spanish Ministry of Science and Innovation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewe

Uso de tecnologías digitales en el diseño de una autoevaluación formativa en el curso de Genética General de la Facultad de Ciencias Veterinarias

Los nuevos planteamientos curriculares en la universidad demandan una integración de los contenidos, saberes y una actitud renovada de los docentes frente a las estrategias metodológicas, hechos estos que evocan la evaluación formativa como la manera más propia de acompañar el aprendizaje y la enseñanza. En la FCV- UNLP, las nuevas tecnologías de la información y comunicación (TIC), se comenzaron a utilizar ampliamente en los últimos cinco años para mejorar los modelos formativos y organizativos que sustentan el aprendizaje. El curso Genética General de la Carrera de Ciencias Veterinarias- UNLP (Plan 406/04) se concibe como la base del conocimiento de la Genética y el individuo. El objetivo fue diseñar una autoevaluación virtual optativa, utilizando el entorno virtual Moodle. A partir de los conceptos desarrollados por los docentes, se diseño un cuestionario con 20 preguntas del tipo opciones múltiples; respuesta corta; de emparejamiento y verdadero o falso. Sobre un total de 193 (100%) alumnos, 85 (44%) resolvieron el cuestionario; 47 (55%) aprobaron. En una Universidad presencial, el uso de tecnologías digitales como herramienta pedagógica representa una propuesta innovadora, se utiliza como complemento de las actividades curriculares presenciales.Facultad de Ciencias Veterinaria

Dendritic Cell‐Mediated Cross‐Priming by a Bispecific Neutralizing Antibody Boosts Cytotoxic T Cell Responses and Protects Mice against SARS‐CoV‐2

SARS-CoV-2 B.1.351 and B.1.167.2 viruses used in this study were obtained through the European Virus Archive Global (EVA-GLOBAL) project that has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 653316. SARS-CoV-2 B.1 (MAD6 isolate) was kindly provided by José M. Honrubia and Luis Enjuanes (CNB-CSIC, Madrid, Spain). The authors thank Centro de Investigación en Sanidad Animal (CISA)-Instituto Nacional de Investigaciones Agrarias (INIA-CSIC) (Valdeolmos, Madrid, Spain) for the BSL-3 facilities. Research in LAV laboratory was funded by the BBVA Foundation (Ayudas Fundación BBVA a Equipos de Investigación Científica SARS-CoV-2 y COVID19); the MCIN/AEI/10.13039/501100011033 (PID2020-117323RB-I00 and PDC2021-121711-I00), partially supported by the European Regional Development Fund (ERDF); the Carlos III Health Institute (ISCIII) (DTS20/00089), partially supported by the ERDF, the Spanish Association Against Cancer (AECC 19084); the CRIS Cancer Foundation (FCRISIFI-2018 and FCRIS-2021-0090), the Fundación Caixa-Health Research (HR21-00761 project IL7R_LungCan), and the Comunidad de Madrid (P2022/BMD-7225 NEXT_GEN_CART_MAD-CM). Work in the DS laboratory was funded by the CNIC; the European Union’s Horizon 2020 research and innovation program under grant agreement ERC-2016-Consolidator Grant 725091; MCIN/AEI/10.13039/501100011033 (PID2019-108157RB); Comunidad de Madrid (B2017/BMD-3733 Immunothercan-CM); Atresmedia (Constantes y Vitales prize); Fondo Solidario Juntos (Banco Santander); and “La Caixa” Foundation (LCF/PR/HR20/00075). The CNIC was supported by the ISCIII, the MCIN and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (CEX2020- 001041-S funded by MCIN/AEI/10.13039/501100011033). Research in RD laboratory was supported by the ISCIII (PI2100989) and CIBERINFEC; the European Commission Horizon 2020 Framework Programme (grant numbers 731868 project VIRUSCAN FETPROACT-2016, and 101046084 project EPIC-CROWN-2); and the Fundación CaixaHealth Research (grant number HR18-00469 project StopEbola). Research in CNB-CSIC laboratory was funded by Fondo Supera COVID19 (Crue Universidades-Banco Santander) grant, CIBERINFEC, and Spanish Research Council (CSIC) grant 202120E079 (to J.G.-A.), CSIC grant 2020E84 (to M.E.), MCIN/AEI/10.13039/501100011033 (PID2020- 114481RB-I00 to J.G-A. and M.E.), and by the European CommissionNextGenerationEU, through CSIC’s Global Health Platform (PTI Salud Global) to J.G.-A. and M.E. Work in the CIB-CSIC laboratory was supported by MCIN/AEI/10.13039/501100011033 (PID2019-104544GB-I00 and 2023AEP105 to CA, and PID2020-113225GB-I00 to F.J.B.). Cryo-EM data were collected at the Maryland Center for Advanced Molecular Analyses which was supported by MPOWER (The University of Maryland Strategic Partnership). I.H.-M. receives the support of a fellowship from la Caixa Foundation (ID 100010434, fellowship code: LCF/BQ/IN17/11620074) and from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 71367. L.R.-P. was supported by a predoctoral fellowship from the Immunology Chair, Universidad Francisco de Vitoria/Merck.S

A primary healthcare information intervention for communicating cardiovascular risk to patients with poorly controlled hypertension: The Education and Coronary Risk Evaluation (Educore) study-A pragmatic, cluster-randomized trial

PURPOSE: Uncertainty exists regarding the best way to communicate cardiovascular risk (CVR) to patients, and it is unclear whether the comprehension and perception of CVR varies according to the format used. The aim of the present work was to determine whether a strategy designed for communicating CVR information to patients with poorly controlled high blood pressure (HBP), but with no background of cardiovascular disease, was more effective than usual care in the control of blood pressure (BP) over the course of a year. METHODS: A pragmatic, two-arm, cluster-randomized controlled trial was performed. Consecutive patients aged 40-65 years, all diagnosed with HBP in the last 12 months, and all of whom showed poor control of their condition (systolic BP ≥140 mmHg and/or diastolic BP ≥90 mmHg), were recruited at 22 primary healthcare centres. Eleven centres were randomly assigned to the usual care arm, and 11 to the informative intervention arm (Educore arm). At the start of the study, the Educore arm subjects were shown the "low risk SCORE table", along with impacting images and information pamphlets encouraging the maintenance of good cardiovascular health. The main outcome variable measured was the control of HBP; the secondary outcome variables were SCORE table score, total plasma cholesterol concentration, use of tobacco, adherence to prescribed treatment, and quality of life. RESULTS: The study participants were 411 patients (185 in the Educore arm and 226 in the usual care arm). Multilevel logistic regression showed that, at 12 months, the Educore intervention achieved better control of HBP (OR = 1.57; 1.02 to 2.41). No statistically significant differences were seen between the two arms at 12 months with respect to the secondary outcomes. CONCLUSIONS: Compared to usual care, the Educore intervention was associated with better control of HBP after adjusting for age, baseline SBP and plasma cholesterol, at 12 months.This study was funded by the Spanish Ministry of Science and Innovation via the Instituto de Salud Carlos III, Subprograma de Proyectos de Investigación en Evaluación de Tecnologías Sanitarias y Servicios de Salud (PI 09/90354), and the Fundación de Investigación e Innovación Biomédica en Atención Primaria (FIIBAP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscriptS

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

Healthcare workers hospitalized due to COVID-19 have no higher risk of death than general population. Data from the Spanish SEMI-COVID-19 Registry

Aim To determine whether healthcare workers (HCW) hospitalized in Spain due to COVID-19 have a worse prognosis than non-healthcare workers (NHCW). Methods Observational cohort study based on the SEMI-COVID-19 Registry, a nationwide registry that collects sociodemographic, clinical, laboratory, and treatment data on patients hospitalised with COVID-19 in Spain. Patients aged 20-65 years were selected. A multivariate logistic regression model was performed to identify factors associated with mortality. Results As of 22 May 2020, 4393 patients were included, of whom 419 (9.5%) were HCW. Median (interquartile range) age of HCW was 52 (15) years and 62.4% were women. Prevalence of comorbidities and severe radiological findings upon admission were less frequent in HCW. There were no difference in need of respiratory support and admission to intensive care unit, but occurrence of sepsis and in-hospital mortality was lower in HCW (1.7% vs. 3.9%; p = 0.024 and 0.7% vs. 4.8%; p<0.001 respectively). Age, male sex and comorbidity, were independently associated with higher in-hospital mortality and healthcare working with lower mortality (OR 0.211, 95%CI 0.067-0.667, p = 0.008). 30-days survival was higher in HCW (0.968 vs. 0.851 p<0.001). Conclusions Hospitalized COVID-19 HCW had fewer comorbidities and a better prognosis than NHCW. Our results suggest that professional exposure to COVID-19 in HCW does not carry more clinical severity nor mortality

EstuPlan: Methodology for the development of creativity in the resolution of scientific and social problems

[EN] Creative thinking is necessary to generate novel ideas and solve problems. "EstuPlan" is a methodology in which knowledge and creativity converge for the resolution of scientific problems with social projection. It is a training programme that integrates teachers, laboratory technicians and PhD students, master and undergraduate students which form working groups for the development of projects. Projects have a broad and essential scope and projection in terms of environmental problems, sustainable use of natural resources, food, health, biotechnology or biomedicine. The results show the success of this significant learning methodology using tools to develop creativity in responding to scientific and social demand for problem-solving to transfer academic knowledge to different professional environments. Bioplastics, Second Life of Coffee, LimBio, Algae oils, Ecomers, Caring for the life of your crop and Hate to Deforestate are currently being developed.Astudillo Calderón, S.; De Díez De La Torre, L.; García Companys, M.; Ortega Pérez, N.; Rodríguez Martínez, V.; Alzahrani, S.; Alonso Valenzuela, R.... (2019). EstuPlan: Methodology for the development of creativity in the resolution of scientific and social problems. En HEAD'19. 5th International Conference on Higher Education Advances. Editorial Universitat Politècnica de València. 711-717. https://doi.org/10.4995/HEAD19.2019.9205OCS71171

Envejecimiento de la población

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