El Delirium. Una revisión orientada a la práctica clínica

El delirium es un síndrome clínico que afecta a un importante porcentaje de los pacientes hospitalizados. A pesar de su elevada incidencia, es un síndrome a menudo infradiagnosticado, que implica relevantes consecuencias negativas para los pacientes y profesionales, y además puede prevenirse. Un abordaje inadecuado puede condicionar un peor pronóstico tanto a inmediato como a largo plazo para el paciente, en cuanto a su estado de salud y calidad de vida, así como incrementar los costes sanitarios las causas que pueden desencadenarlo, evitar complicaciones iatrogénicas, garantizar adecuado soporte de hidratación y nutrición, evitar el deterioro funcional, así como educar al paciente y su familia forman parte de los principios generales de su manejo. El objetivo de este artículo, es señalar lo que se considera esencial para el reconocimiento y tratamiento de este síndrome

Revista de libros

Se reseñan los siguientes libros: * Noam Chomsky: Conocimiento y libertad. Prólogo y notas de Carlos Peregrín Otero. Barcelona, Ediciones Ariel, 1972 (Colección “Ariel quincenal”, N°70). Volumen en rústica, 192 págs. * Varios autores: Historia y mito en la obra de Alejo Carpentier. Editorial Fernando García Cambeiro, Buenos Aires, 1972 (Colección “Estudios latinoamericanos”, 3). Volumen en rústica, 189 págs. * Georgi Schischkoff: La masificación dirigida. Contribución filosófico-social a la crítica de nuestro tiempo. Estudio preliminar y traducción de Antonio Gómez Moriana. Editora Nacional, Madrid, 1969. Volumen en rústica, 356 págs. * Juan Cuatrecasas: Lenguaje, semántica y campo simbólico. Editorial Paidós, Buenos Aires, 1972. Volumen en rústica, 242 págs. * Gillo Dorfles: Naturaleza y artificio. Traducción del italiano por Alejandro Saderman, colección “Palabra en el Tiempo”, volumen Nº 75, de Editorial Lumen, Barcelona (España), 1972. Volumen en rústica, 280 págs. * Darcy Ribeiro: La universidad nueva. Un proyecto. Editorial Ciencia Nueva, Buenos Aires, 1973. Volumen en rústica, 159 págs. * Tomas A. Vasconi e Inés Reca: Modernización y crisis de la universidad latinoamericana. Cuadernos de estudios socioeconómicos Nº 14 (Centro de Estudios Socioeconómicos, CESO, de la Universidad de Santiago de Chile); Santiago de Chile, 1971. Volumen en rústica, 154 págs. * W. Weischedel: Los filósofos entre bambalinas. Fondo de Cultura Económica, México, 1972. Volumen en rústica, 281 págs. * Varios autores: José Hernández (Estudios reunidos en conmemoración del centenario de El Gaucho Martín Fierro) 1872-1972. Facultad de Humanidades y Ciencias de la Educación de la Universidad Nacional de La Plata, La Plata 1973. Volumen en rústica, 272 págs. * Ariel Dorfman: Imaginación y violencia en América Latina. Editorial Anagrama, Barcelona (España), 1972. Volumen en rústica, 248 págs. * Ferruccio Rossi-Landi, Julia Kristeva, Yuri M. Lotman, Boris A. Uspenski, Jan Mukarovski: Semiótica y praxis. Barcelona, A. Redondo, 1973. Volumen en rústica, 103 págs.Universidad Nacional de La Plat

Evolution of CRISPR-associated endonucleases as inferred from resurrected proteins

Clustered regularly interspaced short palindromic repeats (CRISPR)-associated Cas9 is an effector protein that targets invading DNA and plays a major role in the prokaryotic adaptive immune system. Although Streptococcus pyogenes CRISPR–Cas9 has been widely studied and repurposed for applications including genome editing, its origin and evolution are poorly understood. Here, we investigate the evolution of Cas9 from resurrected ancient nucleases (anCas) in extinct firmicutes species that last lived 2.6 billion years before the present. We demonstrate that these ancient forms were much more flexible in their guide RNA and protospacer-adjacent motif requirements compared with modern-day Cas9 enzymes. Furthermore, anCas portrays a gradual palaeoenzymatic adaptation from nickase to double-strand break activity, exhibits high levels of activity with both single-stranded DNA and single-stranded RNA targets and is capable of editing activity in human cells. Prediction and characterization of anCas with a resurrected protein approach uncovers an evolutionary trajectory leading to functionally flexible ancient enzymes.This work has been supported by grant nos. PID2019-109087RB-I00 (to R.P.-J.) and RTI2018-101223-B-I00 and PID2021-127644OB-I00 (to L.M.) from the Spanish Ministry of Science and Innovation. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 964764 (to R.P.-J.). The content presented in this document represents the views of the authors, and the European Commission has no liability in respect to the content. We acknowledge financial support from the Spanish Foundation for the Promotion of Research of Amyotrophic Lateral Sclerosis. A.F. acknowledges Spanish Center for Biomedical Network Research on Rare Diseases (CIBERE) intramural funds (no. ER19P5AC756/2021). F.J.M.M. acknowledges research support by Conselleria d’Educació, Investigació, Cultura i Esport from Generalitat Valenciana, research project nos. PROMETEO/2017/129 and PROMETEO/2021/057. M.M. acknowledges funding from CIBERER (grant no. ER19P5AC728/2021). The work has received funding from the Regional Government of Madrid (grant no. B2017/BMD3721 to M.A.M.-P.) and from Instituto de Salud Carlos III, cofounded with the European Regional Development Fund ‘A way to make Europe’ within the National Plans for Scientific and Technical Research and Innovation 2017–2020 and 2021–2024 (nos. PI17/1659, PI20/0429 and IMP/00009; to M.A.M.-P. B.P.K. was supported by an MGH ECOR Howard M. Goodman Award and NIH P01 HL142494

Functional screen identifies regulators of murine hematopoietic stem cell repopulation.

Understanding the molecular regulation of hematopoietic stem and progenitor cell (HSPC) engraftment is paramount to improving transplant outcomes. To discover novel regulators of HSPC repopulation, we transplanted >1,300 mice with shRNA-transduced HSPCs within 24 h of isolation and transduction to focus on detecting genes regulating repopulation. We identified 17 regulators of HSPC repopulation: Arhgef5, Armcx1, Cadps2, Crispld1, Emcn, Foxa3, Fstl1, Glis2, Gprasp2, Gpr56, Myct1, Nbea, P2ry14, Smarca2, Sox4, Stat4, and Zfp251. Knockdown of each of these genes yielded a loss of function, except in the cases of Armcx1 and Gprasp2, whose loss enhanced hematopoietic stem cell (HSC) repopulation. The discovery of multiple genes regulating vesicular trafficking, cell surface receptor turnover, and secretion of extracellular matrix components suggests active cross talk between HSCs and the niche and that HSCs may actively condition the niche to promote engraftment. We validated that Foxa3 is required for HSC repopulating activity, as Foxa3(-/-) HSC fails to repopulate ablated hosts efficiently, implicating for the first time Foxa genes as regulators of HSPCs. We further show that Foxa3 likely regulates the HSC response to hematologic stress. Each gene discovered here offers a window into the novel processes that regulate stable HSPC engraftment into an ablated host

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Análisis genético de las funciones moleculares de CDK7

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Bioquímica. Fecha de lectura; 19 de Octubre de 2009

El Delirium. Una revisión orientada a la práctica clínica

El delirium es un síndrome clínico que afecta a un importante porcentaje de los pacientes hospitalizados. A pesar de su elevada incidencia, es un síndrome a menudo infradiagnosticado, que implica relevantes consecuencias negativas para los pacientes y profesionales, y además puede prevenirse. Un abordaje inadecuado puede condicionar un peor pronóstico tanto a inmediato como a largo plazo para el paciente, en cuanto a su estado de salud y calidad de vida, así como incrementar los costes sanitarios las causas que pueden desencadenarlo, evitar complicaciones iatrogénicas, garantizar adecuado soporte de hidratación y nutrición, evitar el deterioro funcional, así como educar al paciente y su familia forman parte de los principios generales de su manejo. El objetivo de este artículo, es señalar lo que se considera esencial para el reconocimiento y tratamiento de este síndrome