Predictors of in-hospital mortality in HIV-infected patients with COVID-19

Background Underlying immunodeficiency is associated with severe COVID-19, but the prognosis of persons with human immunodeficiency virus (HIV) (PWH) with COVID-19 is under debate. Aim: assessment of the mortality rate and major determinants of death in HIV-infected patients hospitalized with COVID-19 in Spain before vaccine availability. Design: Retrospective nationwide public database analysis. Methods Nationwide, retrospective, observational analysis of all hospitalizations with COVID-19 during year 2020 in Spain. Stratification was made according to HIV status. The National Registry of Hospital Discharges was used with the ICD-10 coding list. Results A total of 117 694 adults were hospitalized with COVID-19 during 2020. Only 234 (0.2%) were HIV-positives. More than 95% were on antiretroviral therapy. Compared to HIV-negatives, PWH were younger (mean age 53.2 vs. 66.5 years old; P<0.001) and more frequently male (74.8% vs. 56.6%; P<0.001). Most co-morbidities predisposing to severe COVID-19 (diabetes, hypertension, dementia and cardiovascular disease) were more frequent in HIV-negatives. In contrast, the rate of baseline liver disease was over 6-fold higher in PWH (27.4% vs. 4.4%; P<0.001). In-hospital mortality was lower in PWH (9.4% vs. 16%; P=0.004). In multivariate analysis, older age, dementia and especially advanced liver disease (relative risk (RR): 7.6) were the major determinants of death in PWH hospitalized with COVID-19. Conclusion HIV-infected patients hospitalized in Spain with COVID-19 during 2020 had better survival than HIV-negatives, most likely explained by younger age and lower rate of co-morbidities. However, advanced liver disease was a major predictor of death in PWH hospitalized with COVID-19

Propuesta del farmacovigilancia para un establecimiento farmacéutico minorista

En esta investigación se revisa la problemática generada en el establecimiento farmacéutico donde se evidencia problemas de almacenamiento, en la recepción de medicamentos, faltantes frecuentes de varios medicamentos, un auxiliar nuevo que no conocía bien el establecimiento ni su forma de almacenamiento, porque no hubo tiempo de realizarle una correcta inducción. Este estudio fue hecho durante el primer semestre del año 2022 en donde se analiza la farmacovigilancia y su importancia en la vida del regente contribuyendo de esta forma a la gestión y control del riesgo de los medicamentos, siendo así un estudio que tiene una utilidad metodológica ya que se pueden realizar diferentes estudios compatibles de manera que se podrá analizar, y ayudar a gestionar los riesgos del establecimiento farmacéutico y evaluar las intervenciones que se llevan a cabo.This research reviews the problems generated in the pharmaceutical establishment where storage problems are evident, in the reception of medicines, frequent shortages of several medicines, a new assistant who did not know well the establishment or its form of storage, because there was no time to perform a correct induction. This study was done during the first quarter of 2022 where pharmacovigilance and its importance in the life of the regent are analyzed, thus contributing to the management and control of the risk of medicines, thus, being a study that has a methodological utility since different compatible studies can be carried out so that it can be analyzed and help manage the risks of the pharmaceutical establishment and evaluate the interventions that are carried out

Polisacáridos de Porphyridium cruentum presentan actividad antiviral diferencial frente a infecciones causadas de VHSV y VNN

Los microorganismos del medio marino constituyen una importante fuente de compuestos cuya utilización en la prevención y/o tratamiento de enfermedades de etiología viral está siendo sugerida en los últimos años. En concreto, diversos estudios demuestran que los polisacáridos de Porphyridium cruentum presentan funciones biológicas en mamíferos, entre ellas acción antiviral, siendo un buen candidato para analizar su posible papel frente a patologías víricas de peces cultivados. En este trabajo se ha evaluado la actividad de los polisacáridos de P. cruentum frente a la infección por el virus de la septicemia hemorrágica viral (VHSV, genotipo I), y el virus de la necrosis nerviosa (VNN, genotipo RGNNV). El análisis se ha realizado in vitro mediante dos aproximaciones: (a) evaluando la capacidad de los polisacáridos de bloquear la unión virus-célula, y (b) su papel durante el proceso de replicación vírica. En cada ensayo se analizó la replicación viral mediante cuantificación de genoma vírico a diferentes tiempos post-inoculación (p.i.). Los resultados muestran actividad de los polisacáridos de P. cruentum frente a la infección por VHSV en ambas aproximaciones, observándose disminución significativa de genoma viral a las 24 y 36 h p.i. en las células tratadas con el polisacárido respecto a las no tratadas. Por el contrario, no se ha observado actividad frente a VNN, indicando que los polisacáridos de P. cruentum presentan actividad antiviral diferencial, dependiente del patógeno.Financiación: AGL2017-84644-R, Ministerio de Ciencia e Innovación (MINECO/AEI/FEDER, UE) y P18-RT-1067, Junta de Andalucía. G.P. beca ANID-PFCHA (2018- No. 21180059). I Plan Propio Integral de Docencia. Universidad de Málaga Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Protein 4.1B Contributes to the Organization of Peripheral Myelinated Axons

Neurons are characterized by extremely long axons. This exceptional cell shape is likely to depend on multiple factors including interactions between the cytoskeleton and membrane proteins. In many cell types, members of the protein 4.1 family play an important role in tethering the cortical actin-spectrin cytoskeleton to the plasma membrane. Protein 4.1B is localized in myelinated axons, enriched in paranodal and juxtaparanodal regions, and also all along the internodes, but not at nodes of Ranvier where are localized the voltage-dependent sodium channels responsible for action potential propagation. To shed light on the role of protein 4.1B in the general organization of myelinated peripheral axons, we studied 4.1B knockout mice. These mice displayed a mildly impaired gait and motility. Whereas nodes were unaffected, the distribution of Caspr/paranodin, which anchors 4.1B to the membrane, was disorganized in paranodal regions and its levels were decreased. In juxtaparanodes, the enrichment of Caspr2, which also interacts with 4.1B, and of the associated TAG-1 and Kv1.1, was absent in mutant mice, whereas their levels were unaltered. Ultrastructural abnormalities were observed both at paranodes and juxtaparanodes. Axon calibers were slightly diminished in phrenic nerves and preterminal motor axons were dysmorphic in skeletal muscle. βII spectrin enrichment was decreased along the axolemma. Electrophysiological recordings at 3 post-natal weeks showed the occurrence of spontaneous and evoked repetitive activity indicating neuronal hyperexcitability, without change in conduction velocity. Thus, our results show that in myelinated axons 4.1B contributes to the stabilization of membrane proteins at paranodes, to the clustering of juxtaparanodal proteins, and to the regulation of the internodal axon caliber

Anti-Spike antibodies 3 months after SARS-CoV-2 mRNA vaccine booster dose in patients on hemodialysis: the prospective SENCOVAC study

Background: Patients on hemodialysis are at high-risk for complications derived from coronavirus disease 2019 (COVID-19). The present analysis evaluated the impact of a booster vaccine dose and breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections on humoral immunity 3 months after the booster dose. Methods: This is a multicentric and prospective study assessing immunoglobulin G anti-Spike antibodies 6 and 9 months after initial SARS-CoV-2 vaccination in patients on hemodialysis that had also received a booster dose before the 6-month assessment (early booster) or between the 6- and 9-month assessments (late booster). The impact of breakthrough infections, type of vaccine, time from the booster and clinical variables were assessed. Results: A total of 711 patients [67% male, median age (range) 67 (20-89) years] were included. Of these, 545 (77%) received an early booster and the rest a late booster. At 6 months, 64 (9%) patients had negative anti-Spike antibody titers (3% of early booster and 29% of late booster patients, P =. 001). At 9 months, 91% of patients with 6-month negative response had seroconverted and there were no differences in residual prevalence of negative humoral response between early and late booster patients (0.9% vs 0.6%, P =. 693). During follow-up, 35 patients (5%) developed breakthrough SARS-CoV-2 infection. Antibody titers at 9 months were independently associated with mRNA-1273 booster (P =. 001), lower time from booster (P =. 043) and past breakthrough SARS-CoV-2 infection (P <. 001). Conclusions: In hemodialysis patients, higher titers of anti-Spike antibodies at 9 months were associated with mRNA-1273 booster, lower time from booster and past breakthrough SARS-CoV-2 infectionThe present project has been supported by Fresenius Medical Care, Diaverum, Vifor Pharma, Vircell, Fundación Renal Iñigo Álvarez de Toledo and ISCIII FEDER funds RICORS2040 (RD21/0005

Temas Socio-Jurídicos. Volumen 20 No. 43 Diciembre 2002

Con la edición del número 43 de la Revista Temas Socio-Jurídicos se cierra el ciclo de los primeros veinte años, continuos, de labores de este medio académico destinado a divulgar la labor intelectual de docentes y discentes de la Facultad de Derecho de la Universidad Autónoma de Bucaramanga. En medio del convulso e inestable escenario jurídico del país, se pretende contribuir a la construcción de un pensamiento jurídico ligado a la realidad social que plantea desde las distintas vertientes de la opinión tópicos inquietantes para el medio académico, procurando decantamiento y comprensión de los fenómenos al tiempo que propicia la controversía y la libre expresión de los diferentes puntos de vista, en desarrollo de los principios que orientan esta casa de estudios.With the edition of number 43 of the Socio-Legal Issues Magazine, the cycle of the first twenty continuous years of work of this academic environment is closed, aimed at disseminating the intellectual work of teachers and students of the Faculty. of Law of the Autonomous University of Bucaramanga. In the midst of the convulsive and unstable legal scenario in the country, intends to contribute to the construction of a legal thought linked to the social reality that raises from the different slopes of the opinion disturbing topics for the academic environment, seeking decantation and understanding of the phenomena while fostering controversy and the free expression of the different points of view, in development of the principles that guide this house of studies

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

SUMOylation controls Hu antigen R posttranscriptional activity in liver cancer

© 2024 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).The posttranslational modification of proteins critically influences many biological processes and is a key mechanism that regulates the function of the RNA-binding protein Hu antigen R (HuR), a hub in liver cancer. Here, we show that HuR is SUMOylated in the tumor sections of patients with hepatocellular carcinoma in contrast to the surrounding tissue, as well as in human cell line and mouse models of the disease. SUMOylation of HuR promotes major cancer hallmarks, namely proliferation and invasion, whereas the absence of HuR SUMOylation results in a senescent phenotype with dysfunctional mitochondria and endoplasmic reticulum. Mechanistically, SUMOylation induces a structural rearrangement of the RNA recognition motifs that modulates HuR binding affinity to its target RNAs, further modifying the transcriptomic profile toward hepatic tumor progression. Overall, SUMOylation constitutes a mechanism of HuR regulation that could be potentially exploited as a therapeutic strategy for liver cancer.This work was supported by grants to M.L.M.-C. from Departamento de Industria del Gobierno Vasco, Spain; Ministerio de Ciencia e Innovación, Spain (grant no. PID2020-117116RB-I00); European Regional Development Fund (ERDF), EU; and CIBERehd, which is funded by Instituto de Salud Carlos III (ISCIII), Spain. M.L.M.-C. and J.S. received funding from Ministerio de Ciencia e Innovación (grant no. RTC2019-007125-1) and ISCIII (grant no. DTS20/00138). M.L.M.-C. and R.M.L. acknowledge Ministerio de Ciencia e Innovación (grant no. RED2022-134397-T). M.L.M.-C. and J.M.B. were awarded with a grant from Fundación la Caixa, Spain (grant no. HR17-00601). M.L.M.-C., J.M.B., M.A.A., and J.J.G.M. acknowledge financial support from Fundación Científica de la Asociación Española Contra el Cáncer (AECC), Spain. M.S.R. recognizes funding from Fondo Sectorial de Investigación SRE - CONACYT, Mexico (grant no. 0280365); Horizon 2020 Research and Innovation Program funded under Marie Skłodowska-Curie Actions, EU (grant no. 765445); and REPÈRE and Programme de Prématuration from Région Occitanie, France. M.G., S.D., and K.M.-M. were supported by the National Institute on Aging (NIA), National Institutes of Health (NIH), US (grant no. Z01-AG000511-23). I.D.-M. is grateful for the grants received from Junta de Andalucía, Spain (grant no. BIO-198, US-1254317, P18-FR-3487, and P18-HO-4091); Ministerio de Ciencia, Innovación y Universidades, Spain (grant no. PGC2018-096049-BI00); and Fundación Ramón Areces, Spain. T.D. acknowledges Fondation ARC, France (grant no. 208084). J.J.G.M. was supported by Junta de Castilla y León, Spain (grant no. SA063P17); Fundación La Marató TV3, Spain (grant no. 201916-31); ISCIII (grant no. PI19/00819); CIBERehd; and ERDF (grant no. OLD-HEPAMARKER). M.A.A. recognizes Gobierno de Navarra, Spain (grant no. GºNa 42/21); Eurorregión Nueva Aquitania-Euskadi-Navarra, Spain; Ministerio de Ciencia e Innovación (grant no. PID2019-104878RB-I00); and CIBERehd. A.P. expresses gratitude to the European Research Council (ERC), EU (grant no. 804236) for their support. M.D.G. received financial support from Junta de Andalucía (grant no. PEMP-0036-2020 and BIO-0139); Ministerio de Universidades, Spain (grant no. FPU20/03957); ISCIII (grant no. PI20/01301), Fundación Sociedad Española de Endocrinología y Nutrición (FSEEN), Spain; CIBERehd; and CIBERobn, which is also funded by ISCIII. J.M.B. acknowledges Euskadi RIS3 (grant no. 2019222054, 2020333010, and 2021333003) and Elkartek programs from Gobierno Vasco (grant no. KK-2020/00008); ISCIII (grant no. PI18/01075, CPII19/00008, and PI21/00922); CIBERehd; PSC Support, UK; AMMF The Cholangiocarcinoma Charity, UK (grant no. EU/2019/AMMFt/001); Horizon 2020 Research and Innovation Program (grant no. 825510); ERDF; and PSC Partners Seeking a Cure, US. A.L. received financial support from the Damon Runyon-Rachleff Innovation Award, US (grant no. DR52-18) and the MERIT Award (R37) from the National Cancer Institute (NCI), NIH (grant no. R37CA230636). F.E. expresses his gratitude to ProteoRed from ISCIII (grant no. PT13/0001/0027) and CIBERehd. N.G.A.A. was funded by Ministerio de Ciencia, Innovación y Universidades (grant no. RTI2018-095700-B-I00). R.B. acknowledges financial support from Gobierno Vasco (grant no. IT1165-19); Ministerio de Economía, Industria y Competitividad, Spain (grant no. SAF2017-90900-REDT); Ministerio de Economía, Industria y Competitividad, ERDF (grant no. BFU2017-84653-P); Ministerio de Ciencia e Innovación (grant no. PID2020-114178GB-I00); and Horizon 2020 funded under Marie Skłodowska-Curie Actions (grant no. 765445-EU). A.M.A. acknowledges CIBERehd. L.A.M.-C. obtained grants from Ministerio de Economía y Competitividad (grant no. CSD2008-00005); Ministerio de Economía, Industria y Competitividad (grant no. BFU2016-77408-R); ISCIII; and EJP RD, EU (grant no. EJPRD19-040). I.G.-R. was supported by Ministerio de Economía, Industria y Competitividad (grant no. BES-2017-080435 ). M.S.-M. is grateful to the AECC, Sede de Bizkaia, Spain for the financial support. J.D.Z. was awarded with a grant from Ministerio de Economía, Industria y Competitividad (grant no. SEV-2016-0644-18-2). C.M. acknowledges Gobierno Vasco (grant no. IT-1264-19) and Ministerio de Ciencia e Innovación (grant no. PID2022-136788OB-I00). A.V.-C. was supported by Ministerio de Educación, Cultura y Deporte, Spain (grant no. FPU016/01513). C.F.-R. thanks Tekniker, Spain and CIC bioGUNE, Spain for financial support. A.G.-d.R. was funded by Bikaintek program from Gobierno Vasco (grant no. 48-AF-W1-2019-00012). N.G.-U. obtained a grant from Gobierno Vasco. T.C.D. expresses gratitude to AECC. J.S. received financial support from CIBERehd. C.M.R.-G. was supported by Ayudas a la Recualificación Margarita Salas from Universidad de Extremadura, Ministerio de Universidades financed by NextGenerationEU.Peer reviewe

The PREDICTS database: a global database of how local terrestrial biodiversity responds to human impacts

Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species’ threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project – and avert – future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups – including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems – www.predicts.org.uk). We make site-level summary data available alongside this article. The full database will be publicly available in 2015