Structure, morphology, adhesion and in vitro biological evaluation of antibacterial multi-layer HA-Ag/SiO2/TiN/Ti coatings obtained by RF magnetron sputtering for biomedical applications

[EN] Biocompatible and antibacterial multi-layer coatings of hydroxyapatite (HA)-Ag/SiO2/TiN/Ti were obtained on the Ti-6Al-4V alloy, by means of the magnetron sputtering technique. During characterization of the coatings, the chemical composition was evaluated by energy dispersive X-ray spectroscopy and the phase analysis was carried out by X-ray diffraction. The morphology of the coatings was observed by field emission scanning electron microscopy, while transmission electron microscopy was used to appreciate their structure. The adhesion of the coatings to the substrate was evaluated by micro scratch test. The in vitro biological response was evaluated in terms of cytotoxicity, adhesion and differentiation of mouse mesenchymal stem cells, as well as adhesion and bacterial viability of Staphylococcus aureus strain. Through the compositional study carried out, the deposition of the HA phase was verified, with a Ca/P ratio close to 1.67 and the characteristic diffraction peaks of this compound. The structural study of the coatings evidenced the obtention of multi-layer architectures. The use of an intermediate SiO2/TiN/Ti trilayer was found to improve adhesion between HA-Ag and the substrate by 84%. Finally, the in vitro biological tests carried out indicated a potentially non-toxic character in the coatings. Additionally, an antibacterial effect was registered at low concentrations of Ag (3.0.co;2-3Lalueza, P., Monzón, M., Arruebo, M., & Santamaría, J. (2011). Bactericidal effects of different silver-containing materials. Materials Research Bulletin, 46(11), 2070-2076. doi:10.1016/j.materresbull.2011.06.041Peetsch, A., Greulich, C., Braun, D., Stroetges, C., Rehage, H., Siebers, B., … Epple, M. (2013). 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A., Evdokimov, K. E., Pichugin, V. F., Peitsch, T., & Epple, M. (2011). The influence of the deposition parameters on the properties of an rf-magnetron-deposited nanostructured calcium phosphate coating and a possible growth mechanism. Surface and Coatings Technology, 205(12), 3600-3606. doi:10.1016/j.surfcoat.2010.12.039Surmeneva, M. A., Sharonova, A. A., Chernousova, S., Prymak, O., Loza, K., Tkachev, M. S., … Surmenev, R. A. (2017). Incorporation of silver nanoparticles into magnetron-sputtered calcium phosphate layers on titanium as an antibacterial coating. Colloids and Surfaces B: Biointerfaces, 156, 104-113. doi:10.1016/j.colsurfb.2017.05.016Mohseni, E., Zalnezhad, E., Bushroa, A. R., Abdel Magid Hamouda, Goh, B. T., & Yoon, G. H. (2015). Ti/TiN/HA coating on Ti–6Al–4V for biomedical applications. Ceramics International, 41(10), 14447-14457. doi:10.1016/j.ceramint.2015.07.081Ghasemi, S., Shanaghi, A., & Chu, P. K. (2017). Nano mechanical and wear properties of multi-layer Ti/TiN coatings deposited on Al 7075 by high-vacuum magnetron sputtering. Thin Solid Films, 638, 96-104. doi:10.1016/j.tsf.2017.07.049Hamdi, D. A., Jiang, Z.-T., No, K., Rahman, M. M., Lee, P.-C., Truc, L. N. T., … Dlugogorski, B. Z. (2019). Biocompatibility study of multi-layered hydroxyapatite coatings synthesized on Ti-6Al-4V alloys by RF magnetron sputtering for prosthetic-orthopaedic implant applications. Applied Surface Science, 463, 292-299. doi:10.1016/j.apsusc.2018.08.157Qi, J., Yang, Y., Zhou, M., Chen, Z., & Chen, K. (2019). Effect of transition layer on the performance of hydroxyapatite/titanium nitride coating developed on Ti-6Al-4V alloy by magnetron sputtering. Ceramics International, 45(4), 4863-4869. doi:10.1016/j.ceramint.2018.11.183Lenis, J. A., Hurtado, F. M., Gómez, M. A., & Bolívar, F. J. (2019). Effect of thermal treatment on structure, phase and mechanical properties of hydroxyapatite thin films grown by RF magnetron sputtering. Thin Solid Films, 669, 571-578. doi:10.1016/j.tsf.2018.11.045Lenis, J. A., Gómez, M. A., & Bolívar, F. J. (2019). Effect of deposition temperature and target-substrate distance on the structure, phases, mechanical and tribological properties of multi-layer HA-Ag coatings obtained by RF magnetron sputtering. Surface and Coatings Technology, 378, 124936. doi:10.1016/j.surfcoat.2019.124936Sofronia, A. M., Baies, R., Anghel, E. M., Marinescu, C. A., & Tanasescu, S. (2014). Thermal and structural characterization of synthetic and natural nanocrystalline hydroxyapatite. Materials Science and Engineering: C, 43, 153-163. doi:10.1016/j.msec.2014.07.023Lenis, J. A., Bejarano, G., Rico, P., Ribelles, J. L. G., & Bolívar, F. J. (2019). Development of multilayer Hydroxyapatite - Ag/TiN-Ti coatings deposited by radio frequency magnetron sputtering with potential application in the biomedical field. Surface and Coatings Technology, 377, 124856. doi:10.1016/j.surfcoat.2019.06.097Lenis, J. A., Toro, L. J., & Bolívar, F. J. (2019). Multi-layer bactericidal silver - calcium phosphate coatings obtained by RF magnetron sputtering. Surface and Coatings Technology, 367, 203-211. doi:10.1016/j.surfcoat.2019.03.038Valverde, A., Pérez-Álvarez, L., Ruiz-Rubio, L., Pacha Olivenza, M. A., García Blanco, M. B., Díaz-Fuentes, M., & Vilas-Vilela, J. L. (2019). Antibacterial hyaluronic acid/chitosan multilayers onto smooth and micropatterned titanium surfaces. Carbohydrate Polymers, 207, 824-833. doi:10.1016/j.carbpol.2018.12.039Surmeneva, M. A., Chaikina, M. V., Zaikovskiy, V. I., Pichugin, V. F., Buck, V., Prymak, O., … Surmenev, R. A. (2013). The structure of an RF-magnetron sputter-deposited silicate-containing hydroxyapatite-based coating investigated by high-resolution techniques. Surface and Coatings Technology, 218, 39-46. doi:10.1016/j.surfcoat.2012.12.023Nelea, V., Morosanu, C., Iliescu, M., & Mihailescu, I. N. (2003). Microstructure and mechanical properties of hydroxyapatite thin films grown by RF magnetron sputtering. Surface and Coatings Technology, 173(2-3), 315-322. doi:10.1016/s0257-8972(03)00729-1Ding, S.-J., Ju, C.-P., & Lin, J.-H. C. (1999). Characterization of hydroxyapatite and titanium coatings sputtered on Ti-6Al-4V substrate. Journal of Biomedical Materials Research, 44(3), 266-279. doi:10.1002/(sici)1097-4636(19990305)44:33.0.co;2-4Ivanova, A. A., Surmeneva, M. A., Tyurin, A. I., Pirozhkova, T. S., Shuvarin, I. A., Prymak, O., … Surmenev, R. A. (2016). Fabrication and physico-mechanical properties of thin magnetron sputter deposited silver-containing hydroxyapatite films. 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S., Shuvarin, I. A., Syrtanov, M. S., & Surmenev, R. A. (2015). Enhancement of the mechanical properties of AZ31 magnesium alloy via nanostructured hydroxyapatite thin films fabricated via radio-frequency magnetron sputtering. Journal of the Mechanical Behavior of Biomedical Materials, 46, 127-136. doi:10.1016/j.jmbbm.2015.02.025Quirama, A., Echavarría, A. M., Meza, J. M., Osorio, J., & Bejarano G, G. (2017). Improvement of the mechanical behavior of the calcium phosphate coatings deposited onto Ti6Al4V alloy using an intermediate TiN/TiO2 bilayer. Vacuum, 146, 22-30. doi:10.1016/j.vacuum.2017.09.024Surmeneva, M. A., Kleinhans, C., Vacun, G., Kluger, P. J., Schönhaar, V., Müller, M., … Surmenev, R. A. (2015). Nano-hydroxyapatite-coated metal-ceramic composite of iron-tricalcium phosphate: Improving the surface wettability, adhesion and proliferation of mesenchymal stem cells in vitro. Colloids and Surfaces B: Biointerfaces, 135, 386-393. doi:10.1016/j.colsurfb.2015.07.057Chen, Y., Zheng, X., Xie, Y., Ji, H., Ding, C., Li, H., & Dai, K. (2010). Silver release from silver-containing hydroxyapatite coatings. Surface and Coatings Technology, 205(7), 1892-1896. doi:10.1016/j.surfcoat.2010.08.073Actis, L., Gaviria, L., Guda, T., & Ong, J. L. (2013). Antimicrobial surfaces for craniofacial implants: state of the art. Journal of the Korean Association of Oral and Maxillofacial Surgeons, 39(2), 43. doi:10.5125/jkaoms.2013.39.2.43Parvizi, J., Aggarwal, V., & Rasouli, M. (2013). Periprosthetic joint infection: Current concept. Indian Journal of Orthopaedics, 47(1), 10. doi:10.4103/0019-5413.106884Redey, S. A., Nardin, M., Bernache-Assolant, D., Rey, C., Delannoy, P., Sedel, L., & Marie, P. J. (2000). Behavior of human osteoblastic cells on stoichiometric hydroxyapatite and type A carbonate apatite: Role of surface energy. Journal of Biomedical Materials Research, 50(3), 353-364. doi:10.1002/(sici)1097-4636(20000605)50:33.0.co;2-cSpriano, S., Bosetti, M., Bronzoni, M., Vernè, E., Maina, G., Bergo, V., & Cannas, M. (2005). Surface properties and cell response of low metal ion release Ti-6Al-7Nb alloy after multi-step chemical and thermal treatments. Biomaterials, 26(11), 1219-1229. doi:10.1016/j.biomaterials.2004.04.026Vogler, E. A. (1999). Water and the acute biological response to surfaces. Journal of Biomaterials Science, Polymer Edition, 10(10), 1015-1045. doi:10.1163/156856299x00667Lim, J. Y., Liu, X., Vogler, E. A., & Donahue, H. J. (2004). Systematic variation in osteoblast adhesion and phenotype with substratum surface characteristics. Journal of Biomedical Materials Research, 68A(3), 504-512. doi:10.1002/jbm.a.20087Sengstock, C., Diendorf, J., Epple, M., Schildhauer, T. A., & Köller, M. (2014). Effect of silver nanoparticles on human mesenchymal stem cell differentiation. 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PiRNA-associated proteins and retrotransposons are differentially expressed in murine testis and ovary of aryl hydrocarbon receptor deficient mice

Previous studies suggested that the aryl hydrocarbon receptor (AhR) contributes to mice reproduction and fertility. However, the mechanisms involved remain mostly unknown. Retrotransposon silencing by Piwi-interacting RNAs (piRNAs) is essential for germ cell maturation and, remarkably, AhR has been identified as a regulator of murine B1-SINE retrotransposons. Here, using littermate AhR+/+ and AhR-/- mice, we report that AhR regulates the general course of spermatogenesis and oogenesis by a mechanism likely to be associated with piRNA-associated proteins, piRNAs and retrotransposons. piRNA-associated proteins MVH and Miwi are upregulated in leptotene to pachytene spermatocytes with a more precocious timing in AhR-/- than in AhR+/+ testes. piRNAs and transcripts from B1-SINE, LINE-1 and IAP retrotransposons increased at these meiotic stages in AhR-null testes. Moreover, B1-SINE transcripts colocalize with MVH and Miwi in leptonema and pachynema spermatocytes. Unexpectedly, AhR-/- males have increased sperm counts, higher sperm functionality and enhanced fertility than AhR+/+ mice. In contrast, piRNA-associated proteins and B1-SINE and IAP-derived transcripts are reduced in adult AhR-/- ovaries. Accordingly, AhR-null female mice have lower numbers of follicles when compared with AhR+/+ mice. Thus, AhR deficiency differentially affects testis and ovary development possibly by a process involving piRNA-associated proteins, piRNAs and transposable elements.Trabajo financiado por: Ministerio de Ciencia e Innovación. Ayuda BFU2011-22678 para Pedro María Fernández Salguero Ministerio de Economía y Competitividad. Ayuda SAF2014-51813-R para Pedro María Fernández Salguero Junta de Extremadura. Ayuda GR15008, para Pedro María Fernández Salguero Red Temática de Investigación Cooperativa en Cáncer (RTICC), Instituto Carlos III y Ministerio de Economía y Competitividad (RD12/0036/0032). Trabajos de laboratorio de Pedro María Fernández Salguero Ministerio de Economía y Competitividad. Ayuda AGL2013-43211-R, para Fernando Juan Peña Vega Red Temática de Investigación Cooperativa en Cáncer (RTICC), Instituto Carlos III. Ayuda para Eva María Rico Leo Ministerio de Economía y Competitividad. Ayuda para Francisco Javier González Rico Junta de Extremadura. Ayuda para Eva María Barrasa Ardila Ministerio de Educación, Cultura y Deportes. Beca de Formación de Personal de Investigación, para Nuria Moreno Marín Ministerio de Educación, Cultura y Deportes. Beca FPU13/03991, de Formación de Profesorado Universitario, para Patricia Martín Muñoz Ministerio de Economía y Competitividad. Beca Juan de la Cierva IJCI-2014-21671, para Cristina Ortega Ferrusola Ministerio de Economía y Competitividad, Beca BFU2014-59307-R, para Alberto M. Pendás y Elena Llano Cuadro MEIONet, Junta de Castilla y León y el Programa de Fondeos FEDER, de la Unión EuropeapeerReviewe

Involvement of phage ϕ29 DNA polymerase and terminal protein subdomains in conferring specificity during initiation of protein-primed DNA replication

To initiate ϕ29 DNA replication, the DNA polymerase has to form a complex with the homologous primer terminal protein (TP) that further recognizes the replication origins of the homologous TP-DNA placed at both ends of the linear genome. By means of chimerical proteins, constructed by swapping the priming domain of the related ϕ29 and GA-1 TPs, we show that DNA polymerase can form catalytically active heterodimers exclusively with that chimerical TP containing the N-terminal part of the homologous TP, suggesting that the interaction between the polymerase TPR-1 subdomain and the TP N-terminal part is the one mainly responsible for the specificity between both proteins. We also show that the TP N-terminal part assists the proper binding of the priming domain at the polymerase active site. Additionally, a chimerical ϕ29 DNA polymerase containing the GA-1 TPR-1 subdomain could use GA-1 TP, but only in the presence of ϕ29 TP-DNA as template, indicating that parental TP recognition is mainly accomplished by the DNA polymerase. The sequential events occurring during initiation of bacteriophage protein-primed DNA replication are proposed

Superplastic deformation of directionally solidified nanofibrillar Al2O3-Y3Al5O12-ZrO2 eutectics

Nanofibrillar Al2O3–Y3Al5O12–ZrO2 eutectic rods were manufactured by directional solidification from the melt at high growth rates in an inert atmosphere using the laser-heated floating zone method. Under conditions of cooperative growth, the ternary eutectic presented a homogeneous microstructure, formed by bundles of single-crystal c-oriented Al2O3 and Y3Al5O12 (YAG) whiskers of ≈100 nm in width with smaller Y2O3-doped ZrO2 (YSZ) whiskers between them. Owing to the anisotropic fibrillar microstructure, Al2O3–YAG–YSZ ternary eutectics present high strength and toughness at ambient temperature while they exhibit superplastic behavior at 1600 K and above. Careful examination of the deformed samples by transmission electron microscopy did not show any evidence of dislocation activity and superplastic deformation was attributed to mass-transport by diffusion within the nanometric domains. This combination of high strength and toughness at ambient temperature together with the ability to support large deformations without failure above 1600 K is unique and shows a large potential to develop new structural materials for very high temperature structural applications

Depression and Anxiety Disorders and Associated Factors in the Adolescent Colombian Population, 2015 National Mental Health Survey

Introducción La prevalencia de trastornos mentales entre los adolescentes es del 17% en el último año. Dichos trastornos tienden a ser crónicos y su aparición a esta edad se asocia a un peor pronóstico que las que aparecen en la edad adulta. Objetivos Determinar la prevalencia y los factores asociados a los principales trastornos mentales depresivos y ansiosos de los adolescentes. Métodos Datos obtenidos de la Encuesta Nacional de Salud Mental 2015 con representatividad de 5 regiones. Se realiza una encuesta estructurada computarizada con el CIDI-CAPI adolescentes, centrada en los más frecuentes trastornos depresivos y ansiosos. Se tomó una muestra de 1.754 adolescentes entre 12 y 17 años. Resultados La prevalencia de cualquier trastorno alguna vez en la vida es del 7,2%, (intervalo de confianza del 95% [IC95%], 5,8-8,9). El trastorno más frecuente fue la fobia social, que se manifestó alguna vez en la vida en un 4,8% (IC95%, 3,7-6,2); los menos frecuentes fueron el trastorno de pánico en las mujeres (0,2%; IC95%, 0,1-1,0) y otros trastornos bipolares en los varones (0,2%; IC95%, 0,1-0,7). De los factores asociados a sufrir cualquier trastorno, se encontró: ser mujer (odds ratio [OR] = 2,1), tener poco apoyo familiar (OR = 2,0), haber presenciado al menos un evento traumático (OR = 2,6) y haber hecho un intento de suicidio (OR = 3,4). Como factor protector, se encontró la participación en por lo menos un grupo (OR = 0,5). Conclusiones Los trastornos mentales de ansiedad y depresión representan una importante carga de enfermedad para Colombia.Q476-88Introduction There was a prevalence of mental disorders of 17% in adolescents in the past year. These tended to be chronic and their appearance at this age is associated with a worse prognosis than those in adulthood. Objectives To determine the prevalence and mental factors associated with major depression and anxiety disorders. Methods Data were obtained from the IV National Mental Health Survey representing 5 regions. A structured computerised survey was conducted using the Computer Assisted Personal Interview-Composite International Diagnostic Interview-Adolescent Version (CAPI-CIDI-A), focused on the most common depression and anxiety disorders. It included a sample of 1754 adolescents between 12 and 17 years old. Results The prevalence of any disorder at some point in life was 7.2% (95%CI, 5.8-8.9). The most common disorder corresponded to social phobia manifested sometime in life in 4.8% (95%CI, 3.7-6.2). Less frequent were panic disorder in girls (0.2%; 95% CI, 0.1-1.0) and other bipolar disorders in boys (0.2%; 95%CI, 0.1-0.7). Among the associated factors of suffering from any disorder were, being female (OR = 2.1), having little family support (OR = 2.0), having witnessed at least one traumatic event (OR = 2.6), and having had a previous suicide attempt (OR = 3.4). Participation in at least one group was a protective factor (OR = 0.5). Conclusions Mental disorders of anxiety and depression represent a major burden of disease for Colombia

Panorámica actual de las especies no indígenas marinas en el mar Cantábrico y Atlántico adyacente (NO-N de la península Ibérica): primera aproximación a la Directiva Marco de Estrategias Marinas en la demarcación noroeste

Simposio Ibérico de Estudios de Biología Marina (18º. 2014. Gijón (España))La introducción de especies invasoras no indígenas es un problema cada vez más común a escala mundial, siendo considerado una de mayores amenazas para la conservación de la biodiversidad de todo el planeta. Estas invasiones biológicas causan graves problemas ecológicos y en muchos casos ocasionan también importantes pérdidas a la economía local. La gravedad y el alcance de los impactos generados por las especies invasoras es tal, que en los últimos años ha trascendido del ámbito científico al político-social, siendo considerado como uno de los descriptores de la calidad ambiental en la Directiva Marco de la Estrategia Marina (MSFD 2008/56/EC). A pesar de la envergadura y repercusión de este problema, el estudio de las especies invasoras en aguas de la península Ibérica no ha sido abordado hasta fechas muy recientes, estando en su mayoría centrado en el ámbito continental de los ecosistemas dulceacuícolas y en el ámbito marino de la cuenca mediterránea de la península. Para las costas noratlánticas españolas(las cuales constituyen la demarcación noroeste de la Directiva Marco de la Estrategia Marina) los datos existentes son bastante escasos y sobre todo dispersos, siendo también en muchos casos de afiliación taxonómica dudosa. En este trabajo se presenta la primera revisión actualizada de las especies marinas reportadas como no indígenas (exóticas, no autóctonas, alóctonas o “alien”) ocriptogénicas para el mar Cantábrico y el Atlántico adyacente (costas de Galicia) hasta la actualidad; incluyendo también nuevas adiciones procedentes de los muestreos realizadosen las costas cantábricas y atlántico-gallegas entre los años 2010 y 2014. El área de estudio fue dividida en cuatro zonas (A-D) de Oeste a Este. En esta revisión no se reconocen como alóctonosy/o criptogénicosalgunos taxones previamente reportados como tales, ya que según nuestro criterio se tratan de especies nativas y/o especies que están extendiendo sus rangos de distribución de forma natural, en muchos casos como consecuencia de los fenómenos de calentamiento global. Se listan un total de 287 taxones considerados como no indígenas y/o criptogénicos para el área de estudio, constituyendo estos últimos aproximadamente un tercio del total (92 taxones). Para las taxones alóctonos(195), se ha seguido la clasificación de Zenetoset al. basada en el grado de invasión de las mismas. Las especies consideradas como “casuales” representaron aproximadamente una quinta parte del total (17%), mientras que las especies “establecidas” constituyeron algo menos de la mitad (41%). Finalmente, alrededor de un 6% de los taxones recogidos (17) se categorizaron como “invasores” para las aguas objeto de estudio. En función de las zonas geográficas en las que fue dividida el área de estudio, la gran mayoría de las especies (78%) fueron detectadas para una sola zona; un 21% lo fueron para al menos dos zonas; un 11% para tres y sólo un 6% de las especies fueron detectadas en las cuatro zonas (formando parte de éstas, 10 de las especies consideradas “invasoras”). Taxonómicamente, los filos con un mayor número de especies introducidas son los moluscos y los anélidos, agrupando, cada uno de ellos, un 21% del total de especies; seguidos del grupo de las algas rojas (16%) y de los artrópodos (14%). Otros filos que representan porcentajes mucho menores son los cnidarios (7%), los briozoos (5%), las algas pardas (4%), las ascidias (4%), los poríferos (3%), las algasverdes (2%), los gusanos nemertinos (<1%) y los equinodermos (<1%). El filo con mayor número de especies consideradas como “invasoras” es el grupo las algas rojas con 7 especies

Alterations in Circulating Monocytes Predict COVID-19 Severity and Include Chromatin Modifications Still Detectable Six Months after Recovery

This study was supported by the Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation (COVID-19 research call COV20/00181)—co-financed by the European Development Regional Fund “A way to achieve Europe” and by Consejería de Sanidad de la Comunidad de Madrid (CÍVICO study 2020/0082). R.L.G. and O.C.M. hold a research contract “Rio Hortega” (CM19/00120 and CM19/00092, respectively) from the Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation. MCL holds a predoctoral fellowship (FPU19/06393) from the Spanish Ministry of Science and Innovation.An early analysis of circulating monocytes may be critical for predicting COVID-19 course and its sequelae. In 131 untreated, acute COVID-19 patients at emergency room arrival, monocytes showed decreased surface molecule expression, including low HLA-DR, in association with an inflammatory cytokine status and limited anti-SARS-CoV-2-specific T cell response. Most of these alterations had normalized in post-COVID-19 patients 6 months after discharge. Acute COVID-19 monocytes transcriptome showed upregulation of anti-inflammatory tissue repair genes such as BCL6, AREG and IL-10 and increased accessibility of chromatin. Some of these transcriptomic and epigenetic features still remained in post-COVID-19 monocytes. Importantly, a poorer expression of surface molecules and low IRF1 gene transcription in circulating monocytes at admission defined a COVID-19 patient group with impaired SARS-CoV-2-specific T cell response and increased risk of requiring intensive care or dying. An early analysis of monocytes may be useful for COVID-19 patient stratification and for designing innate immunity-focused therapies.Depto. de MedicinaFac. de MedicinaTRUEUnión EuropeaMinisterio de Ciencia e Innovación (España)Comunidad de MadridInstituto de Salud Carlos IIIpu

Endothelial dysfunction is an early indicator of sepsis and neutrophil degranulation of septic shock in surgical patients

Producción CientíficaBackground: Stratification of the severity of infection is currently based on the Sequential Organ Failure Assessment (SOFA) score, which is difficult to calculate outside the ICU. Biomarkers could help to stratify the severity of infection in surgical patients. Methods: Levels of ten biomarkers indicating endothelial dysfunction, 22 indicating emergency granulopoiesis, and six denoting neutrophil degranulation were compared in three groups of patients in the first 12 h after diagnosis at three Spanish hospitals. Results: There were 100 patients with infection, 95 with sepsis and 57 with septic shock. Seven biomarkers indicating endothelial dysfunction (mid-regional proadrenomedullin (MR-ProADM), syndecan 1, thrombomodulin, angiopoietin 2, endothelial cell-specific molecule 1, vascular cell adhesion molecule 1 and E-selectin) had stronger associations with sepsis than infection alone. MR-ProADM had the highest odds ratio (OR) in multivariable analysis (OR 11·53, 95 per cent c.i. 4·15 to 32·08; P = 0·006) and the best area under the curve (AUC) for detecting sepsis (0·86, 95 per cent c.i. 0·80 to 0·91; P < 0·001). In a comparison of sepsis with septic shock, two biomarkers of neutrophil degranulation, proteinase 3 (OR 8·09, 1·34 to 48·91; P = 0·028) and lipocalin 2 (OR 6·62, 2·47 to 17·77; P = 0·002), had the strongest association with septic shock, but lipocalin 2 exhibited the highest AUC (0·81, 0·73 to 0·90; P < 0·001). Conclusion: MR-ProADM and lipocalin 2 could be alternatives to the SOFA score in the detection of sepsis and septic shock respectively in surgical patients with infection.Instituto de Salud Carlos III (grants PI15/01959, PI15/01451 and PI16/01156

Longitudinal dynamics of SARS-CoV-2-specific cellular and humoral immunity after natural infection or BNT162b2 vaccination

The timing of the development of specific adaptive immunity after natural SARS-CoV-2 infection, and its relevance in clinical outcome, has not been characterized in depth. Description of the long-term maintenance of both cellular and humoral responses elicited by real-world anti-SARS-CoV-2 vaccination is still scarce. Here we aimed to understand the development of optimal protective responses after SARS-CoV-2 infection and vaccination. We performed an early, longitudinal study of S1-, M- and N-specific IFN-γ and IL-2 T cell immunity and anti-S total and neutralizing antibodies in 88 mild, moderate or severe acute COVID-19 patients. Moreover, SARS-CoV-2-specific adaptive immunity was also analysed in 234 COVID-19 recovered subjects, 28 uninfected BNT162b2-vaccinees and 30 uninfected healthy controls. Upon natural infection, cellular and humoral responses were early and coordinated in mild patients, while weak and inconsistent in severe patients. The S1-specific cellular response measured at hospital arrival was an independent predictive factor against severity. In COVID-19 recovered patients, four to seven months post-infection, cellular immunity was maintained but antibodies and neutralization capacity declined. Finally, a robust Th1-driven immune response was developed in uninfected BNT162b2-vaccinees. Three months post-vaccination, the cellular response was comparable, while the humoral response was consistently stronger, to that measured in COVID-19 recovered patients. Thus, measurement of both humoral and cellular responses provides information on prognosis and protection from infection, which may add value for individual and public health recommendations

The interplay between functioning problems and symptoms in first episode of psychosis: an approach from network analysis

The relationship between psychotic symptoms and global measures of functioning has been widely studied. No previous study has assessed so far the interplay between specific clinical symptoms and particular areas of functioning in first-episode psychosis (FEP) using network analysis methods. A total of 191 patients with FEP (age 24.45 ± 6.28 years, 64.9% male) participating in an observational and longitudinal study (AGES-CM) comprised the study sample. Functioning problems were assessed with the WHO Disability Assessment Schedule (WHODAS), whereas the Positive and Negative Syndrome Scale (PANSS) was used to assess symptom severity. Network analysis were conducted with the aim of analysing the patterns of relationships between the different dimensions of functioning and PANSS symptoms and factors at baseline. According to our results, the most important nodes were “conceptual disorganization”, “emotional withdrawal”, “lack of spontaneity and flow of conversation”, “delusions”, “unusual thought content”, “dealing with strangers” and “poor rapport”. Our findings suggest that these symptoms and functioning dimensions should be prioritized in the clinical assessment and management of patients with FEP. These areas may also become targets of future early intervention strategies, so as to improve quality of life in this populationThis work was supported by the Madrid Regional Government (R&D activities in Biomedicine (grant number S2017/BMD-3740 - AGES-CM 2-CM)) and Structural Funds of the European Union. Ana Izquierdo’s work is supported by the PFIS predoctoral program (FI17/00138) from the Instituto de Salud Carlos III (Spain) and co-funded by the European Union (ERDF/ESF, "A way to make Europe”/ “Investing in your future”) and The Biomedical Research Foundation of La Princesa University Hospital. Angela Ib´a˜nez thanks the support of CIBERSAM and of the Spanish Ministry of Science, Innovation and Universities. Instituto de Salud Carlos III (PI16/00834 and PI19/01295) co-financed by ERDF Funds from the European Commission. Covadonga M. Díaz-Caneja holds a Juan Rod´es Grant from Instituto de Salud Carlos III (JR19/00024). Celso Arango was supported by the Spanish Ministry of Science and Innovation. Instituto de Salud Carlos III (SAM16PE07CP1, PI16/02012, PI19/ 024), co-financed by ERDF Funds from the European Commission, “A way of making Europe”, CIBERSAM. Madrid Regional Government (B2017/BMD-3740 AGES-CM-2), European Union Structural Funds. European Union Seventh Framework Program under grant agreements FP7-4-HEALTH-2009-2.2.1-2-241909 (Project EU-GEI), FP7- HEALTH- 2013-2.2.1-2-603196 (Project PSYSCAN) and FP7- HEALTH-2013- 2.2.1-2-602478 (Project METSY); and European Union H2020 Program under the Innovative Medicines Initiative 2 Joint Undertaking (grant agreement No 115916, Project PRISM, and grant agreement No 777394, Project AIMS-2-TRIALS), Fundaci´on Familia Alonso, Fundaci´on Alicia Koplowitz and Fundaci´on Mutua Madrile˜n