Optimising the Therapeutic Interval for Biologics in Patients with Psoriasis

In our clinical experience, more than half of patients do not present a complete response to biologic drugs, or drug loses its efficacy over time. Plasma determinations of drug and antidrug antibodies levels are an objective tool for optimisation in these patients; however, established therapeutic ranges are not suitable, so the objective of this study was to study these patients and optimise their healthcare. We have made a retrospective, observational study, using data of plasma levels of drugs and anti-drugs antibodies of infliximab, adalimumab or Etanercept, we summarise all data and make a study of sensitivity, specificity, positive and negative predictive value on current therapeutic ranges. We have found a statistically significant association between subtherapeutic levels and therapeutic failure in psoriasis treated with infliximab and adalimumab. New ranges were found with higher sensitivity than the established ones, we propose 2–10 g/mL therapeutic range for infliximab, 3–11 g/mL for adalimumab, and 1–7 g/mL for etanercept. In conclusion, levels of drug and anti-drug antibodies are a decisive tool for predicting therapeutic response. The current therapeutic ranges may have minimum values that are excessively high, owing to which lowering them significantly increases the sensitivity of the test in all cases, and negative predictive value in the case of etanercept. Further prospective studies are needed to prove the usefulness of these new ranges.9 página

CARB-ES-19 Multicenter Study of Carbapenemase-Producing Klebsiella pneumoniae and Escherichia coli From All Spanish Provinces Reveals Interregional Spread of High-Risk Clones Such as ST307/OXA-48 and ST512/KPC-3

ObjectivesCARB-ES-19 is a comprehensive, multicenter, nationwide study integrating whole-genome sequencing (WGS) in the surveillance of carbapenemase-producing K. pneumoniae (CP-Kpn) and E. coli (CP-Eco) to determine their incidence, geographical distribution, phylogeny, and resistance mechanisms in Spain.MethodsIn total, 71 hospitals, representing all 50 Spanish provinces, collected the first 10 isolates per hospital (February to May 2019); CPE isolates were first identified according to EUCAST (meropenem MIC > 0.12 mg/L with immunochromatography, colorimetric tests, carbapenem inactivation, or carbapenem hydrolysis with MALDI-TOF). Prevalence and incidence were calculated according to population denominators. Antibiotic susceptibility testing was performed using the microdilution method (EUCAST). All 403 isolates collected were sequenced for high-resolution single-nucleotide polymorphism (SNP) typing, core genome multilocus sequence typing (cgMLST), and resistome analysis.ResultsIn total, 377 (93.5%) CP-Kpn and 26 (6.5%) CP-Eco isolates were collected from 62 (87.3%) hospitals in 46 (92%) provinces. CP-Kpn was more prevalent in the blood (5.8%, 50/853) than in the urine (1.4%, 201/14,464). The cumulative incidence for both CP-Kpn and CP-Eco was 0.05 per 100 admitted patients. The main carbapenemase genes identified in CP-Kpn were blaOXA–48 (263/377), blaKPC–3 (62/377), blaVIM–1 (28/377), and blaNDM–1 (12/377). All isolates were susceptible to at least two antibiotics. Interregional dissemination of eight high-risk CP-Kpn clones was detected, mainly ST307/OXA-48 (16.4%), ST11/OXA-48 (16.4%), and ST512-ST258/KPC (13.8%). ST512/KPC and ST15/OXA-48 were the most frequent bacteremia-causative clones. The average number of acquired resistance genes was higher in CP-Kpn (7.9) than in CP-Eco (5.5).ConclusionThis study serves as a first step toward WGS integration in the surveillance of carbapenemase-producing Enterobacterales in Spain. We detected important epidemiological changes, including increased CP-Kpn and CP-Eco prevalence and incidence compared to previous studies, wide interregional dissemination, and increased dissemination of high-risk clones, such as ST307/OXA-48 and ST512/KPC-3

Remote ischaemic preconditioning ameliorates anthracycline-induced cardiotoxicity and preserves mitochondrial integrity.

Anthracycline-induced cardiotoxicity (AIC) is a serious adverse effect among cancer patients. A central mechanism of AIC is irreversible mitochondrial damage. Despite major efforts, there are currently no effective therapies able to prevent AIC. Forty Large-White pigs were included. In Study 1, 20 pigs were randomized 1:1 to remote ischaemic preconditioning (RIPC, 3 cycles of 5 min leg ischaemia followed by 5 min reperfusion) or no pretreatment. RIPC was performed immediately before each intracoronary doxorubicin injections (0.45 mg/kg) given at Weeks 0, 2, 4, 6, and 8. A group of 10 pigs with no exposure to doxorubicin served as healthy controls. Pigs underwent serial cardiac magnetic resonance (CMR) exams at baseline and at Weeks 6, 8, 12, and 16, being sacrifice after that. In Study 2, 10 new pigs received 3 doxorubicin injections (with/out preceding RIPC) and were sacrificed at week 6. In Study 1, left ventricular ejection fraction (LVEF) depression was blunted animals receiving RIPC before doxorubicin (RIPC-Doxo), which had a significantly higher LVEF at Week 16 than doxorubicin treated pigs that received no pretreatment (Untreated-Doxo) (41.5 ± 9.1% vs. 32.5 ± 8.7%, P = 0.04). It was mainly due to conserved regional contractile function. In Study 2, transmission electron microscopy (TEM) at Week 6 showed fragmented mitochondria with severe morphological abnormalities in Untreated-Doxo pigs, together with upregulation of fission and autophagy proteins. At the end of the 16-week Study 1 protocol, TEM revealed overt mitochondrial fragmentation with structural fragmentation in Untreated-Doxo pigs, whereas interstitial fibrosis was less severe in RIPC+Doxo pigs. In a translatable large-animal model of AIC, RIPC applied immediately before each doxorubicin injection resulted in preserved cardiac contractility with significantly higher long-term LVEF and less cardiac fibrosis. RIPC prevented mitochondrial fragmentation and dysregulated autophagy from AIC early stages. RIPC is a promising intervention for testing in clinical trials in AIC.This study is part of a project that has received funding from the European Research Council (ERC) under the European Union Horizon 2020 Research and Innovation Programme (ERCConsolidator Grant agreement No. 819775 to B.I). The study was also partially funded by an ERA-CVD Joint Translational Call 2016 (funded through the Instituto de Salud Carlos III (ISCIII) and the European Regional Development Fund (ERDF), # AC16/00021) and by a Health Research Project from the ISCIII-FIS (# PI16/02110). Carlos Galán-Arriola and Rocío Villena-Gutiérrez are P-FIS fellows (Instituto de Salud Carlos III). This study forms part of a research agreement between the CNIC and Philips Healthcare. The CNIC is supported by the ISCIII, the Ministerio de Ciencia e Innovación, and the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence (MEIC award SEV-2015-0505).S

Catalytic Aspects of Pt/Pd Supported on ZnO Rods for Hydrogen Production in Methanol Steam Reforming

We present a combined experimental and theoretical study for catalytic performance of Pt/Pd supported on ZnO rods for methanol steam reforming reaction (MSR) for hydrogen production. The samples were extensively characterized by Adsorption– Desorption of N2 (BET), electron microscopy in scanning and transmission mode (SEM/TEM), X-ray diffraction (XRD), temperature programed reduction (TPR), and mass spectroscopy (MS). Results, showed typical diffraction peaks corresponding to hexagonal Zincite structure and tetragonal PtZn, PdZn and PtPdZn alloys which were identified by XRD, HRTEM and the last structure by modeling simulation. The crystallographic characterization after catalytic testing indicates that intermetallic PtZn phase on Pt/ZnO sample was more stable in comparison to PdZn on Pd/ZnO catalyst. In addition, Pt stabilize the PdZn structure in the bimetallic catalyst. The catalytic reactivity measured from 200 to 450 °C, indicates that Pt/ZnO-rod sample possess superior catalytic activity from the series as completed on this study. The methanol conversion was tracked by mass spectroscopy concluding minimal changes in outlet signals which suggests samples are chemically stable throughout the complete catalytic reaction. Furthermore, the computer assisted density of states calculations indicate that electron donation from platinum into the zinc oxide support might be the explanation for better catalytic performance

Risk factor for breast cancer development under exposure to bovine leukemia virus in Colombian women : A case-control study

Q2Q1Viruses have been implicated in cancer development in both humans and animals. The role of viruses in cancer is typically to initiate cellular transformation through cellular DNA damage, although specific mechanisms remain unknown. Silent and long-term viral infections need to be present, in order to initiate cancer disease. In efforts to establish a causative role of viruses, first is needed to demonstrate the strength and consistency of associations in different populations. The aim of this study was to determine the association of bovine leukemia virus (BLV), a causative agent of leukemia in cattle, with breast cancer and its biomarkers used as prognosis of the severity of the disease (Ki67, HER2, hormonal receptors) in Colombian women. An unmatched, observational case–control study was conducted among women undergoing breast surgery between 2016–2018. Malignant samples (n = 75) were considered as cases and benign samples (n = 83) as controls. Nested-liquid PCR, in-situ PCR and immunohistochemistry were used for viral detection in blood and breast tissues. For the risk assessment, only BLV positive samples from breast tissues were included in the analysis. BLV was higher in cases group (61.3%) compared with controls (48.2%), with a statistically significant association between the virus and breast cancer in the unconditional logistic regression (adjusted-OR = 2.450,95%CI:1.088–5.517, p = 0.031). In this study, BLV was found in both blood and breast tissues of participants and an association between breast cancer and the virus was confirmed in Colombia, as an intermediate risk factor.https://orcid.org/0000-0002-0084-0339Revista Internacional - IndexadaS

INSOCTEA V. Advanced methodologies on social research of work, gender and global chains to teaching in sociology of work and critical economics

El proyecto “Intersoc y Economía Crítica. Metodologías avanzadas sobre investigación social del trabajo, género y cadenas globales”, llamado coloquialmente INSOCTEA V, es el resultado de las inquietudes docentes e investigadoras de un grupo de PDI y estudiantes universitarios interesados por el Trabajo y su centralidad. En esta edición, se profundizará en la reflexión crítica de las Nuevas Formas de Organización del Trabajo (NFOT) y/o cadenas de valor globales (CVG), que comenzó en la edición anterior, y que conlleva dinámicas complejas, en cuanto a su reflexión, para el personal investigador y alumnado. Los modelos productivos actuales, analizados con perspectiva de género, serán objeto de análisis experto y colectivo a través de dos seminarios de gran reconocimiento académico - Cadenas Globales de Valor y K. Marx. El Capital- que junto al Aula Laboratorio, promotor originario de este proyecto, pretenden avanzar en la reflexión crítica a través de saberes diversos. Dicho de otro modo, con este proyecto, se trata de confrontar el saber experto con la subjetividad de otros saberes, en este caso con el del alumnado universitario, con el objetivo de profundizar en el análisis de las relaciones sociales asimétricas y, por ende, opresoras que se encuentran en el sistema económico actual. En los últimos años, dentro del Aula Laboratorio de Teatro Social de la Facultad de CCPP y Sociología de la UCM (en adelante Aula Laboratorio), donde se integra este proyecto y los anteriores, se han realizado cuatro investigaciones docentes que ha supuesto un gran avance entorno a la inclusión de metodologías participativas a través del Teatro Social como arte escénica que sirve para reflexionar sobre la complejidad social al alumnado. Proyectos docentes como “INSOCTEA. Innovación metodológica del Teatro Social (Teatro Intervención Sociológica) para el aprendizaje de las Ciencias Sociales en el aula” (2017-2018) (véase: https://eprints.ucm.es/56352/) que planteo dotar de un marco científico a un proceso metodológico de aprendizaje iniciado en el curso 2016 - 2017 en dicho Aula-Laboratorio, y el proyecto INSOCTEA II “Innovación metodológica para el aprendizaje de las ciencias sociales en el aula. Teatro Foro y Sociología” (2018-2019) (Véase: https://eprints.ucm.es/56352/) que cubrió las necesidades teóricas en torno al teatro y la docencia que habían surgido en el proyecto anterior y que conllevo un seminario de lectura muy enriquecedoras en torno a la creación como autoría e investigación y el espectador o espectadora como sujeto y objeto de investigación. INSOCTEA III, “El teatro social como forma de investigación acción participativa y aprendizaje de la sociología del trabajo y el género en el Aula” donde se ahondó en la multidimensionalidad de la investigación-acción-participación (IAP). E INSOCTEA IV “INTERSOC y economía crítica. Jóvenes, trabajo y empleo en modelos productivos periféricos en crisis” dedicado a cómo enfrentar los procesos de subjetivación individuales y colectivos las transformaciones actuales del trabajo y el empleo, a partir del conocimiento situado del modelo productivo español en el marco de las Cadenas Globales de Valor. Y cuyas evidencias, de todos los proyectos, pueden verse resumidas en los videos subidos al canal del Aula Laboratorio UCM vinculado a los proyectos citados: https://www.youtube.com/channel/UCLJ7IP1NwgRELQe1WhUILDg. En esta nueva edición del proyecto docente, tras los aprendizajes surgidos en las ediciones anteriores, como se ha esbozado anteriormente se pretende aumentar las sinergias entre los diferentes nodos del proyecto para confrontar ese saber experto con el vivencial, con el objeto de fomentar el aprendizaje de conceptos y prácticas complejas en materia de trabajo y empleo al alumnado. Con ello, el estudiante podrá desvelar las bases simbólicas, materiales y pre- supuestos que se asientan en el sistema y que legitiman las decisiones del poder a través de sus propias vivencias. Unas vivencias cuyo tránsito a la vida adulta se desarrollan en unos mercados de trabajo cada vez más complejos y vulnerables. Es en este sentido, en ese innovar en el aprendizaje de la Sociología del Trabajo con perspectiva de género dentro del ámbito de la sociología comprensiva, lo que hace que en esta edición se siga trabajando lo más cerca posible de las vivencias del alumnado de ciencias sociales en la construcción de los objetos y métodos de investigación, pero aumentando las sinergias entre la experiencia y la teoría con herramientas como los seminarios y los relatos biográficos diseñados por el Aula Laboratorio, con el objeto de profundizar en las trayectorias individuales del alumnado que les permita entender al estudiante las vivencias colectivas insertas en los orígenes sociales, el deseo de sus educadores, su historia colectiva condicionada y condicionante, toda vez que sus deseos, rupturas, etc.The project "Intersoc and Critical Economy. Advanced methodologies on social research of labor, gender and global chains", colloquially called INSOCTEA V, is the result of the teaching and research concerns of a group of PDI and university students interested in Labor and its centrality. In this edition, the critical reflection on the New Forms of Work Organization (NFOT) and / or global value chains (GVC), which began in the previous edition, and which involves complex dynamics, in terms of its reflection, for the research staff and students, will be deepened. The current productive models, analyzed from a gender perspective, will be the subject of expert and collective analysis through two seminars of great academic recognition - Global Value Chains and K. Marx. Capital - which, together with the Aula Laboratorio, the original promoter of this project, aim to advance critical reflection through diverse knowledge. In other words, with this project, the aim is to confront expert knowledge with the subjectivity of other knowledge, in this case with that of university students, in order to deepen the analysis of the asymmetrical and therefore oppressive social relations found in the current economic system. In recent years, within the Aula Laboratorio de Teatro Social de la Facultad de CCPP y Sociología de la UCM (hereinafter Aula Laboratorio), where this project and the previous ones are integrated, four teaching researches have been carried out, which have meant a great advance in the inclusion of participatory methodologies through Social Theater as a performing art that serves to reflect on social complexity to students. Teaching projects such as "INSOCTEA. Methodological innovation of Social Theater (Sociological Intervention Theater) for the learning of Social Sciences in the classroom" (2017-2018) (see: https://eprints.ucm.es/56352/) that proposed to provide a scientific framework to a methodological learning process initiated in the course 2016 - 2017 in said Classroom-Laboratory, and the INSOCTEA II project "Methodological innovation for the learning of social sciences in the classroom. Forum Theater and Sociology" (2018-2019) (See: https://eprints.ucm.es/56352/) which covered the theoretical needs around theater and teaching that had arisen in the previous project and which entailed a very enriching reading seminar around creation as authorship and research and the spectator as subject and object of research. INSOCTEA III, "Social theater as a form of participatory action research and learning the sociology of work and gender in the classroom" where the multidimensionality of participatory action research (PAR) was explored in depth. And INSOCTEA IV "INTERSOC and critical economy. Young people, work and employment in peripheral productive models in crisis" dedicated to how to confront the processes of individual and collective subjectivation of the current transformations of work and employment, based on the situated knowledge of the Spanish productive model within the framework of the Spanish productive models in crisis. Spanish productive model in the framework of Global Value Chains. And whose evidence, of all the projects, can be seen summarized in the videos uploaded to the UCM Classroom Laboratory channel linked to the above mentioned projects: https://www.youtube.com/channel/UCLJ7IP1NwgRELQe1WhUILDg. In this new edition of the teaching project, after the lessons learned in previous editions, as outlined above, the aim is to increase the synergies between the different nodes of the project to confront this expert knowledge with the experiential, in order to promote the learning of complex concepts and practices in the field of labor and employment to students. With this, the student will be able to unveil the symbolic, material and pre-assumptions bases that are based on the system and that legitimize the decisions of power through their own experiences. Experiences whose transition to adulthood takes place in increasingly complex and vulnerable labor markets. It is in this sense, innovating in the learning of the Sociology of Work with a gender perspective within the scope of comprehensive sociology, that makes this edition continue working as close as possible to the experiences of students of social sciences in the construction of objects and methods of research, but increasing the synergies between experience and theory with tools such as seminars and biographical stories designed by the Laboratory Classroom, in order to deepen the individual trajectories of students that allow them to understand the collective experiences embedded in social origins, the desire of their educators, their collective history conditioned and conditioning, as long as their desires, ruptures, etc.Fac. de Ciencias Económicas y EmpresarialesFALSEVicerrectorado de Calidadsubmitte

X chromosome inactivation does not necessarily determine the severity of the phenotype in Rett syndrome patients

Rett syndrome (RTT) is a severe neurological disorder usually caused by mutations in the MECP2 gene. Since the MECP2 gene is located on the X chromosome, X chromosome inactivation (XCI) could play a role in the wide range of phenotypic variation of RTT patients; however, classical methylation-based protocols to evaluate XCI could not determine whether the preferentially inactivated X chromosome carried the mutant or the wild-type allele. Therefore, we developed an allele-specific methylation-based assay to evaluate methylation at the loci of several recurrent MECP2 mutations. We analyzed the XCI patterns in the blood of 174 RTT patients, but we did not find a clear correlation between XCI and the clinical presentation. We also compared XCI in blood and brain cortex samples of two patients and found differences between XCI patterns in these tissues. However, RTT mainly being a neurological disease complicates the establishment of a correlation between the XCI in blood and the clinical presentation of the patients. Furthermore, we analyzed MECP2 transcript levels and found differences from the expected levels according to XCI. Many factors other than XCI could affect the RTT phenotype, which in combination could influence the clinical presentation of RTT patients to a greater extent than slight variations in the XCI pattern

Quorum sensing network in clinical strains of A. baumannii : AidA is a new quorum quenching enzyme

Acinetobacter baumannii is an important pathogen that causes nosocomial infections generally associated with high mortality and morbidity in Intensive Care Units (ICUs). Currently, little is known about the Quorum Sensing (QS)/Quorum Quenching (QQ) systems of this pathogen. We analyzed these mechanisms in seven clinical isolates of A. baumannii. Microarray analysis of one of these clinical isolates, Ab1 (A. baumannii ST-2-clon-2010), previously cultured in the presence of 3-oxo-C12-HSL (a QS signalling molecule) revealed a putative QQ enzyme (α/β hydrolase gene, AidA). This QQ enzyme was present in all nonmotile clinical isolates (67% of which were isolated from the respiratory tract) cultured in nutrient depleted LB medium. Interestingly, this gene was not located in the genome of the only motile clinical strain growing in this medium (A. baumannii strain Ab421-GEIH-2010 [Ab7], isolated from a blood sample). The AidA protein expressed in E. coli showed QQ activity. Finally, we observed downregulation of the AidA protein (QQ system attenuation) in the presence of HO (ROS stress). In conclusion, most of the A. baumannii clinical strains were not surface motile (84%) and were of respiratory origin (67%). Only the pilT gene was involved in surface motility and related to the QS system. Finally, a new QQ enzyme (α/β hydrolase gene, AidA protein) was detected in these strains