Antimicrobial Power of Organic Acids and Nature-Identical Compounds against Two Vibrio spp.: An In Vitro Study

Vibrosis is one of the major threats in aquaculture farming, and due to the increasing antimicrobial resistance of different Vibrio species, there is an urgent need to replace conventional treatments with more sustainable solutions. Antimicrobial molecules such as organic acids (OA) and nature-identical compounds (NIC) are currently finding a central role in the infection management of terrestrial livestock, but little is known about their usage in aquaculture. The aim of this study was to perform a preliminary screening of the in vitro antimicrobial activity of a wide panel of OA and NIC against 2 Vibrio species characteristic of the Mediterranean area, Vibrio harveyi and Vibrio anguillarum, through minimal inhibitory/bactericidal concentration tests. The active principles that showed the best effective pathogen control were medium-chain fatty acids, sorbic and benzoic acid among OA and phenolic monoterpenoids (thymol, carvacrol and eugenol) and aromatic monoterpene aldehydes (vanillin and cinnamaldehyde) among NIC. These results showed how the usage of OA and NIC can open promising perspectives in terms of Vibrio spp. load control in aquaculture. Natural or nature-identical feed additives can make aquaculture production not only more efficient by reducing the need for medicated treatments, but also more sustainable

Synthesis of water-soluble hemicoronenediimides by photocyclization of perylenediimides: Turn-on fluorescent probes in water by complexation with Cucurbit[7]uril or binding to G-quadruplex Motifs

A new series of perylene and hemicoronene diimides, obtained by visible light photocyclization, are presented, between them some remarkable examples that are soluble in only water, and give nanoparticles by selfassociation. Those compounds work as new fluorescent materials in water by complexation with cucurbit[7] uril, as well as selective G-quadruplex binding ligands with remarkable cytotoxic activity when the interaction with G4 was sufficiently strong.We acknowledge the Ministerio de Ciencia, Innovación y Universidades-FEDER (Grants PID2019-111215RB-100 and RTI2018- 102040-B-100), the Junta de Castilla y León, Consejería de Educación y Cultura y Fondo Social Europeo (Grants BU263P18 and BU305P18), “la Caixa” Foundation (LCF/PR/PR12/11070003) for financial support. A. R.C. thanks Secretaría General de Universidades for a FPU18/03225 Grant. This research has made use of the high-performance computing resources of the Castilla y León Supercomputing Center (SCAYLE, htt ps://www.scayle.es), financed by FEDER (Fondo Europeo de Desarrollo Regional). We thank Ms. Ma del Pilar Castroviejo-Fernández, from PCT, UBU, for assistance in AFM studies and Mr. Javier Gutierrez-Reguera from LTI, UVA, for assistance in DLS studies

Processing and characterisation of calcium sulphoaluminate ecocements containing Microencapsulated Phase Change Materials

Calcium SulphoAluminate (CSA) cements can be considered as ecocements, since their production releases up to 40% less CO2 than Ordinary Portland Cement (OPC) [1]. In addition, Microencapsulated Phase Change Materials (MPCM) are receiving a growing attention in the last years for their capability of storing and releasing high energy (latent heat storage) at a narrow temperature range. Thus, the use of CSA ecocements blended with MPCM would let control the inner temperature of buildings. This would allow a double reduction of CO2 emissions due to the use of CSA rather than OPC, and the better reconditioning of houses, with the consequent social, economic and environmental benefits. This work is focused on the dispersion of MPCM in a CSA ecocement matrix and the further characterisation of the corresponding materials. All the important parameters evolved in the preparation of homogeneous CSA pastes and CSA+MPCM pastes were optimised (e.g. percentage of superplasticiser) through rheological studies. MPCM particles were well dispersed in the paste and were kept unaltered in the matrix. The thermal analysis confirmed the phase change properties of the blended cement pastes. In addition, a CSA paste was successfully coated by CSA+MPCM paste, supporting the technical viability of this type of coatings in buildings. Finally, the optimal thickness of a coating of CSA+PCM mortar adhered in a typical building located in Malaga (south of Spain) was theoretically calculated to avoid/minimise the use of air conditioning/heating, resulting in an economically viable project with a considerable reduction of CO2 emissions. [1] M.A.G. Aranda, A.G. De la Torre, Sulfoaluminate cement, in: F. Pacheco-Torgal, S. Jalali, J. Labrincha, V.M. John (Eds.), Eco-efficient concrete. Woodhead Publishing Limited, Cambridge, 2013.Universidad de Málaga. Campus de Excelencia Internacional Angalucía Tech

Self-Assembly Hydrosoluble Coronenes: A Rich Source of Supramolecular Turn-On Fluorogenic Sensing Materials in Aqueous Media

Water-soluble coronenes, that form nanoparticles by self-association, work as new fluorescent materials by complexation with cucurbit[7]uril, as well as selective turn-on fluorogenic sensors for nitroaromatic explosives with remarkable selectivity, by using only water as solvent.NATO Science for Peace and Security Programme (SPS G5536), Ministerio de Ciencia, Innovación y Universidades-FEDER (PID2019-111215RB-100 and RTI2018-102040-B-100), Junta de Castilla y León, Consejería de Educación y Cultura y Fondo Social Europeo (BU263P18) and “la Caixa” Foundation (LCF/PR/PR12/11070003) for financial support. A.R.C. thanks Secretaría General de Universidades (FPU18/03225)

Critical requirement of SOS1 for tumor development and microenvironment modulation in KRASG12D-driven lung adenocarcinoma

The impact of genetic ablation of SOS1 or SOS2 is evaluated in a murine model of KRASG12D-driven lung adenocarcinoma (LUAD). SOS2 ablation shows some protection during early stages but only SOS1 ablation causes significant, specific long term increase of survival/lifespan of the KRASG12D mice associated to markedly reduced tumor burden and reduced populations of cancer-associated fibroblasts, macrophages and T-lymphocytes in the lung tumor microenvironment (TME). SOS1 ablation also causes specific shrinkage and regression of LUAD tumoral masses and components of the TME in pre-established KRASG12D LUAD tumors. The critical requirement of SOS1 for KRASG12D-driven LUAD is further confirmed by means of intravenous tail injection of KRASG12D tumor cells into SOS1KO/KRASWT mice, or of SOS1-less, KRASG12D tumor cells into wildtype mice. In silico analyses of human lung cancer databases support also the dominant role of SOS1 regarding tumor development and survival in LUAD patients. Our data indicate that SOS1 is critically required for development of KRASG12D-driven LUAD and confirm the validity of this RAS-GEF activator as an actionable therapeutic target in KRAS mutant LUAD.Work supported by grants ISCIII-MCUI (FIS PI19/00934), JCyL (SA264P18-UIC 076), Areces Foundation (CIVP19A5942), and ISCIII-CIBERONC (group CB16/12/00352) to E.S.; Solorzano-Barruso Foundation (FS/32-2020) and Eugenio Rodriguez Pascual Foundation to F.C.B.; MCI (RTI2018-099161-A-I00) to E.C. This research was co-financed by FEDER funds. These CIC groups are supported by the Programa de Apoyo a Planes Estratégicos de Investigación de Estructuras de Investigación de Excelencia of Castilla y León autonomous government (CLC-2017-01) and AECC Excellence program Stop Ras Cancers (EPAEC222641CICS)

Genetic Study of SARS-CoV-2 Non Structural Protein 12 in COVID-19 Patients Non Responders to Remdesivir

Remdesivir (RDV) was the first antiviral drug approved by the FDA to treat severe coronavirus disease-2019 (COVID-19) patients. RDV inhibits SARS-CoV-2 replication by stalling the non structural protein 12 (nsp12) subunit of the RNA-dependent RNA polymerase (RdRp). No evidence of global widespread RDV-resistance mutations has been reported, however, defining genetic pathways to RDV resistance and determining emergent mutations prior and subsequent antiviral therapy in clinical settings is necessary. This study identified 57/149 (38.3%) patients who did not respond to one course (5-days) (n = 36/111, 32.4%) or prolonged (5 to 20 days) (n = 21/38, 55.3%) RDV therapy by subgenomic RNA detection. Genetic variants in the nsp12 gene were detected in 29/49 (59.2%) non responder patients by Illumina sequencing, including the de novo E83D mutation that emerged in an immunosuppressed patient after receiving 10 + 8 days of RDV, and the L838I detected at baseline and/or after prolonged RDV treatment in 9/49 (18.4%) non responder subjects. Although 3D protein modeling predicted no interference with RDV, the amino acid substitutions detected in the nsp12 involved changes on the electrostatic outer surface and in secondary structures that may alter antiviral response. It is important for health surveillance to study potential mutations associated with drug resistance as well as the benefit of RDV retreatment, especially in immunosuppressed patients and in those with persistent replication. IMPORTANCE This study provides clinical and microbiologic data of an extended population of hospitalized patients for COVID-19 pneumonia who experienced treatment failure, detected by the presence of subgenomic RNA (sgRNA). The genetic variants found in the nsp12 pharmacological target of RDV bring into focus the importance of monitoring emergent mutations, one of the objectives of the World Health Organization (WHO) for health surveillance. These mutations become even more crucial as RDV keeps being prescribed and new molecules are being repurposed for the treatment of COVID-19. The present article offers new perspectives for the clinical management of non responder patients treated and retreated with RDV and emphasizes the need of further research of the benefit of combinatorial therapies and RDV retreatment, especially in immunosuppressed patients with persistent replication after therapy.This work was financed by a Gilead Sciences grant (IN-ES-540-6089) and CIBER Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, España (CB21/13/00081). This work was financed by ad hoc patronage funds for research on COVID-19 from donations from citizens and organizations to the Hospital Clínic de Barcelona-Fundació Clínic per a la Recerca Biomèdica.S

Intercomparison and characterization of 23 Aethalometers under laboratory and ambient air conditions: procedures and unit-to-unit variabilities

Aerosolized black carbon is monitored worldwide to quantify its impact on air quality and climate. Given its importance, measurements of black carbon mass concentrations must be conducted with instruments operating in qualitychecked and ensured conditions to generate data which are reliable and comparable temporally and geographically. In this study, we report the results from the largest characterization and intercomparison of filter-based absorption photometers, the Aethalometer model AE33, belonging to several European monitoring networks. Under controlled laboratory conditions, a total of 23 instruments measured mass concentrations of black carbon from three wellcharacterized aerosol sources: synthetic soot, nigrosin particles, and ambient air from the urban background of Leipzig, Germany. The objective was to investigate the individual performance of the instruments and their comparability; we analyzed the response of the instruments to the different aerosol sources and the impact caused by the use of obsolete filter materials and the application of maintenance activities. Differences in the instrument-to-instrument variabilities from equivalent black carbon (eBC) concentrations reported at 880 nm were determined before maintenance activities (for soot measurements, average deviation from total least square regression was-2.0% and the range-16% to 7 %; for nigrosin measurements, average deviation was 0.4% and the range-15% to 17 %), and after they were carried out (for soot measurements, average deviation was-1.0% and the range-14% to 8 %; for nigrosin measurements, the average deviation was 0.5%and the range-12%to 15 %). The deviations are in most of the cases explained by the type of filter material employed by the instruments, the total particle load on the filter, and the flow calibration. The results of this intercomparison activity show that relatively small unit-to-unit variability of AE33-based particle light absorbing measurements is possible with wellmaintained instruments. It is crucial to follow the guidelines for maintenance activities and the use of the proper filter tape in the AE33 to ensure high quality and comparable black carbon (BC) measurements among international observational networks. © 2021 Author(s). This work is distributed under the Creative Commons Attribution 4.0 License

Intercomparison and characterization of 23 Aethalometers under laboratory and ambient air conditions : procedures and unit-to-unit variabilities

Aerosolized black carbon is monitored worldwide to quantify its impact on air quality and climate. Given its importance, measurements of black carbon mass concentrations must be conducted with instruments operating in quality-checked and ensured conditions to generate data which are reliable and comparable temporally and geographically. In this study, we report the results from the largest characterization and intercomparison of filter-based absorption photometers, the Aethalometer model AE33, belonging to several European monitoring networks. Under controlled laboratory conditions, a total of 23 instruments measured mass concentrations of black carbon from three well-characterized aerosol sources: synthetic soot, nigrosin particles, and ambient air from the urban background of Leipzig, Germany. The objective was to investigate the individual performance of the instruments and their comparability; we analyzed the response of the instruments to the different aerosol sources and the impact caused by the use of obsolete filter materials and the application of maintenance activities. Differences in the instrument-to-instrument variabilities from equivalent black carbon (eBC) concentrations reported at 880 nm were determined before maintenance activities (for soot measurements, average deviation from total least square regression was -2.0% and the range -16% to 7 %; for nigrosin measurements, average deviation was 0.4% and the range -15% to 17 %), and after they were carried out (for soot measurements, average deviation was 1:0% and the range -14% to 8 %; for nigrosin measurements, the average deviation was 0.5% and the range -12% to 15 %). The deviations are in most of the cases explained by the type of filter material employed by the instruments, the total particle load on the filter, and the flow calibration. The results of this intercomparison activity show that relatively small unit-to-unit variability of AE33-based particle light absorbing measurements is possible with well-maintained instruments. It is crucial to follow the guidelines for maintenance activities and the use of the proper filter tape in the AE33 to ensure high quality and comparable black carbon (BC) measurements among international observational networks.Peer reviewe

“Pasapalabra” de la Psicología Clínica 2: Una herramienta de aprendizaje basada en el juego

El objetivo general del proyecto de innovación “Pasapalabra” de la Psicología Clínica 2: Una herramienta de aprendizaje basada en el juego era potenciar el aprendizaje activo de términos y conceptos relativos a la Psicología Clínica a través de una herramienta basada en las nuevas tecnologías y el juego. Se basa en el popular concurso “Pasapalabra”, concretamente en la prueba final denominada “El rosco”, en la cual el/la participante debe averiguar palabras a partir de su definición y teniendo como pista la letra inicial de la palabra o una letra contenida en ella. Este proyecto surgió como la continuación del proyecto de innovación concedido en la convocatoria PIMCD 2018-2019. Su propósito era dar continuidad, profundizar y divulgar el proyecto “Pasapalabra” de la Psicología Clínica

Economic impact of immunoglobulin replacement therapy in secondary immunodeficiency to hematological cancer: a single center observational study

This is the first report of the health economic benefits derived from preventing infections through Immunoglobulin Replacement Therapy (IgRT) in patients with secondary immunodeficiency due to hematological malignancies. We conducted a retrospective population-based cohort study using patient medical history and pharmacy data from the Hospital Clínico San Carlos for 21 patients between 2011 and 2020. The pharmacoeconomic impact of using prophylactic IgRT was assessed by comparing characteristics of the SID patients 1 year before and after initiating IgRT measured by direct medical and tangible indirect costs. Results indicate a marked reduction in hospitalization days following IgRT initiation, decreasing from an average of 13.9 to 6.1 days per patient, with the elimination of ICU admissions. While emergency department visits decreased significantly, the number of routine consultations remained unchanged. Notably, absenteeism from work dropped substantially. The financial analysis revealed significant reductions in medication use and fewer ancillary tests, resulting in considerable cost savings. Specifically, total expenditure dropped from €405,088.18 pre-IgRT to €295,804.42 post-IgRT—including the cost of IgRT itself at €156,309.60. Overall, the annual savings amounted to €109,283.84, validating the cost-effectiveness of IgRT in managing SID in patients with hematological cancers