An Effective Solution for Drug Discovery Based on the Tangram Meta-Heuristic and Compound Filtering

Ligand-Based Virtual Screening accelerates and cheapens the design of new drugs. However, it needs efficient optimizers because of the size of compound databases. This work proposes a new method called Tangram CW. The proposal also encloses a knowledge-based filter of compounds. Tangram CW achieves comparable results to the state-of-the-art tools OptiPharm and 2LGO- Pharmusing about a tenth of their computational budget without filtering. Activating it discards more than two thirds of the database while keeping the desired compounds. Thus, it is possible to consider molecular flexibility despite increasing the options. The implemented software package is public.Grant PID2021-123278OB-I00 funded by MCIN/AEI/ 10.13039/501100011033 and by “ERDF A way of making Europe”Projects PDC2022-133370-I00 and TED2021-132020B-I00 funded by MCIN/AEI/ 10.13039/5011 00011033 and by European Union Next GenerationEU/PRTRMinistry of Economic Transformation, Industry, Knowledge and Universities from the Andalusian government (PAIDI 2021: POSTDOC_21_00124)“Margarita Salas” grant (RR_A_2021_21), financed by the European Union (NextGenerationEU

The Church Tower of Santiago Apóstol in Montilla: An Eco-Sustainable Rehabilitation Proposal

Is it possible to carry out eco-sustainable rehabilitations on specially protected buildings? This is the main question and starting point for this research. We will use the tower of the Church of “Santiago Apóstol” in Montilla as a case study; with its most remote antecedents in the 15th century, it is an emblematic building of one of the most important cities in the Cordovan countryside and is listed as an Asset of Cultural Interest (Bien de Interés Cultural or BIC) as of 2001. The application of eco-efficiency criteria in the rehabilitation of this type of building might stimulate the reactivation of the construction sector in the rural area, positively impacting the promotion of a circular economy. To this end, a general methodology has been established for carrying out eco-sustainable renovations on this type of building, which defines indicators for evaluating the eco-sustainability of such interventions. This methodology is applied to the case study of this important building in Montilla to ensure that a feasible intervention has been proposed, aligned with three basic pillars of sustainability that considers its environmental, economic, and social impact

Preliminary study for simultaneous detection and quantification of androgenic anabolic steroids using ELISA and pattern recognition techniques

A first step towards the multidetection, identification and quantification of anabolic androgenic steroids by enzyme-linked immunosorbent assay (ELISA) has been performed in this study. This proposal combines multiple competitive ELISA assays with different cross-reactivity profiles and multivariate data analysis techniques. Data have been analyzed by principal component analysis in conjunction with a novel K-nearest line classifier. This proposal allows simultaneous detection of up to four different steroids in the range of concentration from 0.1 to 316.2 nM with a total rate of 90.6% of correct detection, even in the presence of cross-reactivities. A methodology for concentration prediction is also presented with satisfactory results

Recalling the Biological Significance of Immune Checkpoints on NK Cells: A Chance to Overcome LAG3, PD1, and CTLA4 Inhibitory Pathways by Adoptive NK Cell Transfer?

Immune checkpoint receptors (IC) positively or negatively regulate the activation of the host immune response, preventing unwanted reactions against self-healthy tissues. In recent years the term IC has been mainly used for the inhibitory ICs, which are critical to control Natural Killer (NK) and Cytotoxic CD8(+) T cells due to its high cytotoxic potential. Due to the different nature of the signals that regulate T and NK cell activation, specific ICs have been described that mainly regulate either NK cell or T cell activity. Thus, strategies to modulate NK cell activity are raising as promising tools to treat tumors that do not respond to T cell-based immunotherapies. NK cell activation is mainly regulated by ICs and receptors from the KIR, NKG2 and NCRs families and the contribution of T cell-related ICs is less clear. Recently, NK cells have emerged as contributors to the effect of inhibitors of T cell-related ICs like CTLA4, LAG3 or the PD1/PD-L1 axes in cancer patients, suggesting that these ICs also regulate the activity of NK cells under pathological conditions. Strikingly, in contrast to NK cells from cancer patients, the level of expression of these ICs is low on most subsets of freshly isolated and in vitro activated NK cells from healthy patients, suggesting that they do not control NK cell tolerance and thus, do not act as conventional ICs under non-pathological conditions. The low level of expression of T cell-related ICs in "healthy" NK cells suggest that they should not be restricted to the detrimental effects of these inhibitory mechanisms in the cancer microenvironment. After a brief introduction of the regulatory mechanisms that control NK cell anti-tumoral activity and the conventional ICs controlling NK cell tolerance, we will critically discuss the potential role of T cell-related ICs in the control of NK cell activity under both physiological and pathological (cancer) conditions. This discussion will allow to comprehensively describe the chances and potential limitations of using allogeneic NK cells isolated from a healthy environment to overcome immune subversion by T cell-related ICs and to improve the efficacy of IC inhibitors (ICIs) in a safer way

Seguridad del paciente en atención primaria de salud : magnitud del problema

La seguridad del paciente (SP) ha preocupado desde siempre a los profesionales sanitarios en todos los escenarios de la práctica clínica. Es importante asumir una taxonomía común para hablar de SP y conocer cuales son las amenazas mediante el estudio de los eventos adversos (EA). El estudio APEAS mostró una prevalencia de EA de un 11,18‰, de los cuales un 47,8% estaban relacionados con la medicación. Al analizar la gravedad e impacto de los mismos pudo observarse que la mayor parte eran leves y se resolvían en el propio centro de salud. La causalidad de los EA es compleja. La medicación prescrita es un factor causal esencial en casi la mitad de los EA, junto con factores como la comunicación, la gestión y los cuidados. Aplicando el conocimiento disponible, el 70% de los EA que aparecen en el primer nivel asistencial fueron valorados por los propios profesionales como evitables. En el primer nivel asistencial confluyen varios factores diferenciales en relación con la SP que podrían incrementar el riesgo de aparición de EA e incidentes relacionados con la SP: la elevada presión asistencial, la hiperfrecuentación, la ambulatorización de cuidados y seguimientos, la deficiente continuidad asistencial y escasa comunicación entre atención primaria y especializada, la medicalización incontrolada y desmedida de procesos banales, al igual que la generalización de pruebas diagnósticas y tratamientos sin evidencia razonable de efectividad son una amenaza para la SP. El hecho de que los incidentes relacionados con la SP y los EA sean un problema común y en gran parte evitable, sitúa la mejora de la SP en el primer nivel asistencial como una estrategia prioritaria, siendo conscientes de que se trata de un problema crónico que requiere perseverancia y tratamiento continuado

Role of Rhinovirus C in Apparently Life-Threatening Events in Infants, Spain

To assess whether infants hospitalized after an apparently life-threatening event had an associated respiratory virus infection, we analyzed nasopharyngeal aspirates from 16 patients. Nine of 11 infants with positive virus results were infected by rhinoviruses. We detected the new genogroup of rhinovirus C in 6 aspirates

New approach to designing functional materials for stealth technology: Radar experiment with bilayer absorbers and optimization of the reflection loss

Microwave power absorption by a two-layer system deposited on a metallic surface has been studied in the experimental setup emulating the response to a radar signal. Layers containing hexaferrite and iron powder in a dried paint of thickness under 1mm have been used. The data have been analyzed within a theoretical model derived for a bilayer system from the transmission line theory. Good agreement between experimental and theoretical results have been found. The advantage of using a bilayer system over a single-layer system has been demonstrated. We show how the maximum microwave absorption (minimum reflection loss) can be achieved through the optimization of the filling factors and thicknesses of the two layers

New Approach to Designing Functional Materials for Stealth Technology: Radar Experiment with Bilayer Absorbers and Optimization of the Reflection Loss

Microwave power absorption by a two-layer system deposited on a metallic surface is studied in the experimental setup emulating the response to a radar signal. Layers containing hexaferrite and iron powder in a dried paint of thickness under 1 mm are used. The data is analyzed within a theoretical model derived for a bilayer system from the transmission line theory. A good agreement between experimental and theoretical results is found. The advantage of using a bilayer system over a single-layer system is demonstrated. How the maximum microwave absorption (minimum reflection) can be achieved through the optimization of the filling factors and thicknesses of the two layers is shown

The singular properties of photosynthetic cytochrome c 550 from the diatom Phaeodactylum tricornutum suggest new alternative functions

Cytochrome c 550 is an extrinsic component in the luminal side of photosystem II (PSII) in cyanobacteria, as well as in eukaryotic algae from the red photosynthetic lineage including, among others, diatoms. We have established that cytochrome c 550 from the diatom Phaeodactylum tricornutum can be obtained as a complete protein from the membrane fraction of the alga, although a C-terminal truncated form is purified from the soluble fractions of this diatom as well as from other eukaryotic algae. Eukaryotic cytochromes c 550 show distinctive electrostatic features as compared with cyanobacterial cytochrome c 550 . In addition, co-immunoseparation and mass spectrometry experiments, as well as immunoelectron microscopy analyses, indicate that although cytochrome c 550 from P. tricornutum is mainly located in the thylakoid domain of the chloroplast – where it interacts with PSII –, it can also be found in the chloroplast pyrenoid, related with proteins linked to the CO 2 concentrating mechanism and assimilation. These results thus suggest new alternative functions of this heme protein in eukaryotes.Ministerio de Economía, Industria y Competitividad BIO2015-64169-PJunta de Andalucía PAIDI BIO-02

Neurodevelopmental Outcomes of Infants Younger Than 90 Days Old Following Enterovirus and Parechovirus Infections of the Central Nervous System

Enteroviruses (EVs) and human parechoviruses (HPeVs) are a major cause of central nervous system (CNS) infection in young infants. They have been implicated in neurodevelopmental delay, however limited data are available. The aim of this study is to describe the clinical outcome of young infants and to assess and compare the medium-term neurodevelopment following CNS infections caused by EV and HPeV. A multicentre observational ambispective study was conducted between May 2013 and March 2018. Children under 3 months of age with EV or HPeV CNS infection excluding encephalitis were included. Infants were contacted 1 year after the acute infection and their neurological development was evaluated using the Ages and Stages Questionnaire-3 (ASQ-3). If any area assessed was abnormal during the first round of tests, a second round was completed 6 to 12 months later. Forty-eight young infants with EV and HPeV CNS infection were identified: 33 (68.8%) were positive for EV and 15 (31.3%) for HPeV. At first assessment 14 out of 29 EV (48.3%) and 3 out of 15 HPeV (20%) positive cases presented some developmental concern in the ASQ-3 test. EV-positive infants showed mild and moderate alteration in all domains analyzed and HPeV-positive infants showed mild alterations only in gross and fine motor domains. Significant alterations in communication were observed in EV-positive but not in HPeV-positive infants (31 vs. 0%, p = 0.016). At second assessment 4 out of 13 EV-positive patients (30.8%) showed mild to moderate concerns in communication and gross motor function domains and 3 out of 13 (23.1%) showed significant concern in fine motor function. Although CNS infections without associated encephalitis are generally assumed to be benign our study shows that at a median age of 18 months almost half of the EV-infected infants (48.3%) and 20% of HPeV-positive infants presented some developmental concern in the ASQ-3 test. We recommend monitor the neurological development of infants during the first years of life after HPeV CNS infection and especially after EV CNS infection, even in mild cases, for an early intervention and stimulation of psychomotor development if necessary.This study was partially supported by grant from Instituto de Salud Carlos III (number PI18CIII/00017).S