Drug properties and host factors contribute to biochemical presentation of drug-induced liver injury: a prediction model from a machine learning approach

Drug-induced liver injury (DILI) presentation varies biochemically and histologically. Certain drugs present quite consistent injury patterns, i.e., DILI signatures. In contrast, others are manifested as broader types of liver injury. The variety of DILI presentations by a single drug suggests that both drugs and host factors may contribute to the phenotype. However, factors determining the DILI types have not been yet elucidated. Identifying such factors may help to accurately predict the injury types based on drugs and host information and assist the clinical diagnosis of DILI. Using prospective DILI registry datasets, we sought to explore and validate the associations of biochemical injury types at the time of DILI recognition with comprehensive information on drug properties and host factors. Random forest models identified a set of drug properties and host factors that differentiate hepatocellular from cholestatic damage with reasonable accuracy (69-84%). A simplified logistic regression model developed for practical use, consisting of patient’s age, drug’s lipoaffinity, and hybridization ratio, achieved a fair prediction (68%-74%), but suggested potential clinical usability, computing the likelihood of liver injury type based on two properties of drugs taken by a patient and patient’s age. In summary, considering both drug and host factors in evaluating DILI risk and phenotypes open an avenue for future DILI research and aid in the refinement of causality assessment.The present study has been supported by grants of Instituto de Salud Carlos III cofounded by Fondo Europeo de Desarrollo Regional – FEDER (contract numbers: PI 18/01804; PT20/00127) and Agencia Española del Medicamento. Plataforma ISCiii de Investigación Clínica and CIBERehd are funded by Instituto de Salud Carlos III. IAA holds a Sara Borrell research contract from the National Health System, Instituto de Salud Carlos III (CD20/00083)

Organophosphate ester pollution in the oceans

The large-scale use of organophosphate esters (OPEs) as flame retardants and plasticizers has led to their prevalence in the environment, with still unknown broader impacts. This Review describes the transport and occurrence of OPEs in marine systems and summarizes emerging evidence of their biogeochemical and ecosystem impacts. Long-range environmental transport via the atmosphere and ocean currents distributes OPEs from industrialized regions to the open ocean. OPEs are most prevalent in coastal regions, but notable concentrations are also found in the Arctic and regions far from shore. Air–water interactions are important for the transport of OPEs to remote oceans and polar regions. Processes such as degradation and sinking of particle-bound compounds modulate the properties and fate of OPEs in the water column, where they are potentially a non-accounted source of anthropogenic organic phosphorus for microbial communities. Some OPEs have toxic effects in marine species and are found in measurable quantities in fish and other aquatic organisms. However, there is conflicting evidence on the potential for bioaccumulation and biomagnification of OPEs. Future work must constrain the large-scale impact of OPEs on marine biota and biogeochemistry to support more effective regulation and mitigation

Body composition, nutritional profile and muscular fitness affect bone health in a sample of schoolchildren from Colombia: The Fuprecol Study

This is the final version of the article. Available from the publisher via the DOI in this record.The objective of the present study is to investigate the relationships between body composition, nutritional profile, muscular fitness (MF) and bone health in a sample of children and adolescents from Colombia. Participants included 1118 children and adolescents (54.6% girls). Calcaneal broadband ultrasound attenuation (c-BUA) was obtained as a marker of bone health. Body composition (fat mass and lean mass) was assessed using bioelectrical impedance analysis. Furthermore height, weight, waist circumference and Tanner stage were measured and body mass index (BMI) was calculated. Standing long-jump (SLJ) and isometric handgrip dynamometry were used respectively as indicators of lower and upper body muscular fitness. A muscular index score was also computed by summing up the standardised values of both SLJ and handgrip strength. Dietary intake and degree of adherence to the Mediterranean diet were assessed by a 7-day recall questionnaire for food frequency and the Kidmed questionnaire. Poor bone health was considered using a z-score cut off of ≤−1.5 standard deviation. Once the results were adjusted for age and Tanner stage, the predisposing factors of having a c-BUA z-score ≤−1.5 standard deviation included being underweight or obese, having an unhealthy lean mass, having an unhealthy fat mass, SLJ performance, handgrip performance, and unhealthy muscular index score. In conclusion, body composition (fat mass and lean body mass) and MF both influenced bone health in a sample of children and adolescents from Colombia. Thus promoting strength adaptation and preservation in Colombian youth will help to improve bone health, an important protective factor against osteoporosis in later life.: We would like to acknowledge to Bogota District Education Department for supporting data collection for this study. The authors also thank the participating Bogota District students, teachers, schools, and staff. The “FUPRECOL Study” was possible given the financial support provided by the Instituto Colombiano para el Desarrollo de la Ciencia y la Tecnología “Francisco José de Caldas” COLCIENCIAS (Contract Number 671-2014 Code 122265743978). Also, during the completion of this paper, AG-H was visiting researchers at the University of Rosario (CEMA, Bogotá, Colombia), supported with grants awarded by Proyectos Basales y Vicerrectoría de Investigación, Desarrollo e Innovación” (Universidad de Santiago de Chile, USACH)

Validación de un cuestionario para la identificación de problemas relacionados con los medicamentos en usuarios de un servicio de urgencias hospitalario

Los problemas relacionados con los medicamentos (PRM) son problemas de salud asociados al uso de medicamentos.Son muchos los PRM que podemos encontrar si analizamos la medicación que toman los pacientes y los problemasde salud que refieren y muy variadas las causas que los ocasionan. La entrevista con el paciente constituye uninstrumento imprescindible para la obtención de información sobre qué medicamentos toma, como los toma y sobrela experiencia que de ellos tiene. Los servicios de urgencias hospitalarios constituyen cada día más una puerta deentrada al sistema sanitario para los ciudadanos, de forma que constituye un escenario adecuado para conocer laprevalencia de PRM, sin embargo las características propias de un servicio de urgencias de hospital requiere laadaptación de la entrevista con el usuario. Objetivo: El presente trabajo pretende diseñar y validar un cuestionariocomo instrumento para la obtención de información suficiente para la evaluación e identificación de PRM en losusuarios de un servicio de urgencias hospitalario. Metodología: Se procederá al diseño de un cuestionario con laintervención de expertos en Seguimiento Farmacoterapéutico, igualmente se procederá a la validación del mismopilotandolo sobre una muestra de 222 pacientes usuarios de un servicio de urgencias hospitalario. Resultado: Trasel pilotaje el cuestionario fue validado

Genome expansion by allopolyploidization in the fungal strain <i>Coniochaeta </i>2T2.1 and its exceptional lignocellulolytic machinery

Background Particular species of the genus Coniochaeta (Sordariomycetes) exhibit great potential for bioabatement of furanic compounds and have been identified as an underexplored source of novel lignocellulolytic enzymes, especially Coniochaeta ligniaria. However, there is a lack of information about their genomic features and metabolic capabilities. Here, we report the first in-depth genome/transcriptome survey of a Coniochaeta species (strain 2T2.1). Results The genome of Coniochaeta sp. strain 2T2.1 has a size of 74.53 Mbp and contains 24,735 protein-encoding genes. Interestingly, we detected a genome expansion event, resulting similar to 98% of the assembly being duplicated with 91.9% average nucleotide identity between the duplicated regions. The lack of gene loss, as well as the high divergence and strong genome-wide signatures of purifying selection between copies indicates that this is likely a recent duplication, which arose through hybridization between two related Coniochaeta-like species (allopolyploidization). Phylogenomic analysis revealed that 2T2.1 is related Coniochaeta sp. PMI546 and Lecythophora sp. AK0013, which both occur endophytically. Based on carbohydrate-active enzyme (CAZy) annotation, we observed that even after in silico removal of its duplicated content, the 2T2.1 genome contains exceptional lignocellulolytic machinery. Moreover, transcriptomic data reveal the overexpression of proteins affiliated to CAZy families GH11, GH10 (endoxylanases), CE5, CE1 (xylan esterases), GH62, GH51 (alpha-l-arabinofuranosidases), GH12, GH7 (cellulases), and AA9 (lytic polysaccharide monoxygenases) when the fungus was grown on wheat straw compared with glucose as the sole carbon source. Conclusions We provide data that suggest that a recent hybridization between the genomes of related species may have given rise to Coniochaeta sp. 2T2.1. Moreover, our results reveal that the degradation of arabinoxylan, xyloglucan and cellulose are key metabolic processes in strain 2T2.1 growing on wheat straw. Different genes for key lignocellulolytic enzymes were identified, which can be starting points for production, characterization and/or supplementation of enzyme cocktails used in saccharification of agricultural residues. Our findings represent first steps that enable a better understanding of the reticulate evolution and "eco-enzymology" of lignocellulolytic Coniochaeta species

New mechanism for continuous and bidirectional displacement of heavy structures: Design and analysis

The aim of this paper is to design and study a new mechanism for moving heavy structures using the force of friction. The mechanism designed is called DCACLM and was patented in 2011. This new device is based on an inverted crawler which is able to displace heavy structures such as large span bridges in a continuous and bidirectional way. Furthermore, the DCACLM design has taken into account other important aspects such as safety and sustainability in order to develop new construction methods. Nonlinear numerical models using the Finite Element Method have been developed to study the complex structural behavior of this new mechanism. The main conclusions provide acceptable results in terms of stresses and strains for the main elements of DCACLM.the authors wish to acknowledge the financial support provided by the Spanish Ministry of Science and Innovation with funds from ALCANZA Research Project number IPT-380000-2010-12. This project has been co-financed with FEDER funds, “A Way of Making Europe”

Caracterización fisicoquímica, actividad antioxidante y contenido de fenoles y flavonoides totales de nopal morado (Opuntia gosseliniana) en dos etapas de coloración

Nopal (Opuntia gosseliniana) is considered a food product of interest due to its functional properties, including its antioxidant activity. The objective of this work was to evaluate the physical-chemical properties (color, pH and total soluble solids), antioxidant activity (DPPH, ABTS and FRAP), content of total phenols and flavonoids and betalain content of ethanolic extracts of nopal in two stages of coloration: green and purple. The highest values for total phenols and flavonoids were found in the purple samples, with values of 2.31 mg EAG/gps and 3.06 mg EQ/gps, respectively. Similarly, in the antioxidant activity (in the three techniques used) and betalain content, higher values were obtained in the purple color stage. Therefore, this species of cacti could be a potential source of antioxidants and pigments of agroindustrial interest.El nopal (Opuntia gosseliniana) es considerado un producto alimenticio de interés debido a sus propiedades funcionales, incluyendo su actividad antioxidante. El objetivo de este trabajo fue evaluar las propiedades físico-químicas (color, pH y sólidos solubles totales), actividad antioxidante (DPPH, ABTS y FRAP), contenido de fenoles y flavonoides totales y contenido de betalaínas extractos etanólicos de nopal en dos etapas de coloración: verde y morado. Los valores más altos para fenoles y flavonoides totales se encontraron en las muestras de color morado, con valores de 2.31 mg EAG/gps y 3.06 mg EQ/gps, respectivamente. De igual manera, en la actividad antioxidante se obtuvieron valores más altos en la etapa de color morado en las tres técnicas utilizadas. Por lo que, esta especie de cactácea podría ser una fuente potencial de antioxidantes y pigmentos de interés agroindustrial

Valley polarization in MoS2 monolayers by optical pumping

We report experimental evidences on selective occupation of the degenerate valleys in MoS2 monolayers by circularly polarized optical pumping. Over 30% valley polarization has been observed at K and K' valley via the polarization resolved luminescence spectra on pristine MoS2 monolayers. It demonstrates one viable way to generate and detect valley polarization towards the conceptual valleytronics applications with information carried by the valley index