Covalent grafting of titanium with a cathelicidin peptide produces an osteoblast compatible surface with antistaphylococcal activity

Bacterial infection of orthopaedic implants, often caused by Staphylococcus species, may ultimately lead to implant failure. The development of infection-resistant, osteoblast-compatible biomaterials could represent an effective strategy to prevent bacterial colonization of implants, reducing the need for antibiotics. In this study, the widely used biomaterial titanium was functionalized with BMAP27(1-18), an \uf061-helical cathelicidin antimicrobial peptide that retains potent staphylocidal activity when immobilized on agarose beads. A derivative bearing a short spacer with a free thiol at the N-terminus was coupled to silanized titanium disks via thiol-maleimide chemistry. Tethering was successful, as assessed by Contact angle, Quartz Crystal Microbalance with Dissipation monitoring (QCM-D), and X-ray Photoelectron Spectroscopy (XPS), with an average surface mass density of 456 ng/cm2 and a layer thickness of 3 nm. The functionalized titanium displayed antimicrobial properties against a reference strain of Staphylococcus epidermidis with well-known biofilm forming capability. Reduction of bacterial counts and morphological alterations of adhering bacteria, upon 2h incubation, indicate a rapid contact-killing effect. The immobilized peptide was not toxic to osteoblasts, which adhered and spread better on functionalized titanium when co-cultured with bacteria, compared to non-coated surfaces. Results suggest that functionalization of titanium with BMAP27(1-18) could be promising for prevention of bacterial colonization in bone graft applications

Informe del Comité Científico de la Agencia Española de Consumo, Seguridad Alimentaria y Nutrición (AECOSAN) sobre la programación de los controles oficiales de peligros químicos

La Agencia Española de Consumo, Seguridad Alimentaria y Nutrición (AECOSAN) y las comunidades autónomas han elaborado un Documento de priorización y distribución de muestras para control oficial de peligros químicos con el propósito de mejorar la calidad y homogeneidad de los controles oficiales en el marco del Plan Nacional de Control Oficial de la Cadena Alimentaria (PNCOCA). Dicho Documento se ha basado en el modelo de planificación de los controles oficiales en base al riesgo desarrollado por la Direcció General de Salut Pública de la Consellería de Sanitat Universal i Salut Pública de la Generalitat Valenciana. Este Documento de priorización pretende distribuir la toma de muestras para control oficial en toda España, previa evaluación de los riesgos y de la capacidad analítica de los laboratorios. Además servirá de apoyo y orientación a las comunidades autónomas para que ejecuten sus programas de control oficial. El Documento de priorización define un modelo semicuantitativo, en el que se establecen las variables a las que se les asigna un valor numérico relativo para obtener una calificación final. La metodología de jerarquización se basa en aproximarse a la medida del riesgo dependiente de la presencia de un contaminante en un alimento, siendo el riesgo la suma de dos variables, el impacto en la salud de la población y la prevalencia en los productos de consumo. El Comité Científico concluye que el Documento de priorización y distribución de muestras de control oficial dirigidas a la determinación de peligros químicos es adecuado, en el momento actual, para el fin previsto. Este Documento deberá actualizarse periódicamente a la luz de la experiencia de su aplicación, el avance en los conocimientos científicos, los cambios en la legislación y las directrices y herramientas sobre priorización y muestreo que puedan desarrollarse a nivel nacional o de la Unión Europea

Mechanism of biomolecular recognition of trimethyllysine by the fluorinated aromatic cage of KDM5A PHD3 finger

The understanding of biomolecular recognition of posttranslationally modified histone proteins is centrally important to the histone code hypothesis. Despite extensive binding and structural studies on the readout of histones, the molecular language by which posttranslational modifications on histone proteins are read remains poorly understood. Here we report physical-organic chemistry studies on the recognition of the positively charged trimethyllysine by the electron-rich aromatic cage containing PHD3 finger of KDM5A. The aromatic character of two tryptophan residues that solely constitute the aromatic cage of KDM5A was fine-tuned by the incorporation of fluorine substituents. Our thermodynamic analyses reveal that the wild-type and fluorinated KDM5A PHD3 fingers associate equally well with trimethyllysine. This work demonstrates that the biomolecular recognition of trimethyllysine by fluorinated aromatic cages is associated with weaker cation-π interactions that are compensated by the energetically more favourable trimethyllysine-mediated release of high-energy water molecules that occupy the aromatic cage

Plasma lipidome and risk of atrial fibrillation: results from the PREDIMED trial

The potential role of the lipidome in atrial fibrillation (AF) development is still widely unknown. We aimed to assess the association between lipidome profiles of the Prevenci\uf3n con Dieta Mediterr\ue1nea (PREDIMED) trial participants and incidence of AF. We conducted a nested case–control study (512 incident centrally adjudicated AF cases and 735 controls matched by age, sex, and center). Baseline plasma lipids were profiled using a Nexera X2 U-HPLC system coupled to an Exactive Plus orbitrap mass spectrometer. We estimated the association between 216 individual lipids and AF using multivariable conditional logistic regression and adjusted the p values for multiple testing. We also examined the joint association of lipid clusters with AF incidence. Hitherto, we estimated the lipidomics network, used machine learning to select important network-clusters and AF-predictive lipid patterns, and summarized the joint association of these lipid patterns weighted scores. Finally, we addressed the possible interaction by the randomized dietary intervention. Forty-one individual lipids were associated with AF at the nominal level (p < 0.05), but no longer after adjustment for multiple-testing. However, the network-based score identified with a robust data-driven lipid network showed a multivariable-adjusted ORper+1SD of 1.32 (95% confidence interval: 1.16–1.51; p < 0.001). The score included PC plasmalogens and PE plasmalogens, palmitoyl-EA, cholesterol, CE 16:0, PC 36:4;O, and TG 53:3. No interaction with the dietary intervention was found. A multilipid score, primarily made up of plasmalogens, was associated with an increased risk of AF. Future studies are needed to get further insights into the lipidome role on AF. Current Controlled Trials number, ISRCTN35739639

Report of the Scientific Committee of the Spanish Agency for Consumer Affairs, Food Safety and Nutrition (AECOSAN) on the programming of official controls on chemical hazards

La Agencia Española de Consumo, Seguridad Alimentaria y Nutrición (AECOSAN) y las comuni dades autónomas han elaborado un Documento de priorización y distribución de muestras para control oficial de peligros químicos con el propósito de mejorar la calidad y homogeneidad de los controles oficiales en el marco del Plan Nacional de Control Oficial de la Cadena Alimentaria (PN COCA). Este Documento de priorización pretende distribuir la toma de muestras para control oficial en toda España, previa evaluación de los riesgos y de la capacidad analítica de los laboratorios. Ade más servirá de apoyo y orientación a las comunidades autónomas para que ejecuten sus progra mas de control oficial. El Documento de priorización define un modelo semicuantitativo, en el que se establecen las variables a las que se les asigna un valor numérico relativo para obtener una calificación final. La metodología de jerarquización se basa en aproximarse a la medida del riesgo dependiente de la presencia de un contaminante en un alimento, siendo el riesgo la suma de dos variables, el impacto en la salud de la población y la prevalencia en los productos de consumo. El Comité Científico concluye que el Documento de priorización y distribución de muestras de control oficial dirigidas a la determinación de peligros químicos es adecuado, en el momento actual, para el fin previsto. Este Documento deberá actualizarse periódicamente a la luz de la experiencia de su aplicación, el avance en los conocimientos científicos, los cambios en la legislación y las directrices y herramientas sobre priorización y muestreo que puedan desarrollarse a nivel nacional o de la Unión Europea.The Spanish Agency for Consumer Affairs, Food Safety and Nutrition (AECOSAN) and the autonomous communities have prepared a Document for the prioritisation and distribution of samples for the official control of chemical hazards with the aim of improving the quality and uniformity of official controls in the framework of the National Food Chain Official Control Plan (PNCOCA). The prioritisation Document aims to distribute the sampling for official controls throughout Spain, following prior assessment of the risks and the analytical capacity of the laboratories. It will also serve to provide support and guidance to the autonomous communities in the implementation of their official control programmes. The prioritisation Document defines a semi-quantitative model which sets out the variables to which a relative numerical value is allocated in order to obtain a final qualification. The hierarchical methodology is based on estimating the extent of the risk depending on the presence of a contaminant in a food, where the risk is the sum of two variables, the impact on the health of the population and the prevalence in consumer products. The Scientific Committee concludes that the Document for the prioritisation and distribution of official control samples aimed at determining chemical hazards is adequate, at present, for the intended purpose. This Document should be regularly updated in light of the experience obtained from its application, progress in scientific knowledge, changes in the legislation and the directives and tools on prioritisation and sampling which may be developed at national or European Union level

Wage inequality, segregation by skill and the price of capital in an assignment model

Some pieces of empirical evidence suggest that in the U.S., over the last few decades, (i) wage inequality between-plants has risen much more than wage inequality within-plants and (ii) there has been an increase in the segregation of workers by skill into separate plants. This paper presents a frictionless assignment model in which these two features can be explained simultaneously as the result of the decline in the relative price of capital. Additional implications of the model regarding the skill premium and the dispersion in labor productivity across plants are also consistent with the empirical evidence. [resumen de autor