Functional and molecular characterization of inherited platelet disorders in the Iberian Peninsula: results from a collaborative study

12 p.-6 tab. Sánchez-Guiu et al.[Background] The diagnostic evaluation of inherited platelet disorders (IPDs) is complicated and time-consuming, resulting in a relevant number of undiagnosed and incorrectly classified patients. In order to evaluate the spectrum of IPDs in individuals with clinical suspicion of these disorders, and to provide a diagnostic tool to centers not having access to specific platelets studies, we established the project “Functional and Molecular Characterization of Patients with Inherited Platelet Disorders” under the scientific sponsorship of the Spanish Society of Thrombosis and Haemostasis.[Patients/methods] Subjects were patients from a prospective cohort of individuals referred for clinical suspicion of IPDs as well as healthy controls. Functional studies included light transmission aggregation, flow cytometry, and when indicated, Western-blot analysis of platelet glycoproteins, and clot retraction analysis. Genetic analysis was mainly performed by sequencing of coding regions and proximal regulatory regions of the genes of interest.[Results] Of the 70 cases referred for study, we functionally and molecularly characterized 12 patients with Glanzmann Thrombasthenia, 8 patients with Bernard Soulier syndrome, and 8 with other forms of IPDs. Twelve novel mutations were identified among these patients. The systematic study of patients revealed that almost one-third of patients had been previously misdiagnosed.[Conclusions] Our study provides a global picture of the current limitations and access to the diagnosis of IPDs, identifies and confirms new genetic variants that cause these disorders, and emphasizes the need of creating reference centers that can help health care providers in the recognition of these defects.Research of the authors’ group is supported by the Instituto de Salud Carlos III (ISCIII, PI10/02594), RECAVA RD12/0042/0050(ISCIII and FEDER), and Fundación Séneca (07703/GERM/07). ISG holds a fellowship from ISCIII (FI10/00535). CGM is supported by the Spanish Plan of Research & Development (BFU2010-15237).Peer reviewe

Preliminary Checklist for Reporting Observational Studies in Sports Areas: Content Validity

Observational studies are based on systematic observation, understood as an organized recording and quantification of behavior in its natural context. Applied to the specific area of sports, observational studies present advantages when comparing studies based on other designs, such as the flexibility for adapting to different contexts and the possibility of using non-standardized instruments as well as a high degree of development in specific software and data analysis. Although the importance and usefulness of sports-related observational studies have been widely shown, there is no checklist to report these studies. Consequently, authors do not have a guide to follow in order to include all of the important elements in an observational study in sports areas, and reviewers do not have a reference tool for assessing this type of work. To resolve these issues, this article aims to develop a checklist to measure the quality of sports-related observational studies based on a content validity study. The participants were 22 judges with at least 3 years of experience in observational studies, sports areas, and methodology. They evaluated a list of 60 items systematically selected and classified into 12 dimensions. They were asked to score four aspects of each item on 5-point Likert scales to measure the following dimensions: representativeness, relevance, utility, and feasibility. The judges also had an open-format section for comments. The Osterlind index was calculated for each item and for each of the four aspects. Items were considered appropriate when obtaining a score of at least 0.5 in the four assessed aspects. After considering these inclusion criteria and all of the open-format comments, the resultant checklist consisted of 54 items grouped into the same initial 12 dimensions. Finally, we highlight the strengths of this work. We also present its main limitation: the need to apply the resultant checklist to obtain data and, thus, increase quality indicators of its psychometric properties. For this reason, as relevant actions for further development, we encourage expert readers to use it and provide feedback; we plan to apply it to different sport areas.Fondo para el Desarrollo Científico y Tecnológico de Chile-FONDECYT 1150096Ministerio de Economía y Competitividad de España PSI2015-71947- REDTMinisterio de Economía y Competitividad de España, Fondo Europeo de Desarrollo Regional DEP2015-66069-PMinisterio de Ciencia e Innovación de España PSI2011-2958

Preliminary Experience With the Use of Electromagnetic Navigation for the Diagnosis of Peripheral Pulmonary Nodules and Enlarged Mediastinal Lymph Nodes

Electromagnetic navigation is a new technique that can be used with bronchoscopy to obtain samples of small peripheral nodular lesions and enlarged mediastinal lymph nodes. It is very versatile in that it enables both transbronchial biopsies and fine-needle aspiration to be performed. We describe 2 cases in which navigation with the superDimension/ Bronchus system combined with traditional diagnostic techniques facilitated a definitive diagnosis by bronchoscopy. Electromagnetic navigation can obviate the need for more invasive diagnostic procedures such as surgery, thus saving time and money and avoiding complications

The illuminated cavern: a singular Gravettian lamp throws light upon the rock art at the cave of La Pileta (Benaoján, Málaga)

En este trabajo presentamos el estudio arqueológico, paleontológico, tafonómico, cronológico y geoquímico de una valva de ostra hallada en la cueva de La Pileta. El ejemplar procede de depósitos fosilíferos neógenos dis-tantes más de 10 km del yacimiento. Una vez adaptada, la concha fue empleada como lámpara portátil. La cro-nología 14 C/AMS de la costra carbonatada que sellaba la cubeta nos remite al periodo Gravetiense. Según diversos indicios en la lámpara, durante su vida útil se procesaron o almacenaron pigmentos. Los datos aportados informan sobre la dispersión del simbolismo del Paleolítico Supe-rior Inicial hasta el extremo sudoccidental europeo, así mismo, suma nuevos elementos al debate sobre la exis-tencia de una fase presolutrense en el arte parietal de La Pileta y, por ende, de todo el sur de la Península Ibérica.This paper presents an archaeological, paleontologi-cal, taphonomical, chronological and geochemical study of a fossil oyster valve retrieved at the cave of La Pileta. The specimen was taken from Neogene fossiliferous depo- sits located more than 10 km away from the site. The shell was worked so as to become a portable lamp. 14C/AMS dating of the carbonate crust overlying the shell indicates a Gravettian chronology. Different lines of evidence indicate that during its use life, the valve was used to harbor or process pigments. The data presented throw light on the spread of symbolism in the southwestern corner of Europe during the Early Upper Palaeolithic, and add elements to the debate on the existence of a pre-Solutrean stage in the rock art of La Pileta and, by extension, of the southern Iberian Peninsula

A Preliminary Estimation of the Direct Ultraviolet Spectral Irradiance in Valencia (Spain): Comparison with Measured Values

UVSPEC and SMARTS2 models have been used to estimate the UV spectral irradiance values in Valencia, Spain, and the results of these estimations have been compared with experimental measurements of direct irradiance at normal incidence obtained using an Optronic OL 754 in the 300-400 nm range. The relative RMSD and MBD parameters have been used to estimate the deviations of the modelled values with respect to the experimental values. The results indicate that the deviations are smaller when the SMARTS2 model is used with the appropriate aerosol coefficients

Non BPS noncommutative vortices

We construct exact vortex solutions to the equations of motion of the Abelian Higgs model defined in non commutative space, analyzing in detail the properties of these solutions beyond the BPS point. We show that our solutions behave as smooth deformations of vortices in ordinary space time except for parity symmetry breaking effects induced by the non commutative parameter $\theta$.Comment: 17 pages, 5 figure

Applying the adverse outcome pathway (AOP) for food sensitization to support in vitro testing strategies

Background Before introducing proteins from new or alternative dietary sources into the market, a compressive risk assessment including food allergic sensitization should be carried out in order to ensure their safety. We have recently proposed the adverse outcome pathway (AOP) concept to structure the current mechanistic understanding of the molecular and cellular pathways evidenced to drive IgE-mediated food allergies. This AOP framework offers the biological context to collect and structure existing in vitro methods and to identify missing assays to evaluate sensitizing potential of food proteins. Scope and approach In this review, we provide a state-of-the-art overview of available in vitro approaches for assessing the sensitizing potential of food proteins, including their strengths and limitations. These approaches are structured by their potential to evaluate the molecular initiating and key events driving food sensitization. Key findings and conclusions The application of the AOP framework offers the opportunity to anchor existing testing methods to specific building blocks of the AOP for food sensitization. In general, in vitro methods evaluating mechanisms involved in the innate immune response are easier to address than assays addressing the adaptive immune response due to the low precursor frequency of allergen-specific T and B cells. Novel ex vivo culture strategies may have the potential to become useful tools for investigating the sensitizing potential of food proteins. When applied in the context of an integrated testing strategy, the described approaches may reduce, if not replace, current animal testing approaches

The optimisation of the angle of inclination of a solar collector to maximise the incident solar radiation

Irradiation data, recorded on vertical surfaces facing north, south, east and west and on a horizontal surface every ten minutes during daylight hours from January-December 1992 in Valencia, Spain, have been compared with estimated solar irradiation from inclined-surface models. Results show that Hays model most accurately reproduces the variation in irradiation on all vertical surfaces. Hays model has been used to find the hourly variation in the optimum tilt angle for a South-facing solar collector in Valencia, Spain, and also to calculate the yearly average of this angle. This method has been compared with the results provided by another model that uses average monthly values of daily irradiation derived from the same experimental data, to calculate average monthly values of the optimum tilt angle. The results show that the method involving monthly averages is more accurate and easier to work with

Preliminary Study of Recycled Aggregate Mortar for Electric Arc Furnace Dust Encapsulation

This article shows the preliminary results of a study carried out to determine the technical feasibility of encapsulating a high percentage of EAFD in cement-based mortars manufactured with the fine fraction of recycled concrete aggregates (RCA). Two families of mortars, with natural aggregate as a reference and with RCA, were studied. An incorporation rate by weight of two parts mortar to one part EAFD was tested. The mechanical strengths (compressive strength and tensile strength) before and after immersion in water, the rate of delitescence and the leaching behavior were studied. Mortars made with RCA showed similar mechanical strengths to the reference mortars made with natural aggregates; however, the incorporation of EAFD decreased the mechanical strengths. Encapsulation considerably reduced the leaching of heavy metals, although the Pb concentration remained above the hazardous waste limit. With this preliminary study, two wastes are managed together, and the results have shown that the use of RCA instead of natural aggregate is a viable alternative since it does not significantly impair the mechanical or leaching properties of the cement-based matrices used to encapsulate EAFD

Chemical composition and bioactivity potential of the new endosequence BC Sealer formulación hiflow

Aim To evaluate in a laboratory setting the effects of Endosequence BC Sealer HiFlow (Brasseler USA, Savannah, GA, USA), a novel calcium silicate-based sealer developed for use in warm canal filling techniques, on human periodontal ligament stem cells (hPDLSCs). Methodology Eluates of EndoSequence BC Sealer HiFlow (BCHiF) (Brasseler USA), EndoSequence BC Sealer (BCS) (Brasseler USA) and AH Plus (AHP) (Dentsply DeTrey GmbH, Konstanz, Germany), were placed in contact with hPDLSCs. The characterisation of the chemical elements of the root canal sealers was assessed using Scanning Electron Microscopy and Energy Dispersive X-ray analysis (SEM-EDX). Inductively Coupled Plasma Mass Spectrometry (ICP-MS) was used to determine the ion release of the sealers. MTT assay and wound healing techniques were used to determine cell viability and migration, respectively. Cell morphology and cell attachment were assessed using a direct contact technique of hPDLSCs onto the surface of the sealers and analysed by SEM. The bioactivity potential was carried out with the Alizarin Red and qPCR testing methods. The statistical differences were evaluated using one-way ANOVA and Tukey´s test (p0.05). Both BCS and BCHiF had similar rates of cell migration to the control group at 24 and 48 hours. Cell morphology and adhesion capacity were also similar for BCS and BCHiF groups, while the AHP group was associated with reduced adhesion capacity. The Alizarin Red assay revealed a significant difference between the BCS and the control group (p<0.001), as well as for the BCHiF group (p<0.001). Finally, BCS and BCHiF promoted overexpression of osteo/cementogenic genes. Conclusions In general, EndoSequence BC Sealer HiFlow possesses suitable biological properties to be safely used as a root canal filling material and promote increased expression of oste/cementogenic genes by hPDLSCs