Human gut microbiota analysis of cystic fibrosis infants using metaproteomics.

We report a metaproteomic analysis of the gut microbiota of eight infants with cystic fibrosis, during the first year of life. This is the first study in this disease that uses metaproteomics to analyze stool samples from patients at such a young age.

Long-Term Treatment with Alcaligenes faecalis A12C Improves Host Resistance to Pathogens in Septic Rats: Possible Contribution of Curdlan-Like Immune Trainer.

Curdlan, a ß-1,3/1,6-glucan found in Alcaligenes faecalis (A. faecalis) wall, activates innate and humoral immunity. The aim of this study is to evaluate whether pretreated rats with A. faecalis A12C could prevent sepsis disturbances and identify the immunomodulatory mechanisms involved. Experiments occurred in two stages: a survival study with 16 rats randomly divided into septic (SC) (n = 8) and septic pretreated (SA) (n = 8) groups and 45 rats divided into four groups: healthy (AGUSAN) (n = 9), septic (AGUIC) (n = 13), septic pretreated (AGUIA) (n = 14), and healthy pretreated (AGUSTO) (n = 9). Sepsis was induced by cecal ligation and puncture after 30 days of A. faecalis A12C pretreatment or without. SA group had a higher survival rate of 58% vs. 16% for SC group (P < 0.05). Overall, AGUIA showed better status than AGUIC (P < 0.01). Higher monocytosis was found in AGUIA and AGUSTO vs. AGUIC and AGUSAN, respectively (P < 0.05). A gradual increase in curdlan fecal concentration was observed in AGUIA during pretreatment. Fecal concentrations of Escherichia coli significantly decreased in AGUIA and AGUSTO. Bacterial load in urine, peritoneal lavage fluid (PLF), and bronchoalveolar lavage fluid (BALF) decreased (P < 0.05) in AGUIA vs. AGUIC. Finally, lower inflammation was observed in serum, BALF, and PLF, with reduced IL-6, IL-10, IL-1ß, and TNF-α, along with less damage in lungs and peritoneum in AGUIA vs. AGUIC. These findings suggest the connection between curdlan-produced by A. faecalis A12C-with the immune system and the reduction in severity of experimental sepsis.

Assessment of environmental radiological impact in former metallic mines in Extremadura (Spain): A case study.

Metal mining in the Extremadura region was very important in the 19th and 20th centuries. However, due to different reasons the great majority of mines ceased operations, leading to plenty of abandoned mining sites, most of them with on-site waste dumps. Although metal extraction is not radioactive per se, it is considered a NORM activity. In this study, three former mining sites, in which Pb-V-Zn-Ag, Pb-Ag, and Pb-Zn were extracted, were selected to assess the radiological impact on the population and the environment. The external γ exposure was estimated by determining the effective dose and elaborating isodose maps of the sites. The presence of the mining sites increased up to 0.41 mSv/y the effective dose over the surrounding background, which is below the reference value of 1 mSv/y. In only one mining site, the uranium and radium activity concentration of waste dumps were higher than the surrounding soil. The soil to plant (wild grass) transfer factors were similar to other reported values without the influence of NORM activities. So, no enhanced transfer of radionuclides was observed. The radiological impact on the environment was assessed by the risk to non-human biota using the tiered approach developed in ERICA Tool. The sum of the risk quotients of all considered radionuclides in the most conservative Tier 1 was below 1. Total dose rates for several terrestrial Reference Animal and Plants (RAPs) were estimated using Tier 3, obtaining values below 40 µGy/h. Therefore, the impact on non-human biota can be considered as negligible.

Measurements of neutrino oscillation parameters from the T2K experiment using 3.6×1021 protons on target.

The T2K experiment presents new measurements of neutrino oscillation parameters using 19.7(16.3)×1020 protons on target (POT) in (anti-)neutrino mode at the far detector (FD). Compared to the previous analysis, an additional 4.7×1020 POT neutrino data was collected at the FD. Significant improvements were made to the analysis methodology, with the near-detector analysis introducing new selections and using more than double the data. Additionally, this is the first T2K oscillation analysis to use NA61/SHINE data on a replica of the T2K target to tune the neutrino flux model, and the neutrino interaction model was improved to include new nuclear effects and calculations. Frequentist and Bayesian analyses are presented, including results on sin2θ13 and the impact of priors on the δCP measurement. Both analyses prefer the normal mass ordering and upper octant of sin2θ23 with a nearly maximally CP-violating phase. Assuming the normal ordering and using the constraint on sin2θ13 from reactors, sin2θ23=0.561-0.032+0.021 using Feldman-Cousins corrected intervals, and Δm322=2.494-0.058+0.041×10-3eV2 using constant Δχ2 intervals. The CP-violating phase is constrained to δCP=-1.97-0.70+0.97 using Feldman-Cousins corrected intervals, and δCP=0,π is excluded at more than 90% confidence level. A Jarlskog invariant of zero is excluded at more than 2σ credible level using a flat prior in δCP, and just below 2σ using a flat prior in sinδCP. When the external constraint on sin2θ13 is removed, sin2θ13=28.0-6.5+2.8×10-3, in agreement with measurements from reactor experiments. These results are consistent with previous T2K analyses.

Design and development of a detector system and software tool installed on a mobile laboratory to provide both radiological characterisation of large areas and a simple tool for localising radioactive sources.

In emergency situations where an immediate response is required to make appropriate decisions by the competent authorities, it is essential to have measurement tools that provide results as accurate as possible in real-time. This paper presents the description of the upgrade of the mobile laboratory of the Radiological Alert Network of Extremadura, focusing on the characterisation of radioactive-contaminated land during emergency situations and the detection of radioactive sources. The detector system is based on two scintillation detectors and a car-borne dose rate monitor. Additionally, a software tool has been developed to collect information from the different devices involved (detectors, GPS, etc) and display it in an intuitive manner. This system has been tested in an area of a former phosphate facility where soils remain contaminated to varying degrees with radionuclides of TE-NORM origin.

Cumplimiento y adecuación del etiquetado de complementos alimenticios antienvejecimineto distribuidos por el canal farmacéutico / Compliance and adequacy of labelling of anti-ageing food supplements distributed through the pharmaceutical channel

JUSTIFICACIÓN: la búsqueda de un estado y aspecto óptimo de salud, la prevención de enfermedades y el retraso del envejecimiento conlleva el consumo de complementos alimenticios entre otros productos de autocuidado. La comercialización de complementos alimenticios, distribuidos tradicionalmente en farmacias, se ha diversificado, si bien el canal farmacéutico se caracteriza por asegurar la calidad y seguridad que el consumidor exige y precisa, no solamente por la selección de productos que distribuye, sino por la dispensación informada que ofrece. Se sospecha que no todos los complementos alimenticios en el mercado cumplen con la normativa vigente y por ello el consumidor puede exponerse a situaciones de riesgo por desconocimiento. OBJETIVO: este estudio tiene por objeto la verificación de la adecuación a la norma del etiquetado de una selección de complementos alimenticios antienvejecimiento. Material y métodos Se han estudiado las menciones del etiquetado de los 27 complementos alimenticios antienvejecimiento más vendidos en la provincia de S/C de Tenerife, según el volumen de ventas en los dos almacenes mayoristas de medicamentos de Santa Cruz de Tenerife (COFARTE y COFARES). Se ha comprobado su adecuación a la normativa de aplicación; Real Decreto 1487/2009, relativo a los complementos alimenticios), Reglamento (CE) Nº 1170/2009 y Reglamento (UE) Nº 1169/2011. (AU)

Incidentes relacionados con la seguridad del paciente crítico durante los traslados intrahospitalarios / Incidents related to critical patients afety during in hospital transfer

Objective: To analyze the incidents related to patient safety (IRSP) and their risk factors during in-hospital transfer (IHT) of critical patients after the application of a protocol, and to evaluate safety during transfer using quality indicators.DesignA prospective, observational and non-intervention cohort study was carried out.SettingA 10-bed multipurpose Intensive Care Unit (ICU) of a second level university hospital.PatientsAll IHTs of critical patients in the ICU for diagnostic tests and to the operating room between March 2011 and March 2017 were included in the study.Main measurementsDemographic variables, patient severity, transfer priority, moment of the day, reason and type of transfer team. Pre-transport checklist items and IRSP were collected. A biannual analysis was made of quality indicators designed for IHT.ResultsA total of 805 transfers were registered, mostly of an urgent nature (53.7%) and for diagnostic tests (77%). In turn, 112 transfers (13.9%) presented some type of IRSP; 54% related to the equipment and 30% related to team and organization. Adverse events occurred in 19 (2.4%) transfers. Risk factors identified in the multivariate analysis were mechanical ventilation and the transport team. The evolution of the indicators related to transport was significantly favorable.ConclusionsAfter the application of an IHT protocol, IRSP are low. The main risk factor is invasive mechanical ventilation. The experience of the team performing IHT influences the detection of a greater number of incidents (AU)

Objetivo: Analizar los incidentes relacionados con la seguridad del paciente (IRSP) durante los traslados intrahospitalarios (TIH) del paciente crítico tras la aplicación de un protocolo, así como sus factores de riesgo. Evaluar la seguridad durante los traslados mediante indicadores de calidad.DiseñoEstudio de cohorte, prospectivo, observacional y no intervencionista.ÁmbitoUnidad de Cuidados Intensivos (UCI) polivalente de 10 camas de un hospital universitario de segundo nivel.PacientesSe incluyen todos los TIH de pacientes críticos realizados de UCI a pruebas diagnósticas y a quirófano entre marzo de 2011 y marzo de 2017.Principales variables del estudioVariables demográficas, gravedad de los pacientes, prioridad del traslado, momento del día, motivo y tipo de equipo del traslado. Se recogen comprobaciones pre-traslado e IRSP. Análisis semestral de indicadores de calidad diseñados para el TIH.ResultadosDe los 805 traslados registrados, la mayoría urgentes (53,7%) y para pruebas diagnósticas (77%), 112 traslados (13,9%) presentaron algún tipo de IRSP, 54% relacionado con el equipamiento y 30% con el equipo y la organización. En 19 (2,4%) traslados se produjeron eventos adversos. En el análisis multivariante los factores de riesgo fueron la ventilación mecánica y el equipo que realiza el traslado. La evolución de los indicadores relacionados con los traslados es significativamente favorable.ConclusionesTras la aplicación de un protocolo de TIH, los IRSP son bajos y el principal factor de riesgo es la ventilación mecánica invasiva. La experiencia del equipo que realiza el TIH influye en la detección de un mayor número de incidentes (AU)

Incidents related to critical patient safety during in-hospital transfer.

OBJECTIVE: To analyze the incidents related to patient safety (IRSP) and their risk factors during in-hospital transfer (IHT) of critical patients after the application of a protocol, and to evaluate safety during transfer using quality indicators. DESIGN: A prospective, observational and non-intervention cohort study was carried out. SETTING: A 10-bed multipurpose Intensive Care Unit (ICU) of a second level university hospital. PATIENTS: All IHTs of critical patients in the ICU for diagnostic tests and to the operating room between March 2011 and March 2017 were included in the study. MAIN MEASUREMENTS: Demographic variables, patient severity, transfer priority, moment of the day, reason and type of transfer team. Pre-transport checklist items and IRSP were collected. A biannual analysis was made of quality indicators designed for IHT. RESULTS: A total of 805 transfers were registered, mostly of an urgent nature (53.7%) and for diagnostic tests (77%). In turn, 112 transfers (13.9%) presented some type of IRSP; 54% related to the equipment and 30% related to team and organization. Adverse events occurred in 19 (2.4%) transfers. Risk factors identified in the multivariate analysis were mechanical ventilation and the transport team. The evolution of the indicators related to transport was significantly favorable. CONCLUSIONS: After the application of an IHT protocol, IRSP are low. The main risk factor is invasive mechanical ventilation. The experience of the team performing IHT influences the detection of a greater number of incidents.

3D-Printed Floating Cable Traps for MRI guided Microwave Ablation.

Magnetic Resonance Imaging (MRI) guided Microwave Ablation (MWA) allows for real-time therapy monitoring with MRI-thermometry. The MWA generator emits Radio Frequency (RF) interference, which can limit the accuracy of therapy monitoring. The image quality is enhanced by Floating Cable Traps (FCTs) that are used to attenuate common mode currents on supply lines between a MWA generator, and its ablation applicator. The effect of an FCT on the Signal to Noise Ratio (SNR), and changes in the MRI spectrum are discussed in this paper. The application of FCT can bring significant improvements in both, the MRI spectrum and the SNR.Floating Cable Traps are user-friendly. FCT enable coaxial cables to reduce interferences emitted in MRI guided interventions. It is used to selectively attenuate frequencies in the MRI's range. This can increase the image's Signal to Noise Ratio.

Sequential chemotherapy regimen of induction with panitumumab and paclitaxel followed by radiotherapy and panitumumab in patients with locally advanced head and neck cancer unfit for platinum derivatives. The phase II, PANTERA/TTCC-2010-06 study.

BACKGROUND: Sequential treatment of Panitumumab (Pb) plus Paclitaxel (Px) as induction treatment (IT) followed by concurrent bioradiotherapy (Bio-RT) with Pb may be an alternative for locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) in patients ineligible for high-dose cisplatin therapy. METHODS: Phase II, single-arm, multicentre study, with two-stage design, in patients ≥ 18 years with stage III-IVa-b LA-SCCHN unfit for platinum. Patients received Px + Pb (9 weeks) as IT followed by Bio-RT + Pb. Primary endpoint: overall response rate (ORR) after IT, defined as: more than 70% of patients achieving complete response (CR) or partial response (PR) to IT. Secondary end-points: progression-free survival, organ preservation rate, safety profile. RESULTS: Study ended prematurely (51 patients) due to slow recruitment. ORR: 66.7% (95% CI: 53.7-79.6), 8 (15.7%) CR and 26 (51.0%) PR. 39 patients (76%) completed radiotherapy (RT). Pb and/or Px-related adverse events (AEs) grade 3-4: 56.9% during IT and 63.4% during the concomitant phase, of which most common were skin toxicity (33.3%). Five deaths occurred during treatment, two of them (3.9%) were Pb and/or Px-related. CONCLUSIONS: Although underpowered, ORR was higher than the pre-specified boundary for considering the treatment active. Although Px + Pb as IT provides some benefit, the safety profile is worse than expected. To consider Pb + Px as IT as an alternative for platinum-unsuitable LA-SCCHN, further research/investigation would be needed.

Ectopic expression of the atypical HLH FaPRE1 gene determines changes in cell size and morphology.

PACLOBUTRAZOL RESISTANCE (PRE) genes code atypical HLH transcriptional regulators characterized by the absence of a DNA-binding domain but present an HLH dimerization domain. In vegetative tissues, the function of these HLH proteins has been related with cell elongation processes. In strawberry, three FaPRE genes are expressed, two of them (FaPRE2 and FaPRE3) in vegetative tissues while FaPRE1 is fruit receptacle-specific. Ubiquitous FaPRE1 accumulation produced elongated flower receptacles and plants due to the elongation of the main aerial vegetative organs, with the exception of leaves. Histological analysis clearly demonstrated that the observed phenotype was due to significant changes in the parenchymal cell's morphology. In addition, transcriptomic studies of the transgenic elongated flower receptacles allowed to identify a small group of differentially expressed genes that encode cell wall-modifying enzymes. Together, the data seem to indicate that, in the strawberry plant vegetative organs, FaPRE proteins could modulate the expression of genes related with the determination of the size and shape of the parenchymal cells.

Probiotic Properties of Alcaligenes faecalis Isolated from Argyrosomus regius in Experimental Peritonitis (Rat Model).

A strain of Alcaligenes faecalis A12C (A. faecalis A12C) isolated from Argyrosomus regius is a probiotic in fish. Previous experiments showed that A. faecalis A12C had inhibitory effects on the growth of multidrug-resistant bacteria. We aimed to confirm whether A. faecalis A12C is safe and has adequate intestinal colonization in experimental rats, and evaluate its efficacy in an animal model of peritonitis. We used 30 male rats, randomly divided into 6 groups (n = 5): three groups (HA7, HA15, HA30) received A. faecalis A12C in drinking water (6 × 108 CFU/mL) for 7 days, and three control groups received drinking water only. All groups were evaluated at 7, 15, and 30 days. Survival after A. faecalis A12C administration was 100% in all groups. Mild eosinophilia (1.5%, p < 0.01) and increased aspartate aminotransferase (86 IU/L, p < 0.05) were observed in HA7, followed by progressive normalization. No histological signs of organ injury were found. We observed significant E. coli decline in faeces, parallel to an increase in A. faecalis A12C at 7 days. E. coli had a tendency to recover initial values, while A. faecalis A12C disappeared from the intestinal microbiota at 30 days. To evaluate its efficacy against peritonitis, we studied two additional groups of animals: IA group pretreated with A. faecalis A12C before E. coli intra-abdominal inoculation, and IC group inoculated with no A. faecalis A12C. We found an increase in C-reactive protein, alanine aminotransferase, urea, and eosinophils in IC animals when compared with IA. Peritonitis was more evident in IC than in IA animals. Our findings suggest that A. faecalis A12C altered clinically relevant parameters in sepsis and was associated with a lesser spread of infection.

A nearby transiting rocky exoplanet that is suitable for atmospheric investigation.

Spectroscopy of transiting exoplanets can be used to investigate their atmospheric properties and habitability. Combining radial velocity (RV) and transit data provides additional information on exoplanet physical properties. We detect a transiting rocky planet with an orbital period of 1.467 days around the nearby red dwarf star Gliese 486. The planet Gliese 486 b is 2.81 Earth masses and 1.31 Earth radii, with uncertainties of 5%, as determined from RV data and photometric light curves. The host star is at a distance of ~8.1 parsecs, has a J-band magnitude of ~7.2, and is observable from both hemispheres of Earth. On the basis of these properties and the planet's short orbital period and high equilibrium temperature, we show that this terrestrial planet is suitable for emission and transit spectroscopy.

Bacteria associated with periodontal disease are also increased in health.

BACKGROUND: The objective of this cross-sectional clinical study was to analyze the differences in the microbiome in gingival sulci of adult patients in the presence or absence of chronic periodontitis. MATERIAL AND METHODS: Patients with or without periodontal disease were included in this cross-sectional study. Subgingival biofilm samples were collected and analyzed by 16S massive pyrosequencing. Functional analyses were also performed. RESULTS: A total of 15 phyla, 154 genera and 351 species were detected globally. Differences between disease and non-disease samples were observed in all taxonomical levels which suggest functional profile changes in the community. It was found that the main species associated with non-disease samples were reduced in disease but not completely suppressed. Analysis of the functional potential of the biofilms revealed a significantly higher activity related to endocytosis and phosphatidylinositol signaling in the disease group but lower cell adhesion molecules. CONCLUSIONS: Specific differences between health and disease suggest functional profile changes in the community, although bacteria associated with periodontal disease are also increased in health. Transcriptome studies should be conducted to confirm and deepen metabolic dysfunctions.

Incidents related to critical patient safety during in-hospital transfer. / Incidentes relacionados con la seguridad del paciente crítico durante los traslados intrahospitalarios.

OBJECTIVE: To analyze the incidents related to patient safety (IRSP) and their risk factors during in-hospital transfer (IHT) of critical patients after the application of a protocol, and to evaluate safety during transfer using quality indicators. DESIGN: A prospective, observational and non-intervention cohort study was carried out. SETTING: A 10-bed multipurpose Intensive Care Unit (ICU) of a second level university hospital. PATIENTS: All IHTs of critical patients in the ICU for diagnostic tests and to the operating room between March 2011 and March 2017 were included in the study. MAIN MEASUREMENTS: Demographic variables, patient severity, transfer priority, moment of the day, reason and type of transfer team. Pre-transport checklist items and IRSP were collected. A biannual analysis was made of quality indicators designed for IHT. RESULTS: A total of 805 transfers were registered, mostly of an urgent nature (53.7%) and for diagnostic tests (77%). In turn, 112 transfers (13.9%) presented some type of IRSP; 54% related to the equipment and 30% related to team and organization. Adverse events occurred in 19 (2.4%) transfers. Risk factors identified in the multivariate analysis were mechanical ventilation and the transport team. The evolution of the indicators related to transport was significantly favorable. CONCLUSIONS: After the application of an IHT protocol, IRSP are low. The main risk factor is invasive mechanical ventilation. The experience of the team performing IHT influences the detection of a greater number of incidents.

Sobresedación Zero como herramienta de confort, seguridad y gestión en la unidades de cuidados intensivos / Oversedation Zero as a tool for comfort, safety and intensive care unit management

La sedación es necesaria en el tratamiento de los pacientes críticos, tanto para aliviar el sufrimiento como para curar a los pacientes con enfermedades que precisan el ingreso en unidades de cuidados intensivos. Esta sedación debe ser la adecuada a las necesidades del paciente en cada momento de su evolución clínica, ni por debajo (infrasedación) ni por encima (sobresedación). Una sedación adecuada influye en la comodidad, la seguridad, la supervivencia, la calidad de vida posterior, la rotación de camas de las unidades de críticos y los costes. La infrasedación se detecta y corrige rápidamente. Sin embargo, la sobresedación es silente y difícil de prevenir sin unas pautas de actuación, una concienciación colectiva y un trabajo en equipo. El proyecto «Sobresedación Zero» del Grupo de Trabajo de Sedación, Analgesia y Delirium de la Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias pretende ser una herramienta docente, práctica y de concienciación colectiva de comodidad, seguridad y gestión para maximizar el resultado clínico y minimizar los efectos perjudiciales de la sedación excesiva. Se basa en un paquete de medidas que se incluye monitorizar el dolor, la analgesia, la agitación, la sedación, el delirium y el bloqueo neuromuscular, mantener a los pacientes sin dolor, realizar una sedación dinámica según objetivos clínicos, consensuar el protocolo multidisciplinar a seguir y evitar la sedación profunda no indicada clínicamente

Sedation is necessary in the management of critically ill patients, both to alleviate suffering and to cure patients with diseases that require admission to the intensive care unit. Such sedation should be appropriate to the patient needs at each timepoint during clinical evolution, and neither too low (undersedation) nor too high (oversedation). Adequate sedation influences patient comfort, safety, survival, subsequent quality of life, bed rotation of critical care units and costs. Undersedation is detected and quickly corrected. In contrast, oversedation is silent and difficult to prevent in the absence of management guidelines, collective awareness and teamwork. The Zero Oversedation Project of the Sedation, Analgesia and Delirium Working Group of the Spanish Society of Intensive and Critical Care Medicine and Coronary Units aims to offer a practical teaching and collective awareness tool for ensuring patient comfort, safety and management with a view to optimizing the clinical outcomes and minimizing the deleterious effects of excessive sedation. The tool is based on a package of measures that include monitoring pain, analgesia, agitation, sedation, delirium and neuromuscular block, keeping patients pain-free, performing dynamic sedation according to clinical objectives, agreeing upon the multidisciplinary protocol to be followed, and avoiding deep sedation where not clinically indicated

Oversedation Zero as a tool for comfort, safety and intensive care unit management. / Sobresedación Zero como herramienta de confort, seguridad y gestión en la unidades de cuidados intensivos.

Sedation is necessary in the management of critically ill patients, both to alleviate suffering and to cure patients with diseases that require admission to the intensive care unit. Such sedation should be appropriate to the patient needs at each timepoint during clinical evolution, and neither too low (undersedation) nor too high (oversedation). Adequate sedation influences patient comfort, safety, survival, subsequent quality of life, bed rotation of critical care units and costs. Undersedation is detected and quickly corrected. In contrast, oversedation is silent and difficult to prevent in the absence of management guidelines, collective awareness and teamwork. The Zero Oversedation Project of the Sedation, Analgesia and Delirium Working Group of the Spanish Society of Intensive and Critical Care Medicine and Coronary Units aims to offer a practical teaching and collective awareness tool for ensuring patient comfort, safety and management with a view to optimizing the clinical outcomes and minimizing the deleterious effects of excessive sedation. The tool is based on a package of measures that include monitoring pain, analgesia, agitation, sedation, delirium and neuromuscular block, keeping patients pain-free, performing dynamic sedation according to clinical objectives, agreeing upon the multidisciplinary protocol to be followed, and avoiding deep sedation where not clinically indicated.

A giant exoplanet orbiting a very-low-mass star challenges planet formation models.

Surveys have shown that super-Earth and Neptune-mass exoplanets are more frequent than gas giants around low-mass stars, as predicted by the core accretion theory of planet formation. We report the discovery of a giant planet around the very-low-mass star GJ 3512, as determined by optical and near-infrared radial-velocity observations. The planet has a minimum mass of 0.46 Jupiter masses, very high for such a small host star, and an eccentric 204-day orbit. Dynamical models show that the high eccentricity is most likely due to planet-planet interactions. We use simulations to demonstrate that the GJ 3512 planetary system challenges generally accepted formation theories, and that it puts constraints on the planet accretion and migration rates. Disk instabilities may be more efficient in forming planets than previously thought.

Fibroblast activation and abnormal extracellular matrix remodelling as common hallmarks in three cancer-prone genodermatoses.

BACKGROUND: Recessive dystrophic epidermolysis bullosa (RDEB), Kindler syndrome (KS) and xeroderma pigmentosum complementation group C (XPC) are three cancer-prone genodermatoses whose causal genetic mutations cannot fully explain, on their own, the array of associated phenotypic manifestations. Recent evidence highlights the role of the stromal microenvironment in the pathology of these disorders. OBJECTIVES: To investigate, by means of comparative gene expression analysis, the role played by dermal fibroblasts in the pathogenesis of RDEB, KS and XPC. METHODS: We conducted RNA-Seq analysis, which included a thorough examination of the differentially expressed genes, a functional enrichment analysis and a description of affected signalling circuits. Transcriptomic data were validated at the protein level in cell cultures, serum samples and skin biopsies. RESULTS: Interdisease comparisons against control fibroblasts revealed a unifying signature of 186 differentially expressed genes and four signalling pathways in the three genodermatoses. Remarkably, some of the uncovered expression changes suggest a synthetic fibroblast phenotype characterized by the aberrant expression of extracellular matrix (ECM) proteins. Western blot and immunofluorescence in situ analyses validated the RNA-Seq data. In addition, enzyme-linked immunosorbent assay revealed increased circulating levels of periostin in patients with RDEB. CONCLUSIONS: Our results suggest that the different causal genetic defects converge into common changes in gene expression, possibly due to injury-sensitive events. These, in turn, trigger a cascade of reactions involving abnormal ECM deposition and underexpression of antioxidant enzymes. The elucidated expression signature provides new potential biomarkers and common therapeutic targets in RDEB, XPC and KS. What's already known about this topic? Recessive dystrophic epidermolysis bullosa (RDEB), Kindler syndrome (KS) and xeroderma pigmentosum complementation group C (XPC) are three genodermatoses with high predisposition to cancer development. Although their causal genetic mutations mainly affect epithelia, the dermal microenvironment likely contributes to the physiopathology of these disorders. What does this study add? We disclose a large overlapping transcription profile between XPC, KS and RDEB fibroblasts that points towards an activated phenotype with high matrix-synthetic capacity. This common signature seems to be independent of the primary causal deficiency, but reflects an underlying derangement of the extracellular matrix via transforming growth factor-ß signalling activation and oxidative state imbalance. What is the translational message? This study broadens the current knowledge about the pathology of these diseases and highlights new targets and biomarkers for effective therapeutic intervention. It is suggested that high levels of circulating periostin could represent a potential biomarker in RDEB.

Standard comparison of local mental health care systems in eight European countries.

AIMS: There is a need of more quantitative standardised data to compare local Mental Health Systems (MHSs) across international jurisdictions. Problems related to terminological variability and commensurability in the evaluation of services hamper like-with-like comparisons and hinder the development of work in this area. This study was aimed to provide standard assessment and comparison of MHS in selected local areas in Europe, contributing to a better understanding of MHS and related allocation of resources at local level and to lessen the scarcity in standard service comparison in Europe. This study is part of the Seventh Framework programme REFINEMENT (Research on Financing Systems' Effect on the Quality of Mental Health Care in Europe) project. METHODS: A total of eight study areas from European countries with different systems of care (Austria, England, Finland, France, Italy, Norway, Romania, Spain) were analysed using a standard open-access classification system (Description and Evaluation of Services for Long Term Care in Europe, DESDE-LTC). All publicly funded services universally accessible to adults (≥18 years) with a psychiatric disorder were coded. Care availability, diversity and capacity were compared across these eight local MHS. RESULTS: The comparison of MHS revealed more community-oriented delivery systems in the areas of England (Hampshire) and Southern European countries (Verona - Italy and Girona - Spain). Community-oriented systems with a higher proportion of hospital care were identified in Austria (Industrieviertel) and Scandinavian countries (Sør-Trøndelag in Norway and Helsinki-Uusimaa in Finland), while Loiret (France) was considered as a predominantly hospital-based system. The MHS in Suceava (Romania) was still in transition to community care. CONCLUSIONS: There is a significant variation in care availability and capacity across MHS of local areas in Europe. This information is relevant for understanding the process of implementation of community-oriented mental health care in local areas. Standard comparison of care provision in local areas is important for context analysis and policy planning.