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Background and Objectives. Although pets are known to be beneficial for children, they could also imply risks for immunocompromised ones. We report the prevalence of children and young patients living with pets in a cohort of immunosuppressed pediatric patients and describe risk behaviors for acquiring zoonosis and compliance with veterinary recommendations. Methods. A cross-sectional, observational study was performed in a large tertiary hospital in Madrid, including immunosuppressed patients from different regions of Spain. The participants were asked to complete an online questionnaire. Results. Two hundred and eighty-four responses were received: 62.3% solid organ transplantation (177/284), 22.8% hematopoietic stem cell transplantation (65/284), and 14.8% inborn errors of immunity (42/284). The median age was 11 years (interquartile range 5.9–15.4), and 55% were boys (156/284). Up to 45% (130/284) of the respondents lived with 201 pets (74% of them dogs and cats). Half of the patients owning dogs or cats did not comply with at least one of the recommendations regarding vaccination, deworming, feeding, and/or veterinarian recommended controls. The poorest findings were related to deworming regimens. Only 42.8% (117/273) of the participants received specific recommendations from their healthcare professionals about companion animals. However, up to 97% of the families considering acquiring a pet did so when the professional did not contraindicate it (31/32), while 72% of the families having pets got rid of their pets when they were advised against animals (8/11). Conclusions. Pet ownership is frequent among immunocompromised children. They presented risky exposures for acquiring zoonoses, and basic veterinary recommendations were not frequently followed. The opinion of professionals significantly influenced the decision to acquire pets, but less than half of the families received recommendations in this regard. Spanish Pediatrics Association (AEP) (2021 Research Grant) MAPFRE Foundation Carlos III Health Institute - Fondos Feder (BAE21/00022) 4.521 Q1 JCR 2021 0.990 Q1 SJR 2022 No data IDR 2021 UEM

Summary Ensuring cement sheath placement is of paramount importance for the success of a primary cementing operation. Poor mud displacement and fluid contamination can lead to cement isolation failure, loss of production, and even well abandonment. Over time, many cement placement computerized models have been developed, leading to a significant number of theoretical and case history papers. However, using these to design a cement job is difficult because their physical and mathematical assumptions are most of the time unclear, and because their application requires balancing precision with computation time. Models that are too precise may lead to very long runs, while oversimplified models could result in nonpredictive simulations. To the authors’ knowledge, nothing has been published to explain how to perform efficient predictions with a cement placement computerized model. Such is the object of this paper. It presents an extensive analysis of all the available cement placement computerized models, highlighting their advantages and disadvantages and listing their assumptions. This analysis indicates that (1) the actual methods used to estimate the equivalent circulating density window are not rigorous enough; (2) there still exist a lot of uncertainties when predicting the tubular standoff; (3) modeling fluid contamination, especially when the fluids are not compatible, remains very cumbersome, if not impossible, because the true interfaces’ physics is not completely considered; (4) a local contamination observed at an intermediate time can disappear at the end of the simulation due to numerical diffusion, meaning that just looking at the concentration maps at the end of placement is not sufficient to judge the efficiency of a displacement scenario; and (5) changes in geometries along the cement sheath are not considered with precision. This work allows establishing guidelines to help understanding how to manage simulation inputs and analyzing and communicating the produced results.

Hearing loss is a highly prevalent condition in the pediatric population. Pediatric maxillary expansion is a widespread treatment to address transverse maxillary deficiency. First reports describing an association between improvements for patients with HL and PME initiated in the 1960s. In this systematic review and meta-analysis we aim to review the role of maxillary expansion in reducing conductive hearing loss in pediatric population.Pubmed (Medline), the Cochrane Library, EMBASE and Trip Database were checked. Main outcome was expressed as the difference between air-bone gap, compliance, ear volume and conductive hearing thresholds before and after treatment and the 95% confidence interval.A total of 10 studies (218 patients) met inclusion criteria. The pooled data in the meta-analysis under a random effects model shows a statistically significant difference of 10.57dB mean reduction after palatal expansion. The air-bone gap was significantly reduced by 5.39dB (CI 95% 3.68, 7.10). Compliance and volume were assessed in three studies, with a non-significant positive difference in the compliance (0.14) and a statistically significant difference for volume (0.80) after palatal expansion.This systematic review and meta-analysis found a positive effect of pediatric maxillary expansion in conductive hearing loss in well-select children. However, results cannot be extrapolated for children with conductive hearing loss without an accompanying orthodontic indication (maxillary constriction). It showed that the existing prospective studies exhibited qualitative pitfalls, limiting the ability to obtain conclusive evidence about the role of pediatric maxillary expansion on conductive hearing loss in children.

Resumen Introduccion La neurofibromatosis tipo 1 (NF1) es un desorden progresivo multisistemico de herencia autosomica dominante que presenta numerosas manifestaciones neurologicas. Metodos Revision de historias clinicas de pacientes afectos de NF1 controlados en una Unidad de Neuropediatria de mayo de 1990 a 31 de diciembre de 2018 y sus manifestaciones neurologicas asociadas. Resultados Se revisaron 128 pacientes afectos de NF1. Edad media al diagnostico de NF1, 4,43 anos ± 3,38 SDS (rango 6 meses-14,5 anos) con discreto predominio femenino (53,1%). Se asocia macrocefalia (PC> 2SDS) en el 37,5% de los casos. TDAH en el 28,9% de los casos (37), subtipo combinado 20, inatento 15 casos y predominantemente hiperactivo 2 casos. Otras manifestaciones incluyen; cefalea (18,7%), deficit cognitivo (7,8%), afectacion motora (6,2%) y epilepsia (4,68%). Se realizo RM cerebral a 85 pacientes, mostrando 60 (70,5%) hipersenales en T2 en ganglios basales y/o cerebelo, junto con otras alteraciones como Chiari I (4 casos) y quistes aracnoideos (3 casos). Se identificaron gliomas de nervio optico en 22 casos (25,8%). Otros hallazgos diagnosticados por RM incluyen neurofibromas plexiformes (9,3%) y otros gliomas localizados en sistema nervioso central (3,1%). Conclusiones Las manifestaciones neurologicas encontradas concuerdan con lo recogido en la literatura. El seguimiento de estos pacientes se pierde en la edad adulta, siendo necesario establecer adecuadas estrategias de transferencia y posterior seguimiento de pacientes a los servicios de adultos.

Neurofibromatosis type 1 (NF1) is a progressive multisystem disorder following an autosomal dominant inheritance pattern that presents with multiple neurological manifestations.We reviewed medical histories of patients with NF1 followed up at our hospital's paediatric neurology department from May 1990 to 31 December 2018. We collected data on neurological symptoms.A total of 128 patients with NF1 were identified. Mean age (SD) at NF1 diagnosis was 4.43 (3.38) years (range, 0.5-14.5 years). There was a slight female predominance (53.1%). Macrocephaly (head circumference over 2 SDs above average for age) was present in 37.5% of cases. Attention-deficit/hyperactivity disorder was recorded in 28.9% of patients (37): combined type in 20 patients, predominantly inattentive in 15, and predominantly impulsive/hyperactive in 2. Other manifestations included headache (18.6%), cognitive impairment (7.8%), motor deficit (6.2%), and epilepsy (4.68%). Brain MRI was performed in 85 patients, revealing T2-weighted hyperintensities in the basal ganglia and/or cerebellum in 60 patients (70.5%), Chiari malformation type 1 in 4 cases, and arachnoid cysts in 3. Optic nerve gliomas were identified by MRI in 22 patients (25.8%). Other MRI findings included plexiform neurofibromas (9.3%) and central nervous system gliomas (3.1%).The neurological manifestations identified in our sample are consistent with those reported in the literature. Effective transfer strategies from paediatric neurology departments and subsequent clinical follow-up by adult neurology departments are needed to prevent loss to follow-up in adulthood.

This paper presents a surrogate modelling technique based on domain partitioning for Bayesian parameter inference of highly nonlinear engineering models. In order to alleviate the computational burden typically involved in Bayesian inference applications, a multielement Polynomial Chaos Expansion based Kriging metamodel is proposed. The developed surrogate model combines in a piecewise function an array of local Polynomial Chaos based Kriging metamodels constructed on a finite set of non-overlapping subdomains of the stochastic input space. Therewith, the presence of non-smoothness in the response of the forward model (e.g.~ nonlinearities and sparseness) can be reproduced by the proposed metamodel with minimum computational costs owing to its local adaptation capabilities. The model parameter inference is conducted through a Markov chain Monte Carlo approach comprising adaptive exploration and delayed rejection. The efficiency and accuracy of the proposed approach are validated through two case studies, including an analytical benchmark and a numerical case study. The latter relates the partial differential equation governing the hydrogen diffusion phenomenon of metallic materials in Thermal Desorption Spectroscopy tests.

The use of prebiotics and probiotics to improve symptoms associated with autism spectrum disorder (ASD) has varied from study to study, indicating the complex and heterogeneous nature of the disorder and the behaviors and gastrointestinal symptoms associated with ASD. There is a wide variety in the severity of symptoms and developmental impediments across the population. Gut microbiome studies have also shown unique but varied microbial signatures in ASD. While there have been successes in pre-clinical and clinical trials with prebiotic and probiotic components, the limited population sizes have promising yet inconclusive results. This study addresses this issue by 1) enrolling an ASD cohort of 296 children and adults and comparing their deep DNA metagenomic sequencing of gut microbiomes to that of an age-matched neurotypical cohort and 2) individually formulating a precision synbiotic (probiotic and prebiotic) tailored towards each individual’s needs and conducting pre/post evaluations of ASD and GI symptoms and longitudinal whole genome microbiome sequencing. At baseline, there was significantly lower microbiome diversity in the ASD group relative to controls. Microbes, pathways, and gene families significantly differed between the two populations. The ASD microbiome had higher abundances of pathogens, such asShigella, Klebsiella, Mycobacterium, andClostridium, but lower abundances of beneficial microbes, includingFaecalibacterium. With a 3-month synbiotic supplementation, the microbiome diversity of the 170 ASD participants completing the study increased and became closer to the neurotypical controls. Significant shifts in microbial and pathway abundances were also measured at the second ASD timepoint. In addition to changes in the gut microbiome, there was a significant reduction in gastrointestinal discomfort. There were also improvements in some ASD-related symptoms; however, we cannot exclude that these were potentially due to the open-label nature of the study. Changes in the gut microbiome composition and functional capacity, along with a reduction in gastrointestinal symptoms and potential changes in behavior, highlight the importance of metagenomics, longitudinal studies, and the potential for therapeutic microbial supplementation in ASD.

Resumen Presentamos un caso de macrovaso congenito retiniano estudiado mediante retinografia, campo visual, angiografia fluoresceinica y tomografia optica de coherencia macular. El macrovaso atravesaba el meridiano horizontal, nasalmente entre papila y macula. Ademas, se realiza una revision de los macrovasos congenitos retinianos, las alteraciones visuales y estructurales que causan su asociacion con otras enfermedades y su diagnostico diferencial.

Although several numerical techniques have been recently developed for the prediction of the geosynthetic-reinforced pavements performance, it is often unclear how to quantify such properties, specially when the soil is anisotropic and highly heterogeneous. In this work, following Hashin-Shtrikman bounds, explicit expressions describing anisotropic linear elastic moduli of geosynthetic-reinforced soils are presented. Modelling the geosynthetic material by oblate spheroids with spheroidal distribution inside the matrix of asphalt, the derived expressions provide bounds as a function of laminated material geometry and first principles in the elastic setting. The scheme developed can straightforwardly be extended to multiphase composites. We illustrate the implementation of the model by showing reasonable predictions on the transversely isotropic behaviour of the heterogeneous pavement.

This article presents the microneedles analysis where the design parameters studied were length, inner and outer diameter range. The ANSYS software was used to analyze the mechanical behavior of the microneedles. Following this, the range of inner and outer diameters were completed by mechanical simulations, getting from 30 μm to 134 μm, as the inner diameter range and 208 μm to 250 μm as the outer diameter range. With these ranges, a mathematical model was made using fourth-order polynomial regression, with a correlation of 0,9993. This mathematical model generalizes the relationship of the inner diameter to the outer diameter within the ranges, ensuring a safety factor of four, where Von Misses forces of the microneedle are around 17.931 MPa. In addition, the microneedle concept was made by 3D printing using a biocompatible resin of class 1. The features presented by the microneedle designed in this work make it a promising option to be implemented in a transdermal drug delivery device.

Parabolic equation methods are a robust and efficient tool for modeling long-range acoustic propagation in range-dependent waveguides. A lesser known, but equally effective, application of parabolic equations is to the scattering problem. In this paper, we study the applicability and accuracy of the multisector parabolic equation approach to scattering from impenetrable objects – first developed approximately two decades ago for convex objects and recently extended to more complex scatterers – in waveguides in two and three dimensions. We benchmark the method in two dimensions in a range-dependent waveguide consisting of two different fluid media and find very good agreement with finite element methods for both forward scattering and backscattering, including the case where the scatterer is located at the interface between the media. Finally, we provide an example of scattering in a large three-dimensional waveguide, which would be extremely computationally intensive using alternate approaches, but is practical using the parabolic equation method.

Isolated limb perfusion (ILP) is a method for treating unresectable lesions of limbs in patients with melanoma or sarcoma by using high doses of tumor necrosis factor alpha and melphalan. This high doses can result in high systemic toxicity if there is a drug leak from the isolated circulation of the limb to the systemic. This makes it imperative to monitor the leakage rate (F(%)) during the infusion, currently performed with radiotracers. The objective of this work was to develop a leakage monitoring protocol as accurate as possible to ensure safe ILP. Material and method We built a phantom with three compartments (body, limb and precordial area) and a high sensitivity collimator fitted to a portable gamma camera. We simulate ILP with scheduled leaks every 10 min from 1% to 9% (theorical F(%)). We mesured F(%) using two equation: one is the proposed in the literature and another corrected by decay of the radioisotope. We test the optimal radiopharmaceutical doses to minimize the detector dead time error and compare F(%) mesured by both equations regarding the theoretical F(%). The leakage monitoring protocol was used in 17 ILP of 16 patients and an analysis of the recorded data was performed. Results We found significant differences between F(%) mesured using the first equation and theoretical F(%), obtaining results very adjusted to the theorical after applying the decay correction. Conclusions the decay correction of the radioisotope is a simple manner to carry out the procedure more safely, reducing the error in the calculation of F(%).

Resumen La perfusion de miembro aislado (PMA) es un metodo para el tratamiento de extremidades con lesiones irresecables de pacientes con melanoma o sarcoma. Se usan altas dosis de factor de necrosis tumoral α y melfalan, que pueden provocar toxicidad sistemica severa en caso de fuga del farmaco desde la circulacion aislada de la extremidad a la sistemica. Esto hace imperativo monitorizar el porcentaje de fuga (F[%]) durante la perfusion, actualmente realizado con radiotrazadores. El objetivo de este trabajo fue elaborar un protocolo de monitorizacion de fuga lo mas exacto posible que garantizara una PMA segura. Material y metodo Construimos un fantoma con 3 compartimentos (cuerpo, extremidad y area precordial) y un colimador de alta sensibilidad adaptable a una gammacamara portatil. Simulamos PMA con fugas programadas cada 10 min del 1 al 9% (F[%] teoricos). Medimos estos F(%) mediante 2 ecuaciones: una propuesta en la literatura y otra corregida por decaimiento del radioisotopo. Testamos las dosis de radiofarmaco optimas para minimizar el error por tiempo muerto del detector y comparamos los F(%) medidos segun las 2 ecuaciones con los F(%) teoricos. El protocolo de monitorizacion de fuga se utilizo en 17 PMA de 16 pacientes y se analizaron los datos registrados. Resultados Encontramos diferencias significativas entre los F(%) medidos con la primera ecuacion y los F(%) teoricos, con unos resultados muy ajustados a los teoricos al aplicar la correccion por decaimiento. Conclusiones La correccion por decaimiento del radioisotopo es una manera simple de realizar el procedimiento de forma mas segura y de disminuir el error en el calculo de F(%).

The parabolic equation method provides an unrivaled combination of computational efficiency and accuracy for wave propagation problems in the geosciences in which the environment has strong vertical variations and gradual horizontal variations. The development of this approach has been an active area of research for several decades in ocean acoustics, which includes problems involving sediment layers and ice cover that support shear waves. It is demonstrated here that this progress has culminated in a parabolic equation model for fast and accurate seismic computations in laterally varying environments. The model is tested for problems involving sloping boundaries and interfaces, variable layer thickness, continuous variations of the elastic parameters within layers, and a Rayleigh wave propagating along variable topography. The seismic parabolic equation model is based on an outgoing wave equation and rational approximations of operators for generating initial conditions, propagating the solution through stratified regions that approximate a laterally varying environment, and estimating transmitted fields across the vertical interfaces between regions.

Amyotrophic lateral sclerosis (ALS) is an adult onset disorder characterized by progressive neuromuscular junction (NMJ) dismantling and degeneration of motor neurons leading to atrophy and paralysis of voluntary muscles responsible for motion and breathing. Except for a minority of patients harbouring genetic mutations, the origin of most ALS cases remains elusive. Peripheral tissues, and particularly skeletal muscle, have lately demonstrated an active contribution to disease pathology attracting a growing interest for these tissues as therapeutic targets in ALS. In this sense, molecular mechanisms essential for cell and tissue homeostasis have been shown to be deregulated in the disease. These include muscle metabolism and mitochondrial activity, RNA processing, tissue-resident stem cell function responsible for muscle regeneration, and proteostasis that regulates muscle mass in adulthood. This review aims to compile scientific evidence that demonstrates the role of skeletal muscle in ALS pathology and serves as reference for development of novel therapeutic strategies targeting this tissue to delay disease onset and progression. LINKED ARTICLES: This article is part of a themed issue on Neurochemistry in Japan. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.6/issuetoc.

ObjectiveThis study aimed to assess individual preference, symptoms and compliance between habitual use of Provox XtraFlow and the combination of Provox XtraFlow during the day and Provox Luna during the night for heat and moisture exchanger therapy in laryngectomised patients.MethodThis was an open, randomised, crossover trial for 25 days. After this first study period and a 5-day wash-out period, treatments were switched for another 25 days.ResultsA total of 28 patients were enrolled. Differences were found (p = 0.009) in the incidence of dermatological problems with XtraFlow (46.4 per cent) versus Provox Luna (14.3 per cent), as well as in the need to abandon the use of adhesives (46.4 per cent vs 10.7 per cent; p = 0.003). A total of 60.7 per cent of the patients preferred the Provox Luna system as their preference for heat and moisture exchanger therapy.ConclusionThe Provox Luna system is a viable additive to heat and moisture exchanger therapy, especially in the setting of compliance concerns and in patients who desire dermatological relief overnight.

Contains fulltext : 249977.pdf (Publisher’s version ) (Closed access) BACKGROUND: It is important to evaluate whether a new treatment for heart failure with reduced ejection fraction (HFrEF) provides additive benefit to background foundational treatments. As such, we aimed to evaluate the efficacy and safety of empagliflozin in patients with HFrEF in addition to baseline treatment with specific doses and combinations of disease-modifying therapies. METHODS: We performed a post-hoc analysis of the EMPEROR-Reduced randomised, double-blind, parallel-group trial, which took place in 520 centres (hospitals and medical clinics) in 20 countries in Asia, Australia, Europe, North America, and South America. Patients with New York Heart Association (NYHA) classification II-IV with an ejection fraction of 40% or less were randomly assigned (1:1) to receive the addition of either oral empagliflozin 10 mg per day or placebo to background therapy. The primary composite outcome was cardiovascular death and heart failure hospitalisation; the secondary outcome was total heart failure hospital admissions. An extended composite outcome consisted of inpatient and outpatient HFrEF events was also evaluated. Outcomes were analysed according to background use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs) or angiotensin receptor neprilysin inhibitors (ARNIs), as well as β blockers and mineralocorticoid receptor antagonists (MRAs) at less than 50% or 50% or more of target doses and in various combinations. This study is registered with ClinicalTrials.gov, NCT03057977. FINDINGS: In this post-hoc analysis of 3730 patients (mean age 66·8 years [SD 11·0], 893 [23·9%] women; 1863 [49·9%] in the empagliflozin group, 1867 [50·1%] in the placebo group) assessed between March 6, 2017, and May 28, 2020, empagliflozin reduced the risk of the primary outcome (361 in 1863 participants in the empagliflozin group and 462 of 1867 in the placebo group; HR 0·75 [95% CI 0·65-0·86]) regardless of background therapy or its target doses for ACE inhibitors or ARBs at doses of less than 50% of the target dose (HR 0·85 [0·69-1·06]) and for doses of 50% or more of the target dose (HR 0·67 [0·52-0·88]; p(interaction)=0·18). A similar result was seen for β blockers at doses of less than 50% of the target dose (HR 0·66 [0·54-0·80]) and for doses of 50% or more of the target dose (HR 0·81 [0·66-1·00]; p(interaction)=0·15). Empagliflozin also reduced the risk of the primary outcome irrespective of background use of triple therapy with an ACE inhibitor, ARB, or ARNI plus β blocker plus MRA (given combination HR 0·73 [0·61-0·88]; not given combination HR 0·76 [0·62-0·94]; p(interaction)=0·77). Similar patterns of benefit were observed for the secondary and extended composite outcomes. Empagliflozin was well tolerated and rates of hypotension, symptomatic hypotension, and hyperkalaemia were similar across all subgroups. INTERPRETATION: Empagliflozin reduced serious heart failure outcomes across doses and combinations of disease-modifying therapies for HFrEF. Clinically, these data suggest that empagliflozin might be considered as a foundational therapy in patients with HFrEF regardless of their existing background therapy. FUNDING: Boehringer Ingelheim and Eli Lilly and Company.

Producción Científica, ERA5 represents the state of the art for atmospheric reanalyses and is widely used in meteorological and climatological research. In this work, this dataset is evaluated using the wind kinetic energy spectrum. Seasonal climatologies are generated for 30° latitudinal bands in the Northern Hemisphere (periodic domain) and over the North Atlantic area (limited-area domain). The spectra are also assessed to determine the effective resolution of the reanalysis. The results present notable differences between the latitudinal domains, indicating that ERA5 is properly capturing the synoptic conditions. The seasonal variability is adequate too, being winter the most energetic, and summer the least energetic season. The limited area domain results introduce a larger energy density and range. Despite the good results for the synoptic scales, the reanalysis’ spectra are not able to properly reproduce the dissipation rates at mesoscale. This is a source of uncertainties which needs to be taken into account when using the dataset. Finally, a cyclone tropical transition is presented as a case study. The spectrum generated shows a clear difference in energy density at every wavelength, as expected for a highly-energetic status of the atmosphere., Ministerio de Asuntos Económicos y Transformación Digital y Universidad Complutense de Madrid (projects: (PID2019-105306RB-I00 (IBER - CANES), CGL2016-78702 (SAFEFLIGHT), PCIN-2016-080 and FEI-EU-17-16), Publicación en abierto financiada por el Consorcio de Bibliotecas Universitarias de Castilla y León (BUCLE), con cargo al Programa Operativo 2014ES16RFOP009 FEDER 2014-2020 DE CASTILLA Y LEÓN, Actuación:20007-CL - Apoyo Consorcio BUCLE

A critical problem derived from airport operations is the environmental impact of runoff water. Airport runoff includes a complex mixture of pollutants, e.g., from deicing agents, that may affect negatively natural water bodies. This study assesses the spatial and temporal aquatic ecotoxicity of runoff water and possible aeroplane drift in a German airport. Over winter 2012–2013, from November to May, water samples were collected within the airport and surrounding area. These samples were analyzed using traditional physicochemical analysis and biotests with two aquatic organisms from different trophic levels, Lemna gibba and Aliivibrio fischeri. Overall, the samples examined in this study were relatively non-toxic to the tested organisms. The physicochemical parameters were mainly influenced by the sampling period being higher in colder months. In contrast, the ecotoxicity was influenced by the sampling site. For sites within the airport, a high correlation between the physicochemical parameters (EC and TOC) and toxicity in L. gibba was found. These correlations were not evident in samples taken outside the airport or when A. fischeri was used as a bioindicator. However, a pronounced seasonality has been observed, linked to the coldest months with average inhibition values of 50% in L. gibba and 25% in A. fischeri, particularly in January. Both biotests yielded differing results; therefore, more biotests should be included. However, L. gibba showed a good response with this type of water samples to be included in future studies together with detailed chemical analysis. The present study provides data to assess the potential ecotoxicological effects of airport runoff affected by winter operations.

The deregulation of the inflammatory cytokine interleukin (IL)-6 has been associated to a variety of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). The aim of this work was to analyze the variation of IL-6 levels in blood and damaged tissues during the course of the disease. We studied IL-6 protein expression in spinal cord, extensor digital longus (EDL) muscle and soleus (SOL) muscle of the SOD1G93A animal model at four stages of the disease by western blot. Concurrently, we analyzed IL-6 gene and protein expression in blood of ALS patients, healthy subjects and patients with other neuropathies through RTqPCR and ELISA. The results revealed different expression patterns depending on both the tissue analyzed and the stage of the disease, showing increasing IL-6 levels in EDL muscle over time. Moreover, lower IL-6 levels in blood were found in ALS patients. The decreased levels of IL-6 in blood from ALS patients could suggest that IL-6 might not be the main pro-inflammatory biomarker in the last stages in whole blood. In contrast, IL-6 may play a main role in fast glycolytic muscle fibers associated with muscle atrophy, suggesting that modulation of IL-6 in this tissue could be a potential target for anti-inflammatory therapies in ALS.

Given that environmental factors like atmospheric CO2, temperature, and water availability will likely change simultaneously, it is difficult to make accurate predictions about future crop production. Effects of elevated CO2 or drought on aboveground plant growth are relatively well studied, while effects on the rhizosphere are rarely dealt with. The present work investigates the root exudation pattern of different osmotic protectants such as ions and sugars of two cultivars of barley grown under different water and CO2 levels. Barley (Hordeum vulgare L.) plants were grown in plant containers in climate chambers with an optimal and reduced water supply and two CO2 concentrations (380 and 550 ppm) and harvested at the stem elongation growth stage and when the inflorescences emerged. The responses of root exudation to CO2 enrichment, watering level, and cultivar and their interactions varied with the developmental stage. While K+/Na+ ratio in root exudates remained stable at the stem elongation stage (DC30), it was higher at the booting stage (DC49) in the cv. “Bambina” than in cv. “Golden Promise”. At DC30, in general the exudation of sugars, dissolved organic carbon (DOC) and their ratio (SUG/DOC) were lower at e[CO2] compared to ambient CO2 at normal watering conditions. Under reduced watering conditions, plants exuded on average 55% more sucrose than under well-watered conditions. The modern cv. BA exuded on average 53% more fructose than the older cv.GP. In contrast, at DC49, sucrose, DOC and SUG/DOC exudation were not affected by any factor. At e[CO2] plants exuded on average 39% less fructose than under ambient CO2. A water and CO2 interaction on glucose exudation was found at this stage. Under reduced water conditions, plants growing at ambient CO2 exuded less glucose but at e[CO2] exuded similar (GP) or even higher (BA) glucose levels than under normal water supply. Although drought and cultivar factors affected the root exudation of barley, the strongest effects in the exudation pattern were caused by CO2. This study presents a non-destructive percolation method for the collection of root exudates which can be used to give an insight into the complex interaction between global warming-associated environmental factors that cause yield losses and changes in crop quality and components of the belowground plant metabolism.

Resumen: Introducción: La información existente sobre el impacto de la gripe en la población infantil española es escasa. El presente trabajo pretende aumentar este conocimiento estudiando aspectos clave como la incidencia de hospitalización, clínica, comorbilidades y el estado vacunal en los niños hospitalizados. Métodos: Estudio retrospectivo, observacional, por revisión de historias clínicas, en menores de 15 años hospitalizados por gripe adquirida en la comunidad, confirmada microbiológicamente, durante 2 temporadas gripales (2014-2015 y 2015-2016). El estudio se realizó en 10 hospitales de 6 ciudades, que atienden aproximadamente al 12% de la población infantil española. Resultados: Fueron hospitalizados 907 niños con diagnóstico principal de gripe (447 50%) de los casos. Una gran parte de las formas graves de gripe en población infantil podrían ser evitada si se cumplieran las indicaciones actuales de vacunación. Abstract: Introduction: There are only a limited number of studies on the impact of influenza in the Spanish child population. The present work intends to increase this knowledge by studying some key aspects, such as the incidence of hospital admissions, clinic variables, comorbidities, and the vaccination status in the hospitalised children. Methods: A retrospective, observational study was conducted by reviewing the medical records of children under 15 years and hospitalised due to community acquired influenza confirmed microbiologically, during 2 ́flu seasons (2014-2015 and 2015-2016). The study was carried out in 10 hospitals of 6 cities, which represent approximately 12% of the Spanish child population. Results: A total of 907 children were admitted to hospital with main diagnosis of influenza infection (447 10 years. Admission to the PICU was required in 10% (92) of the cases, mainly due to acute respiratory failure. Conclusion: Influenza continues to be an important cause of hospitalisation in the Spanish child population. Children 50%) of the cases. Many of the severe forms of childhood influenza that occur today could be avoided if current vaccination guidelines were met.

Introduction: There are only a limited number of studies on the impact of influenza in the Spanish child population. The present work intends to increase this knowledge by studying some key aspects, such as the incidence of hospital admissions, clinic variables, comorbidities, and the vaccination status in the hospitalised children. Methods: A retrospective, observational study was conducted by reviewing the medical records of children under 15 years and hospitalised due to community acquired influenza confirmed microbiologically, during 2 ́flu seasons (2014–2015 and 2015–2016). The study was carried out in 10 hospitals of 6 cities, which represent approximately 12% of the Spanish child population. Results: A total of 907 children were admitted to hospital with main diagnosis of influenza infection (447 10 years. Admission to the PICU was required in 10% (92) of the cases, mainly due to acute respiratory failure. Conclusion: Influenza continues to be an important cause of hospitalization in the Spanish child population. Children 50%) of the cases. Many of the severe forms of childhood influenza that occur today could be avoided if current vaccination guidelines were met. Resumen: Introducción: La información existente sobre el impacto de la gripe en la población infantil española es escasa. El presente trabajo pretende aumentar este conocimiento estudiando aspectos clave como la incidencia de hospitalización, clínica, comorbilidades y el estado vacunal en los niños hospitalizados. Métodos: Estudio retrospectivo, observacional, por revisión de historias clínicas, en menores de 15 años hospitalizados por gripe adquirida en la comunidad, confirmada microbiológicamente, durante 2 temporadas gripales (2014-2015 y 2015-2016). El estudio se realizó en 10 hospitales de 6 ciudades, que atienden aproximadamente al 12% de la población infantil española. Resultados: Fueron hospitalizados 907 niños con diagnóstico principal de gripe (447 50%) de los casos. Una gran parte de las formas graves de gripe en población infantil podrían ser evitada si se cumplieran las indicaciones actuales de vacunación.

Linkage between clinical databases and population-based cancer registries may serve to evaluate European Reference Networks' (ERNs) activity, by monitoring the proportion of patients benefiting from these and their impact on survival at a population level. To test this, a study targeting neuroblastoma (Nb) was conducted in Spain by the European Joint Action on Rare Cancers.Subjects: Nb cases, incident 1999-2017, aged 15 years. Linkage included: Spanish Neuroblastoma Clinical Database (NbCDB) (1217 cases); Spanish Registry of Childhood Tumours (RETI) (1514 cases); and 10 regional population-based registries (RPBCRs) which cover 33% of the childhood population (332 cases). Linkage was semiautomatic. We estimated completeness, incidence, contribution, deficit, and 5-year survival in the databases and specific subsets.National completeness estimates for RETI and NbCDB were 91% and 72% respectively, using the Spanish RPBCRs on International Incidence of Childhood Cancer (https://iicc.iarc.fr/) as reference. RPBCRs' specific contribution was 1.6%. Linkage required manual crossover in 54% of the semiautomatic matches. Five-year survival was 74% (0-14 years) and 90% (0-18 months).All three databases were incomplete as regards Spain as a whole and should therefore be combined to achieve full childhood cancer registration. A unique personal patient identifier could facilitate such linkage. Most children have access to Nb clinical trials. Consolidated interconnections between the national registry and clinical registries (including ERNs and paediatric oncology clinical groups) should be established to evaluate outcomes.

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Since NLRP3 inflammasome plays a pivotal role in several neurodegenerative disorders, we hypothesized that levels of inflammasome components could help in diagnosis or prognosis of amyotrophic lateral sclerosis (ALS). Gene and protein expression was assayed by RT-PCR and Western blot. Spearman’s correlation coefficient was used to determine the linear correlation of transcriptional expression levels with longevity throughout disease progression in mice models. Kaplan-Meier analysis was performed to evaluate MCC950 effects (NLRP3 inhibitor) on lifespan of SOD1G93A mice. The results showed significant alterations in NLRP3 inflammasome gene and protein levels in the skeletal muscle of SOD1G93A mice. Spearman’s correlation coefficient revealed a positive association between Nlrp3 transcriptional levels in skeletal muscle and longevity of SOD1G93A mice (r = 0.506, p = 0.027). Accordingly, NLRP3 inactivation with MCC950 decreased the lifespan of mice. Furthermore, NLRP3 mRNA levels were significantly elevated in the blood of ALS patients compared to healthy controls (p = 0.03). In conclusion, NLRP3 could be involved in skeletal muscle pathogenesis of ALS, either through inflammasome or independently, and may play a dual role during disease progression. NLRP3 gene expression levels could be used as a biomarker to improve diagnosis and prognosis in skeletal muscle from animal models and also to support diagnosis in clinical practice with the blood of ALS patients.

Protein aggregation is classically considered the main cause of neuronal death in neurodegenerative diseases (NDDs). However, increasing evidence suggests that alteration of RNA metabolism is a key factor in the etiopathogenesis of these complex disorders. Non-coding RNAs are the major contributor to the human transcriptome and are particularly abundant in the central nervous system, where they have been proposed to be involved in the onset and development of NDDs. Interestingly, some ncRNAs (such as lncRNAs, circRNAs and pseudogenes) share a common functionality in their ability to regulate gene expression by modulating miRNAs in a phenomenon known as the competing endogenous RNA mechanism. Moreover, ncRNAs are found in body fluids where their presence and concentration could serve as potential non-invasive biomarkers of NDDs. In this review, we summarize the ceRNA networks described in Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis and spinocerebellar ataxia type 7, and discuss their potential as biomarkers of these NDDs. Although numerous studies have been carried out, further research is needed to validate these complex interactions between RNAs and the alterations in RNA editing that could provide specific ceRNET profiles for neurodegenerative disorders, paving the way to a better understanding of these diseases.

Resumen La pandemia por SARS-CoV-2 ha generado nuevos escenarios que requieren modificaciones de los protocolos habituales de reanimación cardiopulmonar. Las guías clínicas vigentes sobre el manejo de la parada cardiorrespiratoria no incluyen recomendaciones para situaciones aplicables a este contexto. Por ello, el Plan Nacional de Reanimación Cardiopulmonar de la Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias, en colaboración con el Grupo Español de RCP Pediátrica y Neonatal y con el programa de Enseñanza de Soporte Vital en Atención Primaria de la Sociedad Española de Medicina Familiar y Comunitaria, ha redactado las siguientes recomendaciones, que están divididas en cinco partes que tratan los principales aspectos para cada entorno asistencial. En este artículo se presenta un resumen ejecutivo de las mismas.

To evaluate the perception of barriers in healthcare and the impact of intravitreal injections in patients with neovascular age-related macular degeneration (nAMD).Cross-sectional study including 108 patients with nAMD in treatment with intravitreal injections. The patients answered a questionnaire with 26 questions (score from 1 to 5) divided in three sections: 1) the disease and its treatment with injections, 2) healthcare barriers and 3) new technologies.The mean age was 80.4 ± 7.0 years and visual acuity (VA) was 75.2 ± 12.4 letters. The main barriers in healthcare were long waiting times (72%), followed by other comorbidities (10%). Some 63% of patients have to wait between 3 and 5 h to attend their clinical visit. Significant anxiety due to the injections (2.8 ± 1.3) was observed, being present in 71% of the cases the day before. A great fear of blindness and losing independence was observed (4.4 ± 0.9 and 4.3 ± 1.1), with no differences in relation to VA, age or sex (p ≥ 0.135). Moreover, 28% of the patients reported that it was quite or very difficult for them to attend the clinical visit, with 69% of the total showing great interest in having a diagnostic device at home.The nAMD and its treatment represent a significant burden on patients, among whom there is a great fear of blindness and of losing their independence, the main barrier being the long waiting time for the clinical visit.

Highlights • Children with COVID 19 disease are less symptomatic but they can be potential agents of transmission. • Most children with symptoms from COVID 19 disease (cough, fever, respiratory difficulties) show bnormalities in CXR. • Findings in CXR are non-specific and superimpose on other viral pneumonias. • Peripheral distribution of lung abnormalities is not a distinctive feature in paediatric population. • CXR have a role in the management of the disease in children., BACKGROUND The outbreak of COVID-19 has become pandemic. Pediatric population has been less studied than adult population and prompt diagnosis is challenging due to asymptomatic or mild episodes. Radiology is an important complement to clinical and epidemiological features. OBJECTIVE To establish the most common CXR patterns in children with COVID-19, evaluate interobserver correlation and to discuss the role of imaging techniques in the management of children. MATERIALS AND METHODS Forty-four patients between 0 and 16 years of age with confirmed SARS-Cov-2 infection and CXR were selected. Two paediatric radiologists independently evaluated the images and assessed the type of abnormality, distribution and evolution when available. RESULTS Median age was 79.8 months (ranging from 2 weeks to 16 years of age). Fever was the most common symptom (43.5 %). 90 % of CXR showed abnormalities. Peribronchial cuffing was the most common finding (86.3 %) followed by GGOs (50 %). In both cases central distribution was more common than peripheral. Consolidations accounted for 18.1 %. Normal CXR, pleural effusion, and altered cardiomediastinal contour were the least common. CONCLUSION The vast majority of CXR showed abnormalities in children with COVID-19. However, findings are nonspecific. Interobserver correlation was good in describing consolidations, normal x-rays and GGOs. Imaging techniques have a role in the management of children with known or suspected COVID-19, especially in those with moderate or severe symptoms or with underlying risk factors.

This work aims to propose a Ussing chamber system based on electrical impedance spectroscopy (EIS) for measuring impedance in epithelial tissues. The proposed method is composed of two functional parts: Ussing chambers (UC) where the tissue under test is located, and the other is a homemade electrical impedance spectroscopy system. The impedance spectroscopy system architecture uses a sine wave generated by a direct digital synthesizer (DDS) with a frequency range from 1 Hz to 102 kHz, a current source in Howland configuration, and an instrumentation stage that allows applying the four electrodes configuration. The designed system was tested with Eleutherodactylus johnstonei adult frog Epithelial tissue, as well as Cole-Cole models, Real and imaginary, and measured impedances were used to find the transfer function parameters employing a genetic algorithm.

We present an uncommon case of a unilateral congenital retinal macrovessel documented with retinography, perimetry, fluorescein angiography and macular optical coherence tomography. In the case presented the macrovessel crossed the horizontal meridian, between macula and optic disk. A literature review has been performed on congenital retinal macrovessels, possible structural and visual alterations they may cause and their association with other pathologies.

After publication of the original article, the authors noticed an error concerning the ingredients of the used product Vizura®. The product does not contain a triazole, but a pyrazole as part of DMPP (3,4-dimethylpyrazolephosphate).