Clinical outcome of SARS-CoV-2 infection in 7 adults with Duchenne muscular dystrophy attending a specialist neuromuscular centre

Due to their frailty and cardiorespiratory compromise adults with DMD are considered extremely vulnerable and at high risk of severe infection should they contract COVID-19. We report 7 adults with DMD aged 17–26 years who tested positive on a nasopharyngeal PCR swab for SARS-CoV-2. Despite long term corticosteroid treatment, severe respiratory compromise requiring night-time ventilation and receiving treatment for moderate to severe cardiomyopathy, none of the patients developed moderate to severe symptoms; in fact two remained asymptomatic and two developed only anosmia and reduced sensation. The remaining three developed transient fever with or without sore throat, cough and runny nose. All recovered fully without complication and no patient required hospitalization

Five new real-time detections of Fast Radio Bursts with UTMOST

We detail a new fast radio burst (FRB) survey with the Molonglo Radio Telescope, in which six FRBs were detected between June 2017 and December 2018. By using a real-time FRB detection system, we captured raw voltages for five of the six events, which allowed for coherent dedispersion and very high time resolution (10.24 $\mu$s) studies of the bursts. Five of the FRBs show temporal broadening consistent with interstellar and/or intergalactic scattering, with scattering timescales ranging from 0.16 to 29.1 ms. One burst, FRB181017, shows remarkable temporal structure, with 3 peaks each separated by 1 ms. We searched for phase-coherence between the leading and trailing peaks and found none, ruling out lensing scenarios. Based on this survey, we calculate an all-sky rate at 843 MHz of $98^{+59}_{-39}$ events sky$^{-1}$ day$^{-1}$ to a fluence limit of 8 Jy-ms: a factor of 7 below the rates estimated from the Parkes and ASKAP telescopes at 1.4 GHz assuming the ASKAP-derived spectral index $\alpha=-1.6$ ($F_{\nu}\propto\nu^{\alpha}$). Our results suggest that FRB spectra may turn over below 1 GHz. Optical, radio and X-ray followup has been made for most of the reported bursts, with no associated transients found. No repeat bursts were found in the survey.Comment: 13 pages, 11 figures, submitted to MNRA

Acute kidney injury and extrarenal organ dysfunction - A randomized experimental study

Indexación: Web of Science; ScieloIntroducción: La insuficiencia renal aguda (IRA) es una enfermedad grave y causante de disfunciones de órganos distantes que incrementan su mortalidad. Objetivo: Identificar disfunción hemodinámica y respiratoria gatillada por IRA en un modelo pediátrico animal de isquemia-reperfusión renal. Método: Doce cerdos anestesiados (11,9 ± 1,0 kg). En seis animales se indujo lesión renal bilateral por isquemia-reperfusión: 45 min de isquemia y 240 min de reperfusión, mientras que los seis animales restantes fueron grupo control. En condiciones basales y posterior a lesión renal se realizó monitorización hemodinámica convencional y termodilución transpulmonar. Paralelamente se midió gasometría arterial y análisis de mecánica pulmonar. Resultados: Hubo un incremento de la precarga volumétrica en 29% (221 ± 22 ml/m2 vs 286 ± 16 ml/m2, p = 0,04) y de la presión arterial media en 58% (71 ± 6 mmHg vs 112 ± 17 mmHg, p = 0,04) respecto a controles, sin cambios en frecuencia cardíaca, presión venosa central ni gasto cardíaco. Además ocurrió un aumento del agua extravascular pulmonar en 86% (7,6 ± 0,6 ml/kg vs 14,1 ± 1,4 ml/kg, p = 0,02), sin cambios en intercambio gaseoso ni mecánica pulmonar. Simultáneamente hubo un leve deterioro de la creatinina sérica (1,12 ± 0,07 mg/dL vs 1,45 ± 0,10 mg/dL, p = 0,03). Discusión: En este modelo experimental se pudo apreciar el desarrollo temprano de disfunción hemodinámica y pulmonar. Se evidenció un aumento de la precarga volumétrica y de la presión arterial, asociado a un incremento substancial del agua extravascular pulmonar. Creemos que es fundamental monitorizar de forma seriada la función hemodinámica y respiratoria en sujetos con una lesión renal aguda, aún sin una IRA urémica.Acute kidney injury (AKI) is a serious disease that can cause distant organ injuries and is associated with high mortality rates. Objective: To identify the hemodynamic and respiratory dysfunction triggered by AKI, in an animal model of renal ischemia-reperfusion. Method: Twelve anesthetized juvenile pigs (11.9 ± 1.0 kg). Six animals underwent ischemia/reperfusion-induced AKI: 45 min of ischemia and 240 minutes of reperfusion, while the remaining six animals were the control group. In basal conditions and after AKI, a conventional hemodynamic monitoring and transpulmonary thermodilution were performed. At the same time, arterial blood gases and lung mechanics were measured. Results: There was a 29% increase in volumetric preload (221 ± 22 ml/m2 vs 286 ± 16 ml/m2, p = 0.04) and a 58% mean arterial pressure increase (71 ± 6 mmHg vs 112 ± 17 mmHg, p = 0.04) compared to controls, without changes in heart rate, central venous pressure and cardiac output. In addition, an increase of 86% in extravascular lung water (7.6 ± 0.6 ml/kg vs 14.1 ± 1.4 ml/ kg, p = 0.02) was reported, without changes in gas exchange and lung mechanics. Simultaneously, a slight increase in serum creatinine (1.12 ± 0.07 mg/dl vs 1.45 ± 0.10 mg/dl, p = 0.03) was described. Discussion: An early development of hemodynamic and pulmonary dysfunction was observed in this experimental reperfusion model. An increase in volumetric preload and blood pressure associated with a substantial increase in the extravascular lung water were also reported. It is essential serially monitor the hemodynamic and respiratory functions in AKI, including nonuremic subjects.http://www.scielo.cl/pdf/rcp/v84n3/art04.pd

Anthropogenic influence in the Sado estuary (Portugal): a geochemical approach

Two areas of salt marsh in the Sado estuary – Faralhão, on the industrialized north margin and Malha da Costa, on the south bank, sheltered by a uninhabited sand spit – have been cored to study the geochemical signature of anthropogenic activity in recent (19th century onwards) intertidal sediments. Short cores were taken from each site from both the high and low marsh and were studied for texture, organic matter, pH, carbonates and geochemistry, including the heavy metals Cu, Pb and Zn. The marsh sediments are free of carbonate bioclasts and quite uniform in texture, consisting of acid to neutral clayey silt in addition to organic matter, which is higher in the top 20 cm. The vertical concentration profiles of heavy metals indicates enrichment in the top 30 cm of the sediment of the high marsh, in contrast with underlying high and low marsh sediment that has concentrations of metals at both studied sites similar to the Average Shale international reference/ continental crust sediments. The geochemical signal of anthropogenic influence in the marsh sediment was determined to have commenced from 1900-1920 using the sedimentation rates derived from 210Pb and 137Cs analyses. Spatial contrast in contamination levels was found within the estuary, with sediments of the Faralhão marsh showing higher enrichment factors of all metals. The anthropogenic increase of the supply of metal to the Sado estuary resulted from extensive exploitation of pyrite ore in the drainage basin until the1960’s; since that time, the sediments record a break in metal input, which resulted from a decline of the mining industry. However, in the marsh located closer to the industrial area (Faralhão) this break is followed by a local increase of heavy metal fluxes, which is interpreted as the result of intensification of anthropogenic influence. The comparison of metal concentrations in marsh sediments with target values established in quality guidelines indicates the studied area to be of environmental concern.Con el fin de estudiar el registro geoquímico de la actividad antrópica en sedimentos recientes (a partir del siglo XIX) e intermareales, han sido perforadas dos zonas de marisma en el Estuario del Sado- Faralhão, en el industrializado margen norte, y Malha da Costa, en la orilla sur, resguardada por una flecha litoral de arena no ocupada antrópicamente. Los pequeños sondeos realizados en cada punto de muestreo englobaron la marisma alta y baja. Fueron realizados análisis texturales, de contenido en materia orgánica, de pH, carbonatos y geoquímica, incluyendo los metales pesados Cu, Pb y Zn. Los sedimentos de marisma no muestran carbonato bioclástico y son bastante uniformes en la textura, consistiendo en limo arcilloso ácido a neutro junto con materia orgánica cuyo contenido es mayor en los 20 cm más superficiales. La concentración vertical de los perfiles de metales pesados indica un enriquecimiento en los 30 cm superficiales de la marisma alta, en contraste con los sedimentos subyacentes de marisma alta y baja que poseen concentraciones de metales similares a los referenciados internacionalmente para Average Shale / sedimentos de corteza continental. La señal geoquímica de la influencia antrópica en los sedimentos de marisma fue datada de 1900 a 1920 usando las tasas de sedimentación deducidas mediante 210Pb y 137Cs. Un contraste espacial en los niveles de contaminación fue encontrado en el interior del estuario: la marisma de Faralhão muestra valores con mayor enriquecimiento para todos los metales. El aporte antrópico de metales en el estuario de Sado resulta de la extensa explotación de pirita en la cuenca hasta 1960; a partir de ese momento los sedimentos registran una disminución en el aporte antropogénico de metales, consecuencia de la disminución del trabajo minero. Sin embargo, en la marisma cercana a la zona industrial (Faralhão) a esta interrupción le sigue un restablecimiento del flujo de metales pesados, interpretado como resultado del aumento de la influencia antrópica. La comparación de las concentraciones de metales en sedimentos de marisma con valores fijados establecidos en directrices de calidad sugiere una inquietud ambiental para el área de estudio

Cultura organizativa del técnico deportivo y su relación con la Satisfacción y Valor percibido de usuarios de actividades deportivas extraescolares

El elevado abandono deportivo extraescolar preocupa a las organizaciones deportivas. La satisfacción y valor percibido de los usuarios de actividades deportivas extraescolares influye en la continuidad de práctica. Existen relaciones significativas entre las dimensiones de calidad del servicio y cultura organizativa de la organización con la satisfacción y valor percibido del usuario, siendo el factor humano la principal dimensión predictora de calidad percibida. Objetivos del estudio: i) conocer la cultura organizativa que manifiestan los Técnicos deportivos, ii) averiguar la satisfacción, el valor percibido del usuario/a y la cultura organizativa en las diferentes organizaciones y iii) relacionar satisfacción y valor percibido de los usuarios con la cultura organizativa de los Técnicos del deporte extraescolar. Métodos: La población de estudio estuvo formada por 1.080 alumnos/as y 95 Técnicos de actividades deportivas extraescolares de 22 centros de Secundaria. Resultados: La valoración de la satisfacción por los deportistas fue de 4.33±0.78 y del valor percibido fue de 3.72±1.06. La cultura organizativa mostró unos valores medios de 3.63±0.41, siendo la variable Implicación la mejor valorada. Al relacionar cultura organizativa con satisfacción y valor percibido, dio como resultado modelos de regresión lineal conformados por dos variables: Misión con un valor Beta de (coeficientes).173 y de .262 e Implicación con valor Beta (coeficientes).140 y de .198. Conclusión: Una buena cultura organizativa conlleva un aumento de la fidelización, lo que la convierte en un factor más a tener en cuenta en la reducción del abandono deportivo extraescolar y la mejora del beneficio empresarial The high withdrawal rate in extracurricular sports represents a concern for sports organizations. Satisfaction and perceived value of users of extracurricular sports activities is a reason for continuity in them. There are significant relationships between the dimensions of service quality and organizational culture of the organization with satisfaction and perceived value of users, human factor being the main predictive dimension of perceived quality. Objectives of the study: i) to know the organizational culture expressed by sports technicians, ii) to find out satisfaction and perceived value of users, and the organizational culture in the different organizations and iii) to relate satisfaction and perceived value of users with organizational culture of extracurricular sports technicians. Methods: The study population was composed by 1, 080 students and 95 extracurricular sports activities technicians from 22 secondary schools. Results: Satisfaction assessment for athletes was 4.33 +/- 0.78 and perceived value was 3.72 +/- 1.06. The organizational culture showed average values of 3.63 +/- 0.41, the "Implication" variable being the best valued. By relating organizational culture with satisfaction and perceived value, it led to linear regression models consisting of two variables: Mission with a Beta coefficient values of .173 and .262, and Implication with Beta coefficient values of .140 and .198. Conclusion: A good organizational culture leads to increase in loyalty, which points this out as another factor to be taken into account for the reduction of extracurricular drop-out and the improvement of business profit

Metal-THINGS: The association and optical characterization of SNRs with HI holes in NGC 6946

NGC~6946, also known as the `Fireworks' galaxy, is an unusual galaxy that hosts a total of 225 supernova remnant (SNR) candidates, including 147 optically identified with high [SII]/Ha line ratios. In addition, this galaxy shows prominent HI holes, which were analyzed in previous studies. Indeed, the connection between SNRs and HI holes together with their physical implications in the surrounding gas is worth of attention. This paper explores the connection between the SNRs and the HI holes, including an analysis of their physical link to observational optical properties inside and around the rims of the holes, using new integral field unit (IFU) data from the Metal-THINGS survey. We present an analysis combining previously identified HI holes, SNRs candidates, and new integral field unit (IFU) data from Metal-THINGS of the spiral galaxy NGC 6946. We analyze the distributions of the oxygen abundance, star formation rate surface density, extinction, ionization, diffuse ionized gas, and the Baldwin-Phillips-Terlevich classification throughout the galaxy. By analyzing in detail the optical properties of the 121 previously identify HI holes in NGC 6946, we find that the SNRs are concentrated at the rims of the HI holes. Furthermore, our IFU data shows that the star formation rate and extinction are enhanced at the rims of the holes. To a lesser degree, the oxygen abundance and ionization parameter show hints of enhancement on the rims of the holes. Altogether, this provides evidence of induced star formation taking place at the rims of the holes, whose origin can be explained by the expansion of superbubbles created by multiple supernova explosions in large stellar clusters dozens of Myr ago.Comment: Accepted by A&

N-benzylpiperidine derivatives as α7 nicotinic receptor antagonists

This document is the accepted manuscript version of a Published Work that appeared in final form in ACS Chemical Neuroscience 7.8, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see DOI: 10.1021/acschemneuro.6b00122.A series of multitarget directed propargylamines, as well as other differently susbstituted piperidines have been screened as potential modulators of neuronal nicotinic acetylcholine receptors (nAChRs). Most of them showed antagonist actions on α7 nAChRs. Especially, compounds 13, 26, and 38 displayed submicromolar IC50 values on homomeric α7 nAChRs, whereas they were less effective on heteromeric α3β4 and α4β2 nAChRs (up to 20-fold higher IC50 values in the case of 13). Antagonism was concentration dependent and noncompetitive, suggesting that these compounds behave as negative allosteric modulators of nAChRs. Upon the study of a series of less complex derivatives, the N-benzylpiperidine motif, common to these compounds, was found to be the main pharmacophoric group. Thus, 2-(1-benzylpiperidin-4-yl)-ethylamine (48) showed an inhibitory potency comparable to the one of the previous compounds and also a clear preference for α7 nAChRs. In a neuroblastoma cell line, representative compounds 13 and 48 also inhibited, in a concentration-dependent manner, cytosolic Ca2+ signals mediated by nAChRs. Finally, compounds 38 and 13 inhibited 5-HT3A serotonin receptors whereas they had no effect on α1 glycine receptors. Given the multifactorial nature of many pathologies in which nAChRs are involved, these piperidine antagonists could have a therapeutic potential in cases where cholinergic activity has to be negatively modulated.This work was supported by grants SAF2011-22802 to S.S., SAF2012-33304 to J.M.-C., CSD2008-00005 (the Spanish Ion Channel Initiative-CONSOLIDER INGENIO 2010) to M.C. from the Spanish Ministry of Science and Innovation (Ministerio de Economía y Competitividad)

Biochemical and structural characterization of a novel thermophilic esterase EstD11 provide catalytic insights for the HSL family

19 pags., 12 figs., 2 tabs.A novel esterase, EstD11, has been discovered in a hot spring metagenomic library. It is a thermophilic and thermostable esterase with an optimum temperature of 60°C. A detailed substrate preference analysis of EstD11 was done using a library of chromogenic ester substrate that revealed the broad substrate specificity of EstD11 with significant measurable activity against 16 substrates with varied chain length, steric hindrance, aromaticity and flexibility of the linker between the carboxyl and the alcohol moiety of the ester. The tridimensional structures of EstD11 and the inactive mutant have been determined at atomic resolutions. Structural and bioinformatic analysis, confirm that EstD11 belongs to the family IV, the hormone-sensitive lipase (HSL) family, from the α/β-hydrolase superfamily. The canonical α/β-hydrolase domain is completed by a cap domain, composed by two subdomains that can unmask of the active site to allow the substrate to enter. Eight crystallographic complexes were solved with different substrates and reaction products that allowed identification of the hot-spots in the active site underlying the specificity of the protein. Crystallization and/or incubation of EstD11 at high temperature provided unique information on cap dynamics and a first glimpse of enzymatic activity in vivo. Very interestingly, we have discovered a unique Met zipper lining the active site and the cap domains that could be essential in pivotal aspects as thermo-stability and substrate promiscuity in EstD11.We thank the staff from ALBA synchrotron facility (Barcelona, Spain) for support during crystallographic data collection. This work was funded by the UE through the HotDrops Project (FP7- PEOPLE-2012-IAPP, project number 324439). Additionally, this work was supported by the BFU2017-90030-P grant to J.A.H. from the Spanish Ministry of Science and Innovatio

Applications of Direct Injection Soft Chemical Ionisation-Mass Spectrometry for the Detection of Pre-blast Smokeless Powder Organic Additives

Analysis of smokeless powders is of interest from forensics and security perspectives. This article reports the detection of smokeless powder organic additives (in their pre-detonation condition), namely the stabiliser diphenylamine and its derivatives 2-nitrodiphenylamine and 4-nitrodiphenylamine, and the additives (used both as stabilisers and plasticisers) methyl centralite and ethyl centralite, by means of swab sampling followed by thermal desorption and direct injection soft chemical ionisation-mass spectrometry. Investigations on the product ions resulting from the reactions of the reagent ions H3O+ and O2+ with additives as a function of reduced electric field are reported. The method was comprehensively evaluated in terms of linearity, sensitivity and precision. For H3O+, the limits of detection (LoD) are in the range of 41-88 pg of additive, for which the accuracy varied between 1.5 and 3.2%, precision varied between 3.7 and 7.3% and linearity showed R20.9991. For O2+, LoD are in the range of 72 to 1.4 ng, with an accuracy of between 2.8 and 4.9% and a precision between 4.5 and 8.6% and R20.9914. The validated methodology was applied to the analysis of commercial pre-blast gun powders from different manufacturers.(VLID)4826148Accepted versio