Gate-controlled suppression of light-driven proton transport through graphene electrodes.

Recent experiments demonstrated that proton transport through graphene electrodes can be accelerated by over an order of magnitude with low intensity illumination. Here we show that this photo-effect can be suppressed for a tuneable fraction of the infra-red spectrum by applying a voltage bias. Using photocurrent measurements and Raman spectroscopy, we show that such fraction can be selected by tuning the Fermi energy of electrons in graphene with a bias, a phenomenon controlled by Pauli blocking of photo-excited electrons. These findings demonstrate a dependence between graphene's electronic and proton transport properties and provide fundamental insights into molecularly thin electrode-electrolyte interfaces and their interaction with light.

Proton and molecular permeation through the basal plane of monolayer graphene oxide.

Two-dimensional (2D) materials offer a prospect of membranes that combine negligible gas permeability with high proton conductivity and could outperform the existing proton exchange membranes used in various applications including fuel cells. Graphene oxide (GO), a well-known 2D material, facilitates rapid proton transport along its basal plane but proton conductivity across it remains unknown. It is also often presumed that individual GO monolayers contain a large density of nanoscale pinholes that lead to considerable gas leakage across the GO basal plane. Here we show that relatively large, micrometer-scale areas of monolayer GO are impermeable to gases, including helium, while exhibiting proton conductivity through the basal plane which is nearly two orders of magnitude higher than that of graphene. These findings provide insights into the key properties of GO and demonstrate that chemical functionalization of 2D crystals can be utilized to enhance their proton transparency without compromising gas impermeability.

Forgotten giants: Robust climate signal in pollarded trees.

Tree ring records are among the most valuable resources to create high-resolution climate reconstructions. Most climate reconstructions are based on old trees growing in inaccessible mountainous areas with low human activity. Therefore, reconstruction of climate conditions in lowlands is usually based on data from distant mountains. Albeit old trees can be common in humanized areas, they are not used for climate reconstructions. Pollarding was a common traditional management in Europe that enabled trees to maintain great vitality for periods exceeding the longevity of unmanaged trees. We evaluate the potential of pollarded deciduous oaks to record past climate signal. We sampled four pollarded woodlands in Central Spain under continental Mediterranean climate. We hypothesized that pollarded trees have a strong response to water availability during current period without pollarding management, but also in the period under traditional management if pruning was asynchronous among trees. Moreover, we hypothesized that if climate is a regional driver of oak secondary growth, chronologies from different woodlands will be correlated. Pollard oaks age exceeded 500 years with a strong response to Standardized Precipitation-Evapotranspiration Index (SPEI) from 9 to 11 months. Climate signal was exceptionally high in three of the sites (r2 = 0.443-0.655) during low management period (1962-2022). The largest fraction of this climate signal (≈70 %) could be retrieved during the traditional management period (1902-1961) in the three sites where pollarding was asynchronous. Chronologies were significantly correlated since the 19th century for all the studied period, highlighting a shared climate forcing. We identified critical points to optimize pollard tree sampling schema. Our results show the enormous potential of pollarded woodlands to reconstruct hydroclimate conditions in the Mediterranean with a fine spatial grain. Studying pollarded trees is an urgent task, since the temporal window to retrieve the valuable information in pollarded trees is closing as these giants collapse and their wood rots.

Proton transport through nanoscale corrugations in two-dimensional crystals.

Defect-free graphene is impermeable to all atoms1-5 and ions6,7 under ambient conditions. Experiments that can resolve gas flows of a few atoms per hour through micrometre-sized membranes found that monocrystalline graphene is completely impermeable to helium, the smallest atom2,5. Such membranes were also shown to be impermeable to all ions, including the smallest one, lithium6,7. By contrast, graphene was reported to be highly permeable to protons, nuclei of hydrogen atoms8,9. There is no consensus, however, either on the mechanism behind the unexpectedly high proton permeability10-14 or even on whether it requires defects in graphene's crystal lattice6,8,15-17. Here, using high-resolution scanning electrochemical cell microscopy, we show that, although proton permeation through mechanically exfoliated monolayers of graphene and hexagonal boron nitride cannot be attributed to any structural defects, nanoscale non-flatness of two-dimensional membranes greatly facilitates proton transport. The spatial distribution of proton currents visualized by scanning electrochemical cell microscopy reveals marked inhomogeneities that are strongly correlated with nanoscale wrinkles and other features where strain is accumulated. Our results highlight nanoscale morphology as an important parameter enabling proton transport through two-dimensional crystals, mostly considered and modelled as flat, and indicate that strain and curvature can be used as additional degrees of freedom to control the proton permeability of two-dimensional materials.

Ferrozoles: Ferrocenyl derivatives of letrozole with dual effects as potent aromatase inhibitors and cytostatic agents.

In the treatment of hormone-dependent cancers, aromatase inhibitors (AI) are receiving increased attention due to some undesirable effects such as the risk of endometrial cancer and thromboembolism of SERMs (selective estrogen receptor modulators). Letrozole is the most active AI with 99% aromatase inhibition. Unfortunately, this compound also exhibits some adverse effects such as hot flashes and fibromyalgias. Therefore, there is an urgent need to explore new types of AIs that retain the same-or even increased-antitumor ability. Inspired by the letrozole structure, a set of new derivatives has been synthesized that include a ferrocenyl moiety and different heterocycles. The derivative that contains a benzimidazole ring, namely compound 6, exhibits a higher aromatase inhibitory activity than letrozole and it also shows potent cytostatic behavior when compared to other well-established aromatase inhibitors, as demonstrated by dose-response, cell cycle, apoptosis and time course experiments. Furthermore, 6 promotes the inhibition of cell growth in both an aromatase-dependent and -independent fashion, as indicated by the study of A549 and MCF7 cell lines. Molecular docking and molecular dynamics calculations on the interaction of 6 or letrozole with the aromatase binding site revealed that the ferrocene moiety increases the van der Waals and hydrophobic interactions, thus resulting in an increase in binding affinity. Furthermore, the iron atom of the ferrocene fragment can form a metal-acceptor interaction with a propionate fragment, and this results in a stronger coupling with the heme group-a possibility that is consistent with the strong aromatase inhibition of 6.

MAPK11 (p38ß) is a major determinant of cellular radiosensitivity by controlling ionizing radiation-associated senescence: An in vitro study.

Background and purpose: MAPKs are among the most relevant signalling pathways involved in coordinating cell responses to different stimuli. This group includes p38MAPKs, constituted by 4 different proteins with a high sequence homology: MAPK14 (p38α), MAPK11 (p38ß), MAPK12 (p38γ) and MAPK13 (p38δ). Despite their high similarity, each member shows unique expression patterns and even exclusive functions. Thus, analysing protein-specific functions of MAPK members is necessary to unequivocally uncover the roles of this signalling pathway. Here, we investigate the possible role of MAPK11 in the cell response to ionizing radiation (IR). Materials and methods: We developed MAPK11/14 knockdown through shRNA and CRISPR interference gene perturbation approaches and analysed the downstream effects on cell responses to ionizing radiation in A549, HCT-116 and MCF-7 cancer cell lines. Specifically, we assessed IR toxicity by clonogenic assays; DNA damage response activity by immunocytochemistry; apoptosis and cell cycle by flow cytometry (Annexin V and propidium iodide, respectively); DNA repair by comet assay; and senescence induction by both X-Gal staining and gene expression of senescence-associated genes by RT-qPCR. Results: Our findings demonstrate a critical role of MAPK11 in the cellular response to IR by controlling the associated senescent phenotype, and without observable effects on DNA damage response, apoptosis, cell cycle or DNA damage repair. Conclusion: Our results highlight MAPK11 as a novel mediator of the cellular response to ionizing radiation through the control exerted onto IR-associated senescence.

Timing and duration of nutrient restriction and its impacts on placental development and umbilical blood flow in adolescent sheep.

We hypothesized that nutrient restriction from day 50-90 of gestation decreases umbilical blood flow and that umbilical blood flow would recover to control values upon realimentation during late gestation (d 90 to 130) or remain reduced in ewes that continued to be nutrient restricted. On d 50 of gestation, young nulliparous whiteface ewes (6-8 mo; n = 41) carrying singletons were randomly assigned to two dietary treatments: 100% of NRC recommendations (CON) or 60% of CON (RES). On d 90 of gestation, ewes either remained on CON or RES until d 130, or CON ewes were RES from d 90 to 130, or RES ewes were realimented to CON from d 90 to 130. This resulted in 4 treatment groups on day 130: CON-CON, CON-RES, RES-RES, RES-CON. Umbilical blood flow and fetal and placental measurements were obtained via ultrasonography every 10 days from day 50-110. Non-survival surgeries were performed on days 50, 90, and 130 (n = 6-7 ewes/group) where uterine artery and umbilical blood flows were measured during surgery via ultrasonography. Conceptus weights were recorded and placentomes collected to determine binucleate cell numbers. The study was conducted as a completely randomized design arrangement with repeated measures. Data were analyzed using the MIXED procedure of SAS. There was a nutritional treatment by day interaction (P < 0.01) with CON ewes having greater umbilical blood flow compared with RES by d 90. Fetal biparietal distance, abdominal width, and kidney area increased (P < 0.05) in CON-RES with all these measurements increasing during late gestation. We partially accept our hypothesis as nutrient restriction during mid gestation decreased umbilical blood flow. However, blood flow did not return to control levels upon realimentation. By d 130, fetal and placental weights were similar between RES-RES and CON-CON. Binucleate cell numbers in the fetal trophoblast were not influenced by nutritional treatments. Our findings suggest that refeeding previously nutrient restricted pregnant adolescent ewes to control levels does not reestablish umbilical blood flow. Adequate placental development during mid gestation could protect the fetus from a decreased umbilical blood flow later in gestation when nutrients were limited by 40%.

Wait and see en epilepsia pediátrica. Nuestra experiencia / Wait and see in paediatric epilepsy. Our experience

Introducción: El tratamiento farmacológico de la epilepsia no es curativo; pretende, en lo posible, evitar crisis en niños que probablemente van a seguir teniéndolas. Pacientes y métodos: El objeto es analizar nuestra experiencia en niños con epilepsia y con primera crisis no sintomática aguda no tratados con antiepilépticos. Se analizó a pacientes atendidos en una consulta de neuropediatría, desde 2017 hasta 2021, que habían sufrido una o más crisis no sintomáticas agudas y a los que no se les había tratado farmacológicamente. Resultados: Sesenta y cinco pacientes cumplieron los criterios de selección. Veinticuatro habían tenido una única crisis, con un tiempo medio de duración de 12 minutos (1-60). En un 66,7% fue nocturna. Un 41,7% presentó electroencefalograma patológico, y un 21%, hallazgos patológicos en la neuroimagen. El tiempo medio de control fue de 2,7 años (0,003-13,6 años). Cuarenta y uno presentaron más de una crisis, con una duración media de nueve minutos (1-60). Cinco pacientes presentaron más de 20 crisis, y el resto, entre dos y 17. Veinticuatro (58,5%) presentaron únicamente crisis nocturnas. Se realizó un electroencefalograma en todos: grafoelementos epileptiformes en el 63,4%; y neuroimagen en todos: patológica en el 4,9%. El tiempo medio de control fue de 3,8 años (0,01-9,1 años). Conclusiones: La frecuencia de las crisis, la patología de base o los resultados de las pruebas complementarias no deberían ser las únicas variables que habría que considerar para iniciar el tratamiento farmacológico antiepiléptico en los niños. Debería prevalecer, por encima de aquéllos, el potencial perjuicio sobre la calidad de vida y el neurodesarrollo, las funciones atencionales y el comportamiento del niño, y siempre consensuar esta decisión con los padres.(AU)

Introduction: Pharmacological treatment of epilepsy is not healing; it tries to avoid seizures, as far as possible, in children who probably would still have them. Patients and methods: Our purpose is to analyse our experience with epileptic children and those who have a first non-symptomatic seizure without pharmacological treatment. Patients seen in a paediatric neurology consultation, from 2017 to 2021, who had suffered one or more acute non-symptomatic crises and who had not been treated pharmacologically, were analysed. Results: Sixty-five patients meet the selection criteria. Twenty-four patients had had a single crisis with a mean duration of 12 minutes (1-60). In 66.7% it was nocturnal. 41.7% presented pathological electroencephalogram, and 21% pathological findings in neuroimaging. The mean control time was 2.7 years (0.003-13.6 years). Forty-one presented more than one crisis, with a mean duration of nine minutes (1-60). Five patients presented more than 20 seizures, the rest between two and 17. Twenty-four (58.5%) presented only nocturnal seizures. An electroencephalogram was performed in all: epileptiform graphoelements in 63.4%; and neuroimaging in all: pathological in 4.9%. Mean control time was 3.8 years (0.01-9.1 years). Conclusions: Seizure frequency, underlying pathology or test results should not be the only variables to take into consideration when starting antiepileptic drug treatment. The repercussion on their quality of life and neurodevelopment should prevail, agreeing on this decision with the parents.(AU)

['Wait and see' in paediatric epilepsy. Our experience]. / Wait and see en epilepsia pediátrica. Nuestra experiencia.

INTRODUCTION: Pharmacological treatment of epilepsy is not healing; it tries to avoid seizures, as far as possible, in children who probably would still have them. PATIENTS AND METHODS: Our purpose is to analyse our experience with epileptic children and those who have a first non-symptomatic seizure without pharmacological treatment. Patients seen in a paediatric neurology consultation, from 2017 to 2021, who had suffered one or more acute non-symptomatic crises and who had not been treated pharmacologically, were analysed. RESULTS: Sixty-five patients meet the selection criteria. Twenty-four patients had had a single crisis with a mean duration of 12 minutes (1-60). In 66.7% it was nocturnal. 41.7% presented pathological electroencephalogram, and 21% pathological findings in neuroimaging. The mean control time was 2.7 years (0.003-13.6 years). Forty-one presented more than one crisis, with a mean duration of nine minutes (1-60). Five patients presented more than 20 seizures, the rest between two and 17. Twenty-four (58.5%) presented only nocturnal seizures. An electroencephalogram was performed in all: epileptiform graphoelements in 63.4%; and neuroimaging in all: pathological in 4.9%. Mean control time was 3.8 years (0.01-9.1 years). CONCLUSIONS: Seizure frequency, underlying pathology or test results should not be the only variables to take into consideration when starting antiepileptic drug treatment. The repercussion on their quality of life and neurodevelopment should prevail, agreeing on this decision with the parents.

TITLE: Wait and see en epilepsia pediátrica. Nuestra experiencia.El tratamiento farmacológico de la epilepsia no es curativo; pretende, en lo posible, evitar crisis en niños que probablemente van a seguir teniéndolas. Pacientes y métodos. El objeto es analizar nuestra experiencia en niños con epilepsia y con primera crisis no sintomática aguda no tratados con antiepilépticos. Se analizó a pacientes atendidos en una consulta de neuropediatría, desde 2017 hasta 2021, que habían sufrido una o más crisis no sintomáticas agudas y a los que no se les había tratado farmacológicamente. Resultados. Sesenta y cinco pacientes cumplieron los criterios de selección. Veinticuatro habían tenido una única crisis, con un tiempo medio de duración de 12 minutos (1-60). En un 66,7% fue nocturna. Un 41,7% presentó electroencefalograma patológico, y un 21%, hallazgos patológicos en la neuroimagen. El tiempo medio de control fue de 2,7 años (0,003-13,6 años). Cuarenta y uno presentaron más de una crisis, con una duración media de nueve minutos (1-60). Cinco pacientes presentaron más de 20 crisis, y el resto, entre dos y 17. Veinticuatro (58,5%) presentaron únicamente crisis nocturnas. Se realizó un electroencefalograma en todos: grafoelementos epileptiformes en el 63,4%; y neuroimagen en todos: patológica en el 4,9%. El tiempo medio de control fue de 3,8 años (0,01-9,1 años). Conclusiones. La frecuencia de las crisis, la patología de base o los resultados de las pruebas complementarias no deberían ser las únicas variables que habría que considerar para iniciar el tratamiento farmacológico antiepiléptico en los niños. Debería prevalecer, por encima de aquéllos, el potencial perjuicio sobre la calidad de vida y el neurodesarrollo, las funciones atencionales y el comportamiento del niño, y siempre consensuar esta decisión con los padres.

Boosting the photocatalytic properties of NaTaO3 by coupling with AgBr.

AgBr/NaTaO3 composites, with different molar % of NaTaO3 (Br/NTO(X%)), have been synthesized by simple precipitation methods; bare NaTaO3 was synthesized by hydrothermal procedure, while AgBr was synthesized by a precipitation procedure using cetyl-tri-methyl-ammonium bromide (CTAB) and AgNO3. Samples have been characterized by X-ray diffraction (XRD), N2 adsorption, UV-vis diffuse reflectance spectroscopy (DRS), Fourier-transform infrared spectroscopy (FT-IR), Transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS). Photocatalytic activity of the as-prepared photo-catalysts was evaluated through photocatalytic degradation of rhodamine B (RhB), methyl orange (MO) and caffeic acid (CAFA) under UV and visible illumination. Single AgBr material and Br/NTO(X%) composites displayed the ability to absorb light in the visible region, while NaTaO3 is only photoactive under UV irradiation. Based on the position of conduction and valence bands of AgBr and NaTaO3, the heterojunction between these two photo-catalysts corresponds to a type II junction. In the case of photocatalytic degradation of RhB and CAFA, Br/NTO(x%) composites have highest photocatalytic activity than that obtained by both parental materials under the same operational conditions. AgBr and Br/NTO(x%) composites achieve a fast degradation of MO, together with a considerable adsorption capacity, attributed to the presence of a remaining amount of residual CTAB on the AgBr surface. In summary, coupling AgBr with NaTaO3 improves the photocatalytic activity under both UV and visible illumination with respect to the parental components, but the performance of the composites is highly dependent on the type of substrate to be degraded and the illumination conditions.

Carbon footprint, economic benefits and sustainable fishing: Lessons for the future from the Western Mediterranean.

Ensuring an economically viable, sustainable and low CO2 emission extractive fishery is critical in order to achieve the life below water UN sustainable development goals and the climate change commitments of Paris agreement. This challenge is even more relevant in the most overexploited region of the world: The Mediterranean Sea. Here, we use the socio-ecological system of the Spanish Mediterranean commercial fisheries (Northern Alboran Sea, Northern Spain and the Balearic Islands) to develop an integrative impact assessment, including detailed socio-economic, ecosystem indices of the trophic structure of extractive fishery and CO2 emission analyses combining different gear, vessel size classes as well as a wide range estimation of carbon release from the seafloor by bottom trawling. Northern Alboran Sea preferentially requires reduction in purse seine fishery while in Northern Spain bottom trawling should be reduced first to reach sustainable exploitation. Fuel CO2 footprint of purse seine and bottom trawling are among the lowest footprints of animal protein production, but considering sweeping released CO2 from the seafloor the bottom trawling footprint becomes the animal protein production with the highest footprint. Moreover, the lowest bottom released CO2 estimation overrides 2.7-10 times the CO2 buried in the seafloor through the biological pump in trawled areas potentially turning the continental shelf from a CO2 sink to a CO2 source. Net profit per fuel derived CO2 emission for all fleets is lower than 1€ kgCO2-1, being lowest for large bottom trawler (0.025 € kgCO2-1). Thus, urgent mitigation and adaptation measures are necessary to obtain sustainable fishery in terms of net profit, sustainable seafood extraction and CO2 emission reduction. Our study provides scientific bases to develop these measures such as the restriction of harmful fishing gear in carbon rich river influenced areas, reduction of bottom contact of the fishing gear, favouring purse seine fishery and smaller bottom trawlers.

Sistematización del programa preventivo para menores en situación de conflictividad en el ámbito familiar en la comunidad de Andalucía: Programa NAYFA / Systematization of the preventive program for minors in conflict situations in the family environment in the community of Andalusia: NAYFA Program

En este artículo se describe el proceso de investigación-acción llevado a cabo para la redefinición y el diseño de un programa destinado a niños, niñas y adolescentes con dificultades y/o situaciones conflictivas en el ámbito familiar. El diseño del nuevo programa NAYFA se ha realizado siguiendo los estándares de calidad de los programas basados en la evidencia y mediante un proceso colaborativo entre responsables políticos, profesionales e investigadores. Se utilizó la técnica DAFO para identificar las principales fortalezas y debilidades de las actuaciones previas desarrolladas en diferentes provincias andaluzas. Los resultados pusieron de manifiesto una importante falta de sistematización que se ha tratado de solventar definiendo, mediante un proceso colaborativo y de acuerdo con los criterios de calidad más consensuados, los componentes clave del nuevo programa: fundamentación teórica y metodológica, destinatarios, objetivos, contenidos, condiciones de implementación y diseño de la evaluación. El alto grado de acuerdo de profesionales y responsables con las características propuestas puede contribuir a que la implementación del programa se lleve a cabo con fidelidad al diseño original y, con ello, favorecer su efectividad (AU)

This article describes the action-research process carried out to redefine and design a program for children and adolescents with difficulties and/or conflictive situations in the family. The design of the NAYFA program has been carried out following the quality standards of evidence-based programs and through a collaborative process between policymakers, professionals and researchers. The SWOT technique was used to identify the main strengths and weak-nesses of the previous actions carried out in different Andalucía provinces. The results revealed an important lack of systematization that an attempt has been made to solve by defining, through a collaborative process and in accordance with the most agreed quality criteria, the key components of the new program: theoretical and methodological founda-tions, recipients, objectives, contents, implementation conditions and evaluation design. The high degree of agreement of professionals and managers with the proposed characteristics can contribute to the implementation of the program being carried out with fidelity to the original design and, thus, favor its effectiveness. (AU)

Consensus statement on the use of alemtuzumab in daily clinical practice in Spain.

INTRODUCTION: Alemtuzumab is a highly effective drug approved by the European Medicines Agency as a disease-modifying drug for the treatment of relapsing-remitting multiple sclerosis. OBJECTIVE: A consensus document was drafted on the management of alemtuzumab in routine clinical practice in Spain. DEVELOPMENT: A group of multiple sclerosis specialists reviewed articles addressing treatment with alemtuzumab in patients with multiple sclerosis and published before December 2017. The included studies assessed the drug's efficacy, effectiveness, and safety; screening for infections and vaccination; and administration and monitoring aspects. The initial proposed recommendations were developed by a coordinating group and based on the available evidence and their clinical experience. The consensus process was carried out in 2 stages, with the initial threshold percentage for group agreement established at 80%. The final document with all the recommendations agreed by the working group was submitted for external review and the comments received were considered by the coordinating group. CONCLUSION: The present document is intended to be used as a tool for optimising the management of alemtuzumab in routine clinical practice.

Wien effect in interfacial water dissociation through proton-permeable graphene electrodes.

Strong electric fields can accelerate molecular dissociation reactions. The phenomenon known as the Wien effect was previously observed using high-voltage electrolysis cells that produced fields of about 107 V m-1, sufficient to accelerate the dissociation of weakly bound molecules (e.g., organics and weak electrolytes). The observation of the Wien effect for the common case of water dissociation (H2O [Formula: see text] H+ + OH-) has remained elusive. Here we study the dissociation of interfacial water adjacent to proton-permeable graphene electrodes and observe strong acceleration of the reaction in fields reaching above 108 V m-1. The use of graphene electrodes allows measuring the proton currents arising exclusively from the dissociation of interfacial water, while the electric field driving the reaction is monitored through the carrier density induced in graphene by the same field. The observed exponential increase in proton currents is in quantitative agreement with Onsager's theory. Our results also demonstrate that graphene electrodes can be valuable for the investigation of various interfacial phenomena involving proton transport.

Consenso de expertos sobre el uso de alemtuzumab en la práctica clínica diaria en España / Consensus statement on the use of alemtuzumab in daily clinical practice in Spain

Introducción: Alemtuzumab es un fármaco de alta eficacia aprobado por la Agencia Europea de Medicamentos como tratamiento modificador de la enfermedad en pacientes con esclerosis múltiple remitente recurrente.ObjetivoElaborar un documento de consenso sobre el manejo de alemtuzumab en la práctica clínica habitual, que sea de aplicación en el ámbito español.DesarrolloUn grupo de expertos en esclerosis múltiple revisó las publicaciones disponibles hasta diciembre de 2017, de tratamiento con alemtuzumab y esclerosis múltiple. Se incluyeron trabajos sobre eficacia, efectividad y seguridad, despistaje de infecciones y vacunación, administración y monitorización. La propuesta inicial de recomendaciones fue desarrollada por un grupo coordinador con base en la evidencia disponible y en su experiencia clínica. El proceso de consenso se llevó a cabo en 2 etapas; se estableció como porcentaje inicial de acuerdo grupal el 80%. El documento final con todas las recomendaciones acordadas por el grupo de trabajo se sometió a revisión externa y los comentarios recibidos fueron considerados por el grupo coordinador.ConclusionesEl documento aportado pretende ser una herramienta útil para facilitar el manejo del fármaco en condiciones de práctica clínica habitual. (AU)

Introduction: Alemtuzumab is a highly effective drug approved by the European Medicines Agency as a disease-modifying drug for the treatment of relapsing-remitting multiple sclerosis.ObjectiveA consensus document was drafted on the management of alemtuzumab in routine clinical practice in Spain.DevelopmentA group of multiple sclerosis specialists reviewed articles addressing treatment with alemtuzumab in patients with multiple sclerosis and published before December 2017. The included studies assessed the drug's efficacy, effectiveness, and safety; screening for infections and vaccination; and administration and monitoring aspects. The initial proposed recommendations were developed by a coordinating group and based on the available evidence and their clinical experience. The consensus process was carried out in 2 stages, with the initial threshold percentage for group agreement established at 80%. The final document with all the recommendations agreed by the working group was submitted for external review and the comments received were considered by the coordinating group.ConclusionThe present document is intended to be used as a tool for optimising the management of alemtuzumab in routine clinical practice. (AU)

Sexual orientation, gender: Where is the problem? Nowhere! Correct self-identification and minority stigma.

PURPOSE: Self-concept, at the core of minority stress, is associated with negative mental health outcomes. METHODS: We aimed to assess the effectiveness of a one-shot third-wave CBT intervention targeting correct self-identification to address suffering related to minority stress. The study population included 172 participants (n = 98 heterosexuals, n=13 transgenders). The intervention consisted of a 90 minutes conference including overview of LGBT's suffering related to distal and proximal factors, a wisdom understanding of the root of suffering (mistaken self-identification) followed by a Questions & Answers session. Participants completed online self-questionnaires assessing sociodemographic data, acceptance by others (external) and oneself (internal) for sexual orientation and gender variables before the conference, immediately after the conference, and three months later. RESULTS: The conference helped to improve external acceptance of transgender for the whole sample, especially among the majority group. Those belonging to the minority (LGBT) had a positive benefit from the conference by reducing their fear of judgment. Adding a Q&A session to the conference failed to show any additional benefits. CONCLUSION: A specific wisdom-based self-identification conference appears to be an effective and low-cost intervention to target minority stigma, and therefore mental health and social integration of LGBT people.

Intracranial arachnoid cysts and epilepsy in children: Should this be treated surgically? Our 29-year experience and review of the literature / Quistes aracnoideos intracraneales y epilepsia en niños: ¿Debemos tratarlos quirúrgicamente? Nuestra experiencia de 29 años y revisión de la literatura

Introduction and objective: Arachnoid cysts (ACs) are relatively frequent lesions related to different neurological symptoms, being mostly incidentally diagnosed. This study aims to clarify whether AC surgery in epileptic patients is useful in their treatment. Material and methods: The patients registered in the database of the Neuropediatrics Section from May 1990 to August 2019 are analyzed retrospectively. Patients in whom the diagnosis of ACs and epilepsy coincide are studied. The location, size and number of ACs, neurological development, age at diagnosis, follow-up time, the performance of surgery on the cyst, evolution, anatomical relationship between brain electrical activity and location of AC, and type of epilepsy are analyzed. Results: After analyzing the database, we found 1881 patients diagnosed with epilepsy, of which 25 had at least one intracranial AC. In 9 of the patients, cerebral or genetic pathologies were the cause of epilepsy. Of the other 16, only 2 patients showed that the type of epilepsy and the epileptogenic focus coincided with the location of the AC; one of them was surgically treated without success, and the other one remained asymptomatic without receiving medical or surgical treatment(AU)

Introducción y objetivo: Los quistes aracnoideos (QAs) son lesiones relativamente comunes relacionados con diferentes síntomas neurológicos, siendo diagnosticados de forma incidental en su mayoría. Este estudio tiene como objetivo aclarar si la cirugía sobre el QA en pacientes epilépticos es útil en su tratamiento. Material y métodos: Se analizan retrospectivamente los pacientes registrados en la base de datos de la Sección de Neuropediatría desde mayo de 1990 a agosto de 2019. Se estudian los pacientes en los que coincide el diagnóstico de QA y epilepsia. Se analiza la localización, tamaño y número de los QA, el desarrollo neurológico, edad al diagnóstico, tiempo de seguimiento, realización de cirugía sobre el QA, evolución, relación anatómica entre la actividad eléctrica cerebral y la localización del QA, así como el tipo de epilepsia. Resultados: Tras el análisis de la base de datos encontramos 1.881 pacientes diagnosticados de epilepsia, entre ellos 25 con al menos un QA intracraneal. En nueve de los pacientes la patología cerebral o genética por sí misma era causa de epilepsia. De los otros 16, únicamente en dos casos se evidenció que el tipo de epilepsia y el foco epileptogénico coincidían con la localización del QA; uno de ellos fue tratado quirúrgicamente sin éxito y el otro permaneció asintomático sin recibir tratamiento médico ni quirúrgico. Conclusiones: Aunque es necesario diseñar un estudio prospectivo para establecer causalidad, los resultados de nuestro trabajo y la literatura disponible sugieren que no hay relación causal entre la presencia de QAs y epilepsia. El estudio y tratamiento de estos pacientes debería ser completado en una unidad multidisciplinar de cirugía de la epilepsia, sin asumir de inicio que el QA es la causa de la epilepsia(AU)

Uterine kallikrein and arterial bradykinin activities and uterine arterial proliferation in response to acute estradiol-17ß exposure in ovariectomized ewes.

Estradiol-17ß (E2) increases kallikrein in rodent and human reproductive tissues. Kallikrein specific activity is increased in the porcine uterus when conceptus E2 is secreted at maternal recognition of pregnancy. When kallikrein acts on kininogen to liberate bradykinin, angiogenic and vasoactive factors are released. The uterus of ovariectomized ewes administered E2 undergoes rapid vascular changes via different patterns of angiogenic and vasoactive factors. Our hypothesis was that E2 would increase the specific activity and protein secretion of tissue kallikrein in endometrial explants culture media (ECM) and ewes exposed to E2 would have uterine arteries that would be more sensitive to the vasodilatory effects of bradykinin. Ovariectomized ewes received 100 mg of E2 implants for 0, 12, 24, or 48 h. After treatment, uterine weights were determined, and caruncles were processed for ECM. Uterine weights and uterine weight per ewe body weight were significantly greater in the 12 and 24 h ewes compared with the 0 h ewes, with the 48 h ewes being similar to the 24 h ewes. There were no statistically significant differences in caruncular tissue kallikrein protein secretion among the treatment groups. There was a tendency (P = 0.09) for duration of E2 exposure to influence tissue kallikrein specific activity where kallikrein activity was greater (P ≤ 0.05) in the 12 and 48 h ewes compared with the 0 h ewes, with 24 h ewes being intermediate (unprotected F test). Uterine arteries from ewes with E2 for 24 and 48 h had more sensitivity to bradykinin, via the bradykinin receptor 2, than uterine arteries from ewes with 0 or 12 h E2 exposure. We fail to reject our hypothesis as E2 did elicit a positive response in tissue kallikrein specific activity and bradykinin response. Further investigations are needed to determine how kallikrein and bradykinin may be involved in vascular remodeling of the ovine uterus.