Transcriptomic signatures of neuronal differentiation and their association with risk genes for autism spectrum and related neuropsychiatric disorders.

Genes for autism spectrum disorders (ASDs) are also implicated in fragile X syndrome (FXS), intellectual disabilities (ID) or schizophrenia (SCZ), and converge on neuronal function and differentiation. The SH-SY5Y neuroblastoma cell line, the most widely used system to study neurodevelopment, is currently discussed for its applicability to model cortical development. We implemented an optimal neuronal differentiation protocol of this system and evaluated neurodevelopment at the transcriptomic level using the CoNTeXT framework, a machine-learning algorithm based on human post-mortem brain data estimating developmental stage and regional identity of transcriptomic signatures. Our improved model in contrast to currently used SH-SY5Y models does capture early neurodevelopmental processes with high fidelity. We applied regression modelling, dynamic time warping analysis, parallel independent component analysis and weighted gene co-expression network analysis to identify activated gene sets and networks. Finally, we tested and compared these sets for enrichment of risk genes for neuropsychiatric disorders. We confirm a significant overlap of genes implicated in ASD with FXS, ID and SCZ. However, counterintuitive to this observation, we report that risk genes affect pathways specific for each disorder during early neurodevelopment. Genes implicated in ASD, ID, FXS and SCZ were enriched among the positive regulators, but only ID-implicated genes were also negative regulators of neuronal differentiation. ASD and ID genes were involved in dendritic branching modules, but only ASD risk genes were implicated in histone modification or axonal guidance. Only ID genes were over-represented among cell cycle modules. We conclude that the underlying signatures are disorder-specific and that the shared genetic architecture results in overlaps across disorders such as ID in ASD. Thus, adding developmental network context to genetic analyses will aid differentiating the pathophysiology of neuropsychiatric disorders

A behavioral conceptualization of motivation in the therapeutic process

Tradicionalmente la motivación se ha entendido como algo situado dentro de la persona que podría explicar algunos comportamientos y tener un papel causal sobre la conducta manifi esta de cambio. En el campo de la psicología clínica y de la salud el Modelo Transteórico de Cambio y la Entrevista Motivacional abordan el estudio de la motivación siguiendo esta línea de conceptualización. Frente a esta perspectiva, el análisis de la conducta ha formulado el concepto de operación de establecimiento como estímulo u operación ambiental que altera momentáneamente las funciones de estímulos y la probabilidad de respuestas posteriores, lo que permite estudiar la motivación sin recurrir a inferencias o a términos cognitivistas. Desde este punto de vista el estudio de la motivación en terapia pasaría por el análisis del efecto que determinadas verbalizaciones del terapeuta tienen sobre la conducta del cliente. Concretamente, proponemos que el análisis de las verbalizaciones motivadoras del terapeuta se centre en aquellas descripciones que los terapeutas hacen de las situaciones estimulares que han sido, son o serán consecuencia de la conducta del clienteMotivation has traditionally been conceptualized as something situated inside the person, which might explain certain behaviors and play a causal role in overt changes in behavior. This type of approach was assumed by the Transtheoretical Model of Change and Motivational Interviewing in the area of clinical and health psychology. In contrast, the behavioral concept of establishing operation is defi ned as a stimulus or environmental operation that momentarily alters the functions of other stimuli and the response probability, which allows us to study motivation without making inferences or assuming a cognitivist terminology. From this point of view, the study of motivation in therapy implies the analysis of the effect that certain verbalizations of the therapist have on the client’s behavior. Moreover, we propose that the analysis of therapists’ motivating verbalizations should focus on descriptions of the past, present and future consequences of the client’s behavio

The use of pediatric flexible bronchoscopy in the COVID-19 pandemic era

On March 11, 2020, the World Health Organization (WHO) declared the pandemic because of a novel coronavirus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In January 2020, the first transmission to healthcare workers (HCWs) was described. SARS-CoV-2 is transmitted between people because of contact, droplets, and airborne. Airborne transmission is caused by aerosols that remain infectious when suspended in air over long distances and time. In the clinical setting, airborne transmission may occur during aerosol generating procedures like flexible bronchoscopy. To date, although the role of children in the transmission of SARS-CoV-2 is not clear the execution of bronchoscopy is associated with a considerably increased risk of SARS-CoV-2 transmission to HCWs. The aim of this overview is to summarize available recommendations and to apply them to pediatric bronchoscopy. We performed systematic literature searches using the MEDLINE (accessed via PubMed) and Scopus databases. We reviewed major recommendations and position statements published at the moment by the American Association for Bronchology and Interventional Pulmonology, WHO, European Center for Disease Prevention and Control and expert groups on the management of patients with COVID-19 to limit transmission among HCWs. To date there is a lack of recommendations for safe bronchoscopy during the pandemic period. The main indications concern adults and little has been said about children. We have summarized available recommendations and we have applied them to pediatric bronchoscopy

Tetrahedral mesh improvement by shell transformation

Existing flips for tetrahedral meshes simply make a selection from a few possible configurations within a single shell (i.e., a polyhedron that can be filled up with a mesh composed of a set of elements that meet each other at one edge), and their effectiveness is usually confined. A new topological operation for tetrahedral meshes named shell transformation is proposed. Its recursive callings execute a sequence of shell transformations on neighboring shells, acting like composite edge removal transformations. Such topological transformations are able to perform on a much larger element set than that of a single flip, thereby leading the way towards a better local optimum solution. Hence, a new mesh improvement algorithm is developed by combining this recursive scheme with other schemes, including smoothing, point insertion and point suppression. Numerical experiments reveal that the proposed algorithm can well balance some stringent and yet sometimes even conflict requirements of mesh improvement, i.e., resulting in high-quality meshes and reducing computing time at the same time. Therefore, it can be used for mesh quality improvement tasks involving millions of elements, in which it is essential not only to generate high-quality meshes, but also to reduce total computational time for mesh improvement

Manipulating infrared photons using plasmons in transparent graphene superlattices

Superlattices are artificial periodic nanostructures which can control the flow of electrons. Their operation typically relies on the periodic modulation of the electric potential in the direction of electron wave propagation. Here we demonstrate transparent graphene superlattices which can manipulate infrared photons utilizing the collective oscillations of carriers, i.e., plasmons of the ensemble of multiple graphene layers. The superlattice is formed by depositing alternating wafer-scale graphene sheets and thin insulating layers, followed by patterning them all together into 3-dimensional photonic-crystal-like structures. We demonstrate experimentally that the collective oscillation of Dirac fermions in such graphene superlattices is unambiguously nonclassical: compared to doping single layer graphene, distributing carriers into multiple graphene layers strongly enhances the plasmonic resonance frequency and magnitude, which is fundamentally different from that in a conventional semiconductor superlattice. This property allows us to construct widely tunable far-infrared notch filters with 8.2 dB rejection ratio and terahertz linear polarizers with 9.5 dB extinction ratio, using a superlattice with merely five graphene atomic layers. Moreover, an unpatterned superlattice shields up to 97.5% of the electromagnetic radiations below 1.2 terahertz. This demonstration also opens an avenue for the realization of other transparent mid- and far-infrared photonic devices such as detectors, modulators, and 3-dimensional meta-material systems.Comment: under revie

Large tunable valley splitting in edge-free graphene quantum dots on boron nitride

Coherent manipulation of binary degrees of freedom is at the heart of modern quantum technologies. Graphene offers two binary degrees: the electron spin and the valley. Efficient spin control has been demonstrated in many solid state systems, while exploitation of the valley has only recently been started, yet without control on the single electron level. Here, we show that van-der Waals stacking of graphene onto hexagonal boron nitride offers a natural platform for valley control. We use a graphene quantum dot induced by the tip of a scanning tunneling microscope and demonstrate valley splitting that is tunable from -5 to +10 meV (including valley inversion) by sub-10-nm displacements of the quantum dot position. This boosts the range of controlled valley splitting by about one order of magnitude. The tunable inversion of spin and valley states should enable coherent superposition of these degrees of freedom as a first step towards graphene-based qubits

International Veterinary Epilepsy Task Force consensus proposal: Medical treatment of canine epilepsy in Europe

In Europe, the number of antiepileptic drugs (AEDs) licensed for dogs has grown considerably over the last years. Nevertheless, the same questions remain, which include, 1) when to start treatment, 2) which drug is best used initially, 3) which adjunctive AED can be advised if treatment with the initial drug is unsatisfactory, and 4) when treatment changes should be considered. In this consensus proposal, an overview is given on the aim of AED treatment, when to start long-term treatment in canine epilepsy and which veterinary AEDs are currently in use for dogs. The consensus proposal for drug treatment protocols, 1) is based on current published evidence-based literature, 2) considers the current legal framework of the cascade regulation for the prescription of veterinary drugs in Europe, and 3) reflects the authors’ experience. With this paper it is aimed to provide a consensus for the management of canine idiopathic epilepsy. Furthermore, for the management of structural epilepsy AEDs are inevitable in addition to treating the underlying cause, if possible

Eficàcia i seguretat d’un tractament oral a base de mucopolisacàrids, col·lagen tipus I i vitamina C en pacients amb tendinopaties

Introducció i objectius La tendinopatia és una lesió freqüent durant la pràctica esportiva que es manifesta amb una alteració estructural del tendó. L’objectiu d’aquest estudi fou avaluar l’eficàcia i la seguretat d’un complement alimentari a base de mucopolisacàrids, col·lagen tipus i i vitamina C (Tendoactive®) sobre l’evolució clínica i estructural de les tendinopaties del tendó d’Aquil·les, del rotular i de l’epicòndil lateral del colze. Material i mètodes Es realitzà un estudi multicèntric prospectiu, de tipus exploratori en fase iv, obert i no comparatiu. S’inclogueren un total de 98 pacients amb tendinopaties (32 d’Aquil·les, 32 de rotular i 34 de l’epicòndil lateral) que reberen una dosi diària de 435 mg de mucopolisacàrids, 75 mg de col·lagen tipus i i 60 mg de vitamina C (equivalent a 3 càpsules al dia de Tendoactive®) durant 90 dies consecutius. Mensualment s’avaluà el dolor en repòs i en activitat mitjançant una escala visual analògica (EVA), la funció articular mitjançant els qüestionaris VISA-A, VISA-P i PRTEE, i el tendó afectat es caracteritzà ecogràficament. Resultats En els 3 tipus de tendinopatia es registrà una reducció significativa del dolor, tant en repòs com en activitat, des de la primera visita de control (dia 30) fins al final de l’estudi (dia 90). Així mateix, el dia 90 es detectà una millora del 38% en VISA-A, del 46% en VISA-P i del 77% en PRTEE (p < 0,001). Simultàniament es registrà una reducció del 12% en el gruix del tendó d’Aquil·les, del 10% en el rotular i del 20% en el tendó de l’epicòndil lateral (p < 0,05). Conclusions Els resultats de l’estudi indiquen que l’administració de Tendoactive® és segura i eficaç per millorar els símptomes clínics i l’evolució estructural de les tendinopaties del tendó d’Aquil·les, del tendó rotular i del tendó de l’epicòndil lateral

Eficacia y seguridad de un tratamiento oral a base de mucopolisacáridos, colágeno tipo i y vitamina C en pacientes con tendinopatías

Introducción y objetivos La tendinopatía es una lesión frecuente durante la práctica deportiva que cursa con una alteración estructural del tendón. El objetivo de este estudio fue evaluar la eficacia y la seguridad de un complemento alimentario a base de mucopolisacáridos, colágeno tipo i y vitamina C (Tendoactive®) sobre la evolución clínica y estructural de las tendinopatías del tendón de Aquiles, rotuliano y del epicóndilo lateral del codo. Material y métodos Se realizó un estudio multicéntrico prospectivo, de tipo exploratorio en fase iv , abierto y no comparativo. Se incluyeron un total de 98 pacientes con tendinopatías (32 de Aquiles, 32 de rotuliano y 34 del epicóndilo lateral) que recibieron una dosis diaria de 435 mg de mucopolisacáridos, 75 mg de colágeno tipo i y 60 mg de vitamina C (equivalente a 3 cápsulas al día de Tendoactive®) durante 90 días consecutivos. Mensualmente se evaluó el dolor en reposo y en actividad mediante una escala visual analógica (EVA), la función articular mediante los cuestionarios VISA-A, VISA-P y PRTEE, y se caracterizó ecográficamente el tendón afectado. Resultados En los 3 tipos de tendinopatía se registró una reducción significativa del dolor tanto en reposo como en actividad desde la primera visita de control (día 30) hasta el final del estudio (día 90). Asimismo el día 90 se detectó una mejora del 38% en VISA-A, del 46% en VISA-P y del 77% en PRTEE (p < 0,001). Simultáneamente se registró una reducción del 12% en el grosor del tendón de Aquiles, del 10% en el rotuliano y del 20% en el tendón del epicóndilo lateral (p < 0,05). Conclusiones Los resultados del estudio indican que la administración de Tendoactive® es segura y eficaz para mejorar los síntomas clínicos y la evolución estructural de las tendinopatías del tendón de Aquiles, tendón rotuliano y tendón del epicóndilo lateral