Inoculation of swine with foot-and-mouth disease SAP-mutant virus induces early protection against disease.

Foot-and-mouth disease virus (FMDV) leader proteinase (L(pro)) cleaves itself from the viral polyprotein and cleaves the translation initiation factor eIF4G. As a result, host cell translation is inhibited, affecting the host innate immune response. We have demonstrated that L(pro) is also associated with degradation of nuclear factor κB (NF-κB), a process that requires L(pro) nuclear localization. Additionally, we reported that disruption of a conserved protein domain within the L(pro) coding sequence, SAP mutation, prevented L(pro) nuclear retention and degradation of NF-κB, resulting in in vitro attenuation. Here we report that inoculation of swine with this SAP-mutant virus does not cause clinical signs of disease, viremia, or virus shedding even when inoculated at doses 100-fold higher than those required to cause disease with wild-type (WT) virus. Remarkably, SAP-mutant virus-inoculated animals developed a strong neutralizing antibody response and were completely protected against challenge with WT FMDV as early as 2 days postinoculation and for at least 21 days postinoculation. Early protection correlated with a distinct pattern in the serum levels of proinflammatory cytokines in comparison to the levels detected in animals inoculated with WT FMDV that developed disease. In addition, animals inoculated with the FMDV SAP mutant displayed a memory T cell response that resembled infection with WT virus. Our results suggest that L(pro) plays a pivotal role in modulating several pathways of the immune response. Furthermore, manipulation of the L(pro) coding region may serve as a viable strategy to derive live attenuated strains with potential for development as effective vaccines against foot-and-mouth disease.

Consenso Delphi sobre el Trastorno por Déficit de Atención e Hiperactividad (TDAH): valoración por un panel de expertos / Delphi Consensus on Attention Deficit Hyperactivity Disorder (ADHD): evaluation by a panel of experts

Introducción. El Trastorno por Déficit de Atención e Hiperactividad (TDAH) es uno de los trastornos del neurodesarrollo más prevalentes en la infancia, que frecuentemente se mantiene en la adolescencia y edad adulta. Presenta una gran heterogeneidad clínica, afectando notablemente al funcionamiento de quien lo padece. Si bien los tratamientos farmacológicos obtienen resultados por s. mismos, el abordaje debe ser multidisciplinar y adaptado a las necesidades específicas de cada paciente y su familia. Dada la variedad de fármacos disponibles actualmente para tratar el TDAH, existen opiniones diversas sobre cuál es la manera más efectiva de abordar este trastorno. El objetivo de este trabajo es explorar la opinión de un panel clínico experto y conocer el criterio profesional utilizado para definir conceptos clave y las pautas terapéuticas del TDAH en España. Metodología. El proyecto se efectuó en cuatro fases: 1) constitución de un Comité Científico, responsable de la revisión bibliográfica preliminar y de la formulación del cuestionario; 2) selección de un panel experto de especialistas con especial interés y/o experiencia en el tratamiento del TDAH; 3) encuesta estructurada tipo Likert (plataforma online) en dos rondas con procesamiento intermedio de opiniones; y 4) recopilación y análisis final de resultados. Resultados. El panel de expertos logró un consenso en 55 de los 58 ítems que conformaron el cuestionario, encontrando 3 ítems en los que no se consiguió suficiente unanimidad de criterio, debido a que gran cantidad de expertos se situaron en posiciones de indeterminación. Conclusiones. De manera global, los expertos de este estudio alcanzaron un elevado grado de acuerdo en los criterios propuestos en la encuesta, que podrían generalizarse como indicaciones para la práctica clínica en el manejo del TDAH Del mismo modo, y dada la dispersión de los resultados en algunos de los ítems y el no consenso en otros, quedan algunos puntos objeto de discusión (AU)

Introduction. Attention Deficit Hyperactivity Disorder (ADHD) is one of the most prevalent neurodevelopmental disorders in childhood, which is frequently maintained in adolescent and adult age. It presents great clinical heterogeneity, significantly affecting the functioning of those who suffer it. Although drug treatments obtain results by themselves, the approach should be multidisciplinary and be adapted to the specific needs of each patient and his/her family. Given the variety of drugs currently available to treat ADHD, there are diverse opinions on the most effective way to approach this disorder. The objective of this work is to study the opinion of an expert clinical panel and to know the professional criteria used to define key concepts and therapeutic guidelines of ADHD in Spain. Methodology. The project was carried out in four phases: 1) Constitution of a Scientific Committee, responsible for the preliminary biographic review and the formulation of the questionnaire; 2) selection of an expert panel of specialists with special interest and/or experience in the treatment of ADHD; 3) Likert type structured survey (online platform) in two rounds with interim processing of opinions; and 4) collection and final analysis of results. Results. The experts’ panel achieved a consensus in 55 of the 58 items making up the questionnaire, finding 3 items in which sufficient unanimity of criteria was not achieved because of the high number of experts were found in positions of non-certainty. Conclusions. Overall, the experts of this study reached a high level of agreement in the criteria proposed in the survey, which could be generalized as indications for the clinical practice in the management of ADHD. Similarly, and given the dispersion of the results in some of the items and the lack of consensus in others, some points remain as object of discussion (AU)