ZebraReg-a novel platform for discovering regulators of cardiac regeneration using zebrafish.

Cardiovascular disease is the leading cause of death worldwide with myocardial infarction being the most prevalent. Currently, no cure is available to either prevent or revert the massive death of cardiomyocytes that occurs after a myocardial infarction. Adult mammalian hearts display a limited regeneration capacity, but it is insufficient to allow complete myocardial recovery. In contrast, the injured zebrafish heart muscle regenerates efficiently through robust proliferation of pre-existing myocardial cells. Thus, zebrafish allows its exploitation for studying the genetic programs behind cardiac regeneration, which may be present, albeit dormant, in the adult human heart. To this end, we have established ZebraReg, a novel and versatile automated platform for studying heart regeneration kinetics after the specific ablation of cardiomyocytes in zebrafish larvae. In combination with automated heart imaging, the platform can be integrated with genetic or pharmacological approaches and used for medium-throughput screening of presumed modulators of heart regeneration. We demonstrate the versatility of the platform by identifying both anti- and pro-regenerative effects of genes and drugs. In conclusion, we present a tool which may be utilised to streamline the process of target validation of novel gene regulators of regeneration, and the discovery of new drug therapies to regenerate the heart after myocardial infarction.

Evolutionary analysis reveals the role of a non-catalytic domain of peptidyl arginine deiminase 2 in transcriptional regulation.

Peptidyl arginine deiminases (PADIs) catalyze protein citrullination, a post-translational conversion of arginine to citrulline. The most widely expressed member of this family, PADI2, regulates cellular processes that impact several diseases. We hypothesized that we could gain new insights into PADI2 function through a systematic evolutionary and structural analysis. Here, we identify 20 positively selected PADI2 residues, 16 of which are structurally exposed and maintain PADI2 interactions with cognate proteins. Many of these selected residues reside in non-catalytic regions of PADI2. We validate the importance of a prominent loop in the middle domain that encompasses PADI2 L162, a residue under positive selection. This site is essential for interaction with the transcription elongation factor (P-TEFb) and mediates the active transcription of the oncogenes c-MYC, and CCNB1, as well as impacting cellular proliferation. These insights could be key to understanding and addressing the role of the PADI2 c-MYC axis in cancer progression.

Análisis de coste-efectividad de la vacunación antineumocócica en España / Cost-effectiveness analysis of pneumococcal vaccination in Spain

Objetivo: Análisis de coste-efectividad de la vacunación antineumocócica pediátrica en Espa˜na.Métodos: Se utilizó un modelo determinístico poblacional en forma de árbol de decisión con un horizontetemporal de 1 a˜no para estimar el impacto de la vacunación con Synflorix® o Prevenar13® sobre lapoblación menor de 2 a˜nos en Espa˜na, bajo la perspectiva del Sistema Nacional de Salud. Los datos epidemiológicosse obtuvieron del Conjunto Mínimo Básico de Datos al alta hospitalaria y de la literatura.Los datos sobre costes se obtuvieron de bases de datos nacionales de costes sanitarios. Los principalesresultados en salud medidos fueron los casos evitados de enfermedad neumocócica invasora, otitis mediaaguda (OMA), miringotomías y hospitalizaciones por neumonía. Todos los costes se expresaron en eurosde 2010. La efectividad se midió en a˜nos de vida ajustados por calidad (AVAC).Resultados: El potencial demostrado por Synflorix® para prevenir episodios de OMA causados por Haemophilusinfluenzae no tipificable podría traducirse en la prevención adicional de 41.513 episodios deOMA, 36.324 prescripciones de antibióticos y 382 miringotomías, y supondrían la ganancia de 143 AVACfrente a Prevenar13®. El coste total de la vacunación con Synflorix® resultaría unos 22 millones de eurosmenor.Conclusiones: La vacunación antineumocócica de la población menor de 2 a˜nos en Espa˜na con Synflorix®,en comparación con la vacunación con Prevenar13®, podría resultar en un mayor número de AVAC, asícomo en una reducción sustancial del coste total, resultando una estrategia dominante en términos decoste-efectividad (AU)

Objective: To perform a cost-effectiveness analysis of pediatric pneumococcal vaccination in Spain.Methods: A deterministic population-based model in the form of a decision-tree with a 1-year timehorizon was used to estimate the impact of vaccination with Synflorix® or Prevenar13® in children agedless than 2 years in Spain from the perspective of the National Health System. Epidemiological data wereobtained from the hospital discharge minimum data set (MDS) and the literature. Data on costs wereobtained from national health costs databases. The main outcomes measured were the number of casesavoided of invasive pneumococcal disease, acute otitis media (AOM) and myringotomies, and hospitaladmissions for pneumonia. All costs were expressed in 2010 euros. Effectiveness was measured as thenumber of quality-adjusted life years (QALYs) gained.Results: The efficacy of Synflorix® in preventing episodes of AOM caused by non-typeable Haemophilusinfluenzae could lead to additional prevention of 41,513 episodes of AOM, 36,324 antibiotic prescriptionsand 382 myringotomy procedures and 143 QALYs gained compared with Prevenar13®. The totalvaccination cost with Synflorix® would result in savings of 22 million euros.Conclusions: Pneumococcal vaccination with Synflorix® in comparison with Prevenar13® in children agedless than 2 years old in Spain could achieve a higher number of QALYs and a substantial cost offset.Vaccination with Synflorix® would be a dominant strategy in terms of cost-effectiveness (AU)

[Cost-effectiveness analysis of pneumococcal vaccination in Spain]. / Análisis de coste-efectividad de la vacunación antineumocócica en España.

OBJECTIVE: To perform a cost-effectiveness analysis of pediatric pneumococcal vaccination in Spain. METHODS: A deterministic population-based model in the form of a decision-tree with a 1-year time horizon was used to estimate the impact of vaccination with Synflorix® or Prevenar13® in children aged less than 2 years in Spain from the perspective of the National Health System. Epidemiological data were obtained from the hospital discharge minimum data set (MDS) and the literature. Data on costs were obtained from national health costs databases. The main outcomes measured were the number of cases avoided of invasive pneumococcal disease, acute otitis media (AOM) and myringotomies, and hospital admissions for pneumonia. All costs were expressed in 2010 euros. Effectiveness was measured as the number of quality-adjusted life years (QALYs) gained. RESULTS: The efficacy of Synflorix® in preventing episodes of AOM caused by non-typeable Haemophilus influenzae could lead to additional prevention of 41,513 episodes of AOM, 36,324 antibiotic prescriptions and 382 myringotomy procedures and 143 QALYs gained compared with Prevenar13®. The total vaccination cost with Synflorix® would result in savings of 22 million euros. CONCLUSIONS: Pneumococcal vaccination with Synflorix® in comparison with Prevenar13® in children aged less than 2 years old in Spain could achieve a higher number of QALYs and a substantial cost offset. Vaccination with Synflorix® would be a dominant strategy in terms of cost-effectiveness.