Cardiac hypertrophy is inhibited by a local pool of cAMP regulated by phosphodiesterase 2

Rationale: Chronic elevation of 3'-5'-cyclic adenosine monophosphate (cAMP) levels has been associated with cardiac remodelling and cardiac hypertrophy. However, enhancement of particular aspects of cAMP/protein kinase A (PKA) signalling appears to be beneficial for the failing heart. cAMP is a pleiotropic second messenger with the ability to generate multiple functional outcomes in response to different extracellular stimuli with strict fidelity, a feature that relies on the spatial segregation of the cAMP pathway components in signalling microdomains. Objective: How individual cAMP microdomains impact on cardiac pathophysiology remains largely to be established. The cAMP-degrading enzymes phosphodiesterases (PDEs) play a key role in shaping local changes in cAMP. Here we investigated the effect of specific inhibition of selected PDEs on cardiac myocyte hypertrophic growth. Methods and Results: Using pharmacological and genetic manipulation of PDE activity we found that the rise in cAMP resulting from inhibition of PDE3 and PDE4 induces hypertrophy whereas increasing cAMP levels via PDE2 inhibition is anti-hypertrophic. By real-time imaging of cAMP levels in intact myocytes and selective displacement of PKA isoforms we demonstrate that the anti-hypertrophic effect of PDE2 inhibition involves the generation of a local pool of cAMP and activation of a PKA type II subset leading to phosphorylation of the nuclear factor of activated T cells (NFAT). Conclusions: Different cAMP pools have opposing effects on cardiac myocyte cell size. PDE2 emerges as a novel key regulator of cardiac hypertrophy in vitro and in vivo and its inhibition may have therapeutic applications

Realizando evaluaciones de necesidades de capacidades funcionales. Manual para instructores

Este manual fue producido como un recurso para la capacitación de Facilitadores Nacionales de Innovación (FNI) en los ocho países piloto. La capacitación está destinada a ser impartida por la Persona Focal de Agrinatura (PFA) y los Gerentes Nacionales del Proyecto (GNP) en cada país. Estos instructores han pasado por un proceso de capacitación para instructores para familiarizarse con este manual, el enfoque interactivo y participativo requerido y el uso de las diversas herramientas de facilitación que se encuentran en él. El objetivo de este manual es fortalecer las habilidades de facilitación de los FNI y su capacidad para apoyar a los agricultores y otras partes involucradas en analizar los problemas clave que enfrentan, crear una visión de donde ellos quieren estar, y construir la apropiación de este largo proceso. Este manual es adecuado para ser usado por ONGs, departamentos gubernamentales y universidades para desarrollar las capacidades del personal para planear y ejecutar intervenciones de acuerdo con las necesidades de los participantes esperados

Conduire l'évaluation des besoins en capacités fonctionnelles - Un guide pour les formateurs

Ce manuel sur l’évaluation des besoins en capacités fonctionnelles est destiné aux formateurs et a été produit dans le cadre du projet de Renforcement des capacités des systèmes d’innovation agricole (RC des SIA). Ce projet fait intervenir un partenariat mondial (Agrinatura, Organisation des Nations Unies pour l’alimentation et l’agriculture [FAO] et des partenaires nationaux de huit pays pilotes) qui aspire à renforcer la capacité des pays et des acteurs clefs pour innover dans des systèmes agricoles complexes, améliorant ainsi les moyens de subsistance ruraux. Le RC des SIA reconnaît que l’innovation agricole est un processus qui est plus fructueux si ses acteurs sont dotés des capacités fonctionnelles qui leur permettront de faire face à la complexité, de collaborer, de réfléchir et d’apprendre et de s’engager dans des processus stratégiques et politiques (Cadre commun sur le Renforcement des capacités pour les systèmes d’innovation agricole, 2016)

Involving hybrid professionals in top management decision-making: how managerial training can make the difference

Hybrid professionals have a two-fold - professional and managerial - role, which requires appropriate management skills. Investing on managerial training programs aims to empower professionals with managerial skills and competencies. Does this pay back? Assessing the impact of such training programs is still a limited practice. This paper explores whether participation in managerial training programs in healthcare can enhance the involvement of hybrid professionals (namely, clinical directors) in top management decision-making. The mediational effects of knowledge of performance information and its use are explored. Survey data were collected from more than 3,000 clinical directors of 69 public health authorities from five regional healthcare systems in Italy. Relationships between participation in managerial training programs, performance management practices (i.e., knowledge and use of performance information) and the level of clinicians’ involvement by the top management were studied using a three-path mediation analysis with structural equation modelling. Propensity score matching was also performed to mitigate selection bias. Knowledge and use of performance information positively mediate, both independently and sequentially, the relationship between head of departments’ participation in managerial training programs and the level of clinical directors’ involvement in decision-making. The results of the study suggest that managerial training can support hybrid professionals in engaging with managerialism and playing upward influence on top management decision-making