Dependência crônica de ventilação pulmonar mecânica na assistência pediátrica: um debate necessário para o SUS Chronic dependence on mechanical pulmonary ventilation in pediatric care: a necessary debate for Brazil's Unified Health System

Pessoas com dependência prolongada de ventilação pulmonar mecânica necessitam de cuidados permanentes e de equipamentos, que podem alongar muito a permanência hospitalar, determinando uma dificuldade de acesso para pacientes com agravos agudos, assim como transtornos pessoais com limitação da qualidade de vida de seus familiares ou cuidadores, devido aos longos períodos de internação. Esta revisão crítica de publicações sobre dependência de ventilação pulmonar mecânica em crianças e adolescentes objetivou disponibilizar informações organizadas de modo sistemático, a fim de subsidiar o debate sobre o tema, considerando que as mudanças de perfil epidemiológico e o crescente acesso tecnológico determinam necessidades como leitos de terapia intensiva e complexa assistência domiciliar para pacientes crônicos, ainda com limites de oferta e regulação no sistema público de saúde brasileiro.<br>People with prolonged dependence on mechanical ventilation require permanent care and the use of equipment that can result in longer term hospital internment. This can lead to difficulty of access for patients with acute injuries, as well as personal difficulties and stress with reduced quality of life for their families or caregivers due to such longer hospital internment. This critical review of publications dealing with dependence on mechanical ventilation among children and adolescents aimed at making information organized in a systematic manner available in order to support discussion on the subject. It should be borne in mind that changes in epidemiological profile and growing technological access determine needs such as intensive therapy hospital beds and complex home care for chronic patients, which still have limits of supply and regulatory restrictions in the Brazilian public health syste

Phosphorylation-dependent binding of 14-3-3 terminates signalling by the Gab2 docking protein

Grb2-associated binder (Gab)2 functions downstream of a variety of receptor and cytoplasmic tyrosine kinases as a docking platform for specific signal transducers and performs important functions in both normal physiology and oncogenesis. Gab2 signalling is promoted by its association with specific receptors through the adaptor Grb2. However, the molecular mechanisms that attenuate Gab2 signals have remained unclear. We now demonstrate that growth factor-induced phosphorylation of Gab2 on two residues, S210 and T391, leads to recruitment of 14-3-3 proteins. Together, these events mediate negative-feedback regulation, as Gab2S210A/T391A exhibits sustained receptor association and signalling and promotes cell proliferation and transformation. Importantly, introduction of constitutive 14-3-3-binding sites into Gab2 renders it refractory to receptor activation, demonstrating that site-selective binding of 14-3-3 proteins is sufficient to terminate Gab2 signalling. Furthermore, this is associated with reduced binding of Grb2. This leads to a model where signal attenuation occurs because 14-3-3 promotes dissociation of Gab2 from Grb2, and thereby uncouples Gab2 from the receptor complex. This represents a novel regulatory mechanism with implications for diverse tyrosine kinase signalling systems