[User perceptions of a public health program to reduce disability among Chilean older adults]. / Percepción usuaria de beneficios en salud del Programa Más Adultos Mayores Autovalentes en el Servicio de Salud Metropolitano Norte.

BACKGROUND: The Program "Más Adultos Mayores Autovalentes" (Más AMA) started in 2015 as a strategy for the prevention of disability among older adults. AIM: To describe the health benefits, from user's perspective, of the Functional Stimulation Component of the Más AMA program. MATERIAL AND METHODS: Eleven focus groups including 97 participants of the Más AMA program were conducted in Northern Metropolitan Santiago municipalities. RESULTS: The benefits perceived by Más AMA participants were a reduction in loneliness and isolation, physical reactivation, engagement in activities, and the use of support resources within the community. The relationship with professionals working at Más AMA was described as highly satisfactory. CONCLUSIONS: The benefits of attending the Más AMA program from the point of view of their users are mainly related with social and affective dimensions, which contrast with the emphasis in physical and cognitive dimensions given by the technical orientation of the Más AMA program.

Percepción usuaria de beneficios en salud del Programa Más Adultos Mayores Autovalentes en el Servicio de Salud Metropolitano Norte / User perceptions of a public health program to reduce disability among Chilean older adults

Background: The Program "Más Adultos Mayores Autovalentes" (Más AMA) started in 2015 as a strategy for the prevention of disability among older adults. Aim: To describe the health benefits, from user's perspective, of the Functional Stimulation Component of the Más AMA program. Material and Methods: Eleven focus groups including 97 participants of the Más AMA program were conducted in Northern Metropolitan Santiago municipalities. Results: The benefits perceived by Más AMA participants were a reduction in loneliness and isolation, physical reactivation, engagement in activities, and the use of support resources within the community. The relationship with professionals working at Más AMA was described as highly satisfactory. Conclusions: The benefits of attending the Más AMA program from the point of view of their users are mainly related with social and affective dimensions, which contrast with the emphasis in physical and cognitive dimensions given by the technical orientation of the Más AMA program.

Focal adhesion kinase-dependent activation of the early endocytic protein Rab5 is associated with cell migration.

Focal adhesion kinase (FAK) is a central regulator of integrin-dependent cell adhesion and migration and has recently been shown to co-localize with endosomal proteins. The early endocytic protein Rab5 controls integrin trafficking, focal adhesion disassembly, and cell migration and has been shown to be activated upon integrin engagement by mechanisms that remain unclear. Because FAK is a critical regulator of integrin-dependent signaling and Rab5 recapitulates FAK-mediated effects, we evaluated the possibility that FAK activates Rab5 and contributes to cell migration. Pulldown assays revealed that Rab5-GTP levels are decreased upon treatment with a pharmacological inhibitor of FAK, PF562,271, in resting A549 cells. These events were associated with decreased peripheral Rab5 puncta and a reduced number of early endosome antigen 1 (EEA1)-positive early endosomes. Accordingly, as indicated by FAK inhibition experiments and in FAK-null fibroblasts, adhesion-induced FAK activity increased Rab5-GTP levels. In fact, expression of WT FAK and FAK/Y180A/M183A (open conformation), but not FAK/Arg454 (kinase-dead), augmented Rab5-GTP levels in FAK-null fibroblasts and A549 cells. Moreover, expression of a GDP-bound Rab5 mutant (Rab5/S34N) or shRNA-mediated knockdown of endogenous Rab5 prevented FAK-induced A549 cell migration, whereas expression of WT or GTP-bound Rab5 (Rab5/Q79L), but not Rab5/S34N, promoted cell migration in FAK-null fibroblasts. Mechanistically, FAK co-immunoprecipitated with the GTPase-activating protein p85α in a phosphorylation (Tyr397)-dependent manner, preventing Rab5-GTP loading, as shown by knockdown and transfection recovery experiments. Taken together, these results reveal that FAK activates Rab5, leading to cell migration.

Hypoxia promotes Rab5 activation, leading to tumor cell migration, invasion and metastasis.

Hypoxia, a common condition of the tumor microenvironment, is associated with poor patient prognosis, tumor cell migration, invasion and metastasis. Recent evidence suggests that hypoxia alters endosome dynamics in tumor cells, leading to augmented cell proliferation and migration and this is particularly relevant, because endosomal components have been shown to be deregulated in cancer. The early endosome protein Rab5 is a small GTPase that promotes integrin trafficking, focal adhesion turnover, Rac1 activation, tumor cell migration and invasion. However, the role of Rab5 and downstream events in hypoxia remain unknown. Here, we identify Rab5 as a critical player in hypoxia-driven tumor cell migration, invasion and metastasis. Exposure of A549 human lung carcinoma, ZR-75, MDA-MB-231 and MCF-7 human breast cancer and B16-F10 mouse melanoma cells to hypoxia increased Rab5 activation, followed by its re-localization to the leading edge and association with focal adhesions. Importantly, Rab5 was required for hypoxia-driven cell migration, FAK phosphorylation and Rac1 activation, as shown by shRNA-targeting and transfection assays with Rab5 mutants. Intriguingly, the effect of hypoxia on both Rab5 activity and migration was substantially higher in metastatic B16-F10 cells than in poorly invasive B16-F0 cells. Furthermore, exogenous expression of Rab5 in B16-F0 cells predisposed to hypoxia-induced migration, whereas expression of the inactive mutant Rab5/S34N prevented the migration of B16-F10 cells induced by hypoxia. Finally, using an in vivo syngenic C57BL/6 mouse model, Rab5 expression was shown to be required for hypoxia-induced metastasis. In summary, these findings identify Rab5 as a key mediator of hypoxia-induced tumor cell migration, invasion and metastasis.

Impacto de intervención temprana a cuidadores de pacientes secuelados de un accidente cerebrovascular: estudio piloto / Impact of early intervention for stroke caregivers: a pilot study

Introducción: Los cuidadores de personas secueladas de un Accidente Cerebro Vascular (ACV), perciben que durante los primeros meses carecen de la información necesaria sobre el proceso de su familiar, afectando sobre su estado afectivo y percepción de estrés. Objetivo: Evaluar la intervención realizada a cuidadores de pacientes secuelados de un ACV como factor protector en el estado afectivo y de carga en los cuidadores. Sujetos y métodos: Se reclutaron cuidadores directos, de personas con secuelas de ACV, según Escala de Rankin durante el período hospitalario. Se realizo un taller teórico práctico, consistentes en 4 sesiones; 3 durante el periodo hospitalario del usuario y 1 dentro del primer mes posterior al alta, los temas tratados eran organización y distribución de la rutina, integración de rutinas de tiempo libre y relajación y manejo del paciente en el hogar. Se evalúo a los cuidadores con escalas diagnósticas de carga emocional (Zarit, Indice de Esfuerzo del Cuidador) y ansiedad (Goldberg). Resultados: Luego del taller hubo una reducción significativa de 20 por ciento en el número de cuidadores con depresión (p=0,036) y 37 por ciento en el número de cuidadores con ansiedad (p=0,034.). Asimismo hubo una disminución significativa en el puntaje de sobrecarga emocional del cuidador medido mediante la escala de Zarit (p = 0,044). Conclusiones: La intervención evaluada en el presente estudio piloto parece ser una medida que contribuye en disminuir la sobrecarga emocional y ansiedad del cuidador.

Background: Caregivers of ischemic stoke damaged patients feels during the first months after the event a lack of information on how to help their relative, affecting the sense of stress and anxiety. We made an intervention to caregivers of the stroke unit of the University of Chile Hospital, in 2008.Objective: Determine whether the intervention to caregivers of stroke damaged patients is a protective factor in their emotional state and stress on caregivers. Subjects and methods: Direct healthy caregivers were recruited with a severe impaired family member within the hospitalization period. Intervention was conducted in 4 sessions, 3 during the hospital period and 1 in his home within the first month after discharge, where the issues discussed with caregiver was self-care and patient management. To measure the intervention we evaluated before the workshop and 2 months after the last session with some standardized tests (Zarit, Caregiver Stress Index) and anxiety (Goldberg). Results: After the intervention there was a significant 20 percent reduction in the number of caregivers with depression (p=0.036) and 37percent in the number of caregivers with anxiety (p=0.034.). There was also a significant decrease in the score of caregiver's emotional overload measured by the Zarit scale (p=0.044). Conclusions: The intervention evaluated in this pilot study appears to be an effective measure in reducing the emotional overload and anxiety of the caregiver, with an evident improvement in their mood.