Association between biomechanical alterations and migratory ability of semaphorin-3A-treated thymocytes.

BACKGROUND: Class 3 semaphorins are soluble proteins involved in cell adhesion and migration. Semaphorin-3A (Sema3A) was initially shown to be involved in neuronal guidance, and it has also been reported to be associated with immune disorders. Both Sema3A and its receptors are expressed by most immune cells, including monocytes, macrophages, and lymphocytes, and these proteins regulate cell function. Here, we studied the correlation between Sema3A-induced changes in biophysical parameters of thymocytes, and the subsequent repercussions on cell function. METHODS: Thymocytes from mice were treated in vitro with Sema3A for 30min. Scanning electron microscopy was performed to assess cell morphology. Atomic force microscopy was performed to further evaluate cell morphology, membrane roughness, and elasticity. Flow cytometry and/or fluorescence microscopy were performed to assess the F-actin cytoskeleton and ROCK2. Cell adhesion to a bovine serum albumin substrate and transwell migration assays were used to assess cell migration. RESULTS: Sema3A induced filopodia formation in thymocytes, increased membrane stiffness and roughness, and caused a cortical distribution of the cytoskeleton without changes in F-actin levels. Sema3A-treated thymocytes showed reduced substrate adhesion and migratory ability, without changes in cell viability. In addition, Sema3A was able to down-regulate ROCK2. CONCLUSIONS: Sema3A promotes cytoskeletal rearrangement, leading to membrane modifications, including increased stiffness and roughness. This effect in turn affects the adhesion and migration of thymocytes, possibly due to a reduction in ROCK2 expression. GENERAL SIGNIFICANCE: Sema3A treatment impairs thymocyte migration due to biomechanical alterations in cell membranes.

Impacto da reforma de financiamento de hospitais de ensino no Brasil / Impacto de la reforma del financiamiento de hospitales de enseñanza en Brasil / Impact of the funding reform of teaching hospitals in Brazil

OBJETIVO: Avaliar o impacto da reforma de financiamento na produtividade de hospitais de ensino. MÉTODOS: A partir do Sistema de Informações dos Hospitais Universitários Federais, foram construídas fronteiras de eficiência e produtividade em 2003 e 2006 com técnicas de programação linear, por meio de análise envoltória de dados, considerando retornos variáveis de escala e orientação a input. Calculou-se o Índice de Malmquist para identificar mudanças de desempenho ao longo dos anos quanto à eficiência técnica (razão entre os escores de eficiência em tempos distintos) e eficiência tecnológica (deslocamento da fronteira no período considerado). RESULTADOS: Houve aumento do aporte financeiro em 51% e da eficiência técnica dos hospitais de ensino (de 11, passaram a ser 17 na fronteira empírica de eficiência), o mesmo não ocorrendo com a fronteira tecnológica. O uso de análise envoltória de dados estabeleceu os benchmarks para as unidades ineficientes (antes e depois da reforma) e os escores de eficiência mostraram uma possível correlação entre a eficiência técnica encontrada e a intensidade e dedicação de ensino. CONCLUSÕES: A reforma permitiu o desenvolvimento de melhorias gerenciais, mas é necessário maior tempo de acompanhamento para observar mudanças mais efetivas do modelo de financiamento.

OBJECTIVE: To assess the impact of funding reform on the productivity of teaching hospitals. METHODS: Based on the Information System of Federal University Hospitals of Brazil, 2003 and 2006 efficiency and productivity were measured using frontier methods with a linear programming technique, data envelopment analysis, and input-oriented variable returns to scale model. The Malmquist index was calculated to detect changes during the study period: "technical efficiency change," or the relative variation of the efficiency of each unit; and "technological change" after frontier shift. RESULTS: There was 51% mean budget increase and improvement of technical efficiency of teaching hospitals (previously 11, 17 hospitals reached the empirical efficiency frontier) but the same was not seen for the technology frontier. Data envelopment analysis set benchmark scores for each inefficient unit (before and after reform) and there was a positive correlation between technical efficiency and teaching intensity and dedication. CONCLUSIONS: The reform promoted management improvements but there is a need of further follow-up to assess the effectiveness of funding changes.

OBJETIVO: Evaluar el impacto de la reforma de financiamiento en la productividad de hospitales de enseñanza. MÉTODOS: A partir del Sistema de Informaciones de los Hospitales Universitarios Federales de Brasil, se construyeron fronteras de eficiencia y productividad en 2003 y 2006 con técnicas de programación linear, por medio de análisis envoltorio de datos, considerando retornos variables de escala y orientación a input. Se calculó el Índice de Malmquist para identificar cambios de desempeño a lo largo de los años con relación a la eficiencia técnica (cociente entre los puntajes de eficiencia en tiempos distintos) y eficiencia tecnológica (desplazamiento de la frontera en el período considerado). RESULTADOS: Hubo aumento del aporte financiero en 51% y de la eficiencia técnica de los hospitales de enseñanza (de 11, pasaron a ser 17 en la frontera empírica de eficiencia), no ocurriendo el mismo con la frontera tecnológica. El uso del análisis envoltorio de datos estableció los benchmarks para las unidades ineficientes (antes y después de la reforma) y los puntajes de eficiencia mostraron una posible correlación entre la eficiencia técnica encontrada y la intensidad y dedicación de enseñanza. CONCLUSIONES: La reforma permitió el desarrollo de mejoras gerenciales, pero es necesario mayor tiempo de acompañamiento para observar cambios más efectivos del modelo de financiamiento.

[Impact of the funding reform of teaching hospitals in Brazil]. / Impacto da reforma de financiamento de hospitais de ensino no Brasil.

OBJECTIVE: To assess the impact of funding reform on the productivity of teaching hospitals. METHODS: Based on the Information System of Federal University Hospitals of Brazil, 2003 and 2006 efficiency and productivity were measured using frontier methods with a linear programming technique, data envelopment analysis, and input-oriented variable returns to scale model. The Malmquist index was calculated to detect changes during the study period: 'technical efficiency change,' or the relative variation of the efficiency of each unit; and 'technological change' after frontier shift. RESULTS: There was 51% mean budget increase and improvement of technical efficiency of teaching hospitals (previously 11, 17 hospitals reached the empirical efficiency frontier) but the same was not seen for the technology frontier. Data envelopment analysis set benchmark scores for each inefficient unit (before and after reform) and there was a positive correlation between technical efficiency and teaching intensity and dedication. CONCLUSIONS: The reform promoted management improvements but there is a need of further follow-up to assess the effectiveness of funding changes.