Simulador de Técnicas de Depuração Extra-Renal/Hemofiltração: Uso da Simulação para Treino no Manuseamento deste Dispositivo

Introdução: A simulação possibilita o ensino e treino de técnicas de suporte de vida complexas sem riscos para o doente. Até ao momento, as únicas opções de treino no manuseamento de terapêuticas de depuração extra-renal contínua (TDEC) eram a aprendizagem directa em doentes submetidos a esta técnica ou mediante observação dos efeitos da manipulação do circuito não conectado ao doente. Por este motivo foi elaborado um simulador de TDEC, usado em cursos de simulação realizados para treino de equipas de cuidados intensivos pediátricos (UCIP). Objectivos: Analisar a performance e utilidade de um novo simulador que possibilita o controlo externo do dispositivo de TDEC, simulando "in situ" cenários que mimetizam condições de doentes tratados com TDEC. Métodos: Foi criado um dispositivo que, uma vez conectado ao aparelho de TDEC, permite o controlo em tempo real de todas as pressões de hemofiltração, de acordo com as condições clínicas e acções dos participantes. Foram simulados diversos cenários e complicações possíveis em doentes submetidos a estas técnicas e avaliada a performance deste dispositivo "in vitro". A satisfação dos participantes foi avaliada mediante a aplicação de um inquérito. Resultados: Foram realizados 4 cursos de TDEC de Maio de 2009 a Março de 2012. Incluídos 60 participantes, todos com experiência clínica prévia em UCIP. Realizados 32 cenários, abrangendo complicações relacionados com o cateter, coagulação dos filtros e ajuste inadequado dos parâmetros de hemofiltração. Nos cenários simulados, o dispositivo simulador permitiu, em tempo real, mudanças simples e rápidas nas pressões do monitor de TDEC e em resposta às atitudes tomadas pelos participantes para a sua resolução. Não foram registadas intercorrências relacionadas com disfunção do dispositivo. Os participantes consideraram-no muito útil como ferramenta de aprendizagem activa, permitindo uma gestão realista das condições clínicas simuladas, com potencial impacto sobre a sua futura prática diária. Os instrutores consideraram-no fácil de manusear e realista. Conclusões: Este simulador permite uma simulação mais fidedigna dos cenários de TDEC, resolvendo o problema da interferência do instrutor no cenário simulado. Este poderia melhorar as capacidades dos simuladores de alta fidelidade disponíveis e utilizar-se como uma ferramenta docente na formação de profissionais de saúde

Arginine-rich peptides destabilize the plasma membrane, consistent with a pore formation translocation mechanism of cell-penetrating peptides

Recent molecular-dynamics simulations have suggested that the arginine-rich HIV Tat peptides translocate by destabilizing and inducing transient pores in phospholipid bilayers. In this pathway for peptide translocation, Arg residues play a fundamental role not only in the binding of the peptide to the surface of the membrane, but also in the destabilization and nucleation of transient pores across the bilayer. Here we present a molecular-dynamics simulation of a peptide composed of nine Args (Arg-9) that shows that this peptide follows the same translocation pathway previously found for the Tat peptide. We test experimentally the hypothesis that transient pores open by measuring ionic currents across phospholipid bilayers and cell membranes through the pores induced by Arg-9 peptides. We find that Arg-9 peptides, in the presence of an electrostatic potential gradient, induce ionic currents across planar phospholipid bilayers, as well as in cultured osteosarcoma cells and human smooth muscle cells. Our results suggest that the mechanism of action of Arg-9 peptides involves the creation of transient pores in lipid bilayers and cell membranes.Facultad de Ciencias Exacta

Continuous propofol perfusion in critically ill children

Objetivo: Describir la sedación con perfusión continua de propofol en ni˜nos en estado crítico. Dise˜no: Estudio observacional descriptivo retrospectivo. Ámbito: Unidad de cuidados intensivos pediátricos. Pacientes: Pacientes que requirieron sedoanalgesia entre el 1 de octubre de 2009 y el 30 de septiembre de 2010. Intervenciones: Ninguna. Variables recogidas: Demográficas, clínicas, de laboratorio, diagnóstico, tratamiento, complicaciones y evolución de cada paciente. Se analizaron los posibles efectos adversos asociados a la administración de propofol, comparando el grupo de pacientes a los que se les administró con el resto de los ni˜nos críticos. Resultados: Recibieron propofol en perfusión continua 71 de los 222 pacientes recogidos (32%). Los fármacos sedoanalgésicos más utilizados fueron el midazolam, seguido del fentanilo y del propofol. La dosis media de propofol fue de 2,1 mg/kg/h [desviación estándar (DE) 1,3, rango: 0,5-6)] y la duración media de 6,7 días (DE 8,5; rango: 0,5-40). La edad media fue de 45,8 meses (mediana 24; rango intercuartil: 7-65), siendo el 52% varones. Ningún paciente presentó síndrome de infusión por propofol ni otros efectos adversos graves. Los pacientes tratados con propofol presentaron con mayor frecuencia algunas alteraciones analíticas que el resto, pero no se demostró relación causa efecto con la administración del fármaco. No existieron diferencias significativas en los niveles de lactato ni en la incidencia de infecciones entre ambos grupos. Conclusión: el propofol a una dosis de 1 a 4 mg/kg/h puede utilizarse como un fármaco alternativo para la sedación de mantenimiento en los ni˜nos críticamente enfermos. Sin embargo son necesarios más estudios que valoren su eficacia y seguridad.Q3Q3Artículo original410-415Objective: To describe sedation with continuous perfusion of propofol in critically ill children. Design: A retrospective, descriptive observational study was carried out. Setting: A pediatric intensive care unit. Patients: Pediatric patients requiring sedoanalgesia between October 1, 2009 and September 30, 2010. Interventions: None. Data collected: Demographic, clinical and laboratory test variables, diagnosis, treatment, complications and evolution in each patient. In addition, the potential adverse effects associated with propofol administration were analyzed. Results: Midazolam, fentanyl and propofol were the most commonly used sedative and analgesic drugs. Seventy-one out of 222 patients (32%) received propofol in continuous infusion. The average dose was 2.1 mg/kg/h (SD 1.3, range: 0.5 to 6), and the average duration of treatment was of 6.7 days (SD 8.5 range 0.5---40). Fifty-two percent were males, and the mean patient age was 45.8 months (median: 24; interquartile range: 7-65). No patient developed propofol infusion syndrome or other serious drug-related adverse effects. Patients treated with propofol showed more abnormal laboratory test findings, although no relationship to drug administration could be demonstrated. There were no significant differences in lactate level or in the incidence of infection in either group. Conclusions: Propofol at a dose of 1 to 4 mg/kg/h is a safe alternative for sustained sedation in critically ill children. However, further studies are needed to assess its effects and safety profile

Backbone rigidity and static presentation of guanidinium groups increases cellular uptake of arginine-rich cell-penetrating peptides

In addition to endocytosis-mediated cellular uptake, hydrophilic cell-penetrating peptides are able to traverse biological membranes in a non-endocytic mode termed transduction, resulting in immediate bioavailability. Here we analysed structural requirements for the non-endocytic uptake mode of arginine-rich cell-penetrating peptides, by a combination of live-cell microscopy, molecular dynamics simulations and analytical ultracentrifugation. We demonstrate that the transduction efficiency of arginine-rich peptides increases with higher peptide structural rigidity. Consequently, cyclic arginine-rich cell-penetrating peptides showed enhanced cellular uptake kinetics relative to their linear and more flexible counterpart. We propose that guanidinium groups are forced into maximally distant positions by cyclization. This orientation increases membrane contacts leading to enhanced cell penetration

Arginine-rich peptides destabilize the plasma membrane, consistent with a pore formation translocation mechanism of cell-penetrating peptides

Recent molecular-dynamics simulations have suggested that the arginine-rich HIV Tat peptides translocate by destabilizing and inducing transient pores in phospholipid bilayers. In this pathway for peptide translocation, Arg residues play a fundamental role not only in the binding of the peptide to the surface of the membrane, but also in the destabilization and nucleation of transient pores across the bilayer. Here we present a molecular-dynamics simulation of a peptide composed of nine Args (Arg-9) that shows that this peptide follows the same translocation pathway previously found for the Tat peptide. We test experimentally the hypothesis that transient pores open by measuring ionic currents across phospholipid bilayers and cell membranes through the pores induced by Arg-9 peptides. We find that Arg-9 peptides, in the presence of an electrostatic potential gradient, induce ionic currents across planar phospholipid bilayers, as well as in cultured osteosarcoma cells and human smooth muscle cells. Our results suggest that the mechanism of action of Arg-9 peptides involves the creation of transient pores in lipid bilayers and cell membranes.Facultad de Ciencias Exacta

Empty Urbanism: the bursting of the Spanish housing bubble

The depth of the Spanish housing crisis manifests itself in the collapse of construction activity and in the amount of housing and land stocks. The geography of the crisis shows its widespread nature, and the intensity of the previous bubble explains spatial differences. Resulting from this collapse are some problematic areas of 'empty urbanism'. An enormous land bubble, emerging from the peculiar Spanish urban development model, was a key factor in the impacts - caused by the crisis - on the territory and land-use plans. The crisis has demonstrated the unsustainability of this and the urgency of change in the existing land-use plans

Robust averaging protects decisions from noise in neural computations

An ideal observer will give equivalent weight to sources of information that are equally reliable. However, when averaging visual information, human observers tend to downweight or discount features that are relatively outlying or deviant (‘robust averaging’). Why humans adopt an integration policy that discards important decision information remains unknown. Here, observers were asked to judge the average tilt in a circular array of high-contrast gratings, relative to an orientation boundary defined by a central reference grating. Observers showed robust averaging of orientation, but the extent to which they did so was a positive predictor of their overall performance. Using computational simulations, we show that although robust averaging is suboptimal for a perfect integrator, it paradoxically enhances performance in the presence of “late” noise, i.e. which corrupts decisions during integration. In other words, robust decision strategies increase the brain’s resilience to noise arising in neural computations during decision-making