Intravitreal ranibizumab for myopic choroidal neovascularization: 12-month results

PURPOSE: The purpose of this study was to evaluate the safety and efficacy of intravitreal ranibizumab after 12 months in the treatment of choroidal neovascularization secondary to pathologic myopia. METHODS: This was a prospective, multicenter, consecutive, nonrandomized, interventional case series. The study included 34 eyes of 32 patients with choroidal neovascularization secondary to pathologic myopia; 13 eyes had previous photodynamic therapy, and 21 eyes had no previous treatment. The patients were followed for > or = 12 months. Best-corrected visual acuity, optical coherence tomography, and the presence of metamorphopsia were assessed monthly. RESULTS: Mean visual acuity improved 8 letters from baseline to 12-month follow-up, and the difference was statistically significant (P or = 3 lines, 44% improved > or = 2 lines, 65% improved > or = 1 line, and 79% improved > or = 0 lines. Central retinal thickness decreased significantly from baseline to the 12-month follow-up (P < 0.01). A mean of 3.6 treatments were performed during the 12-month follow-up, and no systemic or ocular side effects were registered during that time. CONCLUSION: One-year results of intravitreal ranibizumab for myopic choroidal neovascularization are very promising. Additional prospective studies are necessary to better determine long-term efficacy and safety

A Universal Model of Global Civil Unrest

Civil unrest is a powerful form of collective human dynamics, which has led to major transitions of societies in modern history. The study of collective human dynamics, including collective aggression, has been the focus of much discussion in the context of modeling and identification of universal patterns of behavior. In contrast, the possibility that civil unrest activities, across countries and over long time periods, are governed by universal mechanisms has not been explored. Here, we analyze records of civil unrest of 170 countries during the period 1919-2008. We demonstrate that the distributions of the number of unrest events per year are robustly reproduced by a nonlinear, spatially extended dynamical model, which reflects the spread of civil disorder between geographic regions connected through social and communication networks. The results also expose the similarity between global social instability and the dynamics of natural hazards and epidemics.Comment: 8 pages, 3 figure

Porto-systemic shunt using adrenal vein as a conduit; an alternative procedure for spleno – renal shunt

PubMed ID: 17555599Background. Currently, portal hypertension is still big problem for the patients with serious liver diseases. Variceal bleeding is one of the most important complications of portal hypertension. In case of failure of endoscopic and combined medical treatments, surgical decompressive shunts are required. We emphasized an alternative splenorenal shunt procedure using adrenal vein as a conduit. Case presentation. A 26-year-old male suffered from recurrent variceal bleeding was considered for surgical therapy. Although we planned to perform a distal splenorenal shunt procedure, it was observed to be difficult. Therefore left adrenal vein was used as a conduit between left renal vein and splenic vein after splenic artery was ligated. He did well and was discharged from the hospital on the postoperative day 6. In the follow up period for nine months, endoscopic and ultrasonographic examinations were normal. Conclusion. We concluded that, in case of failure to perform distal splenorenal shunt due to technical problems, alternative porto-systemic shunt procedure using the adrenal vein as a vascular conduit can be safely employed. © 2007 Aydin et al; licensee BioMed Central Ltd

Inhibiting ERK Activation with CI-1040 Leads to Compensatory Upregulation of Alternate MAPKs and Plasminogen Activator Inhibitor-1 following Subtotal Nephrectomy with No Impact on Kidney Fibrosis

Extracellular-signal regulated kinase (ERK) activation by MEK plays a key role in many of the cellular processes that underlie progressive kidney fibrosis including cell proliferation, apoptosis and transforming growth factor β1-mediated epithelial to mesenchymal transition. We therefore assessed the therapeutic impact of ERK1/2 inhibition using a MEK inhibitor in the rat 5/6 subtotal nephrectomy (SNx) model of kidney fibrosis. There was a twentyfold upregulation in phospho-ERK1/2 expression in the kidney after SNx in Male Wistar rats. Rats undergoing SNx became hypertensive, proteinuric and developed progressive kidney failure with reduced creatinine clearance. Treatment with the MEK inhibitor, CI-1040 abolished phospho- ERK1/2 expression in kidney tissue and prevented phospho-ERK1/2 expression in peripheral lymphocytes during the entire course of therapy. CI-1040 had no impact on creatinine clearance, proteinuria, glomerular and tubular fibrosis, and α-smooth muscle actin expression. However, inhibition of ERK1/2 activation led to significant compensatory upregulation of the MAP kinases, p38 and JNK in kidney tissue. CI-1040 also increased the expression of plasminogen activator inhibitor-1 (PAI-1), a key inhibitor of plasmin-dependent matrix metalloproteinases. Thus inhibition of ERK1/2 activation has no therapeutic effect on kidney fibrosis in SNx possibly due to increased compensatory activation of the p38 and JNK signalling pathways with subsequent upregulation of PAI-1

Steady-state modulation of voltage-gated K+ channels in rat arterial smooth muscle by cyclic AMP-dependent protein kinase and protein phosphatase 2B

Voltage-gated potassium channels (Kv) are important regulators of membrane potential in vascular smooth muscle cells, which is integral to controlling intracellular Ca2+ concentration and regulating vascular tone. Previous work indicates that Kv channels can be modulated by receptor-driven alterations of cyclic AMP-dependent protein kinase (PKA) activity. Here, we demonstrate that Kv channel activity is maintained by tonic activity of PKA. Whole-cell recording was used to assess the effect of manipulating PKA signalling on Kv and ATP-dependent K+ channels of rat mesenteric artery smooth muscle cells. Application of PKA inhibitors, KT5720 or H89, caused a significant inhibition of Kv currents. Tonic PKA-mediated activation of Kv appears maximal as application of isoprenaline (a β-adrenoceptor agonist) or dibutyryl-cAMP failed to enhance Kv currents. We also show that this modulation of Kv by PKA can be reversed by protein phosphatase 2B/calcineurin (PP2B). PKA-dependent inhibition of Kv by KT5720 can be abrogated by pre-treatment with the PP2B inhibitor cyclosporin A, or inclusion of a PP2B auto-inhibitory peptide in the pipette solution. Finally, we demonstrate that tonic PKA-mediated modulation of Kv requires intact caveolae. Pre-treatment of the cells with methyl-β-cyclodextrin to deplete cellular cholesterol, or adding caveolin-scaffolding domain peptide to the pipette solution to disrupt caveolae-dependent signalling each attenuated PKA-mediated modulation of the Kv current. These findings highlight a novel, caveolae-dependent, tonic modulatory role of PKA on Kv channels providing new insight into mechanisms and the potential for pharmacological manipulation of vascular tone

Transient Responses to Rapid Changes in Mean and Variance in Spiking Models

The mean input and variance of the total synaptic input to a neuron can vary independently, suggesting two distinct information channels. Here we examine the impact of rapidly varying signals, delivered via these two information conduits, on the temporal dynamics of neuronal firing rate responses. We examine the responses of model neurons to step functions in either the mean or the variance of the input current. Our results show that the temporal dynamics governing response onset depends on the choice of model. Specifically, the existence of a hard threshold introduces an instantaneous component into the response onset of a leaky-integrate-and-fire model that is not present in other models studied here. Other response features, for example a decaying oscillatory approach to a new steady-state firing rate, appear to be more universal among neuronal models. The decay time constant of this approach is a power-law function of noise magnitude over a wide range of input parameters. Understanding how specific model properties underlie these response features is important for understanding how neurons will respond to rapidly varying signals, as the temporal dynamics of the response onset and response decay to new steady-state determine what range of signal frequencies a population of neurons can respond to and faithfully encode

Simulación Clínica para la docencia de la Bioética en Ciencias de la Salud

En Ciencias de la Salud existe una creciente preocupación en cómo pueden adquirir los estudiantes las competencias prácticas sin perjudicar directamente a los pacientes, especialmente en procesos tan complejos como la comunicación de malas noticias o la identificación de conflictos éticos. Una de las estrategias formativas que se ha diseñado para ello es la Simulación Clínica cuyo objetivo es garantizar la seguridad y fomentar el trabajo en equipo, siendo clave poder facilitar dicha herramienta bajo la docencia virtual. Esto permite a los estudiantes interiorizar conceptos, ser críticos antes determinadas actitudes y hacer un entrenamiento de la toma de decisiones ante conflictos éticos. La Simulación Clínica se basa en técnicas de experiencias de aprendizaje estructuradas, donde se enseñan procesos y escenarios clínicos, que suponen una eficaz herramienta para la medición de competencias tanto en la ejecución de un proceso como en el trabajo en equipo, permitiendo adquirir hábitos de comportamiento que disminuyen las posibilidades de sufrir un daño, especialmente cuando se vaya a realizar directamente sobre el paciente. Algunos de los elementos clave de la simulación son: Establecer un objetivo claro y estructurado (uso de guiones); Escenarios y equipos lo más realistas posibles (para su desarrollo virtual será necesario la elaboración de material interactivo mediante el uso de medios audiovisuales específicos que han demostrado ser un material de enorme utilidad educativa en ciencias de la salud, especialmente en el ámbito de la bioética); Deben ser repetitivos ; Los niveles de competencias deben estar adaptadas al grado de dificultad; Se deben incorporar como parte clave de los programas formativos tanto pregrado como posgrado. Para mejorar el aprendizaje, además de la simulación se realizará un Debriefing o Feed-Back a través de la plataforma virtual para realizar una reflexión rigurosa que permita analizar los valores, conocimientos y actitudes que guían las actuaciones de los profesionales. Se basará por tanto en la revisión del evento simulado, a través de la conversación entre el profesor y los estudiantes, en la que los participantes analizarán sus acciones y reflexionarán para mejorar o mantener su rendimiento en el futuro. El objetivo de este proyecto es evaluar el impacto de la simulación clínica virtual en la adquisición de competencias en el ámbito de la bioética en estudiantes de enfermería y medicina. El equipo investigador tiene una gran experiencia en la elaboración e implementación de material audiovisual para la docencia en bioética, pero al no existir un material específico de este tipo para la docencia virtual, con este proyecto se pretende ofrecer al estudiante las herramientas necesarias que le posibiliten adquirir las competencias para poder enfrentarse a situaciones reales en la práctica asistencial