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Mechanosensitive ion channels are expressed in the central nervous system of the medicinal leech. The plasma membranes of neurons whose primary function is not sensory contain stretch-activated cation channels in relatively high density. Different stimuli, associated with membrane deformation, such as perfusion with hypotonic solutions or pressure pulses applied to the patch pipette, increase the channel's open probability. These cation channels contribute to macroscopic elevations of intracellular free calcium concentration produced by cell mechanical stimulation. Leech cation channels exhibit two activity modes differing both in kinetics and in conductance. In regenerating neurons one of these modes, characterized by long mean channel open time and high mechanosusceptibility, is preferentially expressed. Gentamicin, a voltage-dependent blocker of these channels, affects the neurite growth in culture. A possible role of mechanosensitive cation channels in the processes of neurite growth is discussed.

This study deals with the creation of a model to define the best allocation within the area of new projects for road infrastructures, and to evaluate the effectiveness of a road which is part of a wide-ranging project currently under construction, known as the Marches-Umbria Quadrilateral Project. The aim of the work is to develop a speedy, versatile instrument which will be able not only to calculate but also to interpret and correlate the various environmental, social, economic, technical and operational aspects of the construction of road works. Special attention is paid to the dynamics of the use and consumption of the natural habitats and the problems linked to the phenomena of ecological fragmentation caused by the road network and by settlements. The methodology which has been developed includes the collection and implementation within a dedicated territorial informative system of a wide range of information capable of defining the special characteristics of the area under study, which will then be interpreted and summarised by means of the application of a series of specific indicators. The defined indicators are subsequently integrated by applying techniques of multi-criterial analysis to define an index of concise evaluation capable of assessing and supporting the sensitivity of the territory to the integration of new road infrastructures. In order to validate the methodology, the proposed indices were applied to a study area in which a road infrastructure of considerable importance is currently being built to link central Italy from one side of the country to the other. El trabajo contempla la creación de un modelo para definir la mejor localización en el territorio de nuevos proyectos de infraestructuras viarias y su convalidación en una carretera que forma parte de un proyecto de gran envergadura denominado Cuadrilátero Marcas-Umbría, en vías de realización. El objetivo del trabajo consiste en la puesta a punto de una herramienta ágil y versátil, capaz de sopesar, interpretándolos de forma correlacionada, los distintos aspectos de carácter medioambiental, socioeconómico, técnico y operativo, ligados a la construcción de una obra viaria. Se ha prestado especial atención a las dinámicas de uso y consumo de los hábitats naturales y a las problemáticas vinculadas a los fenómenos de fragmentación ecológica provocados por la red viaria y los asentamientos. La metodología que se ha puesto a punto prevé la recogida y la implementación, dentro de un sistema de información territorial dedicado, de un amplio abanico de datos capaces de definir las características peculiares del ámbito que es objeto del estudio, posteriormente interpretados y reconducidos a síntesis mediante la aplicación de una serie de indicadores específicos. Los indicadores definidos se incorporan posteriormente mediante la aplicación de técnicas de análisis multicriterio para definir un índice de evaluación sintético capaz de estimar de forma correlacionada la sensibilidad del territorio ante la introducción de nuevas infraestructuras viarias. Para convalidar la metodología, los índices propuestos se han aplicado a un área de estudio donde se está construyendo una infraestructura viaria de importancia considerable para las conexiones transversales de Italia central.

Objectives: Limited data is available on HCV directly acting agents (DAAs) in haematopoietic stem cell transplant (HSCT) recipients. This study aimed at reporting the characteristics, treatment practices and treatment efficacy in HSCT recipients with chronic HCV. Methods: Prospective observational study from EBMT Infectious Diseases Working Party (IDWP). Patients with chronic HCV infection were included. Results: Between 12/2015 and 07/2018, 45 patients were included: male in 53%; median age 49 years (range, 8-75); acute leukaemia in 48.9%, lymphoma in 17.7%, non-malignant disorders in 22.3%; allogeneic HSCT in 84%; 77.8% no immunosuppressive treatment. Genotypes 1, 2, 3 and 4 were detected in 54.5%, 20.5%, 13.6% and 11.4%, respectively; advanced fibrosis in 40%, including cirrhosis in 11.4%. Overall, 37 (82.2%) patients received DAAs, at a median of 8.4 years after HSCT (16.2% within 6 months from HSCT). Sofosbuvir-based treatment was given to 62.2%. Thirty-five patients completed planned treatment course, with sustained virological response (SVR) of 89.1%, and 94.3% (33/35) in those who completed the treatment. Side effects possibly related to DAAs were reported in 5 (14%) and did not require treatment discontinuation. Conclusions: DAAs treatment was effective, saf e and feasible in this cohort of mainly allogeneic HSCT recipients with mild/moderate liver damage. (c) 2021 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

An unconventional approach to studying ion channel kinetics is exploited. Here we describe the effects of a periodically varying membrane potential on the open-closed transitions of single K+ channels. The use of cycle histograms allows one to measure the transition probabilities as functions of the stimulus phase. The results show that such probabilities vary with the stimulation frequency and with the stimulus history, thus highlighting a dynamic aspect in the switching of this ion channel.

The voltage dependence of stretch-activated cation channels in leech central neurons was studied in cell-free configurations of the patch-clamp technique. We established that stretch-activated channels excised from identified cell bodies of desheathed ganglia, as well as from neurons in culture, were slowly and reversibly activated by depolarizing membrane potentials. Negative pressure stimuli, applied to the patch pipette during a slow periodical modulation of membrane potential, enhanced channel activity, whereas positive pressures depressed it. Voltage-induced channel activation was observed, with soft glass pipettes, both in inside-out and outside-out membrane patches, at negative and positive reference potentials, respectively. The results presented in this study demonstrate that membrane depolarization induces slow activation of stretch-activated channels of leech central neurons. This phenomenon is similar to that found in Xenopus oocytes, however, some peculiar features of the voltage dependence in leech stretch-activated channels indicate that specific membrane-glass interactions might not necessarily be involved. Moreover, following depolarization, stretch-activated channels in membrane patches from neurons in culture exhibited significantly shorter delay to activation (sec) than their counterparts from neurons of freshly isolated ganglia (hundreds of sec).