High incidence of severe cyclosporine neurotoxicity in children affected by haemoglobinopaties undergoing myeloablative haematopoietic stem cell transplantation: early diagnosis and prompt intervention ameliorates neurological outcome

<p>Abstract</p> <p>Background</p> <p>Neurotoxicity is a recognized complication of cyclosporine A (CSA) treatment. The incidence of severe CSA-related neurological complications following hematopoietic stem cell transplantation (HSCT) is 4-11%.</p> <p>Methods</p> <p>We describe 6 cases of CSA related neurotoxicity out of 67 matched related HSCT performed in paediatric Middle East patients affected by haemoglobinopaties (5 beta thalassemia major, 1 sickle cell disease-SCD). Conditioning regimen consisted of iv busulphan, cyclophosphamide and graft-versus-host-disease (GvHD) prophylaxis with CSA, methylprednisolone, methotrexate and ATG.</p> <p>Results</p> <p>All 6 patients presented prodromes such as arterial hypertension, headache, visual disturbances and vomiting, one to two days before overt CSA neurotoxicity. CSA neurotoxicity consisted of generalized seizures, signs of endocranial hypertension and visual disturbances at a median day of onset of 11 days after HSCT (range +1 to +40). Brain magnetic resonance imaging (MRI) performed in all subjects showed reversible leukoencephalopathy predominantly in the posterior regions of the brain (PRES) in 5/6 patients. EEG performed in 5/6 patients was always abnormal. Neurotoxicity was not explainable by high CSA blood levels, as all patients had CSA in the therapeutic range with a median of 178 ng/ml (range 69-250). CSA was promptly stopped and switched to tacrolimus with disappearance of clinical and radiological findings. All patients are symptoms-free at a median follow up of 882 days (range 60-1065).</p> <p>Conclusions</p> <p>Our experience suggests that paediatric patients with haemoglobinopaties have a high incidence of CSA related neurological events with no correlation between serum CSA levels and neurotoxicity. Prognosis is good following CSA removal. Specific prodromes such as arterial hypertension, headache or visual disturbances occurring in the early post-transplant period should be carefully evaluated with electrophysiological and MRI-based imaging in order to intervene promptly and avoid irreversible sequels.</p

The potential of eupraxia@sparc_lab for radiation based techniques

A proposal for building a Free Electron Laser, EuPRAXIA@SPARC_LAB, at the Laboratori Nazionali di Frascati, is at present under consideration. This FEL facility will provide a unique combination of a high brightness GeV-range electron beam generated in a X-band RF linac, a 0.5 PW-class laser system and the first FEL source driven by a plasma accelerator. The FEL will produce ultra-bright pulses, with up to 1012 photons/pulse, femtosecond timescale and wavelength down to 3 nm, which lies in the so called “water window”. The experimental activity will be focused on the realization of a plasma driven short wavelength FEL able to provide high-quality photons for a user beamline. In this paper, we describe the main classes of experiments that will be performed at the facility, including coherent diffraction imaging, soft X-ray absorption spectroscopy, Raman spectroscopy, Resonant Inelastic X-ray Scattering and photofragmentation measurements. These techniques will allow studying a variety of samples, both biological and inorganic, providing information about their structure and dynamical behavior. In this context, the possibility of inducing changes in samples via pump pulses leading to the stimulation of chemical reactions or the generation of coherent excitations would tremendously benefit from pulses in the soft X-ray region. High power synchronized optical lasers and a TeraHertz radiation source will indeed be made available for THz and pump–probe experiments and a split-and-delay station will allow performing XUV-XUV pump–probe experiments.Fil: Balerna, Antonella. Istituto Nazionale Di Fisica Nucleare.; ItaliaFil: Bartocci, Samanta. Università degli studi di Sassari; ItaliaFil: Batignani, Giovanni. Università degli studi di Roma "La Sapienza"; ItaliaFil: Cianchi, Alessandro. Universita Tor Vergata; Italia. Istituto Nazionale Di Fisica Nucleare.; ItaliaFil: Chiadroni, Enrica. Istituto Nazionale Di Fisica Nucleare.; ItaliaFil: Coreno, Marcello. Istituto Nazionale Di Fisica Nucleare.; Italia. Istituto di Struttura della Materia; ItaliaFil: Cricenti, Antonio. Istituto di Struttura della Materia; ItaliaFil: Dabagov, Sultan. Istituto Nazionale Di Fisica Nucleare.; Italia. National Research Nuclear University; Rusia. Lebedev Physical Institute; RusiaFil: Di Cicco, Andrea. Universita Degli Di Camerino; ItaliaFil: Faiferri, Massimo. Università degli studi di Sassari; ItaliaFil: Ferrante, Carino. Università degli studi di Roma “La Sapienza”; Italia. Center for Life Nano Science @Sapienza; ItaliaFil: Ferrario, Massimo. Istituto Nazionale Di Fisica Nucleare.; ItaliaFil: Fumero, Giuseppe. Università degli studi di Roma “La Sapienza”; ItaliaFil: Giannessi, Luca. Elettra-Sincrotrone Trieste; Italia. ENEA C.R. Frascati; ItaliaFil: Gunnella, Roberto. Universita Degli Di Camerino; ItaliaFil: Leani, Juan Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; ArgentinaFil: Lupi, Stefano. Università degli studi di Roma “La Sapienza”; Italia. Istituto Nazionale di Fisica Nucleare (INFN) Sezione di Roma La Sapienza; ItaliaFil: Macis, Salvatore. Università degli Studi di Roma Tor Vergata; Italia. Istituto Nazionale di Fisica Nucleare (INFN) Sezione di Roma Tor Vergata; ItaliaFil: Manca, Rosa. Università degli studi di Sassari; ItaliaFil: Marcelli, Augusto. Istituto Nazionale Di Fisica Nucleare.; Italia. Consiglio Nazionale delle Ricerche; ItaliaFil: Masciovecchio, Claudio. Elettra-Sincrotrone Trieste; ItaliaFil: Minicucci, Marco. Universita Degli Di Camerino; ItaliaFil: Morante, Silvia. Universita Tor Vergata; Italia. Istituto Nazionale Di Fisica Nucleare.; ItaliaFil: Perfetto, Enrico. Universita Tor Vergata; Italia. Consiglio Nazionale delle Ricerche; ItaliaFil: Petrarca, Massimo. Università degli studi di Roma "La Sapienza"; Italia. Istituto Nazionale Di Fisica Nucleare.; ItaliaFil: Pusceddu, Fabrizio. Università degli studi di Sassari; ItaliaFil: Rezvani, Javad. Istituto Nazionale Di Fisica Nucleare.; ItaliaFil: Robledo, José Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; ArgentinaFil: Rossi, Giancarlo. Centro Fermi—Museo Storico della Fisica e Centro Studi e Ricerche “Enrico Fermi”; Italia. Istituto Nazionale Di Fisica Nucleare.; Italia. Universita Tor Vergata; ItaliaFil: Sanchez, Hector Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; ArgentinaFil: Scopigno, Tullio. Center for Life Nano Science @Sapienza; Italia. Università degli studi di Roma "La Sapienza"; ItaliaFil: Stefanucci, Gianluca. Universita Tor Vergata; Italia. Istituto Nazionale Di Fisica Nucleare.; ItaliaFil: Stellato, Francesco. Universita Tor Vergata; Italia. Istituto Nazionale Di Fisica Nucleare.; ItaliaFil: Trapananti, Angela. Universita Degli Di Camerino; ItaliaFil: Villa, Fabio. Istituto Nazionale Di Fisica Nucleare.; Itali

Temporal evolution of neurophysiological and behavioral features of synapsin I/II/III triple knock-out mice

Deletion of one or more synapsin genes in mice results in a spontaneous epilepsy. In these animals, seizures can be evoked by opening or moving the cage. Aim of the present study was to characterize the evolution of the epileptic phenotype by neurophysiological examination and behavioral observation in synapsin triple knock-out (Syn-TKO) mice. Syn-TKO mice were studied from 20 postnatal days (PND) up to 6 months of age by video-EEG recording and behavioral observation. Background EEG spectral analysis was performed and data were compared to WT animals. Syn-TKO revealed rare spontaneous seizures and increased susceptibility to evoked seizures in mice from 60 to 100 PND. Spontaneous and evoked seizures presented similar duration and morphology. At times, seizures were followed by a post-ictal phase characterized by a 4 Hz rhythmic activity and immobility of the animal. Spectral analysis of background EEG evidenced a slowing of the theta-alpha peak in Syn-TKO mice compared to WT mice within the period from PND 40 to 100. These data indicate that Syn-TKO mice do not exhibit a linear progression of the epileptic phenotype, with the period corresponding to a higher susceptibility to evoked seizures characterized by background EEG slowing. This aspect might be connected to brain dysfunction often associated to epilepsy in the interictal period. (C) 2012 Elsevier B.V. All rights reserved

New Graphical User Interface for EXAFS analysis with the GNXAS suite of programs

International audienceGNXAS is a suite of programs based on multiple scattering calculations which performs a structural refinement of EXAFS spectra. It can be used for any system although it has been mainly developed to determine the local structure of disordered substances. We developed a user-friendly graphical user interface (GUI) to facilitate use of the codes by using wxPython. The developed GUI and the codes are multiplatform running on Windows, Macintosh and Linux systems, and are free shareware (http://gnxas.unicam.it). In this work we illustrate features and potentials of this newly developed version of GNXAS (w-GNXAS)

Cognitive dysfunction correlates with physical impairment in frail patients with acute myocardial infarction

To the best of our knowledge, the association of physical impairment and cognitive decline has never been investigated in frail patients with acute myocardial infarction