Treatment with antisense oligonucleotides in Duchenne’s disease

Se revisa el estado actual de los tratamientos de modificación del ARN de distrofina, que persiguen convertir la forma grave de la distrofia muscular de Duchenne a una forma leve (Becker), especialmente con la omisión del exón 51 mediante oligonucleótidos en antisentido y la terapia de restauración de la lectura de la distrofina, suprimiendo un codón de terminación prematura mediante PTC124. Constituyen un avance notable en el tratamiento. Consiguen una producción significativa de distrofina en el músculo esquelético, aunque, por el momento, los resultados clínicos son menos notables. Es de esperar que modificaciones químicas en la liberación y distribución corporal, así como en la captación celular de estos oligonucleótidos, aumenten su eficacia y seguridad, permitiendo el tratamiento crónico de la distrofia muscular de DuchenneIn this paper I review the results of the treatments directed to modify the mRNA of dystrophin with the goal of converting the severe Duchenne type to the milder Becker muscular dystrophy. Antisense oligomers potential to modify Duchenne muscular dystrophy (DMD) gene expression and therapeutic strategies to induce ribosomal read-through of nonsense mutations (PTC124) are described. They are an important advance in the treatment of DMD, so far unspecific. Significant expression of new dystrophin is observed in biopsies of peripheral muscle, although the functional improvement is not so encouraging. New modification of chemistries are expected to improve the liberation, broad distribution in muscles, as well as their efficacy and safety enough to allow a positive chronic treatment of DM

Research on WASH sector, environment and water resources in the Central Rift Valley of Ethiopia

Peer ReviewedPostprint (published version

Stars and brown dwarfs in the sigma Orionis cluster. III. OSIRIS/GTC low-resolution spectroscopy of variable sources

Context. Although many studies have been performed so far, there are still dozens of low-mass stars and brown dwarfs in the young sigma Orionis open cluster without detailed spectroscopic characterisation. Aims. We look for unknown strong accretors and disc hosts that were undetected in previous surveys. Methods. We collected low-resolution spectroscopy (R ~ 700) of ten low-mass stars and brown dwarfs in sigma Orionis with OSIRIS at the Gran Telescopio Canarias under very poor weather conditions. These objects display variability in the optical, infrared, Halpha, and/or X-rays on time scales of hours to years. We complemented our spectra with optical and near-/mid-infrared photometry. Results. For seven targets, we detected lithium in absorption, identified Halpha, the calcium doublet, and forbidden lines in emission, and/or determined spectral types for the first time. We characterise in detail a faint, T Tauri-like brown dwarf with an 18 h-period variability in the optical and a large Halpha equivalent width of -125+/-15 AA, as well as two M1-type, X-ray-flaring, low-mass stars, one with a warm disc and forbidden emission lines, the other with a previously unknown cold disc with a large inner hole. Conclusions. New unrevealed strong accretors and disc hosts, even below the substellar limit, await discovery among the list of known sigma Orionis stars and brown dwarfs that are variable in the optical and have no detailed spectroscopic characterisation yet.Comment: A&A, in press (accepted for publication in section 14. Catalogs and data of Astronomy and Astrophysics

Corpus callosum tumor as the presenting symptom of neurofibromatosis type 1 in a patient and literature review

Introducción. La neurofibromatosis tipo 1 (NF1) es uno de los síndromes neurocutáneos más frecuentes y puede asociarse a tumores intracraneales en cualquier localización, pero excepcionalmente en el cuerpo calloso. Objetivos. Presentar un caso de NF1 que se manifiesta como un tumor de cuerpo calloso y llevar a cabo una revisión de la incidencia de tumores del cuerpo calloso en nuestra casuística y en la bibliografía. Caso clínico. Niño visto desde los 3 años con criterios diagnósticos de NF1 (sin comprobación genética), que fue estudiado por resonancia magnética (RM) y RM espectroscópica. La RM mostró objetos brillantes en la neurofibromatosis en diversas zonas cerebrales y cerebelosas, posible tumor en el tronco cerebral (parte bulbar) y tumor en la zona derecha del esplenio del cuerpo calloso. La RM espectroscópica del posible tumor del tronco mostró hallazgos compatibles con tumoración glial de bajo grado. Se siguió su evolución hasta los 19 años sin que hubieran existido cambios clínicos ni en el tamaño de los tumores en las dos localizaciones. Sólo existen seis casos publicados de tumor del cuerpo calloso en pacientes con NF1. Conclusión. Presentamos un nuevo caso de un paciente con tumor del cuerpo calloso en un paciente con NF1. Las características de la imagen y la evolución clínica van a favor del carácter benigno de este tipo de tumorIntroduction. Neurofibromatosis type 1 (NF1) is one of the most frequent neurocutaneous syndromes. NF1 can be associated with intracranial tumors in any location, but only rarely in the corpus callosum. Aims. To describe a case of NF1 presenting as a tumor of the corpus callosum and to carry out a review of the incidence of the tumors of corpus callosum in our series and in the literature. Case report. We present a child who was studied since 3 years of age because of complete NF1 clinical diagnostic criteria (without genetic study). He was studied by MR and magnetic resonance spectroscopy (MRS). MR study showed neurofibromatosis bright objects distributed over several regions of the cerebral hemispheres and cerebellum, a possible brain stem tumor (bulbar zone) and the splenium of the corpus callosum. The MRS of the brain stem tumor showed changes consistent with a low grade glial tumor. The patient was followed until 19-years of age without demonstrating any changes in the clinical features or the tumor size in both locations Only six cases of corpus callosum tumor in patients with NF1 have been published to date. Conclusions. We present a new case with tumor of the corpus callosum and NF1. The imaging characteristics and the clinical course were in favour of the benign nature of this type of tumo

Optimal generalized quantum measurements for arbitrary spin systems

Positive operator valued measurements on a finite number of N identically prepared systems of arbitrary spin J are discussed. Pure states are characterized in terms of Bloch-like vectors restricted by a SU(2 J+1) covariant constraint. This representation allows for a simple description of the equations to be fulfilled by optimal measurements. We explicitly find the minimal POVM for the N=2 case, a rigorous bound for N=3 and set up the analysis for arbitrary N.Comment: LateX, 12 page