Écriture et réécriture du merveilleux féerique. Autour de Mélusine, études réunies par Matthew Morris et Jean-Jacques Vincensini

M. Morris et J.-J. Vincensini hanno curato questa edizione degli atti del colloquio organizzato a Poitiers nel 2008, durante il quale, a partire dallo studio dei testi e delle riscritture della leggenda della fata Mélusine, la riflessione si è estesa al concetto di meraviglioso in tutte le sue manifestazioni letterarie. Il volume è diviso in due sezioni introdotte dall’intervento di Claudio Galderisi (Mélusine: faber historiae suae, pp. 7-20), che della leggenda di Mélusine sottolinea il cara..

Epstein-Barr Virus (EBV)-Associated Haemophagocytic Syndrome

We describe the case of a 17- year old female who developed fatal haemophagocytic syndrome (HPS) one month following acute infection caused by Epstein-Barr virus (EBV). Despite initiation of treatment and reduction of EBV load, laboratory signs of HPS as severe cytopenia, hypofibrinogenemia, hyperferritinemia and hypertriglyceridemia persisted, and the patient died of multiorgan failure. HPS is a rare, but life-threatening complication of EBV infection

Visualización de cuencas hidrocarburíferas con realidad virtual

Se presenta una aplicación web de realidad virtual, orientada a la industria de Gas y Petróleo, capaz de construir una representación interactiva y tridimensional de una cuenca sedimentaria con potencial hidrocarburífero. Esta herramienta didáctica permite navegar un modelo 3D utilizando un casco de realidad virtual. Las vistas 3D se generan mediante la combinación de las técnicas de rendering tradicional con la técnica de Raymarching. Las superficies se describen a partir de funciones SDF (Signed Distance Functions) y son computadas mediante un píxel shader en la GPU. Esto permite alterar en tiempo real, la forma de las superficies sin utilizar triángulos. El usuario puede controlar con sus manos, un conjunto de operadores que permiten sustraer partes del volumen. La visualización del terreno permite analizar sus propiedades en distintas direcciones, facilitando la comprensión de los componentes de la cuenca y la identificación de reservorios de hidrocarburos.Sociedad Argentina de Informática e Investigación Operativ

Levetiracetam enhances the temozolomide effect on glioblastoma stem cell proliferation and apoptosis

Abstract BACKGROUND: Glioblastoma multiforme (GBM) is a highly aggressive brain tumor in which cancer cells with stem cell-like features, called cancer stem cells (CSCs), were identified. Two CSC populations have been previously identified in GBM, one derived from the GBM area called enhanced lesion (GCSCs) and the other one from the brain area adjacent to the tumor margin (PCSCs) that greatly differ in their growth properties and tumor-initiating ability. To date the most effective chemotherapy to treat GBM is represented by alkylating agents such as temozolomide (TMZ), whose activity can be regulated by histone deacetylases (HDACs) inhibitors through the modulation of O6-methylguanine-DNA methyltransferase (MGMT) expression. Levetiracetam (LEV), a relatively new antiepileptic drug, modulates HDAC levels ultimately silencing MGMT, thus increasing TMZ effectiveness. However, an improvement in the therapeutic efficacy of TMZ is needed. METHODS: Cell proliferation was investigated by BrdU cell proliferation assay and by Western Blot analysis of PCNA expression. Apoptosis was evaluated by Western Blot and Immunofluorescence analysis of the cleaved Caspase-3 expression. MGMT and HDAC4 expression was analyzed by Western Blotting and Immunofluorescence. Statistical analysis was performed using the Student's t test and Mann-Whitney test. RESULTS: Here we evaluated the effect of TMZ on the proliferation rate of the IDH-wildtype GCSCs and PCSCs derived from six patients, in comparison with the effects of other drugs such as etoposide, irinotecan and carboplatin. Our results demonstrated that TMZ was less effective compared to the other agents; hence, we verified the possibility to increase the effect of TMZ by combining it with LEV. Here we show that LEV enhances the effect of TMZ on GCSCs proliferation (being less effective on PCSCs) by decreasing MGMT expression, promoting HDAC4 nuclear translocation and activating apoptotic pathway. CONCLUSIONS: Although further studies are needed to determine the exact mechanism by which LEV makes GBM stem cells more sensitive to TMZ, these results suggest that the clinical therapeutic efficacy of TMZ in GBM might be enhanced by the combined treatment with LEV

Bone marrow megakaryocytic activation predicts fibrotic evolution of Philadelphia-negative myeloproliferative neoplasms

Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) have been traditionally considered as indistinctly slowly progressing conditions; recent evidence proves that a subset of cases have a rapid evolution, so that MPNs' prognosis needs to be personalized. We identified a new morphological parameter, defined as Megakaryocytic Activation (M-ACT) based on the coexistence of megakaryocytic emperipolesis, megakaryocytes (MK) clusters formation and evidence of arrangement of collagen fibers around the perimeter of MK. We retrospectively analyzed the bone marrow biopsy of two MPNs cohorts of patients with polycythemia (PV) (n=64) and non-PV patients [including essential thrombocythemia (ET), and early/prefibrotic primary myelofibrosis (PMF)] (n=222). M-ACT showed a significant correlation with splenomegaly, white blood cell (WBC) count, and LDH serum levels in both groups, with JAK2 V617F allele burden in PV patients, and with CALR mutations, and platelet count in non-PV patients. Progression-free survival, defined as PV-to-secondary MF progression and non-PV-to-overt PMF, was worse in both PV and early/prefibrotic PMF patients with M-ACT in comparison to those without M-ACT (P<.0001). Interestingly, M-ACT was not found in the subgroup of ET patients. In conclusion, M-ACT can be helpful in the differential diagnosis of MPNs and can represent a new morphologic parameter with a predictive value for progression of MPNs

Belantamab mafodotin: an important treatment option for vulnerable patients with triple class exposed relapsed and/or refractory multiple myeloma

Not available

Vitamin D deficiency and supplementation in patients with aggressive B-cell lymphomas treated with immunochemotherapy

Vitamin D deficiency has been reported to be a negative prognostic factor in elderly patients with aggressive B-cell lymphomas. In vitro data suggest that vitamin D supplementation may enhance rituximab-mediated cytotoxicity. We prospectively assessed 25-hydroxyvitamin D [25(OH)D] levels at diagnosis in a cohort of 155 patients with aggressive B-cell lymphomas of whom 128 had diffuse large B-cell lymphoma (DLBCL) not otherwise specified. 25(OH)D levels were deficient (<20\uc2 ng/mL) in 105 (67%), insufficient (20\ue2\u80\u9329\uc2 ng/mL) in 32 (21%), and normal (\ue2\u89\ua530\uc2 ng/mL) in 18 (12%) patients with a seasonal variation. Patient characteristics associated with lower 25(OH)D levels were poor performance status, overweight, B-symptoms, elevated LDH, lower albumin and hemoglobin levels. As a result of a change in practice pattern, 116 patients received vitamin D3 (cholecalciferol) supplementation that included a loading phase with daily replacement and subsequent maintenance phase with a weekly dose of 25,000\uc2 IU until end of treatment. This resulted in a significant increase in 25(OH)D levels, with normalization in 56% of patients. We analyzed the impact of 25(OH)D levels on event-free survival in patients treated with Rituximab-CHOP. 25(OH)D levels below 20\uc2 ng/mL at diagnosis and IPI were independently associated with inferior EFS. Moreover, patients with normalized 25(OH)D levels following supplementation showed better EFS than patients with persistently deficient/insufficient 25(OH)D levels. Our study provides the first evidence that achievement of normal 25(OH)D levels after vitamin D3 supplementation is associated with improved outcome in patients with DLBCL and deficient/insufficient 25(OH)D levels when receiving rituximab-based treatment

A Novel Morphological Parameter Predicting Fibrotic Evolution in Myeloproliferative Neoplasms: New Evidence and Molecular Insights

Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) represent a group of hematological disorders that are traditionally considered as indistinct slow progressing conditions; still, a subset of cases shows a rapid evolution towards myelofibrotic bone marrow failure. Specific abnormalities in the megakaryocyte lineage seem to play a central role in this evolution, especially in the bone marrow fibrosis but also in the induction of myeloproliferation. In this review, we analyze the current knowledge of prognostic factors of MPNs related to their evolution to myelofibrotic bone marrow failure. Moreover, we focused the role of the megakaryocytic lineage in the various stages of MPNs, with updated examples of MPNs in vitro and in vivo models and new therapeutic implications

α,ε-Hybrid Foldamers with 1,2,3-Triazole Rings: Order versus Disorder

Two epimeric series of foldamers characterized by the presence of a repeating alpha-epsilon-dipeptide unit have been prepared and characterized by 1H NMR and ECD spectroscopies together with X-ray diffraction. The first series contains L-Ala and D-4-carboxy-5-methyl-oxazolidin-2-one (D-Oxd). The other series contains L-Ala and L-Oxd. The L,D series of oligomers forms ordered beta-turn foldamers, characterized by a 311 pattern. The L,L series is not ordered. Simulations show that an ordered L,L trimer lies more than 2 kcal/mol higher than the more stable non folded extended conformations. Cu2+ forms complexes with both series, but is not able to order the L,L series. Analysis of the EPR spectra shows that the L,D foldamers bear two types of complexation sites that are assigned as a nitrogen donor of the triazole ring and a carboxylate ligand. The L-Ala-D-Oxd-Tri-CO motif may be introduced in any peptide sequence requiring the presence of a stable β-turn conformations, like in the study of protein-protein interactions