Cost-effectiveness of intravitreal therapy with both anti-VEGF and Dexamethasone implant in patients with Diabetic Macular Edema

Purpose: The aim of this study was to evaluate the cost-effectiveness of intravitreal therapy (IVT) with both anti-VEGF and Dexamethasone implant in patients with Diabetic Macular Edema (DME) during two years’ follow-up. Methods: A retrospective review of 191 patients (382 eyes) with type I and II diabetes and DME was performed. Pre-IVT and final best correct visual acuity (BCVA), central macular thickness (CMT), intraocular pressure (IOP), number and type of IVT,number of examinations, and fluorescein angiography were assessed. Based on surgery procedure other than IVT, patients were divided into 5 groups. To avoid bias, we analysed only patients who had undergone cataract surgery before (group 1) or during enrolment (group 2). Results: 41 eyes from Group 1 and 48 eyes from group 2 were evaluated. Median BCVA ranged between 20/80 and 20/63 Snellen (P = 0.008) in Group 1 and from 20/63 to 20/40 Snellen (P = 0.0035) in Group 2, while improvement up to 1 Snellen line was observed in 58.5 and 68.75% of eyes in Group 1 and 2, respectively.In terms of median CMT, a statistically reduction (P = 0.0007) was found in Group 2 (-85 μm), whereas no statistical differences were found in Group 1. The two groups showed no statistically significant difference in median IOP. The estimated cost per eye was €7803 in Group 1 and €8988 Group 2, whereas the mean cost per patient was €15190 and €16580 in Group 1 and 2, respectively. Analysis between groups did not show any statistical difference in the considered parameters. Conclusions: In this study, despite the high treatment cost, vision improvement in DME patients undergoing IVT was disappointing. Our results emphasise the need for a better understanding of the cost-effectiveness of DME treatmen

Arc Statistics in Clusters: Galaxy Contribution

The frequency with which background galaxies appear as long arcs as a result of gravitational lensing by foreground clusters of galaxies has recently been found to be a very sensitive probe of cosmological models by Bartelmann et al. (1998). They have found that such arcs would be expected far less frequently than observed (by an order of magnitude) in the currently favored model for the universe, with a large cosmological constant $\Omega_\Lambda \sim 0.7$. Here we analyze whether including the effect of cluster galaxies on the likelihood of clusters to generate long-arc images of background galaxies can change the statistics. Taking into account a variety of constraints on the properties of cluster galaxies, we find that there are not enough sufficiently massive galaxies in a cluster for them to significantly enhance the cross section of clusters to generate long arcs. We find that cluster galaxies typically enhance the cross section by only $\lesssim 15$.Comment: 19 pages, 1 figure, uses aasms4.sty, submitted to Ap

Regulation of S1PR2 by the EBV oncogene LMP1 in aggressive ABC subtype diffuse large B cell lymphoma.

The Epstein-Barr virus (EBV) is found almost exclusively in the activated B cell (ABC) subtype of diffuse large B cell lymphoma (DLBCL), yet its contribution to this tumour remains poorly understood. We have focussed on the EBV-encoded latent membrane protein-1 (LMP1), a constitutively activated CD40 homologue expressed in almost all EBV-positive DLBCL and which can disrupt germinal centre (GC) formation and drive lymphomagenesis in mice. Comparison of the transcriptional changes that follow LMP1 expression with those that follow transient CD40 signalling in human GC B cells enabled us to define pathogenic targets of LMP1 aberrantly expressed in ABC-DLBCL. These included the down-regulation of S1PR2, a sphingosine-1-phosphate (S1P) receptor that is transcriptionally down-regulated in ABC-DLBCL, and when genetically ablated leads to DLBCL in mice. Consistent with this we found that LMP1-expressing primary ABC-DLBCL were significantly more likely to lack S1PR2 expression than were LMP1-negative tumours. Furthermore, we showed that the down-regulation of S1PR2 by LMP1 drives a signalling loop leading to constitutive activation of the phosphatidylinositol-3-kinase (PI3-K) pathway. Finally, core LMP1-PI3-K targets were enriched for lymphoma-related transcription factors and genes associated with shorter overall survival in patients with ABC-DLBCL. Our data identify a novel function for LMP1 in aggressive DLBCL

Deregulated sphingolipid metabolism and membrane organization in neurodegenerative disorders

Sphingolipids are polar membrane lipids present as minor components in eukaryotic cell membranes. Sphingolipids are highly enriched in nervous cells, where they exert important biological functions. They deeply affect the structural and geometrical properties and the lateral order of cellular membranes, modulate the function of several membrane-associated proteins, and give rise to important intra- and extracellular lipid mediators. Sphingolipid metabolism is regulated along the differentiation and development of the nervous system, and the expression of a peculiar spatially and temporarily regulated sphingolipid pattern is essential for the maintenance of the functional integrity of the nervous system: sphingolipids in the nervous system participate to several signaling pathways controlling neuronal survival, migration, and differentiation, responsiveness to trophic factors, synaptic stability and synaptic transmission, and neuron-glia interactions, including the formation and stability of central and peripheral myelin. In several neurodegenerative diseases, sphingolipid metabolism is deeply deregulated, leading to the expression of abnormal sphingolipid patterns and altered membrane organization that participate to several events related to the pathogenesis of these diseases. The most impressive consequence of this deregulation is represented by anomalous sphingolipid-protein interactions that are at least, in part, responsible for the misfolding events that cause the fibrillogenic and amyloidogenic processing of disease-specific protein isoforms, such as amyloid beta peptide in Alzheimer's disease, huntingtin in Huntington's disease, alpha-synuclein in Parkinson's disease, and prions in transmissible encephalopathies. Targeting sphingolipid metabolism represents today an underexploited but realistic opportunity to design novel therapeutic strategies for the intervention in these diseases

Contributo alla conoscenza floristica della Liguria: resoconto dell'escursione del Gruppo di Floristica nel 2005 sull'Appennino Ligure orientale.

Contribution to the floristic knowledge of Liguria: report of the excursion of the "Gruppo di Floristica" (S.B.I.) held in 2005. Are here presented the results of the excursion of the "Gruppo di Floristica" of the Italian Botanical Society, held in 1-4 june 2005 in Liguria region. 439 units are recorded. 31 are new and 8 are confirmed for the regional flora