Primary mediastinal lymphoma: diagnosis and treatment options.

Primary mediastinal large B-cell lymphoma (PMBCL) is a unique B-cell lymphoma variant that arises from a putative thymic medulla B cell. It constitutes 2-4% of non-Hodgkin lymphomas and occurs most frequently in young females. PMBCL is characterized by a diffuse proliferation of medium-to-large B cells associated with sclerosis. Molecular analysis shows that PMBCL is a distinct entity compared to other types of diffuse large B-cell lymphomas. PMBCL is characterized by a locally invasive anterior mediastinal bulky mass. The combination of rituximab with CHOP/CHOP-like regimens followed by mediastinal radiation therapy (RT) is associated with a 5-year progression-free survival of 75-85%. However, the role of consolidation RT still remains uncertain. More intensive regimens, such as DA-EPOCH-R without mediastinal RT, have shown very promising results. The conclusive role of PET-CT scan requires prospective studies and there is hope that this may allow to de-escalate RT and accordingly yield reliable prognostic information

Formation of a Unique Cluster of G-Quadruplex Structures in the HIV-1 nef Coding Region: Implications for Antiviral Activity

G-quadruplexes are tetraplex structures of nucleic acids that can form in G-rich sequences. Their presence and functional role have been established in telomeres, oncogene promoters and coding regions of the human chromosome. In particular, they have been proposed to be directly involved in gene regulation at the level of transcription. Because the HIV-1 Nef protein is a fundamental factor for efficient viral replication, infectivity and pathogenesis in vitro and in vivo, we investigated G-quadruplex formation in the HIV-1 nef gene to assess the potential for viral inhibition through G-quadruplex stabilization. A comprehensive computational analysis of the nef coding region of available strains showed the presence of three conserved sequences that were uniquely clustered. Biophysical testing proved that G-quadruplex conformations were efficiently stabilized or induced by G-quadruplex ligands in all three sequences. Upon incubation with a G-quadruplex ligand, Nef expression was reduced in a reporter gene assay and Nef-dependent enhancement of HIV-1 infectivity was significantly repressed in an antiviral assay. These data constitute the first evidence of the possibility to regulate HIV-1 gene expression and infectivity through G-quadruplex targeting and therefore open a new avenue for viral treatment. © 2013 Perrone et al

Intermittent turbulent dynamo at very low and high magnetic Prandtl numbers

Context: Direct numerical simulations have shown that the dynamo is efficient even at low Prandtl numbers, i.e., the critical magnetic Reynolds number Rm_c necessary for the dynamo to be efficient becomes smaller than the hydrodynamic Reynolds number Re when Re -> infinity. Aims: We test the conjecture (Iskakov et al. 2007) that Rm_c actually tends to a finite value when Re -> infinity, and we study the behavior of the dynamo growth factor \gamma\ at very low and high magnetic Prandtl numbers. Methods: We use local and nonlocal shell-models of magnetohydrodynamic (MHD) turbulence with parameters covering a much wider range of Reynolds numbers than direct numerical simulations, but of astrophysical relevance. Results: We confirm that Rm_c tends to a finite value when Re -> infinity. The limit for Rm -> infinity of the dynamo growth factor \gamma\ in the kinematic regime behaves like Re^\beta, and, similarly, the limit for Re -> infinity of \gamma\ behaves like Rm^{\beta'}, with \beta=\beta'=0.4. Conclusion: Comparison with a phenomenology based on an intermittent small-scale turbulent dynamo, together with the differences between the growth rates in the different local and nonlocal models, indicate a weak contribution of nonlocal terms to the dynamo effect.Comment: 5 pages, 6 figure

Self-Organized Criticality model for Brain Plasticity

Networks of living neurons exhibit an avalanche mode of activity, experimentally found in organotypic cultures. Here we present a model based on self-organized criticality and taking into account brain plasticity, which is able to reproduce the spectrum of electroencephalograms (EEG). The model consists in an electrical network with threshold firing and activity-dependent synapse strenghts. The system exhibits an avalanche activity power law distributed. The analysis of the power spectra of the electrical signal reproduces very robustly the power law behaviour with the exponent 0.8, experimentally measured in EEG spectra. The same value of the exponent is found on small-world lattices and for leaky neurons, indicating that universality holds for a wide class of brain models.Comment: 4 pages, 3 figure

Conserved presence of G-quadruplex forming sequences in the Long Terminal Repeat Promoter of Lentiviruses

G-quadruplexes (G4s) are secondary structures of nucleic acids that epigenetically regulate cellular processes. In the human immunodeficiency lentivirus 1 (HIV-1), dynamic G4s are located in the unique viral LTR promoter. Folding of HIV-1 LTR G4s inhibits viral transcription; stabilization by G4 ligands intensifies this effect. Cellular proteins modulate viral transcription by inducing/unfolding LTR G4s. We here expanded our investigation on the presence of LTR G4s to all lentiviruses. G4s in the 5'-LTR U3 region were completely conserved in primate lentiviruses. A G4 was also present in a cattle-infecting lentivirus. All other non-primate lentiviruses displayed hints of less stable G4s. In primate lentiviruses, the possibility to fold into G4s was highly conserved among strains. LTR G4 sequences were very similar among phylogenetically related primate viruses, while they increasingly differed in viruses that diverged early from a common ancestor. A strong correlation between primate lentivirus LTR G4s and Sp1/NF\u3baB binding sites was found. All LTR G4s folded: their complexity was assessed by polymerase stop assay. Our data support a role of the lentiviruses 5'-LTR G4 region as control centre of viral transcription, where folding/unfolding of G4s and multiple recruitment of factors based on both sequence and structure may take place

Recent advances in smart biotechnology: Hydrogels and nanocarriers for tailored bioactive molecules depot

Over the past ten years, the global biopharmaceutical market has remarkably grown, with ten over the top twenty worldwide high performance medical treatment sales being biologics. Thus, biotech R&D (research and development) sector is becoming a key leading branch, with expanding revenues. Biotechnology offers considerable advantages compared to traditional therapeutic approaches, such as reducing side effects, specific treatments, higher patient compliance and therefore more effective treatments leading to lower healthcare costs. Within this sector, smart nanotechnology and colloidal self-assembling systems represent pivotal tools able to modulate the delivery of therapeutics. A comprehensive understanding of the processes involved in the self assembly of the colloidal structures discussed therein is essential for the development of relevant biomedical applications. In this review we report the most promising and best performing platforms for specific classes of bioactive molecules and related target, spanning from siRNAs, gene/plasmids, proteins/growth factors, small synthetic therapeutics and bioimaging probes.Istituto Italiano di Tecnologia (IIT)COST Action [CA 15107]People Program (Marie Curie Actions) of the European Union's Seventh Framework Program under REA [606713 BIBAFOODS]Portuguese Foundation for Science and Technology (FCT) [PTDC/AGR-TEC/4814/2014, IF/01005/2014]Fundacao para a Ciencia e Tecnologia [SFRH/BPD/99982/2014]Danish National Research Foundation [DNRF 122]Villum Foundation [9301]Italian Ministry of Instruction, University and Research (MIUR), PRIN [20109PLMH2]"Fondazione Beneficentia Stiftung" VaduzFondo di Ateneo FRAFRAinfo:eu-repo/semantics/publishedVersio

Has VZV epidemiology changed in Italy? Results of a seroprevalence study

The aim of the study was to evaluate if and how varicella prevalence has changed in Italy. In particular a seroprevalence study was performed, comparing it to similar surveys conducted in pre-immunization era. During 2013–2014, sera obtained from blood samples taken for diagnostic purposes or routine investigations were collected in collaboration with at least one laboratory/center for each region, following the approval of the Ethics Committee. Data were stratified by sex and age. All samples were processed in a national reference laboratory by an immunoassay with high sensitivity and specificity. Statutory notifications, national hospital discharge database and mortality data related to VZV infection were analyzed as well. A total of 3707 sera were collected and tested. In the studied period both incidence and hospitalization rates decreased and about 5 deaths per year have been registered. The seroprevalence decreased in the first year of life in subjects passively protected by their mother, followed by an increase in the following age classes. The overall antibody prevalence was 84%. The comparison with surveys conducted with the same methodology in 1996–1997 and 2003–2004 showed significant differences in age groups 1–19 y. The study confirms that in Italy VZV infection typically occurs in children. The impact of varicella on Italian population is changing. The comparison between studies performed in different periods shows a significant increase of seropositivity in age class 1–4 years, expression of vaccine interventions already adopted in some regions

Four-dimensional distribution of the 2010 Eyjafjallajökull volcanic cloud over Europe observed by EARLINET

© Author(s) 2013. This work is distributed under the Creative Commons Attribution 3.0 License.The eruption of the Icelandic volcano Eyjafjallaj ökull in April-May 2010 represents a "natural experiment" to study the impact of volcanic emissions on a continental scale. For the first time, quantitative data about the presence, altitude, and layering of the volcanic cloud, in conjunction with optical information, are available for most parts of Europe derived from the observations by the European Aerosol Research Lidar NETwork (EARLINET). Based on multi-wavelength Raman lidar systems, EARLINET is the only instrument worldwide that is able to provide dense time series of high-quality optical data to be used for aerosol typing and for the retrieval of particle microphysical properties as a function of altitude. In this work we show the four-dimensional (4-D) distribution of the Eyjafjallajökull volcanic cloud in the troposphere over Europe as observed by EARLINET during the entire volcanic event (15 April-26 May 2010). All optical properties directly measured (backscatter, extinction, and particle linear depolarization ratio) are stored in the EARLINET database available at www.earlinet.org. A specific relational database providing the volcanic mask over Europe, realized ad hoc for this specific event, has been developed and is available on request at www.earlinet.org. During the first days after the eruption, volcanic particles were detected over Central Europe within a wide range of altitudes, from the upper troposphere down to the local planetary boundary layer (PBL). After 19 April 2010, volcanic particles were detected over southern and south-eastern Europe. During the first half of May (5-15 May), material emitted by the Eyjafjallajökull volcano was detected over Spain and Portugal and then over the Mediterranean and the Balkans. The last observations of the event were recorded until 25 May in Central Europe and in the Eastern Mediterranean area. The 4-D distribution of volcanic aerosol layering and optical properties on European scale reported here provides an unprecedented data set for evaluating satellite data and aerosol dispersion models for this kind of volcanic events.Peer reviewe

Abstract of Thesis: Directions in Painting and Drawing

The Culminating Project for completion of graduate work for the Degree of Master of Art in the area of Studio Art consisted of an exhibition and a thesis. The exhibition in the Hendren Gallery, March 22- April 3, 1987, presented thirty-two works of art completed during the course of my graduate studies, which represented the full spectrum of my body of work. The specific pieces I selected for the exhibition include still life and abstractions dealing primarily with non-geometric, organic forms. The range of media included drawings in graphite, pastel, and colored pencil, and watercolor paintings. The accompanying thesis is a discussion and analysis of this body of work. It includes a comparison with earlier work, discussion of trends and developments in my current work, and delineation of goals for the future

Inhibition of intestinal epithelial apoptosis improves survival in a murine model of radiation combined injury

World conditions place large populations at risk from ionizing radiation (IR) from detonation of dirty bombs or nuclear devices. In a subgroup of patients, ionizing radiation exposure would be followed by a secondary infection. The effects of radiation combined injury are potentially more lethal than either insult in isolation. The purpose of this study was to determine mechanisms of mortality and possible therapeutic targets in radiation combined injury. Mice were exposed to IR with 2.5 Gray (Gy) followed four days later by intratracheal methicillin-resistant Staphylococcus aureus (MRSA). While either IR or MRSA alone yielded 100% survival, animals with radiation combined injury had 53% survival (p = 0.01). Compared to IR or MRSA alone, mice with radiation combined injury had increased gut apoptosis, local and systemic bacterial burden, decreased splenic CD4 T cells, CD8 T cells, B cells, NK cells, and dendritic cells, and increased BAL and systemic IL-6 and G-CSF. In contrast, radiation combined injury did not alter lymphocyte apoptosis, pulmonary injury, or intestinal proliferation compared to IR or MRSA alone. In light of the synergistic increase in gut apoptosis following radiation combined injury, transgenic mice that overexpress Bcl-2 in their intestine and wild type mice were subjected to IR followed by MRSA. Bcl-2 mice had decreased gut apoptosis and improved survival compared to WT mice (92% vs. 42%; p<0.01). These data demonstrate that radiation combined injury results in significantly higher mortality than could be predicted based upon either IR or MRSA infection alone, and that preventing gut apoptosis may be a potential therapeutic target