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

Utilising Features of Sport Commentating to Provide a Framework for Co-Teaching the Online Lecture

Higher education teaching abruptly changed during the COVID-19 pandemic to remote, on-line learning and teaching. The use of on-line communication software to teach became the norm and remains at many institutions. This software contains features, such as the chat, that offer teaching and learning advantages; however, potential benefits can be challenging to realise for academics used to traditional modes of lecture delivery. In most cases a solo-taught lecture designed for a physical room does not transition well to the on-line space. Co-teaching, which involves two or more academics teaching the same class, is a pedagogy that can improve engagement and satisfaction for students and academics alike. However, how co-teaching can transition to the on-line space and take full benefit of the communication software features is not well known. We recognised that some aspects of sports announcing (commentating) align with desirable qualities of co-teaching on-line. In this paper we use these features to develop a practical framework for co-teaching in the on-line space and evaluate the model in a second-year university science subject. Using data from student surveys, we found that the co-teaching model helped integrate the chat functionality into the main lecture and led to improved engagement and enjoyment of on-line classes. The model also assisted students in identifying key learning outcomes. Using the framework as a practical guide for how to incorporate co-teaching into on-line classes helps realise the benefits of contemporary communication software

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

Collagen and Stretch Modulate Autocrine Secretion of Insulin-like Growth Factor-1 and Insulin-like Growth Factor Binding Proteins from Differentiated Skeletal Muscle Cells

Stretch-induced skeletal muscle growth may involve increased autocrine secretion of insulin-like growth factor-1 (IGF-1) since IGF-1 is a potent growth factor for skeletal muscle hypertrophy, and stretch elevates IGF-1 mRNA levels in vivo. In tissue cultures of differentiated avian pectoralis skeletal muscle cells, nanomolar concentrations of exogenous IGF-1 stimulated growth in mechanically stretched but not static cultures. These cultures released up to 100 pg of endogenously produced IGF-1/micro-g of protein/day, as well as three major IGF binding proteins of 31, 36, and 43 kilodaltons (kDa). IGF-1 was secreted from both myofibers and fibroblasts coexisting in the muscle cultures. Repetitive stretch/relaxation of the differentiated skeletal muscle cells stimulated the acute release of IGF-1 during the first 4 h after initiating mechanical activity, but caused no increase in the long-term secretion over 24-72 h of IGF-1, or its binding proteins. Varying the intensity and frequency of stretch had no effect on the long-term efflux of IGF-1. In contrast to stretch, embedding the differentiated muscle cells in a three-dimensional collagen (Type I) matrix resulted in a 2-5-fold increase in long-term IGF-1 efflux over 24-72 h. Collagen also caused a 2-5-fold increase in the release of the IGF binding proteins. Thus, both the extracellular matrix protein type I collagen and stretch stimulate the autocrine secretion of IGF-1, but with different time kinetics. This endogenously produced growth factor may be important for the growth response of skeletal myofibers to both types of external stimuli

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

Limits on the violation of g-universality with a Galileo-type experiment

Abstract We present new results for a Galilean experiment using two masses of copper and tungsten in simultaneous free fall. The experiment searches for a possible difference in the free-fall acceleration Δ g and it is sensitive to any composition-dependent interaction between the test masses and the earth, whose range exceeds 10 km. The results show no evidence for any composition-dependent gravity-like interaction within Δg μ Gal

Effect of Mercury on Membrane Proteins, Anionic Transport and Cell Morphology in Human Erythrocytes.

Mercury (Hg) is a heavy metal widespread in all environmental compartments as one of the most hazardous pollutants. Human exposure to this natural element is detrimental for several cellular types including erythrocytes (RBC) that accumulate Hg mainly bound to the SH groups of different cellular components, including protein cysteine residues. The cellular membrane represents a major target of Hg-induced damage in RBC with loss of physiological phospholipid asymmetry, due to phosphatidylserine (PS) exposure to the external membrane leaflet. To investigate Hg-induced cytotoxicity at the molecular level, the possible interaction of this heavy metal with RBC membrane proteins was investigated. Furthermore, Hg-induced alterations in band 3 protein (B3p) transport function, PS-exposing macrovesicle (MVs) formation and morphological changes were assessed. For this aim, human RBC were treated in vitro with different HgCl <sub>2</sub> concentrations (range 10-40 µM) and the electrophoretic profile of membrane proteins as well as the expression levels of Ankyrin and Flottilin-2 evaluated by SDS-PAGE and Western blot, respectively. The effect of alterations in these proteins on RBC morphology was evaluated by digital holographic microscopy and anionic transport efficiency of B3p was evaluated as sulphate uptake. Finally, PS- bearing MVs were quantified by annexin-V binding using FACS analysis. Findings presented in this paper indicate that RBC exposure to HgCl <sub>2</sub> induces modifications in the electrophoretic profile of membrane protein fraction. Furthermore, our study reveals the Hg induced alterations of specific membrane proteins, such as Ankyrin, a protein essential for membrane-cytoskeleton linkage and Flotillin-2, a major integral protein of RBC lipid rafts, likely responsible for decreased membrane stability and increased fragmentations. Accordingly, under the same experimental conditions, RBC morphological changes and PS-bearing MVs release are observed. Finally, RBC treatment significantly affects the B3p-mediated anionic transport, that we report reduced upon HgCl <sub>2</sub> treatment in a dose dependent manner. Altogether, the findings reported in this paper confirm that RBC are particularly vulnerable to Hg toxic effect and provide new insight in the Hg-induced protein modification in human RBC affecting the complex biological system of cellular membrane. In particular, Hg could induce dismantle of vertical cohesion between the plasma membrane and cytoskeleton as well as destabilization of lateral linkages of functional domains. Consequently, decreased membrane deformability could impair RBC capacity to deal with the shear forces in the circulation increasing membrane fragmentations. Furthermore, findings described in this paper have also significant implication in RBC physiology, particularly related to gas exchanges

Development of a self-powered piezo-resistive smart insole equipped with low-power BLE connectivity for remote gait monitoring

The evolution of low power electronics and the availability of new smart materials are opening new frontiers to develop wearable systems for medical applications, lifestyle monitoring, and performance detection. This paper presents the development and realization of a novel smart insole for monitoring the plantar pressure distribution and gait parameters; indeed, it includes a piezoresistive sensing matrix based on a Velostat layer for transducing applied pressure into an electric signal. At first, an accurate and complete characterization of Velostat-based pressure sensors is reported as a function of sizes, support material, and pressure trend. The realization and testing of a low-cost and reliable piezoresistive sensing matrix based on a sandwich structure are discussed. This last is interfaced with a low power conditioning and processing section based on an Arduino Lilypad board and an analog multiplexer for acquiring the pressure data. The insole includes a 3- axis capacitive accelerometer for detecting the gait parameters (swing time and stance phase time) featuring the walking. A Bluetooth Low Energy (BLE) 5.0 module is included for transmitting in real-time the acquired data toward a PC, tablet or smartphone, for displaying and processing them using a custom Processing® application. Moreover, the smart insole is equipped with a piezoelectric harvesting section for scavenging energy from walking. The onfield tests indicate that for a walking speed higher than 1 ms−1, the device’s power requirements (i.e., P = 5.84 mW ) was fulfilled. However, more than 9 days of autonomy are guaranteed by the integrated 380-mAh Lipo battery in the total absence of energy contributions from the harvesting section