Anti-Angiogenic Treatment (Sunitinib) for Disseminated Malignant Haemangiopericytoma: A Case Study and Review of the Literature

Introduction: A meningeal haemangiopericytoma (HP) is a mesenchymal tumour that makes up less than 1% of all CNS tumours. HPs arise from pericytes and present high rates of recurrence and distant metastasis. The primary treatment option is surgery. When the disease is disseminated, chemotherapy produces a weak and short-lived response; therefore, new drugs are needed. Case Presentation: We describe the case of a 65-year-old woman with a 13-year history of recurrent HP. After local treatment with radiotherapy, she developed metastases that required systemic treatment, and treatment with sunitinib, an oral inhibitor of the vascular endothelial growth factor receptor and the platelet-derived growth factor receptor, was initiated. As a result, radiological stabilisation of the systemic disease was maintained for over 12 months. Conclusions: Anti-angiogenic agents can be useful for treating disseminated HP, but further studies are needed to confirm their possible role in controlling metastatic disease

Discrete Breathers in Klein-Gordon Lattices: a Deflation-Based Approach

Deflation is an efficient numerical technique for identifying new branches of steady state solutions to nonlinear partial differential equations. Here, we demonstrate how to extend deflation to discover new periodic orbits in nonlinear dynamical lattices. We employ our extension to identify discrete breathers, which are generic exponentially localized, time-periodic solutions of such lattices. We compare different approaches to using deflation for periodic orbits, including ones based on a Fourier decomposition of the solution, as well as ones based on the solution's energy density profile. We demonstrate the ability of the method to obtain a wide variety of multibreather solutions without prior knowledge about their spatial profile

Mediation of the Translocation of nNOSμ During Unloading-Induced Atrophy of Skeletal Muscle via NOX2 Inhibition

Mechanical unloading results in detachment of the mu-splice variant of neuronal nitric oxidase synthase (nNOSμ) from the dystrophin-glycoprotein complex and sarcolemma and translocation to the cytosol. We recently found that reactive oxygen species (ROS) play a role in nNOSμ translocation during unloading and muscle atrophy. NOX2, an isoform of NADPH oxidase and source of ROS, may play a causal role in nNOSμ translocation. The purpose of the study was to determine the effectiveness of NOX2 peptidyl inhibition in reducing the translocation of nNOSμ from the sarcolemma and subsequently soleus CSA. Adult male Fisher 344 rats were randomly assigned to one of three groups: CON (control), HU-S (hind limb unloaded with gp91ds-tat scramble) and HU-G (hind limb unloaded with gp91ds-tat). The hind limb unloading period was 7 days. Mean body weights for CON (353.26 g ± 15.47), HU-S (305.14 g ± 18.18) and HU-G (306.34 g ± 16.84) at the beginning of the experiment were not significantly different. Muscle mass/body mass ratio for the gastrocnemius complex (gastrocnemius, plantaris and soleus) was significantly reduced in HU-S rats (10.08 mg/g ± 0.24) but was maintained in HU-G rats (10.88 mg/g ± 0.47). SMASH analysis revealed that average soleus CSA in HU-G rats (3293.08 μm2 ± 46.82) decreased significantly less than HU-S rats (2606.66 μm2 ± 33.46) compared with ambulatory controls (p \u3e 0.0001). Immunofluorescence and staining of nNOS activity with NADPH Diaphorase of soleus tissue showed considerable loss of sarcolemmal nNOSμ in the HU-S group while the HU-G group revealed substantial maintenance of nNOSμ at the sarcolemma. The results of this study suggest that NOX2 inhibition via gp91ds-tat is effective in reducing the translocation of nNOSμ from the sarcolemma to the cytosol and maintaining CSA of the soleus with mechanical unloading via the inhibition of NOX2

Treatment of Asthma Exacerbations with the Human-Powered Nebuliser: A Randomised Parallel-Group Clinical Trial

Aims: The aim of this study was to compare a low-cost, human-powered nebuliser compressor with an electric nebuliser compressor for the treatment of mild to moderate asthma exacerbations in adults and children. Methods: This was a non-blinded, parallel-group, equivalence study, with 110 subjects between 6 and 65 years of age, conducted in the emergency department of a district hospital in Ilopango, El Salvador. Participants were assigned by random allocation to receive a 2.5-mg dose of salbutamol from the experimental human-powered nebuliser or the electric nebuliser control. All assigned participants completed treatment and were included in analysis. The study was not blinded as this was clinically unfeasible; however, data analysis was blinded. Results: The mean improvement in peak flow of the experimental and control groups was 37.5 (95% confidence interval (CI) 26.7–48.2) l/min and 38.7 (95% CI, 26.1–51.3) l/min, respectively, with a mean difference of 1.3 (95% CI, −15.1 to 17.7) l/min. The mean improvement in percent-expected peak flow for the experimental and control groups was 12.3% (95% CI, 9.1–15.5%) and 13.8% (95% CI, 9.8–17.9%), respectively, with a mean difference of 1.5% (95% CI, −3.6 to 6.6%). Conclusions: The human-powered nebuliser compressor is equivalent to a standard nebuliser compressor for the treatment of mild-to-moderate asthma. (Funded by the Opus Dean’s Fund, Marquette University College of Engineering; ClinicalTrials.gov NCT01795742.

Immunometabolism modulation in therapy

The study of cancer biology should be based around a comprehensive vision of the entire tumor ecosystem, considering the functional, bioenergetic and metabolic state of tumor cells and those of their microenvironment, and placing particular importance on immune system cells. Enhanced understanding of the molecular bases that give rise to alterations of pathways related to tumor development can open up new therapeutic intervention opportunities, such as metabolic regulation applied to immunotherapy. This review outlines the role of various oncometabolites and immunometabolites, such as TCA intermediates, in shaping pro/anti-inflammatory activity of immune cells such as MDSCs, T lymphocytes, TAMs and DCs in cancer. We also discuss the extraordinary plasticity of the immune response and its implication in immunotherapy efficacy, and highlight different therapeutic intervention possibilities based on controlling the balanced systems of specific metabolites with antagonistic functions

A beam-beam monitoring detector for the MPD experiment at NICA

The Multi-Purpose Detector (MPD) is to be installed at the Nuclotron Ion Collider fAcility (NICA) of the Joint Institute for Nuclear Research (JINR). Its main goal is to study the phase diagram of the strongly interacting matter produced in heavy-ion collisions. These studies, while providing insight into the physics of heavy-ion collisions, are relevant for improving our understanding of the evolution of the early Universe and the formation of neutron stars. In order to extend the MPD trigger capabilities, we propose to include a high granularity beam-beam monitoring detector (BE-BE) to provide a level-0 trigger signal with an expected time resolution of 30 ps. This new detector will improve the determination of the reaction plane by the MPD experiment, a key measurement for flow studies that provides physics insight into the early stages of the reaction. In this work, we use simulated Au+Au collisions at NICA energies to show the potential of such a detector to determine the event plane resolution, providing further redundancy to the detectors originally considered for this purpose namely, the Fast Forward Detector (FFD) and the Hadron Calorimeter (HCAL). We also show our results for the time resolution studies of two prototype cells carried out at the T10 beam line at the CERN PS complex.Comment: 16 pages, 12 figures. Updated to published version with added comments and correction

An approach to assess flooding and erosion risk for open beaches in a changing climate

This paper examines the vulnerability to flooding and erosion of four open beach study sites in Europe. A framework for the quantitative estimation of present and future coastal flood and erosion risks is established using methods, data and tools from across a range of disciplines, including topographic and bathymetric data, climate data from observation, hindcast and model projections, statistical modelling of current and future climates and integrated risk analysis tools. Uncertainties in the estimation of future coastal system dynamics are considered, as are the consequences for the inland systems. Different implementations of the framework are applied to the study sites which have different wave, tidal and surge climate conditions. These sites are: Santander, Spain—the Atlantic Ocean; Bellocchio, Italy—the Adriatic Sea; Varna, Bulgaria—the Black Sea; and the Teign Estuary, UK—the northern Atlantic Ocean. The complexity of each system is first simplified by sub-division into coastal "impact units" defined by homogeneity in the local key forcing parameters: wave, wind, tide, river discharge, run-off, etc. This reduces the simulation to that of a number of simpler linear problems which are treated by applying the first two components of the Source–Pathway–Receptor–Consequence (S–P–R–C) approach. The case studies reveal the flexibility of this approach, which is found useful for the rapid assessment of the risks of flooding and erosion for a range of scenarios and the likely effectiveness of flood defences