Why small particle fixed dose triple therapy? An excursus from COPD pathology to pharmacological treatment evolution

Although bronchodilators are the cornerstone in chronic obstructive pulmonary disease (COPD) therapy, the treatment with a single-agent bronchodilator may not provide adequate symptoms control in COPD. The combination of drugs with different mechanisms of action may be more effective in inducing bronchodilation and preventing exacerbations, with a lower risk of side-effects in comparison with the increase of the dose of a single molecule. Several studies comparing the triple therapy with the association of long-acting ß2 agonist (LABA)/inhaled corticosteroid (ICS) or long-acting muscarinic antagonist (LAMA)/LABA reported improvement of lung function and quality of life. A significant reduction in moderate/severe exacerbations has been observed with a fixed triple combination of beclometasone dipropionate (BDP), formoterol fumarate (FF) and glycopyrronium (G) in a single inhaler. The TRILOGY, TRINITY and TRIBUTE studies have provided confirming evidence for a clinical benefit of triple therapy over ICS/LABA combination treatment, LAMA monotherapy and LABA/LAMA combination, with prevention of exacerbations being a key finding. A pooled post hoc analysis of the published clinical studies involving BDP/FF/G fixed combination demonstrated a reduction in fatal events in patients treated with ICS-containing medications, with a trend of statistical significance [hazard ratio = 0.72, 95% confidence interval (CI) 0.50–1.02, p = 0.066], that becomes significant if we consider reduction in fatal events for non-respiratory reasons (hazard ratio = 0.65, 95% CI 0.43–0.97, p = 0.037). In conclusion, a fixed combination of more drugs in a single inhaler can improve long-term adherence to the therapy, reducing the risk of exacerbations and hospital resources utilization. The twice a day administration may provide a better coverage of night, particularly in COPD patients who are highly symptomatic. The inhaled extrafine formulation that allows drug deposition in both large and small – peripheral – airways, is the value added

Measuring the photon distribution by ON/OFF photodectors

Reconstruction of photon statistics of optical states provide fundamental information on the nature of any optical field and find various relevant applications. Nevertheless, no detector that can reliably discriminate the number of incident photons is available. On the other hand the alternative of reconstructing density matrix by quantum tomography leads to various technical difficulties that are particular severe in the pulsed regime (where mode matching between signal an local oscillator is very challenging). Even if on/off detectors, as usual avalanche PhotoDiodes operating in Geiger mode, seem useless as photocounters, recently it was shown how reconstruction of photon statistics is possible by considering a variable quantum efficiency. Here we present experimental reconstructions of photon number distributions of both continuous-wave and pulsed light beams in a scheme based on on/off avalanche photodetection assisted by maximum-likelihood estimation. Reconstructions of the distribution for both semiclassical and quantum states of light (as single photon, coherent, pseudothermal and multithermal states) are reported for single-mode as well as for multimode beams. The stability and good accuracy obtained in the reconstruction of these states clearly demonstrate the interesting potentialities of this simple technique.Comment: 6 pages, 7 figures, to appear on Laser Physic

Novel self-assembling cyclic peptides with reversible supramolecular nanostructures

Self-assembly peptides (SAPs) are an important class of hydrogels used in nanomedicine for tissue repair and neural regeneration. Due to their unique properties, SAPs may be used in a wide range of applications but some limitations, such as low bioavailability and rapid hydrolysis degradation, need to be overcome. Here, we describe the synthesis and characterization of two novel cyclic SAPs without the use of d/l-alternating amino acids, showing a reversible transition of their supramolecular nanostructures, from nanotubes/nanofibers into nanovesicles/nanospheres. The investigation, characterization and optimization are performed using atomic force microscopy (AFM), attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, Raman analysis, circular dichroism (CD), and rheology measurements. Also, in vitro cell viability assays show negligible toxicity of the representative optimized cyclic SAP towards human neural stem cells (hNSCs). Our results suggest that linear SAP theoretical background can be applied to develop cyclic SAPs, with important implications in the scalable fabrication of inter-changeable nanostructures, as well as for biomedical applications, including tissue regeneration, drug-delivery, drug-design, sensing, imaging, and size selectivity

Evidence of balance training‐induced improvement in soccer‐specific skills in U11 soccer players

The present study aim was to determine the role of balance training in improving technical soccer skills in young players. Two U11 soccer teams were randomly assigned one to either balance training (BT; n=22) or control group (Ctrl; n=21). At the end of their habitual soccer training (identical in BT and Ctrl), BT underwent additional balance training for 12 weeks (3sessions/week, 20 min per session), while Ctrl had a 20\u2010min scrimmage. Before and after the intervention, BT and Ctrl underwent two soccer\u2010specific tests (Loughborough Soccer Passing, LSPT, and Shooting, LSST, Tests), and bipedal and unipedal balance evaluations. After intervention, both groups decreased the trials time and improved passing accuracy, with larger improvements in BT than Ctrl [LSPT penalty time (CI95%): \u20102.20 s (\u20102.72/\u20101.68); ES (CI95%): \u20102.54 s (\u20103.34/\u20101.74)]. Both groups improved balance ability, with BT showing larger increments in bipedal tests than Ctrl [static balance: \u201029 mm (\u201042/\u201016); ES: \u20101.39 (\u20102.05/\u20100.72); limit of stability: 4% (3/5); ES 3.93 (2.90/4.95); unipedal quasi\u2010dynamic balance: 0.07 a.u. (0.03/0.11); ES: 1.04 (0.40/1.67) and active range of motion: \u20105% (\u20108/\u20102); ES \u20100.89 (\u20101.51/\u20100.26)]. Low\u2010to\u2010moderate correlations between the players\u2019 technical level and unipedal balance ability were retrieved, particularly in the non\u2010dominant limb (R from 0.30 to 0.48). Balance training improved some technical soccer skills more than habitual soccer training alone, suggesting that young soccer players may benefit from additional balance training added to their traditional training

Screening for sickle cell disease: Focus on newborn investigations

Drepanocytosis is a genetic disease relevant for its epidemiological, clinical and socio-economic aspects. In our country the prevalence is highly uneven with peaks in former malaria areas, but migration flows in recent years have led to significant changes. In this document we review the screening programs currently existing in Italy with particular emphasis on newborn screening, which in other countries around the world, including within Europe, is at most universal and mandatory. The essential laboratory issues are reviewed, from sampling aspects (cord blood or peripheral), to the analytical (analytical methods dedicated to neonatal screening and adult carrier detection) and post analytical (reporting, informative) ones. An economic analysis based on data collected in the province of Modena is also proposed, clearly showing that neonatal screening is also beneficial from an economic point of view

Multiple Integrated Non-clinical Studies Predict the Safety of Lentivirus-Mediated Gene Therapy for \u3b2-Thalassemia

Gene therapy clinical trials require rigorous non-clinical studies in the most relevant models to assess the benefit-to-risk ratio. To support the clinical development of gene therapy for \u3b2-thalassemia, we performed in vitro and in vivo studies for prediction of safety. First we developed newly GLOBE-derived vectors that were tested for their transcriptional activity and potential interference with the expression of surrounding genes. Because these vectors did not show significant advantages, GLOBE lentiviral vector (LV) was elected for further safety characterization. To support the use of hematopoietic stem cells (HSCs) transduced by GLOBE LV for the treatment of \u3b2-thalassemia, we conducted toxicology, tumorigenicity, and biodistribution studies in compliance with the OECD Principles of Good Laboratory Practice. We demonstrated a lack of toxicity and tumorigenic potential associated with GLOBE LV-transduced cells. Vector integration site (IS) studies demonstrated that both murine and human transduced HSCs retain self-renewal capacity and generate new blood cell progeny in the absence of clonal dominance. Moreover, IS analysis showed an absence of enrichment in cancer-related genes, and the genes targeted by GLOBE LV in human HSCs are well known sites of integration, as seen in other lentiviral gene therapy trials, and have not been associated with clonal expansion. Taken together, these integrated studies provide safety data supporting the clinical application of GLOBE-mediated gene therapy for \u3b2-thalassemia

Many-body perturbation theory calculations using the yambo code

International audienceyambo is an open source project aimed at studying excited state properties of condensed matter systems from first principles using many-body methods. As input, yambo requires ground state electronic structure data as computed by density functional theory codes such as quantum-espresso and abinit. yambo's capabilities include the calculation of linear response quantities (both independent-particle and including electron-hole interactions), quasi-particle corrections based on the GW formalism, optical absorption, and other spectroscopic quantities. Here we describe recent developments ranging from the inclusion of important but oft-neglected physical effects such as electron-phonon interactions to the implementation of a real-time propagation scheme for simulating linear and non-linear optical properties. Improvements to numerical algorithms and the user interface are outlined. Particular emphasis is given to the new and efficient parallel structure that makes it possible to exploit modern high performance computing architectures. Finally, we demonstrate the possibility to automate workflows by interfacing with the yambopy and AiiDA software tools

Large-angle production of charged pions by 3 GeV/c - 12 GeV/c protons on carbon, copper and tin targets

A measurement of the double-differential $\pi^{\pm}$ production cross-section in proton--carbon, proton--copper and proton--tin collisions in the range of pion momentum 100 \MeVc \leq p < 800 \MeVc and angle 0.35 \rad \le \theta <2.15 \rad is presented. The data were taken with the HARP detector in the T9 beam line of the CERN PS. The pions were produced by proton beams in a momentum range from 3 \GeVc to 12 \GeVc hitting a target with a thickness of 5% of a nuclear interaction length. The tracking and identification of the produced particles was done using a small-radius cylindrical time projection chamber (TPC) placed in a solenoidal magnet. An elaborate system of detectors in the beam line ensured the identification of the incident particles. Results are shown for the double-differential cross-sections at four incident proton beam momenta (3 \GeVc, 5 \GeVc, 8 \GeVc and 12 \GeVc)