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Background and aims: Cladribine is a nucleoside analogue, approved for the treatment of active multiple sclerosis (MS). Looking at clinical trial results, during cladribine treatment, there is a marked and long-lasting CD19 B-cell depletion and a modest T-cell depletion. Immunoglobulin (Ig) levels were never explored. In our real-world study, we evaluated changes in lymphocytes, neutrophils and immunoglobulins over the first 12 months of cladribine treatment. Methods: This observational retrospective study has been conducted on prospectively collected data from 2018 to 2021. Clinical and laboratory data at baseline and after 2, 6 and 12 months were included. Results: Using baseline as reference, total lymphocyte count was lower after 2, 6, and 12 months. Neutrophils were lower after 2 and 6 months, but not after 12 months. We observed no changes in IgG, IgM and IgA over 12 months. CD19 B-cell count was lower after 2 and 6 months, but not after 12 months. CD8 T-cell count was lower after 2 and 6 months, but not after 12 months. CD4 T-cell count was lower after 2, and 6 months, but not after 12 months. Conclusion: We observed a significant decrease in total lymphocyte count from 2 months after cladribine treatment start until the end of year 1. After 12 months, we observed complete reconstitution of CD19 B-lymphocytes. Immunoglobulins remained stable over year-1 cladribine treatment that is also in line with observed normal antibody production to COVID-19 infection and vaccination in patients treated with cladribine.
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Digital transformation attracted scholars’ attention in various scientific domains, as business models, strategies, human resources management, and, more in general, social sciences. Additionally, digital transformation drove changes in both businesses and society as a whole. Due to its relevance in recent studies and daily activities, we observed the innovation brought by digital transformation at the time of pandemic to understand the contribution it offered. Some of the solutions proposed worldwide were observed, leading to understand the role of artificial intelligence, machine learning, and blockchain – among others – in the fight against Covid-19. The analysis offers a perspective on the ways smart technologies enabled suitable outcomes in the activities performed by specialists, firms, and people either to counteract the further spreading of the pandemic or to take care of the patients affected by the virus. © 2021, The Author(s), under exclusive license to Springer Nature Switzerland AG.
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The modeling of the viability decay of viruses in sessile droplets is addressed considering a droplet sitting on a smooth surface characterized by a specific contact angle. To investigate, at prescribed temperature, how surface energy of the material and ambient humidity cooperate to determine the virus viability, we propose a model which involves the minimum number of thermodynamically relevant parameters. In particular, by considering a saline water droplet (one salt) as the simplest approximation of real solutions (medium and natural/artificial saliva), the evaporation is described by a first-order time-dependent nonlinear differential equation properly rearranged to obtain the contact angle evolution as the sole unknown function. The analyses were performed for several contact angles and two typical droplet sizes of interest in real situations by assuming constant ambient temperature and relative humidity in the range 0–100%. The results of the simulations, given in terms of time evolution of salt concentration, vapor pressure, and droplet volume, elucidate some previously not yet well-understood dynamics, demonstrating how three main regimes—directly implicated in nontrivial trends of virus viability and to date only highlighted experimentally—can be recognized as the function of relative humidity. By recalling the concept of cumulative dose of salts (CD), to account for the effect of the exposition of viruses to salt concentration on virus viability, we show how the proposed approach could suggest a chart of a virus fate by predicting its survival time at a given temperature as a function of the relative humidity and contact angle. We found a good agreement with experimental data for various enveloped viruses and predicted in particular for the Phi6 virus, a surrogate of coronavirus, the characteristic U-shaped dependence of viability on relative humidity. Given the generality of the model and once experimental data are available that link the vulnerability of a certain virus, such as SARS-CoV-2, to the concentrations of salts or other substances in terms of CD, it is felt that this approach could be employed for antivirus strategies and protocols for the prediction/reduction of human health risks associated with SARS-CoV-2 and other viruses. © Copyright © 2021 Di Novo, Carotenuto, Mensitieri, Fraldi and Pugno.
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Treatment of respiratory viral infections remains a global health concern, mainly due to the inefficacy of available drugs. Therefore, the discovery of novel antiviral compounds is needed; in this context, antimicrobial peptides (AMPs) like temporins hold great promise. Here, we discovered that the harmless temporin G (TG) significantly inhibited the early life-cycle phases of influenza virus. The in vitro hemagglutinating test revealed the existence of TG interaction with the viral hemagglutinin (HA) protein. Furthermore, the hemolysis inhibition assay and the molecular docking studies confirmed a TG/HA complex formation at the level of the conserved hydrophobic stem groove of HA. Remarkably, these findings highlight the ability of TG to block the conformational rearrangements of HA2 subunit, which are essential for the viral envelope fusion with intracellular endocytic vesicles, thereby neutralizing the virus entry into the host cell. In comparison, in the case of parainfluenza virus, which penetrates host cells upon a membrane-fusion process, addition of TG to infected cells provoked ~1.2 log reduction of viral titer released in the supernatant. Nevertheless, at the same condition, an immunofluorescent assay showed that the expression of viral hemagglutinin/neuraminidase protein was not significantly reduced. This suggested a peptide-mediated block of some late steps of viral replication and therefore the impairment of the extracellular release of viral particles. Overall, our results are the first demonstration of the ability of an AMP to interfere with the replication of respiratory viruses with a different mechanism of cell entry and will open a new avenue for the development of novel therapeutic approaches against a large variety of respiratory viruses, including the recent SARS-CoV2.