A new laser device for ultra-rapid and sustainable aerosol sterilization

The current COVID-19 pandemic has highlighted the importance of aerosol-based transmission of human pathogens; this therefore calls for novel medical devices which are able to sterilize contaminated aerosols. Here we describe a new laser device able to sterilize droplets containing either viruses or bacteria. Using engineered viral particles, we determined the 10,600 nm wavelength as the most efficient and exploitable laser source to be manufactured in a commercial device. Given the lack of existing working models to reproduce a human aerosol containing living microbial particles, we developed a new system mimicking human droplet formation and preserving bacterial and viral viability. This evidenced the efficacy of 10,600 nm laser light to kill two aerosol transmitted human pathogens, Legionella pneumophila and SARS-CoV-2. The minimal exposure time of <15 ms was required for the inactivation of over 99% pathogens in the aerosol; this is a key element in the design of a device that is safe and can be used in preventing inter-individual transmission. This represents a major advantage over existing devices, which mainly aim at either purifying incoming air by filters or sterilizing solid surfaces, which are not the major transmission routes for airborne communicable diseases

Viral priming of cell intrinsic innate antiviral signaling by the unfolded protein response

The innate response to a pathogen is critical in determining the outcome of the infection. However, the interplay of different cellular responses that are activated following viral infection and their contribution to innate antiviral signalling has not been clearly established. This work shows that flaviviruses, including Dengue, Zika, West Nile and Tick-borne encephalitis viruses, activate the unfolded protein response before transcription of interferon regulatory factor 3 induced genes. Infection in conditions of unfolded protein response priming leads to early activation of innate antiviral responses and cell intrinsic inhibition of viral replication, which is interferon regulatory factor 3 dependent. These results demonstrate that the unfolded protein response is not only a physiological reaction of the cell to viral infection, but also synergizes with pattern recognition sensing to mount a potent antiviral response

Human neural stem cell transplantation in ALS: initial results from a phase I trial

We report the initial results from a phase I clinical trial for ALS. We transplanted GMP-grade, fetal human neural stem cells from natural in utero death (hNSCs) into the anterior horns of the spinal cord to test for the safety of both cells and neurosurgical procedures in these patients. The trial was approved by the Istituto Superiore di Sanit\ue0 and the competent Ethics Committees and was monitored by an external Safety Board

Viral load decrease in SARS-CoV-2 BA.1 and BA.2 Omicron sublineages infection after treatment with monoclonal antibodies and direct antiviral agents

BACKGROUND: The efficacy on the Omicron variant of the approved early- coronavirus disease 2019 (COVID-19) therapies, especially monoclonal antibodies, has been challenged by in vitro neutralization data, while data on in vivo antiviral activity are lacking. MATERIALS AND METHODS: We assessed potential decrease from day1 to day7 viral load (VL) in nasopharyngeal swabs of outpatients receiving Sotrovimab, Molnupiravir, Remdesivir, or Nirmatrelvir/ritonavir for mild-to-moderate COVID-19 due to sublineages BA.1 or BA.2, and average treatment effect (ATE) by weighted marginal linear regression models. RESULTS: A total of 521 patients [378 BA.1 (73%),143 (27%) BA.2] received treatments (Sotrovimab 202, Molnupiravir 117, Nirmatrelvir/ritonavir 84, and Remdesivir 118): median age 66 years, 90% vaccinated, median time from symptoms onset 3 days. Day1 mean viral load was 4.12 log2 (4.16 for BA.1 and 4.01 for BA.2). The adjusted analysis showed that Nirmatrelvir/ritonavir significantly reduced VL compared to all the other drugs, except vs. Molnupiravir in BA.2. Molnupiravir was superior to Remdesivir in both BA.1 and BA.2, and to Sotrovimab in BA.2. Sotrovimab had better activity than Remdesivir only against BA.1. CONCLUSIONS: Nirmatrelvir/ritonavir showed the greatest antiviral activity against Omicron variant, comparable to Molnupiravir only in the BA.2 subgroup. VL decrease could be a valuable surrogate of drug activity in the context of the high prevalence of vaccinated people and low probability of hospital admission. This article is protected by copyright. All rights reserved

The Italian Draft Law on the \u2018Provisions Concerning the Safeguarding of the Intangible Cultural Heritage\u2019

Intangible cultural heritage in Italy is still in need of a unified approach, capable of providing reliable criteria for identifying its assets and for indicating timescales and means by which they should be safeguarded. In the continued absence of up-to-date, ad hoc state legislation (since the content of those laws which do implement international Conventions is too generic in nature to be sufficiently effective), the Regions have proceeded to act in a somewhat scattered manner, giving rise to an extremely fragmented and very disorderly regulatory framework. The draft law N. 4486, "Provisions Concerning the Safeguarding of the Intangible Cultural Heritage", presented on 12th May 2017 at the Chamber of Deputies of the Italian Republic - as the result of the work of an interdisciplinary and inter-university research team coordinated by Marco Giampieretti, who has drafted the final text with the collaboration of Simona Pinton - seeks to fill the serious void that exists in Italian legal system by aligning it to the principles of international and European law, by redirecting the relevant State and Regional legislation, and by satisfying the fundamental requirements of the national community

Imported arboviral infections in Italy, July 2014-October 2015: A National Reference Laboratory report

BACKGROUND: Imported cases of infections due to Dengue (DENV) and Chikungunya (CHIKV) viruses and, more recently, Zika virus (ZIKV) are commonly reported among travelers returning from endemic regions. In areas where potentially competent vectors are present, the risk of autochthonous transmission of these vector-borne pathogens is relatively high. Laboratory surveillance is crucial to rapidly detect imported cases in order to reduce the risk of transmission. This study describes the laboratory activity performed by the National Reference Laboratory for Arboviruses (NRLA) at the Italian National Institute of Health in the period from July 2014 to October 2015. METHODS: Samples from 180 patients visited/hospitalized with a suspected DENV/CHIKV/ZIKV infection were sent to the NRLA from several Italian Hospitals and from Regional Reference Laboratories for Arboviruses, in agreement with the National Plan on human surveillance of vector-borne diseases. Both serological (ELISA IgM test and Plaque Reduction Neutralization Test-PRNT) and molecular assays (Real Time PCR tests, RT-PCR plus nested PCR and sequencing of positive samples) were performed. RESULTS: DENV infection was the most frequently diagnosed (80 confirmed/probable cases), and all four genotypes were detected. However, an increase in imported CHIKV cases (41 confirmed/probable cases) was observed, along with the detection of the first ZIKV cases (4 confirmed cases), as a consequence of the recent spread of both CHIKV and ZIKV in the Americas. CONCLUSIONS: Main diagnostic issues highlighted in our study are sensitivity limitations of molecular tests, and the importance of PRNT to confirm serological results for differential diagnosis of Arboviruses. The continuous evaluation of diagnostic strategy, and the implementation of laboratories networks involved in surveillance activities is essential to ensure correct diagnosis, and to improve the preparedness for a rapid and proper identification of viral threats

High Risk of Secondary Infections Following Thrombotic Complications in Patients With COVID-19

Background. This study’s primary aim was to evaluate the impact of thrombotic complications on the development of secondary infections. The secondary aim was to compare the etiology of secondary infections in patients with and without thrombotic complications. Methods. This was a cohort study (NCT04318366) of coronavirus disease 2019 (COVID-19) patients hospitalized at IRCCS San Raffaele Hospital between February 25 and June 30, 2020. Incidence rates (IRs) were calculated by univariable Poisson regression as the number of cases per 1000 person-days of follow-up (PDFU) with 95% confidence intervals. The cumulative incidence functions of secondary infections according to thrombotic complications were compared with Gray’s method accounting for competing risk of death. A multivariable Fine-Gray model was applied to assess factors associated with risk of secondary infections. Results. Overall, 109/904 patients had 176 secondary infections (IR, 10.0; 95% CI, 8.8–11.5; per 1000-PDFU). The IRs of secondary infections among patients with or without thrombotic complications were 15.0 (95% CI, 10.7–21.0) and 9.3 (95% CI, 7.9–11.0) per 1000-PDFU, respectively (P = .017). At multivariable analysis, thrombotic complications were associated with the development of secondary infections (subdistribution hazard ratio, 1.788; 95% CI, 1.018–3.140; P = .043). The etiology of secondary infections was similar in patients with and without thrombotic complications. Conclusions. In patients with COVID-19, thrombotic complications were associated with a high risk of secondary infections

The Role of miRNAs in Downregulation of PTEN for Glioblastoma Multiforme

In this paper we show, in silico, the role of miRNAs in the post-transcriptional regulation of the onco suppressor gene PTEN by means of a (stochastic) competitive model including interactions with miRNAs and other concurrent genes. The model also covers protein formation and the mechanism going from the protein back to the miRNAs. The numerical simulations confirm the biologically observed situation that the increase of miRNAs concentration within the cell results in the lower expression of PTEN, thus suggesting severe implications in brain tumorigenesis

La promozione, protezione ed attuazione dei diritti dell’infanzia: strumenti normative, politiche e strategie a livello internazionale ed europeo

Il volume risponde all’esigenza di analizzare e valutare i fattori normativi ed operativi propri del processo di costruzione dell’assetto universale e regionale ai fini della protezione e promozione dei diritti dell’infanzia e dell’adolescenza. Il volume si articola in tre parti principali. Nella parte I sono state individuate le componenti essenziali proprie del sistema Nazioni Unite, comprensive del contenuto materiale della relativa Convenzione e dei Protocolli, esaminando altresì sia le relative procedure di monitoraggio e controllo circa il rispetto degli adempimenti assunti dagli stessi Stati parti contraenti sul piano internazionale sia gli inputs e le buone prassi proprie dei molteplici organismi specializzati del sistema. Nella parte II, articolata in più sezioni, si presentano le novità materiali e funzionali delle principali aree regionali – europea, latino-americana, africana e medio-orientale. La parte III è specificamente dedicata al recepimento degli impegni internazionali in materia da parte dell’Italia ed alla correlata definizione delle misure di carattere legislativo, politico ed amministrativo più idonee per la configurazione di una soddisfacente programmazione degli interventi in materia da parte delle autorità centrali e locali.The volume aims at analyzing all the aspects, namely normative and operative ones, which have characterized the protection and promotion of children’s rights, including the relevant institutional framework, internationally and regionally. The volume is divided into three parts. Under the first section an overview of the UN system has been provided, including both the ratification of the UN Convention on children rights supplemented by the two Optional Protocols, and related monitoring and compliance mechanisms following the common efforts of all CRC Parties for a stronger action in this field, and the reference to several relevant UN Specialized Agencies mandated to improve children’s life all over the world. Under the second section, various instruments and their development, particularly the implementation and their viability within regional organizations in Europe, Latin America, Africa and Middle East are under consideration. The third section deals with the Italian legislative, political and administrative contribution to the protection of children’s rights by both central and local authorities