SARS-CoV-2 diagnostics in the virology laboratory of a University Hospital in Rome during the lockdown period

Italy was one of the most affected nations by coronavirus disease 2019 outside China. The infections, initially limited to Northern Italy, spread to all other Italian regions. This study aims to provide a snapshot of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) epidemiology based on a single-center laboratory experience in Rome. The study retrospectively included 6565 subjects tested for SARS-CoV-2 at the Laboratory of Virology of Sapienza University Hospital in Rome from 6 March to 4 May. A total of 9995 clinical specimens were analyzed, including nasopharyngeal swabs, bronchoalveolar lavage fluids, gargle lavages, stools, pleural fluids, and cerebrospinal fluids. Positivity to SARS-CoV-2 was detected in 8% (527/6565) of individuals, increased with age, and was higher in male patients (P <.001). The number of new confirmed cases reached a peak on 18 March and then decreased. The virus was detected in respiratory samples, in stool and in pleural fluids, while none of gargle lavage or cerebrospinal fluid samples gave a positive result. This analysis allowed to gather comprehensive information on SARS-CoV-2 epidemiology in our area, highlighting positivity variations over time and in different sex and age group and the need for a continuous surveillance of the infection, mostly because the pandemic evolution remains unknown

Computer-based technology and student engagement: a critical review of the literature

Computer-based technology has infiltrated many aspects of life and industry, yet there is little understanding of how it can be used to promote student engagement, a concept receiving strong attention in higher education due to its association with a number of positive academic outcomes. The purpose of this article is to present a critical review of the literature from the past 5 years related to how web-conferencing software, blogs, wikis, social networking sites (Facebook and Twitter), and digital games influence student engagement. We prefaced the findings with a substantive overview of student engagement definitions and indicators, which revealed three types of engagement (behavioral, emotional, and cognitive) that informed how we classified articles. Our findings suggest that digital games provide the most far-reaching influence across different types of student engagement, followed by web-conferencing and Facebook. Findings regarding wikis, blogs, and Twitter are less conclusive and significantly limited in number of studies conducted within the past 5 years. Overall, the findings provide preliminary support that computer-based technology influences student engagement, however, additional research is needed to confirm and build on these findings. We conclude the article by providing a list of recommendations for practice, with the intent of increasing understanding of how computer-based technology may be purposefully implemented to achieve the greatest gains in student engagement. © 2017, The Author(s)

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Approche statistique versus approche linguistique pour l'indexation sémantique des documents multilingues

National audienceDans cet article nous présentons une approche statistique d'indexation sémantique des documents multilingues. L'approche que nous proposons est composée de trois étapes : extraction des termes, détection des concepts et détection des relations à partir des couples de concepts. Notre approche est validée par un ensemble d'expérimentations sur la collection ImageCLEFmed 2007 et une comparaison avec une approche linguistique. Nous montrons ainsi que l'approche statistique obtient des résultats équivalents à l'approche linguistique sans adapter la phase d'indexation à la langue du document

Identification of a miR-146b-FasL axis in the development of neutropenia in T-LGL leukemia

T Large Granular Lymphocytes Leukemia (T-LGLL) is a rare disease characterized by LGLs proliferation. The main clinical manifestation of T-LGLL is a severe neutropenia that is also the most common indication for treatment in this disease. From the molecular point of view, the high levels of soluble Fas ligand (FasL) found in these patients are the main cause of neutropenia. We recently described that the increased FasL expression was induced by the high STAT3 activation that specifically characterizes T-LGLs of neutropenic patients. Although STAT3 is a transcriptional activator of a huge number of oncogenes, so far its relationship with microRNAs has not been evaluated in T-LGLL. Here, we investigated whether STAT3 could carry out its pathogenetic role in T-LGLL through an altered expression of miRNAs. Here, we investigated whether STAT3 could carry out its pathogenetic role in T-LGLL through an altered expression of miRNAs. Hierarchical Clustering Analysis of miRNA expression profile of T-LGLs identified two groups of samples: in the first cluster, patients are characterised by CD8+ T-LGLs, neutropenia and high levels of activated STAT3, while CD4+ TLGLs, normal neutrophil counts and low levels of STAT3 activation distinguish remaining patients. Remarkably, we demonstrate a CD8-specific and STAT3 activation-dependent inhibition of miR-146b expression, this latter being related to miR-146b promoter methylation. We also provide experimental evidence that the STAT3-dependent reduction of miR-146b expression allows increased HuR-mediated stabilization of FasL mRNA, leading to increased FasL production, which in turn has been shown to play a role in neutropenia. Restoring miR-146b expression in CD8 T-LGLs leads to a reduction of HuR protein and, in turn, of FasL mRNA expression. Finally, we demonstrated that treatment with Bortezomib, a proteasome inhibitor, lead to a 70% reduction of STAT3 activation and 67% reduction of DNMT1 expression in T-LGL. Finally, in line with our previous results, reduction of HuR protein expression (-44%) and FasL mRNA (-43%) was observed in Bortezomib-treated T-LGL, consistent with the restoration of miR-146b expression. All together these data provide mechanistic insights for the link between STAT3 activation, miR-146b expression and neutropenia in CD8 T-LGLs and indicate a possible use of Bortezomib in the treatment of neutropenia in T-LGLL

BORTEZOMIB LOWERS THE STAT3 PATHOGENETIC ROLE IN T-LGLL NEUTROPENIA DEVELOPMENT BY RESTORING MIR146B EXPRESSION

Background: Symptomatic or severe neutropenia is the most common indication for treatment in T-Large Granular Lymphocytes Leukemia (T-LGLL) patients. To date, the therapeutic strategy mostly relies on immunosuppressive agents, however the ORR is quite low (<60%). A targeted therapy for neutropenic patients has not been developed yet, due to the lack of knowledge about the pathogenesis of this cytopenia. One of the most supported hypotheses relies on Fas Ligand (FasL) involvement, since high levels of this protein, accounting for regulation of neutrophils lifespan, were detected in sera of neutropenic patients. Of note, we recently found that the increased FasL transcription was induced by the high STAT3 activation that specifically characterizes T-LGLs of neutropenic patients. We also showed that a microRNA(miR)146b down-regulation, that represents a signature of these patients, led to the translation of Human antigen R (HuR), an essential FasL mRNA stabilizer. Several drugs are under pre-clinical evaluation to improve the therapeutic possibilities for T-LGLL. Among these, the proteasome inhibitor Bortezomib (Bz) has been demonstrated to affect in-vitro leukemic LGL viability by increasing the levels of the pro-apoptotic protein BID and by inhibiting the constitutive activation of NF-kB pathway. Despite its promising effects, up to date Bz has never been tested in T-LGLL patients and its effects on STAT3-axis have never been investigated. Aims: Since in different neoplastic conditions miR146b expression is epigenetically silenced and in malignant T-lymphocytes the DNA Methyl-Transferase 1 (DNMT1) is reported to be STAT3-induced, our work aims to investigate the potential linkage between STAT3 and miR146b and to evaluate whether Bz might prevent STAT3 pathogenetic role in neutropenia development. Methods: T-LGL were immunomagnetically purified from peripheral blood of untreated T-LGLL patients. The methylation status of miR146b promoter was assessed by Methylated DNA Immuno-Precipitation (MeDIP). T-LGL were treated for 72h-2.5 µM 5-aza-2’-deoxycytidine (DAC), an inhibitor of methyl-transferase activity, or 24h-15 µM STATTIC, a STAT3 inhibitor, or 48h-5 µM Bz. Transcriptional and protein expression were evaluated by RTq-PCR and western blot assays, respectively. Results: MeDIP analysis highlighted a significantly higher level of 5-methyl-cytosine in −687/−496 bp (+141%) and −149/+98 bp (+58%) regions upstream the miR-146b transcription start site in T-LGL of neutropenic as compared to non-neutropenic patients. DAC treatment restored miR146b primary transcript expression in T-LGL of neutropenic patients, suggesting that it was epigenetically silenced. By specifically inhibiting STAT3 activity, we showed a 58% DNMT1 transcriptional decrease in the STATTIC treated T-LGL, as compared to controls, providing proof of a molecular linkage, likely mediated by DNMT1, between STAT3 activation and miR146b promoter methylation. Regarding Bz evaluation, a reduction of STAT3 activation (70%) and of DNMT1 transcription (67%) was observed in treated vs untreated conditions. Among miR146b downstream targets, a decrease of HuR protein (44%) and, thus, of FasL mRNA (43%) was observed in Bz-treated T-LGL, consistent with the restoration of miR-146b expression. Summary/Conclusion: Our data demonstrate the presence of a STAT3- miR46b-FasL axis in neutropenic T-LGLL patients. We also show for the first time that Bz down-regulates STAT3 activation in in-vitro treated leukemic T-LGL, offering the rationale for testing Bz in clinical trials to manage this high-risk subset of patient