PD1, CTLA4 and TIGIT Expression on T and NK Cells in Granulomatous Diseases: Sarcoidosis and ANCA-Associated Vasculitis

Sarcoidosis is a granulomatous diseases affecting the lungs. Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a histologically granulomatous B-mediated disorder characterized by activated T cells. The expression of immune checkpoint (IC) molecules (PD1, CTLA4, TIGIT) on T- and NK-cells negatively regulate the T-cell immune function. The present study aimed to explore the peripheral distribution of IC molecules to better elucidate their peripheral tolerance failure, which might reflect the development of diseases. Patients referred to Respiratory Diseases and Rheumatology Unit of Siena University Hospital were prospectively and consecutively enrolled. Healthy subjects were also enrolled as a control group. Multicolor flow cytometric analysis was performed to detect IC molecules in the peripheral blood of patients. Twenty-three patients were consecutively and prospectively enrolled in the study: 11 patients had an AAV diagnosis and 12 had sarcoidosis. CD4+PD1+ cells were higher in sarcoidosis and GPA than in HC (p = 0.0250 and p = 0.0253, respectively). CD56+CTLA4+ were higher in sarcoidosis than GPA, MPA and HC (p = 0.0085, p = 0.0042 and p = 0.0004, respectively). CTLA4+NK cells clustered for 100% of sarcoidosis patients according to decision tree analysis, while PD1+CD4 and CD8 cells for clustered for 100% of GPA patients. Our analyses showed substantial differences between sarcoidosis and AAV, further confirming the immunological peculiarity of this disease. Despite these advances, the pathogenesis remains incompletely understood, indicating an urgent need for further research to reveal the distinct immunological events in this process, with the hope to open up new therapeutic avenues and, if possible, to develop preventive measures. © 2022 by the authors

Monitoring of indoor bioaerosol for the detection of SARS-CoV-2 in different hospital settings

BackgroundSpore Trap is an environmental detection technology, already used in the field of allergology to monitor the presence and composition of potentially inspirable airborne micronic bioparticulate. This device is potentially suitable for environmental monitoring of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in hospital, as well as in other high-risk closed environments. The aim of the present study is to investigate the accuracy of the Spore Trap system in detecting SARS-CoV-2 in indoor bioaerosol of hospital rooms.MethodsThe Spore Trap was placed in hospital rooms hosting patients with documented SARS-CoV-2 infection (n = 36) or, as a negative control, in rooms where patients with documented negativity to a Real-Time Polymerase Chain Reaction molecular test for SARS-CoV-2 were admitted (n = 10). The monitoring of the bioaerosol was carried on for 24 h. Collected samples were analyzed by real-time polymerase chain reaction.ResultsThe estimated sensitivity of the Spore Trap device for detecting SARS-CoV-2 in an indoor environment is 69.4% (95% C.I. 54.3-84.4%), with a specificity of 100%.ConclusionThe Spore Trap technology is effective in detecting airborne SARS-CoV-2 virus with excellent specificity and high sensitivity, when compared to previous reports. The SARS-CoV-2 pandemic scenario has suggested that indoor air quality control will be a priority in future public health management and will certainly need to include an environmental bio-investigation protocol

Prolonged higher dose methylprednisolone vs. conventional dexamethasone in COVID-19 pneumonia: a randomised controlled trial (MEDEAS)

Dysregulated systemic inflammation is the primary driver of mortality in severe COVID-19 pneumonia. Current guidelines favor a 7-10-day course of any glucocorticoid equivalent to dexamethasone 6 mg·day-1. A comparative RCT with a higher dose and a longer duration of intervention was lacking

La rete bucata. Le regole e i controlli sulla finanza

Questo libro parte da una domanda: a dieci anni dallo scoppio della crisi finanziaria, cosa \ue8 stato fatto perch\ue9 i problemi delle banche venissero risolti? Risponde proponendo un percorso tra le nuove regole sulla finanza: dai farraginosi requisiti di capitale ai deboli vincoli sui compensi milionari dei manager, dall\u2019unione bancaria europea alla tutela dei risparmiatori, dalla tristemente famosa cartolarizzazione al sistema bancario \u201combra\u201d. La risposta non \ue8 consolante. Le autorit\ue0 si sono lanciate in una produzione di norme di cui hanno perso il controllo: un fiume in piena fatto di migliaia di pagine. Regole molto complicate ma poco efficaci: la complessit\ue0 nasconde l\u2019incapacit\ue0 di incidere sui comportamenti dei soggetti vigilati. E\u2019 una rete fitta ma piena di buchi: eccezioni, scappatoie, manipolazioni. E cos\uec il sistema non \ue8 stato messo in sicurezza

Leveraged buybacks of sovereign debt: a model and an application to Greece

The model presented in this paper shows that the outcome of a leveraged buyback of sovereign debt depends on the priority structure of the deal. If the institution lending the funds needed for the buyback is senior, the debtor country benefits from the deal: the government debt is reduced, implying a lower probability of default; at the same time, the deal makes the price of outstanding bonds go down, since their recovery rate declines. The opposite holds if the lending institution is junior. If the loan is under-priced, the implied subsidy is shared between the borrowing country and its bondholders, who can benefit from a price increase of their bonds. This is actually what happened with the buyback of Greek sovereign bonds in 2012, as it is shown in the empirical section. Those results do not depend on the share of country's endowment devoted to debt repayment, which instead plays a crucial role in shaping the outcome of unlevered buybacks

Shareholders' agreements and voting power: evidence from Italian listed firms

This work provides an empirical investigation of shareholders\u2019 agreements signed in Italy over the past decade. The evidence shows that agreements produce a remarkable reshuffling of voting power (Shapley value) among participants. In particular, the first owner gains much voting power at low levels of ownership concentration, and his gain is decreasing in his ownership stake; the opposite happens for the other participants. In addition, the likelihood that a supermajority rule is included in an agreement contract is increasing in the first owner\u2019s share of equity. These findings are consistent with the hypothesis that agreements are used to correct situations where the first owner\u2019s power is at one of the two extremes: either too low (leading to insufficient monitoring over managers and gridlocks in decision-making) or too high (enabling him to extract large private benefits of control)

MULTIPLE BANKING RELATIONSHIPS: COMPETITION AMONG "INSIDE" BANKS

Why firms apply for credit at several banks? The model presented here provides an answer, based on the customer relationships approach. A bank makes an initial investment in information production on a borrowing firm; such an investment must later be compensated: the firm has to share its profits (if any) with the bank. The bank may be able to impose this sharing, when the firm asks for the roll-over of a short term loan, thanks to the informational advantage she has over other lenders; but this "informational rent" lowers the firm owner's incentives to exert effort. Therefore, the firm needs a way to minimize such a rent: this may be done by applying for credit at more than one bank, thus building up competition among "inside" (informed) banks. On the other hand, it is crucial that this competition does not drive the informational rent to zero: in such a case, no bank would be willing to lend. The alternative of a long term loan is also examined, showing that it creates some incentive distortion as well

Banche di nebbia. Orientarsi nella disinformazione finanziaria

Lo scopo di questo libro è di accendere un faro sulla disinformazione finanziaria, mettendo in luce dove si nascondono le maggiori insidie derivanti dalla opacità delle informazioni che noi risparmiatori riceviamo. Vedremo quali sono i rischi da cui bisogna imparare a difendersi. Cercheremo di orientarci nel labirinto dei costi dei servizi bancari e delle commissioni dei prodotti di investimento. Punteremo il dito anche su una regolamentazione farraginosa e una vigilanza inadeguata. Approfondiremo alcuni problemi sorti con l’avvio della unione bancaria europea: le nuove regole di gestione delle crisi bancarie sono state introdotte in modo particolarmente maldestro, arrecando non pochi danni ai risparmiatori. Infine, cercheremo di capire quali sono i punti di forza e di debolezza delle banche italiane, per capire se possiamo ancora fidarci di loro