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IL-36R signaling plays an important role in the pathogenesis of psoriasis. We ought to assess the specific function of IL-36R in keratinocytes for the pathology of Aldara-induced psoriasis-like dermatitis. Il36r ΔK mice presenting deletion of IL-36R in keratinocytes were similarly resistant to Aldara-induced ear inflammation as Il36r −/− mice, but acanthosis was only prevented in Il36r −/− mice. FACS analysis revealed that IL-36R signaling in keratinocytes is mandatory for early neutrophil infiltration in Aldara-treated ears. RNASeq and qRT-PCR experiments demonstrated the crucial role of IL-36R signaling in keratinocytes for induction of IL-23, IL-17, and IL-22 at early time points. Taken together, our results demonstrate that IL-36R signaling in keratinocytes plays a major role in the induction of Aldara-induced psoriasis-like dermatitis by triggering early production of IL-23/IL-17/IL-22 cytokines and neutrophil infiltration.

Bloodstream infection (BSI) and associated sepsis represent a major source of mortality in industrialized countries. Prompt treatment with targeted antibiotics affects both the financial impact and the clinical outcome of BSI: every hour gained in initiating the correct antimicrobial therapy significantly increases the probability of patient survival. However, the current standard-of-care, which depends on blood culture-based diagnosis, are often unable to provide such a fast response. Fast and sensitive molecular techniques for the detection of sepsis-related pathogens from primary blood samples are strongly needed. The aim of this study was to assess the usefulness of the IRIDICA BAC BSI Assay, a PCR/ESI-MS-based technology for the early diagnosis of bloodstream infections from primary blood samples in critical patients. This evaluation has been performed by comparison with the traditional culture-based methods. The study was performed on a total of 300 prospective whole blood specimens obtained from patients suspected of sepsis, admitted to enrolling ER units from The Greater Romagna Area. The overall concordance between the two techniques was of 86%, with a calculated sensitivity of 76% and an assay specificity of 90%. The clinical significance of discrepant results was evaluated reviewing the patients' clinical records and the results of additional relevant microbiological tests. The data here obtained support the ability of the IRIDICA BAC BSI Assay to identify a broad range of bacteria directly from primary whole blood samples, within eight hours. This might allow a timely administration of a suitable treatment.

Interleukin-18 is a proinflammatory cytokine, the activity of which is regulated by its natural inhibitor, IL-18 binding protein (IL-18BP). Elevated circulating levels of IL-18 have been observed in patients with systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD), two conditions associated with dysregulated innate immune responses. This study examines the expression and function of IL-18 and IL-18BP in K/BxN serum transfer arthritis (STA), a model that is uniquely dependent on innate immune responses. Naïve and serum transfer-induced arthritis (STA) wild-type (WT) mice were used to examine the articular levels of IL-18 and IL-18BP mRNA by RT-qPCR. The cellular sources of IL-18BP in the joints were determined by using - reporter knock-in mice. The incidence and severity of arthritis, including mRNA levels of different cytokines, were compared in IL-18BP or IL-18 knock-out (KO) mice and their WT littermates. IL-18 and IL-18BP mRNA levels were significantly increased in arthritic as compared to normal joints. Synovial neutrophils, macrophages, and endothelial cells represented the cellular sources of IL-18BP in arthritic joints, whereas IL-18BP production was limited to endothelial cells in non-inflamed joints. The incidence and severity of arthritis were similar in IL-18BP KO and IL-18 KO compared to their WT littermates. Transcript levels of different inflammatory cytokines were not different in the two KO mouse lines compared to WT mice. Although IL-18 and IL-18BP levels were increased in arthritic joints, our results show that the IL-18/IL-18BP balance is not involved in the regulation of STA.

The current Italian regulation defines quite precisely the concept of \"copy\" and \"duplicate\" of a digital document however it does not clearly define the concept of \"original document\". This causes problems in all those contexts in which it is necessary to exhibit the \"original\" as evidence as in the case of interceptions in criminal trials. A starting point for opening studies could be a look to the legislations on this subject in other countries. [Publisher's text]

T cells modulate the antiviral and inflammatory responses of airway epithelial cells to human rhinoviruses (HRV). Differentiated primary human nasal epithelial cells (HNEC) grown on collagen-coated filters were exposed apically to HRV14 for 6 h, washed thoroughly and co-cultured with anti-CD3/CD28 activated T cells added in the basolateral compartment for 40 h. HRV14 did not induce IFNγ, NOS2, CXCL8 and IL-6 in HNEC, but enhanced expression of the T cell attractant CXCL10. On the other hand, HNEC co-cultured with activated T cells produced CXCL10 at a level several orders of magnitude higher than that induced by HRV14. Albeit to a much lower degree, activated T cells also induced CXCL8, IL-6 and NOS2. Anti-IFNγ antibodies and TNF soluble receptor completely blocked CXCL10 upregulation. Furthermore, a significant correlation was observed between epithelial CXCL10 mRNA expression and the amounts of IFNγ and TNF secreted by T cells. Likewise, increasing numbers of T cells to a constant number of HNEC in co-cultures resulted in increasing epithelial CXCL10 production, attaining a plateau at high IFNγ and TNF levels. Hence, HNEC activation by T cells is induced mainly by IFNγ and/or TNF. Activated T cells also markedly inhibited viral replication in HNEC, partially through activation of the nitric oxide pathway. Cross-talk between T cells and HNEC results in activation of the latter and increases their contribution to airway inflammation and virus clearance.

L'attuale regolamentazione italiana definisce con precisione il concetto di \"copia\" e \"duplicazione\" di un documento digitale, tuttavia non definisce chiaramente il concetto di \"documento originale\". Ciò causa problemi in tutti quei contesti nei quali è necessario esibire l'originale come prova, come nel caso delle intercettazioni nei processi penali. Un punto di partenza per gli studi iniziali potrebbe essere uno sguardo alle legislazioni su questo argomento in altri paesi.

The current Italian regulation defines quite precisely the concept of “copy” and “duplicate” of a digital document however it does not clearly define the concept of “original document”. This causes problems in all those contexts in which it is necessary to exhibit the “original” as evidence as in the case of interceptions in criminal trials. A starting point for opening studies could be a look to the legislations on this subject in other countries.

The current Italian regulation defines quite precisely the concept of \"copy\" and \"duplicate\" of a digital document however it does not clearly define the concept of \"original document\". This causes problems in all those contexts in which it is necessary to exhibit the \"original\" as evidence as in the case of interceptions in criminal trials. A starting point for opening studies could be a look to the legislations on this subject in other countries. KEYWORDS Original document; Digital document; Copies; Telephone tapping; Penal process.

The current Italian regulation defines quite precisely the concept of “copy” and “duplicate” of a digital document however it does not clearly define the concept of “original document”. This causes problems in all those contexts in which it is necessary to exhibit the “original” as evidence as in the case of interceptions in criminal trials. A starting point for opening studies could be a look to the legislations on this subject in other countries.

The current Italian regulation defines quite precisely the concept of “copy” and “duplicate” of a digital document however it does not clearly define the concept of “original document”. This causes problems in all those contexts in which it is necessary to exhibit the “original” as evidence as in the case of interceptions in criminal trials. A starting point for opening studies could be a look to the legislations on this subject in other countries.