URBAN FLOWS SIMULATOR BASED ON COMPLEX SYSTEM OF QUEUES: PROCEDURES FOR SIMULATOR GENERATION

In a previous work [Pasini L and Feliziani S 2013 TASK Quart. 17 (3) 155], we have defined an object library that allows the building of architectural models of urban traffic systems. In this work we illustrate the procedures that enable us to produce a system simulator starting from the architectural model of an urban vehicular traffic system

In vitro antibacterial activity of ceftazidime/avibactam in combination against planktonic and biofilm carbapenemase-producing Klebsiella pneumoniae isolated from blood

Abstract Objectives The aim of this study was to report on in vitro tests of antibacterial activity of ceftazidime/avibactam in combination against planktonic or biofilm KPC carbapenemase-producing Klebsiella pneumoniae (KPC-Kp), the rate of KPC-Kp blood isolates in University of Perugia Hospital over a 5-year period, and their antimicrobial susceptibility patterns. Methods The antibacterial activity of ceftazidime/avibactam in combination with other antimicrobials was assessed against planktonic and biofilm bacteria by Etest and checkerboard assay. A retrospective review of laboratory data was performed to evaluate the rate of KPC-Kp from blood samples and their antimicrobial susceptibility patterns. Results Between 2014 and 2019, 130/4241 (3.1%) KPC-Kp were identified from blood cultures. Their rate increased from 2.3% in 2014–2015 to 4.5% over the last 3 years. Overall, 4.6% (6/130) of KPC-Kp isolates were susceptible to meropenem, 65.4% (85/130) to colistin, 65.1% (84/129) to tigecycline, 34.6% (45/130) to amikacin, 36.2% (42/116) to gentamicin, 40.2% (39/97) to fosfomycin and 91.5% (65/71) to ceftazidime/avibactam. Five of six ceftazidime/avibactam-resistant KPC-Kp were isolated from patients not treated with ceftazidime/avibactam. Synergism was detected both by Etest and checkerboard assay for the combination of ceftazidime/avibactam plus meropenem against planktonic isolates, whilst lower bactericidal activity was observed in biofilm KPC-Kp isolates. Conclusions Our in vitro data suggest that the combination of ceftazidime/avibactam plus meropenem has a synergistic antibacterial activity against planktonic bacteria, whilst a lower activity was detected against biofilm, suggesting worse clinical outcomes whenever biofilm infections are present. Further analyses are required to confirm these results before extending them to clinical practice

Therapeutic activity of a Saccharomyces cerevisiae-based probiotic and inactivated whole yeast on vaginal candidiasis

Vulvovaginal candidiasis is the most prevalent vaginal infection worldwide and Candida albicans is its major agent. Vulvovaginal candidiasis is characterized by disruption of the vaginal microbiota composition, as happens following large spectrum antibiotic usage. Recent studies support the effectiveness of oral and local probiotic treatment for prevention of recurrent vulvovaginal candidiasis. Saccharomyces cerevisiae is a safe yeast used as, or for, the production of ingredients for human nutrition and health. Here, we demonstrate that vaginal administration of probiotic Saccharomyces cerevisiae live yeast (GI) and, in part, inactivated whole yeast Saccharomyces cerevisiae (IY), used as post-challenge therapeutics, was able to positively influence the course of vaginal candidiasis by accelerating the clearance of the fungus. This effect was likely due to multiple interactions of Saccharomyces cerevisiae with Candida albicans. Both live and inactivated yeasts induced coaggregation of Candida and consequently inhibited its adherence to epithelial cells. However, only the probiotic yeast was able to suppress some major virulence factors of Candida albicans such as the ability to switch from yeast to mycelial form and the capacity to express several aspartyl proteases. The effectiveness of live yeast was higher than that of inactivated whole yeast suggesting that the synergy between mechanical effects and biological effects were dominant over purely mechanical effects. The protection of epithelial cells to Candida-induced damage was also observed. Overall, our data show for the first time that Saccharomyces cerevisiae-based ingredients, particularly the living cells, can exert beneficial therapeutic effects on a widespread vaginal mucosal infection

Secretory Aspartyl Proteinases Cause Vaginitis and Can Mediate Vaginitis Caused by Candida albicans in Mice

Vaginal inflammation (vaginitis) is the most common disease caused by the human-pathogenic fungus Candida albicans. Secretory aspartyl proteinases (Sap) are major virulence traits of C. albicans that have been suggested to play a role in vaginitis. To dissect the mechanisms by which Sap play this role, Sap2, a dominantly expressed member of the Sap family and a putative constituent of an anti-Candida vaccine, was used. Injection of full-length Sap2 into the mouse vagina caused local neutrophil influx and accumulation of the inflammasome-dependent interleukin-1β (IL-1β) but not of inflammasome-independent tumor necrosis factor alpha. Sap2 could be replaced by other Sap, while no inflammation was induced by the vaccine antigen, the N-terminal-truncated, enzymatically inactive tSap2. Anti-Sap2 antibodies, in particular Fab from a human combinatorial antibody library, inhibited or abolished the inflammatory response, provided the antibodies were able, like the Sap inhibitor Pepstatin A, to inhibit Sap enzyme activity. The same antibodies and Pepstatin A also inhibited neutrophil influx and cytokine production stimulated by C. albicans intravaginal injection, and a mutant strain lacking SAP1, SAP2, and SAP3 was unable to cause vaginal inflammation. Sap2 induced expression of activated caspase-1 in murine and human vaginal epithelial cells. Caspase-1 inhibition downregulated IL-1β and IL-18 production by vaginal epithelial cells, and blockade of the IL-1β receptor strongly reduced neutrophil influx. Overall, the data suggest that some Sap, particularly Sap2, are proinflammatory proteins in vivo and can mediate the inflammasome-dependent, acute inflammatory response of vaginal epithelial cells to C. albicans. These findings support the notion that vaccine-induced or passively administered anti-Sap antibodies could contribute to control vaginitis

The Combination of Molnupiravir with Nirmatrelvir or GC376 Has a Synergic Role in the Inhibition of SARS-CoV-2 Replication In Vitro

Introduction: The development of effective vaccines has partially mitigated the trend of the SARS-CoV-2 pandemic; however, the need for orally administered antiviral drugs persists. This study aims to investigate the activity of molnupiravir in combination with nirmatrelvir or GC376 on SARS-CoV-2 to verify the synergistic effect. Methods: The SARS-CoV-2 strains 20A.EU, BA.1 and BA.2 were used to infect Vero E6 in presence of antiviral compounds alone or in combinations using five two-fold serial dilution of compound concentrations <= EC90. After 48 and 72 h post-infection, viability was performed using MTT reduction assay. Supernatants were collected for plaque-assay titration. All experiments were performed in triplicate, each being repeated at least three times. The synergistic score was calculated using Synergy Finder version 2. Results: All compounds reached micromolar EC90. Molnupiravir and GC376 showed a synergistic activity at 48 h with an HSA score of 19.33 (p < 0.0001) and an additive activity at 72 h with an HSA score of 8.61 (p < 0.0001). Molnupiravir and nirmatrelvir showed a synergistic activity both at 48 h and 72 h with an HSA score of 14.2 (p = 0.01) and 13.08 (p < 0.0001), respectively. Conclusion: Molnupiravir associated with one of the two protease-inhibitors nirmatrelvir and GC376 showed good additive-synergic activity in vitro

Erratum to nodal management and upstaging of disease. Initial results from the Italian VATS Lobectomy Registry

[This corrects the article DOI: 10.21037/jtd.2017.06.12.]

Cloud: Presente e futuro

Cloud is an emerging technology that allows making the increasing demand of advanced technology at a lower cost, in an easier and more effective manner. This article will contain some information regarding this new technology. The emphasis will be both on state of the art and objectives of future research about cloud. In particular, Section 1 provides introductory information about cloud. Section 2 provides a set of common definitions and deepens cloud’s features from different perspectives. Section 3 analyzes the usage scenarios for cloud and in particular, what features are considered most important. Section 4 compares the strengths and characteristics of cloud against its current usage. Section 5 explores the major research topics and assesses their complexity and relevance. Section 6 concludes the report with a series of general considerations

Cloud Readiness Assessment of Legacy Application

Applications and services hosted in the cloud are increasing continuously. Cloud technology offers important perspectives (performance, high availability, elasticity) and it enables new business models. Unfortunately, this new paradigm faces unprecedent requirements not addressed in legacy application (multi-tenancy, scalability, etc.). This leads to complex re-engineering phases in order to to migrate existing software into a cloud environment. Before starting a migration, it is important to analyze the cloud compliance of the application, what to expect after the migration and the effort required to fulfill these expectations. This paper assesses a way to extract an index that describes the feasibility of the re-engineering. We test the metric with a real application that needs to be migrated to a private cloud

NLRP3 inflammasome is a key player in human vulvovaginal disease caused by Candida albicans

The expression of host inflammatory and Candida albicans putative virulence factors was studied in women with vulvovaginal candidiasis (VVC; twenty) or colonized by the fungus but asymptomatic (carriers; fifteen) or non-colonized asymptomatic (ten subjects). Overexpression of genes encoding NLRP3 and caspase-1 inflammasome components sharply differentiated VVC patients from asymptomatic colonized or non-colonized women. Inflammasome expression was coupled with neutrophils recruitment in the vagina of VVC women and IL-1\u3b2 and IL-8 production. Both cytokines were present, though to a lower concentration, also in the vaginal fluid of colonized and non-colonized women. Secretory aspartyl proteinases (SAPs) and hyphae associated genes HWP1 and ECE1 were upregulated in VVC but with some differences among infected women. The most overexpressed SAP gene was SAP2, that correlated with neutrophils accumulation. Our data provide clinical evidence that the intracytoplasmic activation of NLRP3 inflammasome complex plays a critical, pathogenesis relevant role in human VVC