Temporal pattern of Klebsiella pneumoniae carbapenemase (KPC) on surface of an intensive care unit of a large hospital

Background: Carbapenem-resistant Enterobacteriaceae are an increasing cause of healthcare-associated infections worldwide. Patients with infections caused by Klebsiella pneumoniae resistant to carbapenems (KPC) have significant increases in both allcause mortality and 30-day mortality. The aims of this study was to investigate the prevalence of KPC on environmental samples collected during and after an outbreak caused by KPC in an intensive care unit (ICU) of a teaching hospital. Methods: Between 2010 and 2014 we conducted a total of 132 environmental monitoring campaigns from different critical surface of ICU ward in a Teaching Hospital Policlinico Umberto I. Samples were collected on surfaces in patient rooms and health care area. All samples were cultured and K. pneumoniae isolates were identified by standard microbiological techniques. The presumptive colonies were confirmed and tested for antibiotic resistance by an automated system. K. pneumoniae resitant to carbapenems were tested for carbapenemase production by modified Hodge test. Results: A total of 2526 environmental samples were collected from November 2010 to July 2014. Of those, 111 resulted positive for K. pneumoniae while KPC were 95 (85.6% of all K. pneumoniae, 3.8% of total samples). KPC was recovered in all patient rooms with similar proportion (5.1-5.6%) with the exception of patient 6 bed room where it was lower (2.4%). The pathogen was not recovered in rooms dedicated to healthcare personnel and doctors. Among surfaces, the highest proportion of KPC resulted on bedrail (6.8%), more than double than other surfaces. Washbasins had nearly half of samples KPC positive (1.2%). Conclusions: Despite previous studies suggested that environment plays a minor role in the transmission of carbapenem-resistant enterobacteriaceae, our data highlighted that surfaces represents a significant reservoir for KPC possibly supporting transiently contamination of hands of healthcare workers in our ICU. Our results confirm that KPC are more likely found on surfaces closer to the patient than on those situated further away

FIBROBLAST GROWTH FACTOR BINDING PROTEIN 1 (FGFBP1) CONTRIBUTES IN THE ESTABLISHMENT AND MAINTENANCE OF THE BLOOD BRAIN BARRIER

The Blood Brain Barrier (BBB) is a highly specialized vascular structure whose aim is to tightly regulate the permeability between the blood flow and the Central Nervous System (CNS). To this purpose, the ECs in the brain need to present some peculiar features: the presence of high-resistance tight junctions (TJs) to block paracellular permeability, the lack of fenestrations, and the expression of some specific transmembrane transporters to selectively allow the entrance of nutrients and the exit of toxic metabolites. The high level of specialization of the brain microvasculature is obtained as a result of the interaction of the endothelial compartment with the other components of the so-called NeuroVascular Unit (NVU), such as the Basement Membrane (BM), pericytes and astrocyte end-feet. The canonical Wnt/\u3b2-catenin pathway, that is specifically activated in CNS vessels during development, regulates BBB initiation and maintenance. Moreover, inactivation of this pathway in vivo leads to angiogenic defects in the CNS and not in other vascular regions. Affymetrix analysis previously performed in our group provided a list of genes whose transcription is selectively regulated upon Wnt3a stimulation in murine primary ECs isolated from brain (bMEC). One of the most upregulated transcripts is that of Fibroblast Growth Factor Binding Protein 1 (FGFBP1) gene. FGFBP1 is a cargo protein that, after being secreted in the extracellular matrix (ECM), is able to non-covalently bind the FGF immobilized in the ECM and to mobilize it, protecting it from degradation and presenting it to FGF tyrosine-kinase receptor on the cell membrane. Given the capability of Wnt3a stimulation to selectively induce FGFBP1 expression in brain ECs, we hypothesized that this protein could be involved in the process of initiation and/or maturation of the BBB. In this work, we demonstrate in vivo in the zebrafish model that FGFBP1 knock down by morpholino presents vascular abnormalities in the brain and in the trunk, together with cerebral hemorrhages and impaired permeability. Taking advantage of the endothelial-specific FGFBP1 knock out murine model, we further demonstrate that inhibition of endothelial FGFBP1 expression affects brain vascular development, causing vascular defects and increased BBB permeability and also influencing the number of pericytes and the composition of the BM. Finally, we show in vitro that FGFBP1 absence promotes a \u201ctip-like\u201d phenotype and an increase in the expression of Plvap in bMECs. In conclusion, our work proposes a novel role for FGFBP1 in the maintenance of the properties of the BBB and in the regulation of the complex interactions of the endothelial compartment with the other components of the NVU

In vivo effect of an immunostimulating bacterial lysate on human B lymphocytes.

The aim of the present study is to investigate in humans the mechanism by which the oral vaccine Polyvalent Mechanical Bacterial Lysate (PMBL) can rapidly mobilize specific immune response and evaluate the efficacy of its immunostimulating activity in preventing recurrent infections of the upper respiratory tract (URTIs) in a group of patients with a medical history of URTI recurrence. Patients received, by sublingual route, PBML, an immunostimulating lysate obtained by mechanical lysis of the most common bacteria responsible for upper respiratory tract infections. The treatment was administered for 10 consecutive days/month for 3 consecutive months. After the end of the treatment period the patients were followed up for an additional 3 months. The frequency of IgM memory B cells and the expression of the activation marker CD25 in peripheral blood lymphocytes were measured using the flow cytometric method before the start and at days 30 and 90 of the treatment cycle. To correlate clinical results to immunological parameters, the patients were monitored at different time-points during the treatment and at the end of follow-up period. The results showed that PMBL exerts a therapeutic and preventing effect in acute and recurrent infections of the upper respiratory tract and that this effect correlated with the activation and enhancement of both IgM memory B lymphocytes (CD24+/CD27+ cells) and IL2 receptor-expressing lymphocytes (CD25+ cells) involved either in humoral or cellular immunity

Multimodal Surveillance of HAI in an Intensive Care Unit of a Large Teaching Hospital

Background: Healthcare associated Infections (HAIs) represent a significant burden in terms of mortality, morbidity, length of stay and costs for patients in intensive care units (ICU). Surveillance systems are recommended to gather data in order to elaborate and evaluate intervention to reduce HAIs risk. Here we describe results of the multimodal surveillance system implemented in the ICU of a large teaching hospital in Rome from April 2016 to October 2018. Methods: The surveillance system integrated four different approaches: i) active surveillance focused on inpatients; ii) environmental microbiological surveillance; iii) surveillance focused on isolated microorganisms; iv) behavioral surveillance of the healthcare personnel. The system included the molecular genotyping of bacterial isolates through the pulsed field gel electrophoresis (PFGE). Moreover, an intervention to improve personnel adherence to hand hygiene (HH) guidelines was conducted. Results: Overall, 773 patients were included in the surveillance. The global incidence rate of the device related HAIs was 14.1 (95%CI: 12.2-16.3) per 1000 patient day. Monthly device related HAIs incidence rate showed a decreasing, from 26.9 per 1000 patient day in October 2016, to 4.9 in September 2018. The most common bacterial isolate was K. pneumoniae (20.7%), the 94.0% of which were multidrug-resistant. A total of 305 environmental bacterial isolates were retrieved and the most frequent was A. baumannii (27.2%), that was always multidrug-resistant. Genotyping showed a limited number of major PFGE patters in clinical and environmental isolates. Behavioral compliance to HH guidelines improved after the educational intervention. Conclusions: The data showed an overall slight decrease over time of the adjusted risk HAIs rates. Through the integration of information gathered from the four approaches, the application of this model returns a precise and detailed view of the infectious risk and of the microbial ecology of the ICU

Anti-inflammatory Effect of Resveratrol and Polydatinby In Vitro IL-17 Modulation.

Interleukin-17 (IL-17) is a proinflammatory cytokine produced, although not exclusively, by T helper 17 recently identified as a distinct T helper lineage mediating tissue inflammation. IL-17 is known to be involved in a number of chronic disorders although the mechanisms regulating its production in inflammatory disease are still unclear. The beneficial properties of the polyphenolic compound resveratrol including its nti-inflammatory, antioxidant, and antitumor effects, its role in the aging process and in the prevention of heart and neurodegenerative diseases are well-known. In addition, derivatives of resveratrol, including glucosylated molecules as polydatin have been linked to similar beneficial effects. We have investigated the effects of resveratrol and polydatin on the in vitro production of IL-17 in a model of inflammation in vitro. The results obtained by activated human peripheral blood mononuclear cells, stimulated with anti-CD3/anti-CD28 monoclonal antibodies and treated with these polyphenolic compounds at different concentrations show that both decrease IL-17 production in a concentration-dependent manner. This study confirms the anti-inflammatory activity of resveratrol and its derivatives and suggests a potential clinical relevance in the therapy of inflammatory diseases

Mitochondrial DNA Regionalism and Historical Demography in the Extant Populations of Chirocephalus kerkyrensis (Branchiopoda: Anostraca)

Background: Mediterranean temporary water bodies are important reservoirs of biodiversity and host a unique assemblage of diapausing aquatic invertebrates. These environments are currently vanishing because of increasing human pressure. Chirocephalus kerkyrensis is a fairy shrimp typical of temporary water bodies in Mediterranean plain forests and has undergone a substantial decline in number of populations in recent years due to habitat loss. We assessed patterns of genetic connectivity and phylogeographic history in the seven extant populations of the species from Albania, Corfu Is. (Greece), Southern and Central Italy. Methodology/Principal Findings: We analyzed sequence variation at two mitochondrial DNA genes (Cytochrome Oxidase I and 16s rRNA) in all the known populations of C. kerkyrensis. We used multiple phylogenetic, phylogeographic and coalescence-based approaches to assess connectivity and historical demography across the whole distribution range of the species. C. kerkyrensis is genetically subdivided into three main mitochondrial lineages; two of them are geographically localized (Corfu Is. and Central Italy) and one encompasses a wide geographic area (Albania and Southern Italy). Most of the detected genetic variation (<81%) is apportioned among the aforementioned lineages. Conclusions/Significance: Multiple analyses of mismatch distributions consistently supported both past demographic and spatial expansions with the former predating the latter; demographic expansions were consistently placed during interglacial warm phases of the Pleistocene while spatial expansions were restricted to cold periods. Coalescence methods revealed a scenario of past isolation with low levels of gene flow in line with what is already known for other co-distributed fairy shrimps and suggest drift as the prevailing force in promoting local divergence. We recommend that these evolutionary trajectories should be taken in proper consideration in any effort aimed at protecting Mediterranean temporary water bodies

Comparing nuclear power trajectories in Germany and the UK: from ‘regimes' to ‘democracies’ in sociotechnical transitions and Discontinuities

This paper focuses on arguably the single most striking contrast in contemporary major energy politics in Europe (and even the developed world as a whole): the starkly differing civil nuclear policies of Germany and the UK. Germany is seeking entirely to phase out nuclear power by 2022. Yet the UK advocates a ‘nuclear renaissance’, promoting the most ambitious new nuclear construction programme in Western Europe.Here,this paper poses a simple yet quite fundamental question: what are the particular divergent conditions most strongly implicated in the contrasting developments in these two countries. With nuclear playing such an iconic role in historical discussions over technological continuity and transformation, answering this may assist in wider understandings of sociotechnical incumbency and discontinuity in the burgeoning field of‘sustainability transitions’. To this end, an ‘abductive’ approach is taken: deploying nine potentially relevant criteria for understanding the different directions pursued in Germany and the UK. Together constituted by 30 parameters spanning literatures related to socio-technical regimes in general as well as nuclear technology in particular, the criteria are divided into those that are ‘internal’ and ‘external’ to the ‘focal regime configuration’ of nuclear power and associated ‘challenger technologies’ like renewables. It is ‘internal’ criteria that are emphasised in conventional sociotechnical regime theory, with ‘external’ criteria relatively less well explored. Asking under each criterion whether attempted discontinuation of nuclear power would be more likely in Germany or the UK, a clear picture emerges. ‘Internal’ criteria suggest attempted nuclear discontinuation should be more likely in the UK than in Germany– the reverse of what is occurring. ‘External’ criteria are more aligned with observed dynamics –especially those relating to military nuclear commitments and broader ‘qualities of democracy’. Despite many differences of framing concerning exactly what constitutes ‘democracy’, a rich political science literature on this point is unanimous in characterising Germany more positively than the UK. Although based only on a single case,a potentially important question is nonetheless raised as to whether sociotechnical regime theory might usefully give greater attention to the general importance of various aspects of democracy in constituting conditions for significant technological discontinuities and transformations. If so, the policy implications are significant. A number of important areas are identified for future research, including the roles of diverse understandings and specific aspects of democracy and the particular relevance of military nuclear commitments– whose under-discussion in civil nuclear policy literatures raises its own questions of democratic accountability