Predicting the tau strange branching ratios and implications for V_{us}

Hadronic tau decays provide several ways to extract the Cabbibo-Kobashi-Maskawa (CKM) matrix element V_{us}. The most precise determination involves using inclusive tau decays and requires as input the total branching ratio into strange final states. Recent results from B-factories have led to a discrepancy of about 3.4 sigma from the value of V_{us} implied by CKM unitarity and direct determination from Kaon semi-leptonic modes. In this paper we predict the three leading strange tau branching ratios, using dispersive parameterizations of the hadronic form factors and taking as experimental input the measured Kaon decay rates and the tau -> K pi nu_tau decay spectrum. We then use our results to reevaluate V_{us}, for which we find |V_{us}|=0.2207 \pm 0.0027, in better agreement with CKM unitarity.Comment: 20 pages, 3 figure

Clinical review: Noninvasive ventilation in the clinical setting – experience from the past 10 years

This brief review analyses the progress of noninvasive ventilation (NIV) over the last decade. NIV has gained the dignity of first line intervention for acute exacerbation of chronic obstructive pulmonary disease, assuring reduction of the intubation rate, rate of infection and mortality. Despite positive results, NIV still remains controversial as a treatment for acute hypoxemic respiratory failure, largely due to the different pathophysiology of hypoxemia. The infection rate reduction effect achieved by NIV application is crucial for immunocompromised patients for whom the endotracheal intubation represents a high risk. Improvements in skills acquired with experience over time progressively allowed successful treatment of more severe patients

Safety and efficacy of colistin versus meropenem in the empirical treatment of ventilator-associated pneumonia as part of a macro-project funded by the Seventh Framework Program of the European Commission studying off-patent antibiotics. study protocol for a randomized controlled trial

Background: Ventilator-associated pneumonia (VAP) is one of the most common and severe hospital-adquired infections, and multidrugresistant gram-negative bacilli (MDR-GNB) constitute the main etiology in many countries. Inappropriate empiric antimicrobial treatment is associated with increased mortality. In this context, the empirical treatment of choice for VAP is unknown. Colistin, is now the antimicrobial with greatest in vitro activity against MDR-GNB. Methods/Design: The MagicBullet clinical trial is an investigator-driven clinical study, funded by the Seventh Framework Program of the European Commission. This is designed as a phase IV, randomized, controlled, open label, non-inferiority and international trial to assess the safety and efficacy of colistin versus meropenem in late onset VAP. The study is conducted in a total of 32 centers in three European countries (Spain, Italy and Greece) with specific high incidences of infections caused by MDR-GNB. Patients older than 18 years who develop VAP with both clinical and radiological signs, and are on mechanical ventilation for more than 96 hours, or less than 96 hours but with previous antibiotic treatment plus one week of hospitalization, are candidates for inclusion in the study. A total sample size of 496 patients will be randomized according to a severity clinical score (at the time of VAP diagnosis in a 1:1 ratio to receive either colistin 4.5 MU as a loading dose, followed by 3 MU every eight hours (experimental arm), or meropenem 2 g every eight hours (control arm), both combined with levofloxacin. Mortality from any cause at 28 days will be considered as the main outcome. Clinical and microbiological cure will be evaluated at 72 hours, eight days, the finalization of antibiotic treatment, and 28 days of follow-up. The efficacy evaluation will be performed in every patient who receives at least one study treatment drug, and with etiologic diagnosis of VAP, intention-to-treat population and per protocol analysis will be performed

HCV derived from sera of HCV-infected patients induces pro-fibrotic effects in human primary fibroblasts by activating GLI2

Hepatitis C virus (HCV) infection is a leading cause of liver fibrosis, especially in developing countries. The process is characterized by the excess accumulation of ECM that may lead, over time, to hepatic cirrhosis, liver failure and also to hepatocarcinoma. The direct role of HCV in promoting fibroblasts trans-differentiation into myofibroblasts, the major fibrogenic cells, has not been fully clarified. In this study, we found that HCV derived from HCV-infected patients infected and directly induced the trans-differentiation of human primary fibroblasts into myofibroblasts, promoting fibrogenesis. This effect correlated with the activation of GLI2, one of the targets of Hedgehog signaling pathway previously reported to be involved in myofibroblast generation. Moreover, GLI2 activation by HCV correlated with a reduction of autophagy in fibroblasts, that may further promoted fibrosis. GLI2 inhibition by Gant 61 counteracted the pro-fibrotic effects and autophagy inhibition mediated by HCV, suggesting that targeting HH/GLI2 pathway might represent a promising strategy to reduce the HCV-induced fibrosis

Lactobacillus Sepsis and Probiotic Therapy in Newborns: Two New Cases and Literature Review

Many term and preterm infants are commonly supplemented with probiotics to prevent adverse effects of antibiotic administration and necrotizing enterocolitis and they are believed to be safe. However, the supplementation with Lactobacillus rhamnosus GG has been associated with the development of sepsis with a cause–effect relationship in six newborns and children. In this study, we report two further cases and discuss the emerging issue of probiotic supplementation safety in neonates. We conclude that physicians must be aware that supplementation with L. rhamnosus GG can cause sepsis in high-risk patients on rare occasions

Hepatitis C virus present in the sera of infected patients interferes with the autophagic process of monocytes impairing their in-vitro differentiation into dendritic cells

AbstractAutophagy has a pivotal role in the in-vitro monocyte differentiation into macrophages and dendritic cells (DCs), the most powerful antigen presenting cells (APC) with the unique capacity to initiate an adaptive immune response. Autophagy is also a mechanism by which these cells of innate immunity may degrade intracellular pathogens and mediate the antigen processing and presentation, essential to clear an infection. For these reasons, pathogens have learned how to manipulate autophagy for their own survival. In this study we found that hepatitis C virus (HCV), derived from sera of infected patients, blocked the autophagic process in differentiating monocytes, seen as LC3 II and p62 expression levels. The suppression of autophagy correlated with a reduction of cathepsins D, B and proteolytic activity, and resulted in impairment of monocyte differentiation into DCs, as indicated by the reduction of CD1a acquirement. These data suggest that the block of autophagy might be one of the underlying mechanisms of the HCV-mediated immune subversion that frequently leads to viral persistence and chronic hepatitis

Early diagnosis of candidemia in intensive care unit patients with sepsis: a prospective comparison of (1→3)-β-D-glucan assay, Candida score, and colonization index

The culture-independent serum (1\u21923)-\u3b2-D-glucan (BG) detection test may allow early diagnosis of invasive fungal disease, but its clinical usefulness needs to be firmly established. A prospective single-center observational study was conducted to compare the diagnostic value of BG assay, Candida score (CS), and colonization index in intensive care unit (ICU) patients at risk for Candida sepsis

Characterization of four novel bacteriophages targeting multi-drug resistant Klebsiella pneumoniae strains of sequence type 147 and 307

Introduction: the development of alternative antimicrobial strategies is deemed to be a high priority to deal with the challenge caused by the spread of multidrug-resistant (MDR) bacteria in clinical settings. according to several international organizations, phages or components thereof are one of these possible options that could be useful to treat bacterial infections. among the drug-resistant bacteria, carbapenem resistant Klebsiella pneumoniae (CR-Kp) are particularly worrisome, given the extensive MDR profiles, their pandemic dissemination and primary role in healthcare associated and life-threatening infections. In this study we isolated and characterised four lytic bacteriophages targeting two major high-risk clones of CR-Kp circulating in hospital environments, i.e., those belonging to Sequence Type (ST) 307 and ST147. Materials and methods: wastewater samples collected from hospitals located in central Italy were screened for the presence of phages by using a previously characterized collection of K. pneumoniae clinical isolates as hosts and the top-agar overlay technique. host specificity and infection efficiency was assessed by spot test and efficiency of plating, respectively. Dynamic of bacterial infections was determined by the one-step growth curve method. Phages were visualized through transmission electron microscopy (TEM) and their genomes were obtained and analysed by a Next Generation Sequencing approach followed by bioinformatics analysis. Results: four bacteriophages, named GP-1, GP-2, GP-4 and GP-5, have been isolated, purified and produced at high titres. collectively, two phages were able to selectively lyse 12/14 K. pneumoniae strains of ST307, while the other two were active only against all the tested K. pneumoniae strains of ST147 (n=12). phages maintain an overall good stability to temperature and pH changes and were characterized by infection cycles having latency periods ranging from 10 to 50 minutes and burst sizes of 10-100 PFU. results from TEM analysis and genome sequencing demonstrated that the four phages were of different families and allowed to rule out the presence of antibiotic resistance genes, virulence factors or toxins. Discussion and Conclusions: Considering their strictly lytic nature and their high selectivity towards two of the major high-risk clones of K. pneumoniae, the isolated phages can be considered as good candidates for their evaluation in animal models as members of cocktails for applications to treat severe infections caused by CR-Kp strains