Structure of the capsular polysaccharide of the KPC-2-producing Klebsiella pneumoniae strain KK207-2 and assignment of the glycosyltransferases functions

Klebsiella pneumoniae strain KK207-2 was isolated in 2010 froma bloodstreaminfection of an inpatient at an Italian hospital. It was previously found to produce the KPC-2 carbapenemase and to belong to clade 1 of sequence type 258. Genotyping of the conserved wzi and wzc genes from strain KK207-2 yielded contrasting results: the wzc-based method assigned the cps207\u20132 to a new K-type, while the wzi-based method assigned it to the known K41 K-type. In order to resolve this contradiction, the capsular polysaccharide of K. pneumoniae KK207-2 was purified and its structure determined by using GLC-MS of appropriate carbohydrate derivatives, ESI-MS of both partial hydrolysis and Smith degradation derived oligosaccharides, andNMR spectroscopy of oligosaccharides, and the lithium degraded, native and de-O-acetylated polysaccharide. All the collected data demonstrated the following repeating unit for the K. pneumoniae KK207-2 capsular polysaccharide: OAc 6 [3)-\u3b2-D-Gal-(1-4)-\u3b2-D-Glc-(1-]n 4 I 1 \u3b2-D-Glcp-(1-6)-\u3b1-D-Glcp-(1-4)-\u3b2-D-GlcpA-(1-6)-\u3b1-D-Glcp The polysaccharide contains about 0.60 acetyl groups per repeating unit on C6 of the Gal residue. The reactions catalysed by each glycosyltransferase in the cpsKK207-2 gene cluster were assigned on the basis of structural homology with other Klebsiella K antigens

Which BRCA genetic testing programs are ready for implementation in health care? A systematic review of economic evaluations

Purpose: There is considerable evidence regarding the efficacy and effectiveness of BRCA genetic testing programs, but whether they represent good use of financial resources is not clear. Therefore, we aimed to identify the main health-care programs for BRCA testing and to evaluate their cost-effectiveness. Methods: We performed a systematic review of full economic evaluations of health-care programs involving BRCA testing. Results: Nine economic evaluations were included, and four main categories of BRCA testing programs were identified: (i) populationbased genetic screening of individuals without cancer, either comprehensive or targeted based on ancestry; (ii) family history (FH)-based genetic screening, i.e., testing individuals without cancer but with FH suggestive of BRCA mutation; (iii) familial mutation (FM)- based genetic screening, i.e., testing individuals without cancer but with known familial BRCA mutation; and (iv) cancer-based genetic screening, i.e., testing individuals with BRCA-related cancers. Conclusions: Currently BRCA1/2 population-based screening represents good value for the money among Ashkenazi Jews only. FHbased screening is potentially very cost-effective, although further studies that include costs of identifying high-risk women are needed. There is no evidence of cost-effectiveness for BRCA screening of all newly diagnosed cases of breast/ovarian cancers followed by cascade testing of relatives, but programs that include tools for identifying affected women at higher risk for inherited forms are promising. Cost-effectiveness is highly sensitive to the cost of BRCA1/2 testing

In vivo emergence of colistin resistance in Klebsiella pneumoniae producing KPC-type carbapenemases mediated by insertional inactivation of the PhoQ/PhoP mgrB regulator

Colistin is one of the few agents that retain activity against extensively drug-resistant strains of Klebsiella pneumoniae producing KPC-type carbapenemases (KPC-KP). However, resistance to colistin is increasingly reported among KPC-KP. Comparative genomic analysis of a pair of sequential KPC-KP isolates from the same patient including a colistin-susceptible isolate (KKBO-1) and a colistin-resistant isolate (KKBO-4) selected after colistin exposure revealed that insertional inactivation of the mgrB gene, encoding a negative regulator of the PhoQ/PhoP signaling system, is a genetic mechanism for acquired colistin resistance. The role of mgrB inactivation in acquired colistin resistance was confirmed by complementation experiments with wild-type mgrB, which restored colistin susceptibility in KKBO-4, and by construction of an mgrB deletion mutant from KKBO-1, which exhibited a colistin-resistant phenotype. Insertional mgrB inactivation was also detected in 60% of colistin-resistant mutants selected from KKBO-1 in vitro, following plating on colistin-containing medium, confirming the role (although not unique) of this mechanism in the emergence of acquired colistin resistance. In colistin-resistant mutants carrying insertional inactivation or deletion of the mgrB gene, upregulated transcription of phoP, phoQ, and pmrK (which is part of the pmrHFIJKLM operon) was detected. These findings confirmed the MgrB regulatory role in K. pneumoniae and were in agreement with the known association between upregulation of the PhoQ/PhoP system and activation of the pmrHFIJKLM operon, which eventually leads to resistance to polymyxins by modification of the lipopolysaccharide target

Are knowledge and skills acquired during the Master Degree in Nursing actually put into practice? A pilot study in Italy

Background. Literature on the evaluation of the Master’s Degree in Nursing is scarce. The objective of this pilot study was to test a questionnaire aimed at monitoring the activities of nurses after receiving the Master’s degree. Methods. An electronic questionnaire was administered to 36 graduates who obtained the Master’s degree during the academic year 2010/2011. Results. Almost 80% of the participants judged their level of improvement in knowledge and skills during the course to have been satisfactory, but the level of implementation of these competencies at work was quite low. Conclusion. Competencies acquired during the Master’s degree course are not always put into practice

Efficacy of Ginkgolide B in the prophylaxis of migraine with aura.

In a multicentric, open, preliminary trial, we evaluated the use of ginkgolide B, a herbal constituent extract from Ginkgo biloba tree leaves, in the prophylactic treatment of migraine with aura (MA). Fifty women suffering from migraine with typical aura, or migraine aura without headache, diagnosed according to International Headache Society criteria, entered a six-month study. They underwent a two month run-in period free of prophylactic drugs, followed by a four month treatment period (subdivided into two bimesters, TI and TII) with a combination of 60 mg ginkgo biloba terpenes phytosome, 11 mg coenzyme Q 10, and 8.7 mg vitamin B2 (Migrasoll), administered twice daily. A detailed diary reporting neurological symptoms, duration, and frequency of MA was compiled by patients throughout the trial. The number of MA significantly decreased during treatment (from 3.7 +/- 2.2 in the run-in period, to 2.0 +/- 1.9 during TI and to 1.2 +/- 1.6 during TII; Anova for repeated measures: P < 0.0001). There was also a statistically significant decrease in the average MA duration, which was 40.4 +/- 19.4 min during run-in, 28.2 +/- 19.9 during TI, and 17.6 +/- 20.6 during TII. Total disappearance of MA was observed in 11.1% patients during TI and in 42.2% of patients during T2. No serious adverse event was provoked by Migrasoll administration. Ginkgolide B is effective in reducing MA frequency and duration. The effect is clearly evident in the first bimester of treatment and is further enhanced during the second

φBO1E, a newly discovered lytic bacteriophage targeting carbapenemase-producing Klebsiella pneumoniae of the pandemic Clonal Group 258 clade II lineage

The pandemic dissemination of KPC carbapenemase-producing Klebsiella pneumoniae (KPC-KP) represents a major public health problem, given their extensive multidrug resistance profiles and primary role in causing healthcare-Associated infections. This phenomenon has largely been contributed by strains of Clonal Group (CG) 258, mostly of clade II, which in some areas represent the majority of KPC-KP isolates. Here we have characterized a newly discovered lytic Podoviridae, named φBO1E, targeting KPC-KP strains of clade II lineage of CG258. Genomic sequencing revealed that φBO1E belongs to the Kp34virus genus (87% nucleotide identity to vB-KpnP-SU552A). ΦBO1E was stable over a broad pH and temperature range, exhibited strict specificity for K. pneumoniae strains of clade II of CG258, and was unable to establish lysogeny. In a Galleria mellonella infection model, φBO1E was able to protect larvae from death following infection with KPC-KP strains of clade II of CG258, including one colistin resistant strain characterized by a hypermucoviscous phenotype. To our best knowledge φBO1E is the first characterized lytic phage targeting K. pneumoniae strains of this pandemic clonal lineage. As such, it could be of potential interest to develop new agents for treatment of KPC-KP infections and for decolonization of subjects chronically colonized by these resistant superbugs

Erectile dysfunction in hyperuricemia: A prevalence meta‐analysis and meta‐regression study

AbstractBackgroundWhether and to what extent an association exists between hyperuricemia and erectile dysfunction (ED) has not yet been fully determined.ObjectiveTo define pooled prevalence estimates and correlates of erectile dysfunction in men with hyperuricemic disorders.Materials and methodsA thorough search of Medline, Scopus, and Cochrane Library databases was performed. Data were combined using random‐effects models and the between‐study heterogeneity was assessed by Cochrane's Q and I2 tests. A funnel plot was used to assess publication bias.ResultsOverall, 8 studies included gave information about 85,406 hyperuricemic men, of whom 5023 complained of erectile dysfunction, resulting in a pooled erectile dysfunction prevalence estimate of 33% (95% Confidence Interval: 13–52%; I² = 99.9%). The funnel plot suggested the presence of a publication bias. At the meta‐regression analyses, among the available covariates that could affect estimates, only type 2 diabetes mellitus was significantly associated with a higher prevalence of erectile dysfunction (β = 0.08; 95% Confidence Interval: 0.01, 0.15, p = 0.025). At the sub‐group analysis, the pooled erectile dysfunction prevalence decreased to 4% (95% Confidence Interval: 0%–8%) when only the largest studies with the lowest prevalence of type 2 diabetes mellitus were included and increased up to 50% (95% Confidence Interval: 17%–84%) when the analysis was restricted to studies enrolling smaller series with higher prevalence of type 2 diabetes mellitus.ConclusionsA not negligible proportion of men with hyperuricemia can complain of erectile dysfunction. While a pathogenetic contribution of circulating uric acid in endothelial dysfunction cannot be ruled out, the evidence of a stronger association between hyperuricemia and erectile dysfunction in type 2 diabetes mellitus points to hyperuricemia as a marker of systemic dysmetabolic disorders adversely affecting erectile function

Stress echo 2020: the international stress echo study in ischemic and non-ischemic heart disease

BACKGROUND: Stress echocardiography (SE) has an established role in evidence-based guidelines, but recently its breadth and variety of applications have extended well beyond coronary artery disease (CAD). We lack a prospective research study of SE applications, in and beyond CAD, also considering a variety of signs in addition to regional wall motion abnormalities. METHODS: In a prospective, multicenter, international, observational study design, > 100 certified high-volume SE labs (initially from Italy, Brazil, Hungary, and Serbia) will be networked with an organized system of clinical, laboratory and imaging data collection at the time of physical or pharmacological SE, with structured follow-up information. The study is endorsed by the Italian Society of Cardiovascular Echography and organized in 10 subprojects focusing on: contractile reserve for prediction of cardiac resynchronization or medical therapy response; stress B-lines in heart failure; hypertrophic cardiomyopathy; heart failure with preserved ejection fraction; mitral regurgitation after either transcatheter or surgical aortic valve replacement; outdoor SE in extreme physiology; right ventricular contractile reserve in repaired Tetralogy of Fallot; suspected or initial pulmonary arterial hypertension; coronary flow velocity, left ventricular elastance reserve and B-lines in known or suspected CAD; identification of subclinical familial disease in genotype-positive, phenotype- negative healthy relatives of inherited disease (such as hypertrophic cardiomyopathy). RESULTS: We expect to recruit about 10,000 patients over a 5-year period (2016-2020), with sample sizes ranging from 5,000 for coronary flow velocity/ left ventricular elastance/ B-lines in CAD to around 250 for hypertrophic cardiomyopathy or repaired Tetralogy of Fallot. This data-base will allow to investigate technical questions such as feasibility and reproducibility of various SE parameters and to assess their prognostic value in different clinical scenarios. CONCLUSIONS: The study will create the cultural, informatic and scientific infrastructure connecting high-volume, accredited SE labs, sharing common criteria of indication, execution, reporting and image storage of SE to obtain original safety, feasibility, and outcome data in evidence-poor diagnostic fields, also outside the established core application of SE in CAD based on regional wall motion abnormalities. The study will standardize procedures, validate emerging signs, and integrate the new information with established knowledge, helping to build a next-generation SE lab without inner walls

Management of meningitis caused by multi drug-resistant Acinetobacter baumannii: Clinical, microbiological and pharmacokinetic results in a patient treated with colistin methanesulfonate

This paper reports on a 71- year-old Caucasian male who underwent neurosurgery for an oligodendroglioma, followed by a cranial-sinus fistula and cerebrospinal fluid rhinorrhea. The clinical course was complicated due to an extensively drug-resistant Acinetobacter baumannii meningitis. The patient was treated with colistin methanesulfonate, intrathecal for 24 days and intravenous for 46 days. In addition, the patient received meropenem and teicoplanin to treat a urinary tract infection and a bacterial aspiration pneumonia. Cerebrospinal fluid trough colistin levels resulted above the MIC of A. baumannii. Colistin cerebrospinal fluid concentration did not increase over the treatment period. Meningitis was cured and A. baumannii eradicated. No side effects from the antimicrobial therapy were observed. In conclusion, this case highlights the issues in treating infections caused by resistant Gram negative bacteria and supports previous findings on the efficacy, pharmacokinetic and tolerability of intravenous and intrathecal colistin treatments