Metabolic adaptation to a high-fat diet is associated with a change in the gut microbiota

Objective The gut microbiota, which is considered a causal factor in metabolic diseases as shown best in animals, is under the dual influence of the host genome and nutritional environment. This study investigated whether the gut microbiota per se, aside from changes in genetic background and diet, could sign different metabolic phenotypes in mice. Methods The unique animal model of metabolic adaptation was used, whereby C57Bl/6 male mice fed a high-fat carbohydrate-free diet (HFD) became either diabetic (HFD diabetic, HFD-D) or resisted diabetes (HFD diabetes-resistant, HFD-DR). Pyrosequencing of the gut microbiota was carried out to profile the gut microbial community of different metabolic phenotypes. Inflammation, gut permeability, features of white adipose tissue, liver and skeletal muscle were studied. Furthermore, to modify the gut microbiota directly, an additional group of mice was given a glucooligosaccharide (GOS)-supplemented HFD (HFD+GOS). Results Despite the mice having the same genetic background and nutritional status, a gut microbial profile specific to each metabolic phenotype was identified. The HFD-D gut microbial profile was associated with increased gut permeability linked to increased endotoxaemia and to a dramatic increase in cell number in the stroma vascular fraction from visceral white adipose tissue. Most of the physiological characteristics of the HFD-fed mice were modulated when gut microbiota was intentionally modified by GOS dietary fibres. Conclusions The gut microbiota is a signature of the metabolic phenotypes independent of differences in host genetic background and diet

Cost-analysis of seven nosocomial outbreaks in an academic hospital

OBJECTIVES:Nosocomial outbreaks, especially with (multi-)resistant microorganisms, are a major problem for health care institutions. They can cause morbidity and mortality for patients and controlling these costs substantial amounts of funds and resources. However, how much is unclear. This study sets out to provide a comparable overview of the costs of multiple outbreaks in a single academic hospital in the Netherlands. METHODS:Based on interviews with the involved staff, multiple databases and stored records from the Infection Prevention Division all actions undertaken, extra staff employment, use of resources, bed-occupancy rates, and other miscellaneous cost drivers during different outbreaks were scored and quantified into Euros. This led to total costs per outbreak and an estimated average cost per positive patient per outbreak day. RESULTS:Seven outbreaks that occurred between 2012 and 2014 in the hospital were evaluated. Total costs for the hospital ranged between €10,778 and €356,754. Costs per positive patient per outbreak day, ranged between €10 and €1,369 (95% CI: €49-€1,042), with a mean of €546 and a median of €519. Majority of the costs (50%) were made because of closed beds. CONCLUSIONS:This analysis is the first to give a comparable overview of various outbreaks, caused by different microorganisms, in the same hospital and all analyzed with the same method. It shows a large variation within the average costs due to different factors (e.g. closure of wards, type of ward). All outbreaks however cost considerable amounts of efforts and money (up to €356,754), including missed revenue and control measures

Use of whole-genome sequencing to trace, control and characterize the regional expansion of extended-spectrum beta-lactamase producing ST15 Klebsiella pneumoniae

The study describes the transmission of a CTX-M-15-producing ST15 Klebsiella pneumoniae between patients treated in a single center and the subsequent inter-institutional spread by patient referral occurring between May 2012 and September 2013. A suspected epidemiological link between clinical K. pneumoniae isolates was supported by patient contact tracing and genomic phylogenetic analysis from May to November 2012. By May 2013, a patient treated in three institutions in two cities was involved in an expanding cluster caused by this high-risk clone (HiRiC) (local expansion, CTX-M-15 producing, and containing hypervirulence factors). A clone-specific multiplex PCR was developed for patient screening by which another patient was identified in September 2013. Genomic phylogenetic analysis including published ST15 genomes revealed a close homology with isolates previously found in the USA. Environmental contamination and lack of consistent patient screening were identified as being responsible for the clone dissemination. The investigation addresses the advantages of wholegenome sequencing in the early detection of HiRiC with a high propensity of nosocomial transmission and prolonged circulation in the regional patient population. Our study suggests the necessity for interinstitutional/regional collaboration for infection/outbreak management of K. pneumoniae HiRiCs

The BioMart community portal: an innovative alternative to large, centralized data repositories.

The BioMart Community Portal (www.biomart.org) is a community-driven effort to provide a unified interface to biomedical databases that are distributed worldwide. The portal provides access to numerous database projects supported by 30 scientific organizations. It includes over 800 different biological datasets spanning genomics, proteomics, model organisms, cancer data, ontology information and more. All resources available through the portal are independently administered and funded by their host organizations. The BioMart data federation technology provides a unified interface to all the available data. The latest version of the portal comes with many new databases that have been created by our ever-growing community. It also comes with better support and extensibility for data analysis and visualization tools. A new addition to our toolbox, the enrichment analysis tool is now accessible through graphical and web service interface. The BioMart community portal averages over one million requests per day. Building on this level of service and the wealth of information that has become available, the BioMart Community Portal has introduced a new, more scalable and cheaper alternative to the large data stores maintained by specialized organizations

The laser shock adhesion test (LASAT) for production control of thermally sprayed ceramic coatings

International audienceThe adhesion strength of a ceramic coating deposited through direct spraying on a roughened substrate is a key issue in the manufacture of high-quality coatings on industrial components. The purpose of this work was to develop a rapid and discerning procedure for establishing adhesion level of a ceramic coating on a metallic substrate. The LAser Shock Adhesion Test, namely LASAT, was successfully applied to ceramic coatings with irradiation impact on the metallic side. Suitable parameters were found to determine the LASAT adhesion threshold using a standard Nd:YAG laser source. With a laser-irradiated area of several millimeters in diameter, it allowed assessment of the coating threshold on several areas of a coated plate sample. A control procedure for a qualitative assessment of coating adhesion was developed. This testing procedure could be easily used in industry, with possible location of the LASAT unit near to the spraying booth, for a direct production control on coated sample to improve the tracability of manufactured parts. Additional work was carried out to investigate a quantitative approach of the LASAT test to ceramic coating. The purpose was to simulate the shock wave propagation with the RADIOSS® code (a 3D software originally developed for car crash simulation). This code was implemented to calculate the velocity of the material and corresponding pressure throughout the substrate and the coating during the shock wave release (less than 2 ms). Experimental VISAR profiles ('Velocity Interferometer System for Any Reflector') were monitored in the straight direction of the laser-irradiated area on the rear side. These experimental signals (velocity measures) of the ceramic coating could be fitted and compared with a fairly good agreement with simulated profiles obtained by RADIOSS®. This modelling work was the first step towards a more comprehensive coating adhesion strength calculation in the future

Positive impact of infection prevention on the management of nosocomial outbreaks at an academic hospital

Aim: Infection prevention (IP) measures are vital to prevent (nosocomial) outbreaks. Financial evaluations of these are scarce. An incremental cost analysis for an academic IP unit was performed. Material & methods: On a yearly basis, we evaluated: IP measures; costs thereof; numbers of patients at risk for causing nosocomial outbreaks; predicted outbreak patients; and actual outbreak patients. Results: IP costs rose on average yearly with (sic)150,000; however, more IP actions were undertaken. Numbers of patients colonized with high-risk microorganisms increased. The trend of actual outbreak patients remained stable. Predicted prevented outbreak patients saved costs, leading to a positive return on investment of 1.94. Conclusion: This study shows that investments in IP can prevent outbreak cases, thereby saving enough money to earn back these investments

Rituximab and dose-dense chemotherapy for adults with Burkitt's lymphoma: a randomised, controlled, open-label, phase 3 trial

International audienceBackground: Short intensive chemotherapy is the standard of care for adult patients with Burkitt's leukaemia or lymphoma. Findings from single-arm studies suggest that addition of rituximab to these regimens could improve patient outcomes. Our objective was to test this possibility in a randomised trial. Methods In this randomised, controlled, open-label, phase 3 trial, we recruited patients older than 18 years with untreated HIV-negative Burkitt's lymphoma (including Burkitt's leukaemia) from 45 haematological centres in France. Exclusion criteria were contraindications to any drug included in the chemotherapy regimens, any serious comorbidity, poor renal (creatinine concentration >150 μmol/L) or hepatic (cirrhosis or previous hepatitis B or C) function, pregnancy, and any history of cancer except for non-melanoma skin tumours or stage 0 (in situ) cervical carcinoma. Patients were stratified into two groups based on disease extension (absence [group B] or presence [group C] of bone marrow or central nervous system involvement). Patients were further stratified in group C according to age (60 years) and central nervous system involvement. Participants were randomly assigned in each group to either intravenous rituximab injections and chemotherapy (lymphome malin B [LMB]) or chemotherapy alone by the Groupe d'Etude des Lymphomes de l'Adulte datacentre. Randomisation was stratified by treatment group and centre using computer-assisted permuted-block randomisation (block size of four; allocation ratio 1:1). We gave rituximab (375 mg/m2) on day 1 and day 6 during the first two courses of chemotherapy (total of four infusions). The primary endpoint is 3 year event-free survival (EFS). We analysed all patients who had data available according to their originally assigned group. This trial is registered with ClinicalTrials.gov, number NCT00180882. Results Between Oct 14, 2004, and Sept 7, 2010, we randomly allocated 260 patients to rituximab or no rituximab (group B 124 patients [64 no rituximab; 60 rituximab]; group C 136 patients [66 no rituximab; 70 rituximab]). With a median follow-up of 38 months (IQR 24–59), patients in the rituximab group achieved better 3 year EFS (75% [95% CI 66–82]) than did those in the no rituximab group (62% [53–70]; log-rank p stratified by treatment group=0·024). The hazard ratio estimated with a Cox model stratified by treatment group, assuming proportionality, was 0·59 for EFS (95% CI 0·38–0·94; p=0·025). Adverse events did not differ between the two treatment groups. The most common adverse events were infectious (grade 3–4 in 137 [17%] treatment cycles in the rituximab group vs 115 [15%] in the no rituximab group) and haematological (mean duration of grade 4 neutropenia of 3·31 days per cycle [95% CI 3·01–3·61] vs 3·38 days per cycle [3·05–3·70]) events. Interpretation Addition of rituximab to a short intensive chemotherapy programme improves EFS in adults with Burkitt's leukaemia or lymphoma. Funding Gustave Roussy Cancer Campus, Roche, Chugai, Sanof