Virulence Potential and Genomic Mapping of the Worldwide Clone Escherichia coli ST131

Recently, the worldwide propagation of clonal CTX-M-15-producing Escherichia coli isolates, namely ST131 and O25b:H4, has been reported. Like the majority of extra-intestinal pathogenic E. coli isolates, the pandemic clone ST131 belongs to phylogenetic group B2, and has recently been shown to be highly virulent in a mouse model, even though it lacks several genes encoding key virulence factors (Pap, Cnf1 and HlyA). Using two animal models, Caenorhabditis elegans and zebrafish embryos, we assessed the virulence of three E. coli ST131 strains (2 CTX-M-15- producing urine and 1 non-ESBL-producing faecal isolate), comparing them with five non-ST131 B2 and a group A uropathogenic E. coli (UPEC). In C. elegans, the three ST131 strains showed intermediate virulence between the non virulent group A isolate and the virulent non-ST131 B2 strains. In zebrafish, the CTX-M-15-producing ST131 UPEC isolates were also less virulent than the non-ST131 B2 strains, suggesting that the production of CTX-M-15 is not correlated with enhanced virulence. Amongst the non-ST131 B2 group isolates, variation in pathogenic potential in zebrafish embryos was observed ranging from intermediate to highly virulent. Interestingly, the ST131 strains were equally persistent in surviving embryos as the non-ST131-group B2 strains, suggesting similar mechanisms may account for development of persistent infection. Optical maps of the genome of the ST131 strains were compared with those of 24 reference E. coli strains. Although small differences were seen within the ST131 strains, the tree built on the optical maps showed that these strains belonged to a specific cluster (86% similarity) with only 45% similarity with the other group B2 strains and 25% with strains of group A and D. Thus, the ST131 clone has a genetic composition that differs from other group B2 strains, and appears to be less virulent than previously suspected

Polybrominated Diphenyl Ether (PBDE) Flame Retardants and Thyroid Hormone during Pregnancy

BACKGROUND: Human exposure to polybrominated diphenyl ether (PBDE) flame retardants has increased exponentially over the last three decades. Animal and human studies suggest that PBDEs may disrupt thyroid function. Although thyroid hormone (TH) of maternal origin plays an essential role in normal fetal brain development, there is a paucity of human data regarding associations between exposure to PBDEs and maternal TH levels during pregnancy. OBJECTIVES: Our goal was to determine whether PBDE serum concentrations are associated with TH levels in pregnant women. METHODS: We measured the concentration of 10 PBDE congeners, free thyroxine (T4), total T4, and thyroid-stimulating hormone (TSH) in 270 pregnant women around the 27th week of gestation. RESULTS: Serum concentrations of individual PBDE congeners with detection frequencies > 50% (BDEs 28, 47, 99, 100, and 153) and their sum (ΣPBDEs) were inversely associated with TSH levels. Decreases in TSH ranged between 10.9% [95% confidence interval (CI), -20.6 to 0.0] and 18.7% (95% CI, -29.2 to -4.5) for every 10-fold increase in the concentration of individual congeners. Odds of subclinical hyperthyroidism (low TSH but normal T4) were also significantly elevated in participants in the highest quartile of ΣPBDEs and BDEs 100 and 153 relative to those in the first quartile. Associations between PBDEs and free and total T4 were not statistically significant. Results were not substantially altered after the removal of outliers and were independent of the method used to adjust for blood lipid levels and to express ΣPBDEs. CONCLUSIONS: Results suggest that exposure to PBDEs is associated with lower TSH during pregnancy. Findings may have implications for maternal health and fetal development

Propolis can potentialise the anti-adhesion activity of proanthocyanidins on uropathogenic Escherichia coli in the prevention of recurrent urinary tract infections

<p>Abstract</p> <p>Background</p> <p><it>Escherichia coli</it>, the main bacteria found in recurrent urinary tract infections (UTI), is now frequently resistant to several currently used antibiotic treatments making new solutions essential. In this study, we evaluated the association propolis and proanthocyanidins type A to reduce bacterial anti-adhesion activity of <it>E. coli </it>on urothelial cells.</p> <p>Results</p> <p>This first double-blind, randomized, cross-over human trial included 5 volunteers that followed 6 different regimens with or without variable doses of cranberry and propolis with a washout period of at least 1 week between each regimen. Urine samples were collected at 0 h, 4-6 h, 12 h and 24 h after cranberry plus propolis or placebo capsule consumption. In vivo urinary bacterial anti-adhesion activity was assessed with a bioassay (a human T24 epithelial cell-line assay) and an in vivo <it>Caenorhabditis elegans </it>model. HPLC-PDA-MS was used to detect propolis and cranberry compounds in urine. Bioassays indicated significant bacterial anti-adhesion activity in urine collected from volunteers who had consumed cranberry plus propolis powder compared to placebo (<it>p </it>< 0.001). This inhibition was clearly dose-dependent, increasing with the amount of PACs and propolis equivalents consumed in each regimen. Results suggested that propolis had an additional effect with PACs and prevent a bacterial anti-adhesion effect over 1 day. An in vivo model showed that the <it>E. coli </it>strain presented a reduced ability to kill <it>C. elegans </it>after their growth in urine samples of patients who took cranberry plus propolis capsules. HPLC confirmed that propolis is excreted in urine.</p> <p>Conclusions</p> <p>This study presents an alternative to prevent recurrent UTI. Administration of PACs plus propolis once daily offers some protection against bacterial adhesion, bacterial multiplication and virulence in the urinary tract, representing an interesting new strategy to prevent recurrent UTI.</p

A new approach to assessing the health benefit from obesity interventions in children and adolescents: the assessing cost-effectiveness in obesity project

OBJECTIVE: To report on a new modelling approach developed for the assessing cost-effectiveness in obesity (ACE-Obesity) project and the likely population health benefit and strength of evidence for 13 potential obesity prevention interventions in children and adolescents in Australia. METHODS: We used the best available evidence, including evidence from non-traditional epidemiological study designs, to determine the health benefits as body mass index (BMI) units saved and disability-adjusted life years (DALYs) saved. We developed new methods to model the impact of behaviours on BMI post-intervention where this was not measured and the impacts on DALYs over the child\u27s lifetime (on the assumption that changes in BMI were maintained into adulthood). A working group of stakeholders provided input into decisions on the selection of interventions, the assumptions for modelling and the strength of the evidence. RESULTS: The likely health benefit varied considerably, as did the strength of the evidence from which that health benefit was calculated. The greatest health benefit is likely to be achieved by the \u27Reduction of TV advertising of high fat and/or high sugar foods and drinks to children\u27, \u27Laparoscopic adjustable gastric banding\u27 and the \u27multi-faceted school-based programme with an active physical education component\u27 interventions. CONCLUSIONS: The use of consistent methods and common health outcome measures enables valid comparison of the potential impact of interventions, but comparisons must take into account the strength of the evidence used. Other considerations, including cost-effectiveness and acceptability to stakeholders, will be presented in future ACE-Obesity papers. Information gaps identified include the need for new and more effective initiatives for the prevention of overweight and obesity and for better evaluations of public health interventions

Effect of Anti-Obesity Drug on Cardiovascular Risk Factors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

BACKGROUND: Anti-obesity drugs are widely used to prevent the complications of obesity, however, the effects of anti-obesity drugs on cardiovascular risk factors are unclear at the present time. We carried out a comprehensively systematic review and meta-analysis to assess the effects of anti-obesity drugs on cardiovascular risk factors. METHODOLOGY AND PRINCIPAL FINDINGS: We systematically searched Medline, EmBase, the Cochrane Central Register of Controlled Trials, reference lists of articles and proceedings of major meetings for relevant literatures. We included randomized placebo-controlled trials that reported the effects of anti-obesity drugs on cardiovascular risk factors compared to placebo. Overall, orlistat produced a reduction of 2.39 kg (95%CI-3.34 to -1.45) for weight, a reduction of 0.27 mmol/L (95%CI: -0.36 to -0.17) for total cholesterol, a reduction of 0.21 mmol/L (95%CI: -0.30 to -0.12) for LDL, a reduction of 0.12 mmol/L (95%CI: -0.20 to -0.04) for fasting glucose, 1.85 mmHg reduction (95%CI: -3.30 to -0.40) for SBP, and a reduction of 1.49 mmHg (95%CI: -2.39 to -0.58) for DBP. Sibutramine only showed effects on weight loss and triglycerides reduction with statistical significances. Rimonabant was associated with statistically significant effects on weight loss, SBP reduction and DBP reduction. No other significantly different effects were identified between anti-obesity therapy and placebo. CONCLUSION/SIGNIFICANCE: We identified that anti-obesity therapy was associated with a decrease of weight regardless of the type of the drug. Orlistat and rimonabant could lead to an improvement on cardiovascular risk factors. However, Sibutramine may have a direct effect on cardiovascular risk factors