Pseudomonas aeruginosa is an opportunistic pathogen that causes severe airway infections in humans. These infections are usually difficult to treat and associated with high mortality rates. While colonizing the human airways, P. aeruginosa could accumulate genetic mutations that often lead to its better adaptability to the host environment. Understanding these evolutionary traits may provide important clues for the development of effective therapies to treat P. aeruginosa infections. In this study, 25 P. aeruginosa isolates were longitudinally sampled from the airways of four ventilator-associated pneumonia (VAP) patients. Pacbio and Illumina sequencing were used to analyse the in vivo evolutionary trajectories of these isolates. Our analysis showed that positive selection dominantly shaped P. aeruginosa genomes during VAP infections and led to three convergent evolution events, including loss-of-function mutations of lasR and mpl, and a pyoverdine-deficient phenotype. Specifically, lasR encodes one of the major transcriptional regulators in quorum sensing, whereas mpl encodes an enzyme responsible for recycling cell wall peptidoglycan. We also found that P. aeruginosa isolated at late stages of VAP infections produce less elastase and are less virulent in vivo than their earlier isolated counterparts, suggesting the short-term in vivo evolution of P. aeruginosa leads to attenuated virulence.

Probiotics supplementation in triple therapy for H. pylori infection may have beneficial effects on eradication and therapy-related side effects, particularly diarrhea, in children.

Adiponectin, as an important adipocytokine, plays a pivotal role in the regulation of insulin sensitivity and metabolism. It has been reported that circulating adiponectin levels were decreased in women with polycystic ovary syndrome (PCOS). However, the results remained inconsistent. In order to derive a more precise estimation of this relationship, a large meta-analysis was performed in this study. A comprehensive systematic electronic search was conducted in electronic databases PubMed, EMBASE, and Web of Science up to November 30, 2013. Pooled weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated to estimate the strength of the association. A meta-analysis technique was used to study 38 trials involving 1,944 PCOS women and 1,654 healthy controls. Overall pooled adiponectin levels in women with PCOS were significantly reduced compared with healthy controls (WMD -2.67, 95% CI -3.22 to -2.13; P = 0.000), yet with significant heterogeneity across studies (I(2) = 95.9%, P = 0.000). In subgroup analysis by HOMA-IR ratio and total testosterone ratio, inconsistent results were presented. No single study was found to affect the overall results by sensitivity testing. Meta-regression suggested that BMI might contribute little to the heterogeneity between including studies. Cumulative meta-analysis demonstrated the reliability and stability of the meta-analysis results. No evidence of publication bias was observed. Our meta-analysis suggested that circulating adiponectin levels in women with PCOS were significantly lower than those in healthy controls, which indicated that circulating adiponectin might play a role in the development of PCOS.

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BackgroundMany epidemiological studies have been conducted to explore the association between a single CYP2D6 gene polymorphism and Parkinson’s disease (PD) susceptibility. However, the results remain controversial.ObjectivesTo clarify the effects of a single CYP2D6 gene polymorphism on the risk of PD, a meta-analysis of all available studies relating to CYP2D6*4 polymorphism and the risk of PD was conducted.MethodsA comprehensive literature search of PubMed, EMBASE, and the China National Knowledge Infrastructure (CNKI) up to September 1, 2013 was conducted. Data were extracted by two independent authors and pooled odds ratio (OR) with 95% confidence interval (CI) were calculated. Meta-regression, Galbraith plots, subgroup analysis, sensitivity analysis, and publication bias analysis were also performed.ResultsTwenty-two separate comparisons consisting of 2,629 patients and 3,601 controls were included in our meta-analysis. The pooled analyses showed a significant association between CYP2D6*4G/A polymorphism and PD risk in all of the comparisons (A vs. G allele: OR = 1.28, 95% CI = 1.14–1.43, P = 0.001; AA vs. GG: OR = 1.43, 95% CI = 1.06–1.93, P = 0.018; AG vs. GG: OR = 1.22, 95% CI = 1.06–1.40, P = 0.006; AG+AA vs. GG: OR = 1.26, 95% CI = 1.10–1.44, P = 0.001; AA vs. AG+GG: OR = 1.37, 95% CI = 1.02–1.83, P = 0.036). In subgroup analysis stratified by ethnicity, significant associations were also demonstrated in Caucasians but not in Asians. No significant association was found in subgroup analysis stratified by age of onset or disease form.ConclusionsWe concluded that the CYP2D6*4G/A polymorphism denotes an increased genetic susceptibility to PD in the overall population, especially in Caucasians. Further large and well-designed studies are needed to confirm this association.