Association between the AUC0-24/MIC Ratio of Vancomycin and Its Clinical Effectiveness: A Systematic Review and Meta-Analysis

Background

A target AUC_0-24/MIC ratio of 400 has been associated with its clinical success when treating Staphylococcus aureus infections but is not currently supported by state-of-the-art evidence-based research.

Objective

This current systematic review aimed to evaluate the available evidence for the association between the AUC_0-24/MIC ratio of vancomycin and its clinical effectiveness on hospitalized patients and to confirm the existing target value of 400.

Methods

PubMed, Embase, Web of Sciences, the Cochrane Library and two Chinese literature databases (CNKI, CBM) were systematically searched. Manual searching was also applied. Both RCTs and observational studies comparing the clinical outcomes of high AUC_0-24/MIC groups versus low AUC_0-24/MIC groups were eligible. Two reviewers independently extracted the data. The primary outcomes were mortality and infection treatment failure. Risk ratios (RRs) with 95% confidence intervals (95%CIs) were calculated.

Results

No RCTs were retrieved. Nine cohort studies were included in the meta-analysis. Mortality rates were significantly lower in high AUC_0-24/MIC groups (RR = 0.47, 95%CI = 0.31–0.70, p<0.001). The rates of infection treatment failure were also significantly lower in high AUC/MIC groups and were consistent after correcting for heterogeneity (RR = 0.39, 95%CI = 0.28–0.55, p = 0.001). Subgroup analyses showed that results were consistent whether MIC values were determined by broth microdilution (BMD) method or Etest method. In studies using the BMD method, breakpoints of AUC_0-24/MIC all fell within 85% to 115% of 400.

Conclusions

This meta-analysis demonstrated that achieving a high AUC_0-24/MIC of vancomycin could significantly decrease mortality rates by 53% and rates of infection treatment failure by 61%, with 400 being a reasonable target.     

Design of a Virtual Player for Joint Improvisation with Humans in the Mirror Game

Joint improvisation is often observed among humans performing joint action tasks. Exploring the underlying cognitive and neural mechanisms behind the emergence of joint improvisation is an open research challenge. This paper investigates jointly improvised movements between two participants in the mirror game, a paradigmatic joint task example. First, experiments involving movement coordination of different dyads of human players are performed in order to build a human benchmark. No designation of leader and follower is given beforehand. We find that joint improvisation is characterized by the lack of a leader and high levels of movement synchronization. Then, a theoretical model is proposed to capture some features of their interaction, and a set of experiments is carried out to test and validate the model ability to reproduce the experimental observations. Furthermore, the model is used to drive a computer avatar able to successfully improvise joint motion with a human participant in real time. Finally, a convergence analysis of the proposed model is carried out to confirm its ability to reproduce joint movements between the participants.     

Rapid and efficient degradation of bisphenol A by chloroperoxidase from <Emphasis Type="Italic">Caldariomyces fumago</Emphasis>: product analysis and ecotoxicity evaluation of the degraded solution

Objectives

To degrade enzymatically bisphenol A (BPA) that causes serious environmental concerns and is difficult to be degraded by chemical or physical methods.

Results

BPA (150 mg l^?1) was completely degraded by chloroperoxidase (CPO)/H₂O₂ within 7 min at room temperature, atmospheric pressure with the enzyme at 6 μg CPO ml^?1. The degradation products were identified by HPLC–MS, which suggested involvement of multiple steps. Enzymatic treatment followed by existing bioremediation technologies (activated sludge) enhanced removal of COD from 9 to 54 %. Using an ecotoxicity evaluation with Chlorella pyrenoidosa, the degradation products had a lower toxicity than BPA.

Conclusion

BPA can be degraded rapidly and efficiently under mild conditions with chloroperoxidase at 6 μg ml^?1. The degradation products had a lower toxicity than BPA.

     

Phytosterol content and the campesterol:sitosterol ratio influence cotton fiber development: role of phytosterols in cell elongation

Phytosterols play an important role in plant growth and development, including cell division, cell elongation, embryogenesis, cellulose biosynthesis, and cell wall formation. Cotton fiber, which undergoes synchronous cell elongation and a large amount of cellulose synthesis, is an ideal model for the study of plant cell elongation and cell wall biogenesis. The role of phytosterols in fiber growth was investigated by treating the fibers with tridemorph, a sterol biosynthetic inhibitor. The inhibition of phytosterol biosynthesis resulted in an apparent suppression of fiber elongation in vitro or in planta. The determination of phytosterol quantity indicated that sitosterol and campesterol were the major phytosterols in cotton fibers; moreover, higher concentrations of these phytosterols were observed during the period of rapid elongation of fibers. Furthermore, the decrease and increase in campesterol:sitosterol ratio was associated with the increase and decease in speed of elongation, respectively, during the elongation stage. The increase in the ratio was associated with the transition from cell elongation to secondary cell wall synthesis. In addition, a number of phytosterol biosynthetic genes were down-regulated in the short fibers of ligon lintless-1 mutant, compared to its near-isogenic wild-type TM-1. These results demonstrated that phytosterols play a crucial role in cotton fiber development, and particularly in fiber elongation.     

水稻耐储藏特性三年动态鉴定与QTL分析

种子耐储藏特性是粮食作物的特殊农艺性状之一, 耐储藏性能对种子生产和种质资源保存有重要意义。以粳型超级稻龙稻5 (LD5)和高产籼稻中优早8 (ZYZ8)杂交衍生的重组自交系(RILs)群体(共180个株系)为实验材料, 自然高温高湿条件下放置1年、2年和3年后, 对不同储藏时段种子发芽率进行比较, 并利用223个分子标记的遗传图谱进行动态QTL鉴定。结果表明, 不同储藏时段龙稻5的发芽率均显著低于中优早8, 株系间耐储性存在较大差异; 不同储藏时段发芽率显著相关, 相邻存储时段发芽率关系紧密。共检测到17个耐储性相关的QTLs, 3个老化时段分别检测到5、4和3个, 检测到5个动态条件QTLs, 单一QTL解释5.60%-32.76%的表型变异, 加性效应在-16.78%-16.95%范围内。主效QTL簇qSSC2、qSSC6、qSSC7和qSSC8能调控不同储藏时段的发芽率, qSSC6具有明显降低发芽率的效应。共检测到26对上位性互作位点, 主效QTL qSS1和qSS4参与上位性互作, 这表明上位性互作是调控耐储藏性状的重要遗传组成。研究结果为水稻(Oryza sativa)耐储性相关QTL的精细定位奠定基础, 同时丰富了耐储性分子标记辅助选择育种的基因资源。     

Alpha lipoic acid inhibits oxidative stress‐induced apoptosis by modulating of Nrf2 signalling pathway after traumatic brain injury

Alpha lipoic acid (ALA) is a powerful antioxidant which has been widely used in the treatment of different system diseases, such as cardiovascular and cerebrovascular diseases. But, there are few studies that refer to protective effects and potential mechanisms on traumatic brain injury (TBI). This study was carried out to investigate the neuroprotective effect following TBI and illuminate the underlying mechanism. Weight drop‐injured model in rats was induced by weight‐drop. ALA was administrated via intraperitoneal injection after TBI. Neurologic scores were examined following several tests. Neurological score was performed to measure behavioural outcomes. Nissl staining and TUNEL were performed to evaluate the neuronal apoptosis. Western blotting was engaged to analyse the protein content of the Nuclear factor erythroid 2‐related factor 2 (Nrf2) and its downstream protein factors, including hemeoxygenase‐1 (HO‐1) and quinine oxidoreductase‐1 (NQO1). ALA treatment alleviated TBI‐induced neuron cell apoptosis and improved neurobehavioural function by up‐regulation of Nrf2 expression and its downstream protein factors after TBI. This study presents new perspective of the mechanisms responsible for the neuronal apoptosis of ALA, with possible involvement of Nrf2 pathway.