Synthetic antimicrobial β‐peptide in dual‐treatment with fluconazole or ketoconazole enhances the in vitro inhibition of planktonic and biofilm Candida albicans

Fungal infections are a pressing concern for human health worldwide, particularly for immunocompromised individuals. Current challenges such as the elevated toxicity of common antifungal drugs and the emerging resistance towards these could be overcome by multidrug therapy. Natural antimicrobial peptides, AMPs, in combination with other antifungal agents are a promising avenue to address the prevailing challenges. However, they possess limited biostability and susceptibility to proteases, which has significantly hampered their development as antifungal therapies. β‐peptides are synthetic materials designed to mimic AMPs while allowing high tunability and increased biostability. In this work, we report for the first time the inhibition achieved in Candida albicans when treated with a mixture of a β‐peptide model and fluconazole or ketoconazole. This combination treatment enhanced the biological activity of these azoles in planktonic and biofilm Candida, and also in a fluconazole‐resistant strain. Furthermore, the in vitro cytotoxicity of the dual treatment was evaluated towards the human hepatoma cell line, HepG2, a widely used model derived from liver tissue, which is primarily affected by azoles. Analyses based on the LA‐based method and the mass‐action law principle, using a microtiter checkerboard approach, revealed synergism of the combination treatment in the inhibition of planktonic C. albicans. The dual treatment proved to be fungicidal at 48 and 72 h. Interestingly, it was also found that the viability of HepG2 was not significantly affected by the dual treatments. Finally, a remarkable enhancement in the inhibition of the highly azole‐resistant biofilms and fluconazole resistant C. albicans strain was obtained. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.     

涡旋磁纳米颗粒——崭新的生物医用磁性纳米平台

相比于超顺磁性纳米颗粒,具有涡旋磁畴的磁性纳米颗粒,由于独特的磁化闭合分布、较大的粒径尺寸及外加磁场中的磁化翻转特性,使得其兼具弱的颗粒间磁相互作用和更优异的磁学性能,在生物医学领域展现出了更好的应用优势和潜力.本综述结合近年来国内外对涡旋磁畴的研究及涡旋磁纳米颗粒在生物医学领域的报道,提出了一类新型的生物医用涡旋磁溶胶体系,并以涡旋磁氧化铁纳米盘和纳米环为例,介绍了涡旋磁纳米颗粒的化学合成,并着重论述了这类具有独特涡旋畴结构的纳米颗粒在磁共振成像、抗肿瘤治疗等生物医学应用上的最新研究进展.     

盐胁迫对低温预处理石榴种子萌发及幼苗生理生化的影响

以催芽‘峄城大青皮甜’石榴种子为材料,经2~4℃低温预处理5、10和15d,置于不同盐分梯度下进行种子萌发试验,并测定分析幼苗生长、细胞保护酶活性、可溶性糖和脯氨酸含量及电导率变化,以阐明盐胁迫下低温预处理对石榴种子萌发和幼苗生长及生理生化的影响。结果显示:(1)适当的低温预处理和低盐胁迫能提高石榴种子的发芽率和发芽势,低温处理5d和0.1%低盐环境下有利于壮苗生长。(2)适当时间的低温预处理(5d)可显著提高石榴幼苗的保护酶(SOD、POD、CAT)活性,长时间的低温预处理(15d)却降低了幼苗的保护酶活性;随着盐浓度的升高石榴幼苗的保护酶活性也逐渐升高,并在盐浓度为0.3%时均达到最大值,说明当盐浓度高于0.3%时超出了石榴幼苗保护酶系统的调节范围,从而发生盐害。(3)低温预处理5d和10d降低了幼苗可溶性蛋白和脯氨酸的含量;随着盐浓度的升高幼苗可溶性蛋白和脯氨酸的含量也逐渐升高。(4)5d和10d的低温预处理可以提高石榴幼苗细胞膜透性,随着盐浓度的升高相对电导率也显著升高。研究表明,在低盐环境下,适当时间的低温预处理能显著促进石榴种子萌发生长,其幼苗能通过调整自身渗透调节物质可溶性蛋白和脯氨酸含量以及体内保护酶活性,降低细胞膜脂过氧化程度,保证细胞膜的完整性,维持正常的细胞代谢活性,从而有效减轻盐胁迫对植株的伤害,表现出较强的抗盐性。     

Kaiser模型在患者间接诊疗风险管理中的应用

医院风险管理作为风险管理的重要一环,可以分为患者直接诊疗风险和患者间接诊疗风险,本文将重点讨论患者间接诊疗风险,运用KAISER模型对患者间接诊疗风险进行分析,从KAISER模型介绍、体系构建等方面来打造某医院的患者间接诊疗风险管理体系。     

Optimising the capacity of field trials to detect the effect of genetically modified maize on non‐target organisms through longitudinal sampling

To assess risks of cultivation of genetically modified crops (GMCs) on non‐target arthropods (NTAs), field tests are necessary to verify laboratory results and in situations where exposure pathways are very complex and cannot be reproduced in the laboratory. A central concern in the design of field trials for this purpose is whether the tests are capable of detecting differences in the abundance or activity of NTAs in a treated crop in comparison with a non‐treated comparator plot. The detection capacity of a trial depends on the abundance and variability of the taxon, the values assumed for type I (α) and II (β) errors, and the characteristics of the trial and statistical design. To determine the optimal trial layout and statistical analysis, 20 field trials carried out in Spain from 2000 to 2009 to assess risks of GMCs on NTAs were examined with α and β set at 0.05 and 0.20, respectively. In this article we aim to determine the optimal number of sampling dates during a season, or longitudinal samples, in the design of field trials for assessing effects of GM maize on NTAs, and the ones that contribute most to achieving detectable treatment effects (d_c) less than 50% of the mean of the control. Detection capacities are a function of the number of individual samples taken during the season but a high number of samples is rarely justified because gains of repeated sampling can be relatively low. These gains depend primarily on field tests relative experimental variability in individual samplings (i.e. experimental variability relative to the mean of the control in each sampling date) which in turn depends on the sampling method (visual counts, pitfall traps or yellow sticky traps) and the density (or abundance) of the taxon in question. Taxa showing more density (or abundance) have less relative experimental variability. The smaller the experimental variability, the lower the profit of increasing the number of sampling dates. Sticky traps have a good effect detection capacity and need very few sampling dates, whereas visual counts and pitfall traps have a poorer effect detection capacity and need more individual samples to achieve d_c values lower than 50%. In maize field trials, it is recommended to concentrate sampling efforts in certain growth stages; the optimal ones for achieving an acceptable detection capacity are variable but, in general, samples in the first half of the season render better detection capacity than samples in the second half.