Derivation of occupational exposure limits: Differences in methods and protection levels

Frameworks for deriving occupational exposure limits (OELs) and OEL-analogue values (such as derived-no-effect levels [DNELs]) in various regulatory areas in the EU and at national level in Germany were analysed. Reasons for differences between frameworks and possible means of improving transparency and harmonisation were identified. Differences between assessment factors used for deriving exposure limits proved to be one important reason for diverging numerical values. Distributions for exposure time, interspecies and intraspecies extrapolation were combined by probabilistic methods and compared with default values of assessment factors used in the various OEL frameworks in order to investigate protection levels. In a subchronic inhalation study showing local effects in the respiratory tract, the probability that assessment factors were sufficiently high to protect 99% and 95% of the target population (workers) from adverse effects varied considerably from 9% to 71% and 17% to 87%, respectively, between the frameworks. All steps of the derivation process, including the uncertainty associated with the point of departure (POD), were further analysed with two examples of full probabilistic assessments. It is proposed that benchmark modelling should be the method of choice for deriving PODs and that all OEL frameworks should provide detailed guidance documents and clearly define their protection goals by stating the proportion of the exposed population the OEL aims to cover and the probability with which they intend to provide protection from adverse effects. Harmonisation can be achieved by agreeing on the way to perform the methodological steps for deriving OELs and on common protection goals.     

Effect of iron deficiency without anaemia on days alive and out of hospital in patients undergoing valvular heart surgery

Comprehensive evidence regarding the treatment of non-anaemic iron deficiency in patients undergoing valvular heart surgery is lacking. This study aimed to investigate the association between non-anaemic iron deficiency and postoperative outcomes in these patients. We retrospectively analysed 321 patients of which 180 (56%) had iron deficiency (defined as serum ferritin < 100 ng.ml^-1 or < 300 ng.ml^-1 with transferrin saturation < 20%). While the iron-deficient group had lower pre-operative haemoglobin levels than the non-iron deficient group (median (IQR [range]) 134 (127–141 [120–172]) g.l^-1, 143 (133–150 [120–179]) g.l^-1, p = 0.001), there was no between-group difference in allogeneic red blood cell transfusion. Median (IQR [range]) days alive and out of hospital at postoperative day 90 was 1 day shorter in the iron-deficient group (80 (77–82 [9–85]) days vs. 81 (79–83 [0–85]) days, p = 0.026). In multivariable analysis, only cardiopulmonary bypass duration (p = 0.032) and intra-operative allogeneic red blood cell transfusion (p = 0.011) were significantly associated with reduced days alive and out of hospital at postoperative day 90. Iron deficiency did not exert any adverse influence on secondary outcomes except length of hospital stay. Our findings indicate that non-anaemic iron deficiency alone is not associated with adverse effects in patients undergoing valvular heart surgery when it does not translate into an increased risk of allogeneic transfusion.     

基于NF-κB信号通路的细柱五加中impressic acid的抗炎作用研究

目的 研究细柱五加Acanthopanax gracilistylus W.W.Smith中impressic acid（IA）对脂多糖（LPS）诱导的小鼠单核巨噬细胞RAW264.7的抗炎作用。方法 以LPS诱导RAW264.7细胞建立炎症模型；使用EZ4U细胞增殖与细胞毒性分析试剂盒检测IA对RAW264.7细胞的毒性作用；Griess法测定一氧化氮（NO）水平；ELISA法测肿瘤坏死因子-α（TNF-α）、白介素-1β（IL-1β）水平；RT-PCR法检测TNF-α、IL-1β mRNA表达；Western blotting检测高迁移率族蛋白B1（HMGB1）蛋白表达；ELISA法细胞质和细胞核的核因子-κB（NF-κB）水平。结果 Impressic acid可以显著抑制LPS诱导的RAW264.7细胞中TNF-α、IL-1β水平和HMGB1蛋白表达，并抑制NF-κB从细胞质向细胞核的转移（P<0.05、0.01）。结论 细柱五加中IA对LPS诱导的RAW264.7细胞具有抗炎作用。     

Temporal Trends of Women Enrollment in Major Cardiovascular Randomized Clinical Trials

Background

Although it is known that women do not participate in trials as frequently as men, there are limited recent data examining how women recruitment has changed over time.