Approaches and considerations for the assessment of immunotoxicity for environmental chemicals: A workshop summary

As experience is gained with toxicology testing and as new assays and technologies are developed, it is critical for stakeholders to discuss opportunities to advance our overall testing strategies. To facilitate these discussions, a workshop on practices for assessing immunotoxicity for environmental chemicals was held with the goal of sharing perspectives on immunotoxicity testing strategies and experiences, developmental immunotoxicity (DIT), and integrated and alternative approaches to immunotoxicity testing. Experiences across the chemical and pharmaceutical industries suggested that standard toxicity studies, combined with triggered-based testing approaches, represent an effective and efficient approach to evaluate immunotoxic potential. Additionally, discussions on study design, critical windows, and new guideline approaches and experiences identified important factors to consider before initiating DIT evaluations including assay choice and timing and the impact of existing adult data. Participants agreed that integrating endpoints into standard repeat-dose studies should be considered for fulfilling any immunotoxicity testing requirements, while also maximizing information and reducing animal use. Participants also acknowledged that in vitro evaluation of immunosuppression is complex and may require the use of multiple assays that are still being developed. These workshop discussions should contribute to developing an effective but more resource and animal efficient approach for evaluating chemical immunotoxicity.     

瞬时弹性成像测定肝脾硬度值评估乙型肝炎肝硬化患者食管静脉曲张初步研究

目的 应用瞬时弹性成像技术检测乙型肝炎(CHB)肝硬化患者肝脏硬度值(LSM)和脾脏硬度值(SSM),预测食管胃底静脉曲张(EGV)。方法 2016年1月～2020年1月我院收治的乙型肝炎肝硬化患者166例,接受胃镜检查,将EGV分为无或轻度(非显著)及中和重度(显著),并使用FibroTouch检测LSM和SSM。采用单因素和多因素Logistic回归分析应用显著EGV发生的独立预测因素,绘制受试者工作特征曲线(ROC),计算曲线下面积(AUC),分析各指标诊断的敏感性、特异性和准确性。结果 胃镜检查发现本组患者非显著EGV 92例,显著EGV 74例;非显著EGV组Child-Pugh A级、B级和C级分别占63.0%、37.0%和0.0%,与显著EGV组比,差异显著(分别为40.5%、40.5%和18.0%, P<0.05);非显著EGV组腹水发生率为3.3%,显著低于显著EGV组的59.5%(P<0.05);非显著EGV组血清白蛋白水平为(34.1±5.6)g/L,显著高于显著EGV组;非显著EGV组INR为(1.1±0.4),显著低于显著EGV组;非显著EGV组PLT为(132.8±38.0)×10⁹/L,显著高于显著EGV组;门静脉内径为(12.6±1.8)mm,显著小于显著EGV组;脾脏厚度为(100.4±14.6)mm,显著小于显著EGV组;LSM为(17.2±10.2)kPa,显著低于显著EGV组;SSM为(26.6±9.1)kPa,显著低于显著EGV组;多因素分析结果显示ALB、INR、PLT、门静脉内径、脾脏厚度、LSM和SSM是影响乙型肝炎肝硬化患者发生显著EGV的独立预测因素(P<0.05);应用LSM等于26.6 kPa和SSM等于43.2 kPa为截断点联合诊断显著EGV,其AUC、敏感性、特异性和准确性分别为0.87、83.5%、91.8%和89.6%。结论 应用FibroTouch检测乙型肝炎肝硬化患者肝脾硬度能够有效预测患者EGV的发生,值得临床进一步验证。     

Where Does Research Occur in Geriatrics and Gerontology?

The International Plan of Action on Aging 2002 emphasized the need to promote and develop research on aging, especially in underdeveloped countries. This article aims at describing the current situation with regard to the international scientific production in the field of geriatrics and gerontology. All articles published in journals included in the categories "Geriatrics and Gerontology" of the Science Citation Index or "Gerontology" of the Social Science Citation Index in 2002 were analyzed. There is unquestionable predomination by the United States, which participates in 53.8% of the articles analyzed, followed by the United Kingdom (9.66%) and Canada (6.66%). The production of the 15 European Union countries together is 31.2%. When adjustments are made for economic or population factors, other countries show their importance: Israel and Sweden, for example. Authors from richer countries participate in more than 95% of the articles, whereas those in less-developed countries tend to publish less, and when they do so, it is through collaboration with more-developed countries. In general, only 10.5% of the articles are written in collaboration with institutions from different countries. One of the keys to stimulating research in less wealthy countries would seem to be precisely through collaboration. This would aid the transfer of knowledge and experience, allowing researchers in these countries to obtain autonomy to perform their own studies independently and to provide them with the ability to gain access for their publications at the international level.     

Increased intercellular adhesion molecule-1 serum concentration in cholestasis

Background/Aims: Increase of serum levels of the soluble intercellular adhesion molecules in patients with the cholestatic liver diseases primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are known and have been thought to indicate activation of the immune system and the grade of the inflammatory process. In hepatitis and cholestatic diseases, expression of adhesion molecules was found on the surface of bile duct epithelia and hepatocytes.Materials and Methods: Serum levels of sICAM-1 in patients with intrahepatic cholestasis in PBC (n=42) and extrahepatic cholestasis (n=18) due to choledocholithiasis were investigated. sICAM-1 levels and “classical” cholestasis parameters as alkaline phosphatase (ALP), γ-glutamyl-transpeptidase (γ-GTP) and bilirubin levels were compared. Furthermore, sICAM-1 concentrations and “classical” cholestasis parameters were analysed before and after therapy with ursodeoxycholic acid (UDCA). In addition, sICAM-1 was detected in serum and bile fluid of four patients with cholestasis due to choledocholithiasis. Soluble ICAM-1 levels in sera and, if accessible, in bile fluids were determined using a commercially available ELISA system. Statistics were done by Wilcoxon's signed rank exact test and Spearman's rank correlation test. Sensitivity and specificity of cholestasis parameters and sICAM-1 concentrations was analysed by receiver operating characteristic (ROC) curves.Results: Increased sICAM-1 serum concentrations in a similar range were found in patients with PBC (range 251–2620 μg/l; median 966 μg/l) as well as in patients with extrahepatic cholestasis (257–2961 μg/l; median 760 μg/l) compared to healthy controls (n=12; 220–500 gmg/l; median 318 μg/l). sICAM-1 levels correlated significantly to histological stage I to IV (p<0.001), ALP (range 107–1877 U/l; median 545 U/l; r=0.496, p=0.0008), bilirubin (range 0.3–26 mg/dl; median 0.8 mg/dl; r=0.52; p<0.0004) and γ-GTP levels (range 43–705 U/l; median 221 U/l; r=0.36; p=0.02) in PBC patients. In PBC patients a histological stage III or IV (n=21) could be predicted with high sensitivity (95%) and specificity (85%) if sICAM-1 levels were above 840 μg/l. After treatment of PBC patients with UDCA, sICAM-1 levels decreased significantly with decline of other “classical” cholestasis parameters. Increased sICAM-1 levels (range 257–2961, median 745 μg/l) in extrahepatic cholestasis correlated also significantly with serum concentrations of bilirubin (r=0.8; p<0.01; range 0.3–19.7, median 1.6 mg/dl), γ-GTP (r=0.55; p=0.03; range 33–1401, median 179 U/l) and ALP (r=0.61; p=0.1; range 110–1378, median 562 U/l). sICAM-1 2as detectable in bile fluid (264–919 μg/l) of four patients with extrahepatic cholestasis and nose-biliary catheterisation.Conclusions: sICAM-1 concentrations were found to discriminate between histological stage I/II and stage III/IV of PBC with higher sensitivity and specificity than “classical” cholestasis parameters. Increased serum concentrations for sICAM-1 in intra- and in extrahepatic cholestasis and detection of sICAM-1 in the bile may indicate that sICAM-1 is eliminated through the bile. In other words, not only increased synthesis but also decreased elimination may be responsible for increased sICAM-1 serum levels in patients with cholestatic liver diseases.     

非酒精性脂肪性肝炎患者血清肝纤维化指标的变化

NFALD可并发脂肪性肝炎(NASH)、肝纤维化和肝硬化,NASH可能是隐源性肝硬化的病因之一。本研究通血清Ⅲ型前胶原肽(PCⅢ)、CⅣ、LN、HA四项指标的测定,探讨NFALD肝纤维化倾向,并应用临床诊断性能(ROC)曲线综合评估了这些指标在单纯非酒精性脂肪肝(NAFL)、NASH中的检测意义。一、资料与方法     

环境与健康保护：从理论到行动的转化之路——“第六届环境与职业医学国际学术研讨会”纪要

＂第六届环境与职业医学国际学术研讨会暨《环境与职业医学》杂志创办30周年研讨会＂于2014年10月16—18日在上海市召开,会议的主题是＂环境与健康保护：从理论到行动＂。此次会议由上海市疾病预防控制中心、上海市预防医学研究院、上海市预防医学会、《环境与职业医学》杂志主办,复旦大学公共卫生学院、江苏省预防医学会、浙江省预防医学会协办。共有44位中外专家进行了报告,200余位参会者就＂环境相关疾病的预防与控制＂＂职业人群的健康保护＂＂环境与职业医学中的组学研究＂＂环境政策与公共卫生＂等内容展开讨论。本次会议收到中英文论文投稿近200篇,同时设置了壁报展示并评选出3份优秀壁报。在＂《环境与职业医学》编者、审者、作者交流会＂上,编委会成员和审稿专家共同回顾了杂志创办30年来的发展历程,为杂志的发展提出了缩短出版周期、提供增值服务、进入重要数据库等意见。本次会议的成功举办可望进一步加深加强上海与国际国内在相应领域的联系与合作,更好地促进环境与职业医学领域理论与实际的结合、基础与临床的整合、微观与宏观的融合,为环境健康研究注入新的活力。     

异地医疗服务模式及关键问题研究

分析了异地医疗服务模式的概念和服务的主要内容,对异地医疗服务模式进行了分类和归纳,总结了异地医疗服务中的主要问题,为促进异地医疗卫生服务模式的转变提供有益的探索。     

Use of AUDIT-C as a tool to identify hazardous alcohol consumption in admitted trauma patients

Introduction

Alcohol use is an important contributor to injuries. Simple bedside tools to identify trauma patients with potentially harmful drinking may assist in brief intervention efforts in clinical practice. The objective of the study was to determine and compare the accuracy of alcohol use disorders identification test (AUDIT) and an abbreviated version of this test, in the detection of hazardous drinking.

Methods

A cross-sectional study of a convenience sample of admitted trauma patients at a single Australian major trauma centre. Eligible patients completed the AUDIT. AUDIT survey responses were scored in two ways, using the full form scale and secondly an abbreviated (AUDIT C) scale which uses only the first 3 questions. AUDIT and AUDIT-C scores were then evaluated with respect to the primary study measure; the detection of hazardous alcohol consumption based on a full alcohol consumption history. Sensitivities for each relevant score were calculated and receiver operator characteristic (ROC) curve analysis was used to determine test accuracy.

Results

During the study period, 523 trauma admissions were identified and of these 146 (28%) were screened. The optimum cut off scores for AUDIT and AUDIT-C were 8 and 5 respectively corresponding to sensitivities of 88% and 91% and both tests had excellent overall accuracy for the detection of hazardous alcohol consumption. There was no significant difference between AUDIT-C and AUDIT performance (p = 0.395) (AUDIT-C AUROC 0.96 95%CI 0.93, 0.99).

Conclusion

AUDIT-C appears to be a potentially useful screening tool for use trauma centres, but that further research with larger samples is required.     

The Usefulness of the Korean Version of Penn State Worry Questionnaire for Screening Generalized Anxiety Disorder: A Receiver Operating Characteristic Analysis

Objective

Excessive worry about minor matters and a state in which this worry is experienced as uncontrollable are known to be key symptoms of generalized anxiety disorder (GAD). Given the importance of pathological worry in GAD, the need for psychometrically sound measures of this construct has increased. The purpose of this study was to investigate the usefulness of the Korean version of Penn State Worry Questionnaire (K-PSWQ) for screening GAD.

Methods

Two hundred and forty six patients were initially screened, from which 102 GAD patients and 118 patients with anxiety disorder not otherwise specified (anxiety disorder NOS) were finally enrolled. Patients were diagnosed by a structured clinical interview for the DSM-IV Axis I. We also enrolled 114 control subjects who had no medical or psychiatric history. Pathological worry in both patients and control subjects were assessed at baseline using the PSWQ and we estimated optimal cutoff score by the receiver operating characteristic (ROC) analysis.

Results

We found that in the first ROC analysis, a score of 53 could simultaneously optimize sensitivity and specificity in order to discriminate GAD patients from control subjects. From the second receiver operating characteristic analysis, when both sensitivity and specificity were optimized, we can suggest a score of 61 as being the cutoff for differentiating GAD patients from patients with anxiety disorder NOS.

Conclusion

The Korean version of PSWQ is a useful method for screening GAD patients, although ethnic and cultural differences may affect the cutoff score of PSWQ for GAD.