Derivation of internal dose-based thresholds of toxicological concern for occupational inhalation exposure to systemically acting organic chemicals

This study aimed at deriving occupational thresholds of toxicological concern for inhalation exposure to systemically-acting organic chemicals using predicted internal doses. The latter were also used to evaluate the quantitative relationship between occupational exposure limit and internal dose. Three internal dose measures were identified for investigation: (i) the daily area under the venous blood concentration vs. time curve, (ii) the daily rate of the amount of parent chemical metabolized, and (iii) the maximum venous blood concentration at the end of an 8-hr work shift. A dataset of 276 organic chemicals with 8-hr threshold limit values-time-weighted average was compiled along with their molecular structure and Cramer classes (Class I: low toxicity, Class II: intermediate toxicity, Class III: suggestive of significant toxicity). Using a human physiologically-based pharmacokinetic model, the three identified dose metrics were predicted for an 8-hr occupational inhalation exposure to the threshold limit value for each chemical. Distributional analyses of the predicted dose metrics were performed to identify the percentile values corresponding to the occupational thresholds of toxicological concern. Also, simple linear regression analyses were performed to evaluate the relationship between the 8-hr threshold limit value and each of the predicted dose metrics, respectively. No threshold of toxicological concern could be derived for class II due to few chemicals. Based on the daily rate of the amount of parent chemical metabolized, the proposed internal dose-based occupational thresholds of toxicological concern were 5.61?×?10^?2 and 9?×?10^?4 mmol/d at the 10th percentile level for classes I and III, respectively, while they were 4.55?×?10^?1 and 8.5?×?10^?3 mmol/d at the 25th percentile level. Even though high and significant correlations were observed between the 8-hr threshold limit values and the predicted dose metrics, the one with the rate of the amount of chemical metabolized was remarkable regardless of the Cramer class (r² = 0.81; n = 276). The proposed internal dose-based occupational thresholds of toxicological concern are potentially useful for screening-level assessments as well as prioritization within an integrated occupational risk assessment framework.     

2019年重庆市30岁及以上人群归因于被动吸烟的肺癌疾病负担研究

目的 分析重庆市肺癌发病死亡和疾病负担归因于被动吸烟的情况,为开展肺癌防治提供建议。 方法 肺癌死亡个案数据来源于2019年重庆市肿瘤登记报告系统,被动吸烟率来自2013年重庆市慢性病及危险因素监测。计算人群归因危险度百分比(population attributable risk percent, PAR%)、被动吸烟导致的肺癌发病、死亡和疾病负担。采用Excel 2010与SPSS 25.0进行统计分析,率的比较采用χ²检验。 结果 2013年30岁及以上成年人被动吸烟率为52.37%。2019年重庆市30岁及以上人群肺癌发病率与标化发病率分别为118.44/10万与80.83/10万,死亡率与标化死亡率分别为96.51/10万、63.58/10万。肺癌发病率和死亡率归因于被动吸烟的PAR%分别为19.76和19.04,归因发病率与归因标化发病率分别为23.41/10万和16.34/10万,归因死亡率与归因标化死亡率分别为18.38/10万和12.40/10万。2019年重庆市30岁及以上肺癌早死所致寿命损失年率(years of life lost,YLL)、残疾所致寿命损失年率(years lived with disability,YLD)、调整伤残寿命损失年率(disability adjusted life year,DALY)分别为21.16‰、0.31‰、21.47‰,YLL率、YLD率、DALY率归因于被动吸烟的PAR%分别为21.16、19.76和20.49,归因YLL率为4.34‰,归因YLD率为0.06‰,归因DALY率为4.40‰。 结论 2019年重庆市30岁及以上人群肺癌发病率、死亡率、YLL率、DALY率高,被动吸烟率高,肺癌归因于被动吸烟的疾病负担重,应加强落实控烟工作。     

Safety profile of the adjuvanted recombinant zoster vaccine: Pooled analysis of two large randomised phase 3 trials

Background

The ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials showed that the adjuvanted recombinant zoster vaccine (RZV) was ≥90% efficacious in preventing herpes zoster in adults. Here we present a comprehensive overview of the safety data from these studies.

Epithelial ovarian cancer risk: A review of the current genetic landscape

Ovarian cancer is the fourth most common cause of cancer-related death in women in the developed world, and one of the most heritable cancers. One of the most significant risk factors for epithelial ovarian cancer (EOC) is a family history of breast and/or ovarian cancer. Combined risk factors can be used in models to stratify risk of EOC, and aid in decisions regarding risk-reduction strategies. Germline pathogenic variants in EOC susceptibility genes including those involved in homologous recombination and mismatch repair pathways are present in approximately 22% to 25% of EOC. These genes are associated with an estimated lifetime risk of EOC of 13% to 60% for BRCA1 variants and 10% to 25% for BRCA2 variants, with lower risks associated with remaining genes. Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) thought to explain an additional 6.4% of the familial risk of ovarian cancer, with 34 susceptibility loci identified to date. However, an unknown proportion of the genetic component of EOC risk remains unexplained. This review comprises an overview of individual genes and SNPs suspected to contribute to risk of EOC, and discusses use of a polygenic risk score to predict individual cancer risk more accurately.     

磁共振结合高分辨率CT在中耳乳突炎患者术前评估中的临床应用

目的探讨磁共振结合高分辨率CT在中耳乳突炎患者术前评估中的临床应用。方法选取我院2018年11月~2020年12月接收患有中耳乳突炎的患者40例为研究对象,所有患者均采用磁共振以及高分辨率CT进行诊断检查,比较两组患者诊断后手术特征显示度。结果诊断后,磁共振联合高分辨率CT检查图像显示度高于单独使用磁共振或高分辨率CT诊断(P<0.05)。结论使用磁共振结合高分辨率CT对中耳乳突炎患者进行术前评估,显示度较高,提高诊断准确度,值得推广。     

护理专案改善在减少住院患者跌倒中的应用

目的了解护理专案改善在降低住院患者跌倒发生率中的应用效果。方法将医院2016年1月—2018年12月的80例住院患者随机分组,传统护理组对于住院患者给予传统护理,护理专案模式组对于住院患者采取护理专案模式。比较两组满意评分;护理人员工作积极性评分;护理前后住院患者对跌倒危险因素的掌握水平、住院患者遵医行为;跌倒的发生率。结果护理专案模式组满意评分、住院患者对跌倒危险因素的掌握水平、住院患者遵医行为、护理人员工作积极性评分、跌倒的发生率对比传统护理组有优势,P<0.05。结论住院患者实施护理专案模式效果确切,可提高护理服务质量和住院患者自我防护能力,降低跌倒的发生率。     

The combined relations of gender,enculturation, and depressive symptoms with health risk behaviors in Mexican-Americans: a moderated mediation analysis

ABSTRACT

Objectives: The present study investigated the relationships of enculturation and depressive symptoms with health risk behavior engagement in Mexican-American college students and examined how these relationships differed by gender. Previous research has noted consistent gender differences in health risk behavior (e.g. alcohol use, substance use, and risky sexual behavior) among Latina/os, and emphasized the role of U.S. acculturation in this difference. Research examining the role of heritage cultural retention (i.e. enculturation), and including the added influence of mental health variables, such as depressive symptoms, is currently lacking. This study sought to address this gap.

Design: A large sample (N?=?677) of Mexican-American college students from four universities (located in New York, California, Florida, and Texas) completed an online questionnaire assessing health risk behaviors and corresponding variables.

Results: We found that males who endorsed more behavioral enculturation and depressive symptoms were more likely to engage in health risk behavior than all others in the sample. Contrary to previous literature, no relationship was found between behavioral enculturation and health risk behavior in females.

Conclusion: The current study found behavioral enculturation to be associated with depressive symptoms, and in turn with health risk behaviors among the males in our sample. Additional research will be needed to identify the mechanism underlying the relationship between enculturation and depressive symptoms as well as between depressive symptoms and risky behavior.     

Demonstration of a modelling-based multi-criteria decision analysis procedure for prioritisation of occupational risks from manufactured nanomaterials

Several tools to facilitate the risk assessment and management of manufactured nanomaterials (MN) have been developed. Most of them require input data on physicochemical properties, toxicity and scenario-specific exposure information. However, such data are yet not readily available, and tools that can handle data gaps in a structured way to ensure transparent risk analysis for industrial and regulatory decision making are needed. This paper proposes such a quantitative risk prioritisation tool, based on a multi-criteria decision analysis algorithm, which combines advanced exposure and dose-response modelling to calculate margins of exposure (MoE) for a number of MN in order to rank their occupational risks. We demonstrated the tool in a number of workplace exposure scenarios (ES) involving the production and handling of nanoscale titanium dioxide, zinc oxide (ZnO), silver and multi-walled carbon nanotubes. The results of this application demonstrated that bag/bin filling, manual un/loading and dumping of large amounts of dry powders led to high emissions, which resulted in high risk associated with these ES. The ZnO MN revealed considerable hazard potential in vivo, which significantly influenced the risk prioritisation results. In order to study how variations in the input data affect our results, we performed probabilistic Monte Carlo sensitivity/uncertainty analysis, which demonstrated that the performance of the proposed model is stable against changes in the exposure and hazard input variables.