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.     

Methylene Blue Absorption in Sentinel Lymph Node Biopsy for Early Breast Cancer after Neoadjuvant Chemotherapy

Introduction: Chemotherapy is claimed to cause lymphatic drainage damage because of the tumor cell’s apoptosis process. This event might cause decreased marker (radioactive solution and/or blue dye) absorption on sentinel lymph nodes (SLN). In this study, the researchers used methylene blue only and wished to evaluate the methylene blue absorption of the SLNB procedure on early-stage breast-cancer patients after neoadjuvant chemotherapy (NAC). Materials and methods: The method used was the historical cohort study conducted from 2016-2019 in Indonesia. Samples were collected from 117 patients of stage I and II breast cancer with clinically negative axillary lymph nodes, who were then grouped into post-NAC and no-NAC (control group), in which SLNB procedures were conducted on the two groups by using single-method methylene blue. The results of methylene blue absorption were then analyzed by the Chi-square hypothesis test. Results: From the total of 564 early-stage patients who were referred to surgical oncologists, 117 patients were found to meet criteria of inclusion, consisting of the control group (52 patients) and the post-NAC group (65 patents). Of 65 patients who had undergone NAC treatment and SLNB procedure, it was found that 40 patients (61.5%) showed positive blue SLN. Of 52 pre-NAC breast-cancer patients, it was found that 47 patients (90.4%) showed methylene blue absorption on SLN with the p-value of 0.000 (P<0.05, significant). The relative risk value amounted to 0.522. Post-NAC patients had a tendency of decreased absorption of methylene blue. Conclusion: Neoadjuvant chemotherapy can cause the decrease of methylene blue absorption on SLNB procedure.     

Copper and Zinc Levels in Myelodysplastic Syndrome Patients versus Healthy Subjects

Background: Myelodysplastic syndrome (MDS) is a heterogeneous hematological disease and certain serum factors are assumed to be involved in its pathogenesis and progression. Given this, our aim was to comparatively investigate the copper, zinc, and iron levels in MDS patients and healthy individuals. Methods: This case-control study was conducted on 31 patients with MDS (according to the WHO criteria after investigating laboratory tests such as peripheral blood smear and bone marrow aspiration) attending Bahonar Hospital, Kerman, Iran, and 31 healthy subjects from 2016 to 2018. The levels of copper, ceruloplasmin, zinc, ferritin, and iron were compared between the two groups. Results: Among the MDS patients, five individuals (16.13%) had low serum copper level (mean: 67.8 ± 4.35 µg/dl). Serum copper level was 111.3 ± 27.7 and 138.3 ± 26.6 in case and control groups, respectively (P = 0.0001). The serum zinc level and bone marrow iron level were also significantly different between the two groups (P < 0.05). Conclusion: Overall, it can be concluded that because only a small proportion of the MDS patients enrolled in this study were found to have lower copper levels compared with the MDS patients population, further studies with a larger sample size and also clinical trials in MDS patients with serum zinc, and copper deficiency are recommended, and post-treatment hematological reassessment would also be beneficial to achieving more definitive results.     

Arg399Gln XRCC1 Polymorphism and Risk of Squamous Cell Carcinoma of the Head and Neck in Jordanian Patients

Background and objective: X-ray repair cross-complementing group1 (XRCC1) is a key protein in base excision repair and closely associated with the coordination of the base excision repair pathway. Many studies have focused on XRCC1 SNPs and have shown an associated between these SNPs and the risk of several types of cancers, including head and neck cancer. There are many single nucleotide polymorphisms XRCC1 gene (SNPs) and the most common SNP that result in amino acid substitutions is exon 10 (Arg399Gln). This study aimed to investigate the association between Arg399Gln SNP and the risk of squamous cell carcinoma of the head and neck. Material and method: Ninety nine patients with squamous cell carcinomas of the head and neck and 89 healthy adult controls were enrolled in this study. The Arg399Gln in XRCC1 allele was genotyped using polymerase chain reaction-restriction fragment length polymorphism method. Results: In the single-locus analyses, Arg399Gln SNP showed a significant association with head and neck cancer risk (p value = 0.016 and odd ratio of 1.8). On the genotype level, we applied three analysis models, namely co-dominant, dominant, and recessive genotypes. Arg/Arg homozygous major genotype was significantly (p value <0.05) associated with head and neck squamous cell carcinoma incidence with odd ratio of 2.23 and 2.24 for the co-dominant and recessive models, respectively. Conclusion: The findings indicated that Arg399Gln allele was associated with squamous cell carcinoma of the head and neck among Jordanian patients. This allele might be used as a genetic biomarker of squamous cell carcinoma of the head and neck.     

HDAC1和CDK1在结肠癌组织中的表达及其临床意义

目的:研究组蛋白去乙酰化酶1（histone deacetylase 1,HDAC1）和细胞周期蛋白依赖性激酶1（cyclin-dependent kinase 1,CDK1）在结肠癌组织中的表达水平及其与患者临床病理特征及预后的关系。方法:收集2012年2月至2013年6月在本院普外科进行手术切除的51例结肠癌患者的肿瘤组织和癌旁非肿瘤组织，采用qRT-PCR法检测组织中HDAC1和CDK1 mRNA相对表达量，采用免疫组织化学染色法检测HDAC1和CDK1蛋白阳性表达率，分析肿瘤组织中HDAC1和CDK1表达的相关性及其与患者肿瘤直径、淋巴结转移等临床病理特征的关系，采用Kaplan-Meier生存函数分析HDAC1和CDK1不同表达情况与患者5年总生存率的关系。结果:肿瘤组织中HDAC1和CDK1 mRNA表达水平和蛋白阳性表达率均高于癌旁非肿瘤组织（P＜0.05）；肿瘤组织中HDAC1表达水平与CDK1表达水平呈显著正相关（P=0.012）；肿瘤组织中HDAC1表达与患者肿瘤直径和组织分化程度有关（P＜0.05），CDK1与肿瘤直径、TNM分期、分化程度、淋巴结转移有关（P＜0.05）；HDAC1、CDK1阳性表达患者5年总生存率均低于其相应阴性表达患者（P＜0.05），HDAC1和CDK1共阳性表达患者5年总生存率低于HDAC1和（或）CDK1阴性患者（P＜0.05）。结论:HDAC1和CDK1在结肠癌组织中高表达，与患者不良预后有关且两者呈正相关，推测两者在促进结肠癌进展中可能存在协同作用。