The significance of mycotoxins in the framework of assessing workplace related risks

Mycotoxins are fungal metabolite which may in some cases exhibit a high health hazard potential. Mycotoxins can show carcinogenic, mutagenic, toxic, teratogenic or immunotoxic effects. Mycotoxin exposure in the workplace may occur through inhalation and skin contact,e.g. during occupational handling of organic matter such as livestock feed, food products, or waste. Various studies suggest that both acute and chronic effects can occur, depending at least on the exposure level. The magnitude of the potential health risks associated with a respiratory or dermal intake of mycotoxins has largely remained unclear to date. However, according to the directive 2000/54/EC on biological agents and the corresponding German Biological Agents Ordinance, employers are also required to consider the potential hazards posed by toxic effects of biological agents when assessing workplace risks. The aim of this article, therefore, is to present some basis information that should facilitate an evaluation of the significance of mycotoxins in the context of assessing workplace risks. It also provides suggestions for occupational health and safety measures.     

The Thr300Ala variant of ATG16L1 is associated with decreased risk of brain metastasis in patients with non-small cell lung cancer

Non-small cell lung cancer (NSCLC) often metastasizes to the brain, but identifying which patients will develop brain metastases (BM) is difficult. Macroautophagy/autophagy is critical for cancer initiation and progression. We hypothesized that genetic variants of autophagy-related genes may affect brain metastases (BM) in NSCLC patients. We genotyped 16 single nucleotide polymorphisms (SNPs) in 7 autophagy-related (ATG) genes (ATG3, ATG5, ATG7, ATG10, ATG12, ATG16L1, and MAP1LC3/LC3) by using DNA from blood samples of 323 NSCLC patients. Further, we evaluated the potential associations of these genes with subsequent BM development. Lung cancer cell lines stably transfected with ATG16L1: rs2241880 (T300A) were established. Mouse models of brain metastasis were developed using cells transfected with ATG16L1–300T or ATG16L1–300A. ATG10: rs10036653 and ATG16L1: rs2241880 were significantly associated with a decreased risk of BM (respective hazard ratios [HRs]=0.596, 95% confidence interval [CI] 0.398–0.894, P = 0.012; and HR = 0. 655, 95% CI 0.438–0.978, P = 0.039, respectively). ATG12: rs26532 was significantly associated with an increased risk of BM (HR=1.644, 95% CI 1.049–2.576, P = 0.030). Invasion and migration assays indicated that transfection with ATG16L1–300T (vs. 300A) stimulated the migration of A549 cells. An in vivo metastasis assay revealed that transfection with ATG16L1–300T (vs. 300A) significantly increased brain metastasis. Our results indicate that genetic variations in autophagy-related genes can predict BM and that genome analysis would facilitate stratification of patients for BM prevention trials.     

Focus: Addiction: Relapse Prevention and the Five Rules of Recovery

There are four main ideas in relapse prevention. First, relapse is a gradual process with distinct stages. The goal of treatment is to help individuals recognize the early stages, in which the chances of success are greatest. Second, recovery is a process of personal growth with developmental milestones. Each stage of recovery has its own risks of relapse. Third, the main tools of relapse prevention are cognitive therapy and mind-body relaxation, which are used to develop healthy coping skills. Fourth, most relapses can be explained in terms of a few basic rules. Educating clients in these rules can help them focus on what is important: 1) change your life (recovery involves creating a new life where it is easier to not use); 2) be completely honest; 3) ask for help; 4) practice self-care; and 5) don’t bend the rules.     

Drugs,genes and screens: The ethics of preventing and treating spinal muscular atrophy

Spinal muscular atrophy (SMA) is the most common genetic disease that causes infant mortality. Its treatment and prevention represent the paradigmatic example of the ethical dilemmas of 21st-century medicine. New therapies (nusinersen and AVXS-101) hold the promise of being able to treat, but not cure, the condition. Alternatively, genomic analysis could identify carriers, and carriers could be offered in vitro fertilization and preimplantation genetic diagnosis. In the future, gene editing could prevent the condition at the embryonic stage. How should these different options be evaluated and compared within a health system? In this paper, we discuss the ethical considerations that bear on the question of how to prioritize the different treatments and preventive options for SMA, at a policy level. We argue that despite the tremendous value of what we call ‘ex-post’ approaches to treating SMA (such as using pharmacological agents or gene therapy), there is a moral imperative to pursue ‘ex-ante’ interventions (such as carrier screening in combination with prenatal testing and preimplantation genetic diagnosis, or gene editing) to reduce the incidence of SMA. There are moral reasons relating to autonomy, beneficence and justice to prioritize ex-ante methods over ex-post methods.     

Gut Microbiome Fermentation Determines the Efficacy of Exercise for Diabetes Prevention

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Effect of Adding Branched-chain Amino Acids to a Nicotinic Acid-free,Low-protein Diet on the Conversion Ratio of Tryptophan to Nicotinamide in Rats

The effects of adding branched-chain amino acids to a nicotinic acid-free, low-protein diet on the conversion of tryptophan to nicotinamide were investigated in rats. The conversion ratio [urinary excretion of nicotinamide and its metabolites (μmol/day) × 100/tryptophan intake during urine collection (μmol/day)] was significantly lower in the groups fed with the 3% Leu-, Val-, or Ile-added diet than in the group fed with the control diet. Namely, the inhibition of this conversion was observed not only by the addition of Leu, but also by the addition of Val or Ile. The addition of Ile and/or Val to the Leu-added diet did not antagonize the Leu effect.     

Prevention of Cancer-by Agents that Suppress Oxygen Radical Formation

The prevention of cancer by agents in our diet has led to the concept that oxygen radicals are a necessary component of a variety of human cancers including breast, colon and prostatic cancer. These cancers are putatively promoted by estradiol, bile acids and androgens. Epidemiological studies have shown that these cancers are suppressed in vegetarian populations. Vegetable components that may be responsible for this cancer prevention are Vitamin A, retinoids and protease inhibitors (PIS). These agents have been shown to suppress the formation of hydrogen peroxide in promoter-induced neutrophils. They also have been shown to block two-stage carcinogenesis and breast cancer when fed to animals. PIS also suppress experimentally-induced colon cancer and spontaneous liver cancer. Moreover, a new series of cancer-preventive agents, Sarcophytols (isolated by Fujiki and co-workers), are capable of suppressing two-stage carcinogenesis, breast and colon cancers in rodents when given in low concentrations. Sarcophytols were also active suppressors of H₂O₂ formation of 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced neutrophils. These observations point to an essential role of oxygen radicals in carcinogenesis. Suppression of the oxygen radical response of neutrophils in relation to cancer preventive agents is a facile assay of these important substances. The mechanism of action of oxygen radicals in promoting carcinogenesis is a multiple one. including: (1) activation of oncogenes, (2) modification of DNA bases, and (3) formation of single-strand breaks leading to poly(ADP)ribose polymerase activation.     

Low-Fat Diets May Prevent Weight Gain in Sedentary Women: Prospective Observations From the Population Study of Women in Gothenburg,Sweden

The Population Study of Women in Gothenburg, Sweden is an ongoing prospective study of female residents who were recruited from the local registry in 1968–1969 when they were 38–60 years old. The data presented here were collected from 361 healthy women who underwent a baseline physical examination including a supplementary dietary history interview and returned for a second general health examination 6 years later. This report identifies a subgroup of 57 women who were sedentary during their leisure time and appear to have been particularly susceptible to gaining weight as a function of the fat content of their diets. Specifically, longitudinal analysis of body weights in the whole sample revealed a statistical interaction between leisure-time physical activity and habitual dietary fat intake (energy-%), as reported at the baseline examination, in the prediction of subsequent weight change. Further stratified analysis suggested that weight changes were significantly dependent on dietary fat intake among the sedentary women only. High energy intake also predicted weight gain in the sedentary group, although the predictive value for a high-fat diet was of marginal significance after adjusting for total energy consumption. These results suggest that sedentary recreational activity plus a low-fat diet may have a combined contribution to weight change that is not equivalent to the sum of the separate effects. Such a synergy between two modifiable lifestyle factors seems highly relevant for prevention of obesity.     

Rational targeting of population groups and residential areas for colorectal cancer screening

BackgroundSociodemographic and spatial disparities in incidence and mortality burden of colorectal cancer (CRC) are important to consider in the implementation of population screening, in order to achieve expected benefit and not increase health inequities. Analytic methods should be adapted to provide rational support for targeted interventions.MethodsCRC incidence rates by tumor stage (I-IV) and location (colon vs. rectum) were analyzed for the time period 2008–2016 within a screening-relevant age interval of 55–74 years for the population of South and West Sweden, where screening is planned for. The study population was stratified by sex, country of birth, educational level (for Swedish-born citizens) and residential area. We also estimated disparities in excess mortality from CRC across groups of patients accordant to relevant population groups.ResultsThe analyses were based on 8961 patients with a first CRC diagnosis. There were marked socioeconomic gradients in the stage II-IV CRC incidence rates among Swedish-born men and women. Compared to men with high educational level, the incidence rate ratios (IRRs) of stage II, III, and IV CRC in men with low educational level were 1.38 (95% confidence interval 1.18, 1.62), 1.09 (0.95, 1.26), and 1.18 (1.02, 1.37), respectively. In women, the corresponding figures were 1.26 (1.06, 1.51), 1.19 (1.01, 1.39), and 1.45 (1.20, 1.80). The groups of patients with low educational level showed relatively high excess mortality burdens from CRC.ConclusionsOur analytic approach provided rational support for targeted intervention when implementing CRC screening, aiming at optimizing participation in groups with low educational level.     

入侵植物马缨丹研究进展

马缨丹原产于热带美洲,现已扩散至世界热带和亚热带地区,并严重威胁入侵地本地植物的生长。马缨丹因具有观赏价值而被我国大量引进,但由于疏于管理,发展成为入侵杂草,对我国农业、畜牧业及生态环境造成严重危害。目前对马缨丹的入侵机制还没有全面系统的认识。本文从马缨丹的生物学特性、入侵机制、生态学效应、防治与应用等方面进行综述,总结其研究进展,以期为马缨丹的防治工作提供依据。研究结果显示:马缨丹成功入侵的关键因素源于其独特的生物学性征;对农林业造成的危害的原因主要为它的化感作用;马缨丹的防治方法主要包括物理、化学和生物防治;马缨丹在防虫除虫、污染修复、药用价值等方面有所应用。此外,分析当前研究中的不足后发现,今后应加强马缨丹在自然环境中的适应机制、应用潜力、防治方法等的研究。