Switching from usual brand cigarettes to a tobacco-heating cigarette or snus: Part 2. Biomarkers of exposure

Abstract

A randomized, multi-center study of adult cigarette smokers switched to tobacco-heating cigarettes, snus or ultra-low machine yield tobacco-burning cigarettes (50/group) was conducted, and subjects’ experience with the products was followed for 24 weeks. Differences in biomarkers of tobacco exposure between smokers and never smokers at baseline and among groups relative to each other and over time were assessed. Results indicated reduced exposure to many potentially harmful constituents found in cigarette smoke following product switching. Findings support differences in exposure from the use of various tobacco products and are relevant to the understanding of a risk continuum among tobacco products.

Trial registration: ClinicalTrials.gov identifier: NCT02061917.     

Responses of serum chemokines to dramatic changes of air pollution levels,a panel study

Abstract

Background: Despite the in vitro and in vivo evidence, studies are limited in evaluating whether chemokines are potential inflammatory mediators in response to air pollution exposure in humans.

Methods: We conducted a panel study coinciding with the Beijing Olympics, when temporary air pollution controls were implemented. We measured a suite of serum chemokines among healthy adults before, during and after the Olympics, respectively. Linear mixed-effect models were used to evaluate changes in chemokine levels over the three time periods.

Results: In response to the 50% drop in air pollution levels during the games, levels of RANTES, MCP-2, and TARC decreased by 25.8%, 20.9% and 35.3%, respectively (p?<?0.001) from pre-Olympics, and then increased by 45.8%, 34.9% and 61.5%, respectively (p?<?0.001) after the games when air pollution levels went up again. Similar patterns were observed in subgroup analyses by sex, age, smoking and body mass index. GRO-α and IL-8 decreased significantly during the games (22.5% and 30.4%), and increased non-significantly after the games. Eotaxin-1 only increased significantly from during- to post-games.

Conclusions: The strongest associations with air pollution levels were observed among RANTES, TARC and MCP-2. Those chemokines may play important roles in the air pollution-induced inflammatory pathway.     

The New Perspectives on Genetic Studies of Type 2 Diabetes and Thyroid Diseases

Recently, genome-wide association studies (GWAS) have led to the discovery of hundreds of susceptibility loci that are associated with complex metabolic diseases, such as type 2 diabetes and hyperthyroidism. The majority of the susceptibility loci are common across different races or populations; while some of them show ethnicity-specific distribution. Though the abundant novel susceptibility loci identified by GWAS have provided insight into biology through the discovery of new genes or pathways that were previously not known, most of them are in introns and the associated variants cumulatively explain only a small fraction of total heritability. Here we reviewed the genetic studies on the metabolic disorders, mainly type 2 diabetes and hyperthyroidism, including candidate genes-based findings and more recently the GWAS discovery; we also included the clinical relevance of these novel loci and the gene-environmental interactions. Finally, we discussed the future direction about the genetic study on the exploring of the pathogenesis of the metabolic diseases.     

实验诊断学PBL教学案例的设计原则

由临床检验专业人员承担的《实验诊断学》教学应以临床检验学为教学重点,案例的教学目标及学习重点应围绕临床检验基本原理,检验结果质量保证和检验结果影响因素三方面进行。案例选择应遵循以下原则：①选择质量保证的过程中容易出现问题的环节;②选择物质代谢过程清楚,相关疾病的病理生理改变明确的检验项目,如血糖;③选择在,临床检验中应用较多的方法,比如酶的连续监测法。     

Association study of 37 genes related to serotonin and dopamine neurotransmission and neurotrophic factors in cocaine dependence

Cocaine dependence is a neuropsychiatric disorder in which both environmental and genetic factors are involved. Several processes, that include reward and neuroadaptations, mediate the transition from use to dependence. In this regard, dopamine and serotonin neurotransmission systems are clearly involved in reward and other cocaine‐related effects, whereas neurotrophic factors may be responsible for neuroadaptations associated with cocaine dependence. We examined the contribution to cocaine dependence of 37 genes related to the dopaminergic and serotoninergic systems, neurotrophic factors and their receptors through a case–control association study with 319 single nucleotide polymorphisms selected according to genetic coverage criteria in 432 cocaine‐dependent patients and 482 sex‐matched unrelated controls. Single marker analyses provided evidence for association of the serotonin receptor HTR2A with cocaine dependence [rs6561333; nominal P‐value adjusted for age = 1.9e?04, odds ratio = 1.72 (1.29–2.30)]. When patients were subdivided according to the presence or absence of psychotic symptoms, we confirmed the association between cocaine dependence and HTR2A in both subgroups of patients. Our data show additional evidence for the involvement of the serotoninergic system in the genetic susceptibility to cocaine dependence.     

A study of the possible association between adenosine A2A receptor gene polymorphisms and attention‐deficit hyperactivity disorder traits

The adenosine A_2A receptor (ADORA2A) is linked to the dopamine neurotransmitter system and is also implicated in the regulation of alertness, suggesting a potential association with attention‐deficit hyperactivity disorder (ADHD) traits. Furthermore, animal studies suggest that the ADORA2A may influence ADHD‐like behavior. For that reason, the ADORA2A gene emerges as a promising candidate for studying the etiology of ADHD traits. The aim of this study was to examine the relationship between ADORA2A gene polymorphisms and ADHD traits in a large population‐based sample. This study was based on the Child and Adolescent Twin Study in Sweden (CATSS), and included 1747 twins. Attention‐deficit hyperactivity disorder traits were assessed through parental reports, and samples of DNA were collected. Associations between six single nucleotide polymorphisms (SNPs) and ADHD traits were examined, and results suggested a nominal association between ADHD traits and three of these SNPs: rs3761422, rs5751876 and rs35320474. For one of the SNPs, rs35320474, results remained significant after correction for multiple comparisons. These results indicate the possibility that the ADORA2A gene may be involved in ADHD traits. However, more studies replicating the present results are warranted before this association can be confirmed .     

Apolar distal pocket mutants of yeast cytochrome c peroxidase: Hydrogen peroxide reactivity and cyanide binding of the TriAla,TriVal, and TriLeu variants

Three yeast cytochrome c peroxidase (CcP) variants with apolar distal heme pockets have been constructed. The CcP variants have Arg48, Trp51, and His52 mutated to either all alanines, CcP(triAla), all valines, CcP(triVal), or all leucines, CcP(triLeu). The triple mutants have detectable enzymatic activity at pH 6 but the activity is less than 0.02% that of wild-type CcP. The activity loss is primarily due to the decreased rate of reaction between the triple mutants and H₂O₂ compared to wild-type CcP. Spectroscopic properties and cyanide binding characteristics of the triple mutants have been investigated over the pH stability region of CcP, pH 4 to 8. The absorption spectra indicate that the CcP triple mutants have hemes that are predominantly five-coordinate, high-spin at pH 5 and six-coordinate, low-spin at pH 8. Cyanide binding to the triple mutants is biphasic indicating that the triple mutants have two slowly-exchanging conformational states with different cyanide affinities. The binding affinity for cyanide is reduced at least two orders of magnitude in the triple mutants compared to wild-type CcP and the rate of cyanide binding is reduced by four to five orders of magnitude. Correlation of the reaction rates of CcP and 12 distal pocket mutants with H₂O₂ and HCN suggests that both reactions require ionization of the reactants within the distal heme pocket allowing the anion to bind the heme iron. Distal pocket features that promote substrate ionization (basic residues involved in base-catalyzed substrate ionization or polar residues that can stabilize substrate anions) increase the overall rate of reaction with H₂O₂ and HCN while features that inhibit substrate ionization slow the reactions.     

马铃薯致病疫霉研究进展

马铃薯致病疫霉(Phytophthora infestans)属卵菌纲(Oomycetes)霜霉目(Peronosporales)腐霉科(Pythiaceae)疫霉属(Phytophthora),是马铃薯和番茄晚疫病病原菌。由于晚疫病对马铃薯生产的毁灭性和严重性,对致病疫霉的研究一直是关注的重点。本文首先对病害引起的症状、发生特点及流行规律进行阐述,对有性生殖发生的遗传规律和多种交配型共存的大环境下病原菌群体结构变异特点进行归纳总结。随着2009年致病疫霉基因组测序的完成,本文比对了疫霉属目前已完成测序各个种的基因组学特点,介绍了致病疫霉在效应子克隆方面的研究进展及线粒体基因组研究现状,阐述了功能基因组学的两个重要技术:高密度遗传连锁图谱(high density linkage mapping)和全基因组关联分析(genome-wide association study,GWAS),及其在挖掘致病疫霉重要功能基因上的应用。本文有助于了解致病疫霉研究热点及后续突破方向,可为深入解析致病疫霉的功能基因及致病机制提供参考,对开发马铃薯晚疫病菌药物靶标及预测病害的大规模流行趋势也具有重要意义。