广西地区结核分枝杆菌异烟肼耐药基因突变特征分析

目的 分析广西地区结核分枝杆菌异烟肼(INH)耐药基因的突变特征,为耐药结核病的分子诊断提供依据。方法 选取2018年广西30个结核病耐药监测点收集的结核分枝杆菌菌株库中122株耐INH菌株和530株全敏感菌株进行全基因组测序。结果 652株结核分枝杆菌复合群菌株中,127株(19.48%)发生INH耐药基因突变,分别为katG(15.64%,102株)、fabG1(1.69%,11株)、ahpC(1.07%,7株)、kasA(0.61%,4株)和inhA(0.46%,3株)基因突变。INH耐药表型与基因突变的符合率为90.03%,比例法药敏检测INH耐药与基因测序检测基因突变结果吻合度不高(Kappa=0.677)。突变类型共有19种,单位点突变占96.85%,联合位点突变占3.15%。突变比率最高的位点为katG315(71.65%),碱基变化以AGC-ACC形式占比最高(12.13%)。katG、ahpC和kasA基因突变比例在INH耐药株中高于敏感株(均P<0.05),INH耐药株和敏感株inhA、fabG1基因突变比例比较,差异均无统计学意义(均P>0.05)。北...     

合肥地区异烟肼耐药结核分枝杆菌KatG基因突变的分子特征

目的 了解合肥地区结核分枝杆菌异烟肼(Isoniazid,INH)耐药株katG基因突变特点.方法 应用PCR-直接测序法对合肥地区肺结核病人痰液中分离的86株结核分枝杆菌的katG基因731bp序列进行测定分析.结果 86株结核分枝杆菌中67株对INH耐药,19株对INH敏感;67株耐INH临床分离株中PCR成功扩增61株,其中56株发生katG基因突变,突变率为91.8％ (56/61);katG基因发生联合突变的有30株,突变率为49.2％ (30/61),26株发生katG基因单位点突变,突变率为42.6％ (26/61).突变位点主要集中在463位精氨酸和315位丝氨酸,突变率分别为93.4％(57/61)和42.6％ (26/61).而在19株INH敏感株中发现有78.9％ (15/19)株存在Arg4631eu突变,突变形式与INH耐药株相同.结论 在合肥地区,KatG基因315位密码子突变是菌株INH表型耐药的重要分子基础,以Ser315Thr错义突变为主.KatG基因463位密码子突变与INH耐药表型没有相关性,不是结核杆菌INH耐药的分子标志.该位点突变可能是基因多态性,与结核菌治疗带来的选择性压力无关.     

江苏省结核分枝杆菌耐药相关基因突变特征研究

目的探讨江苏省结核分枝杆菌耐药相关基因的基因型特点及其与耐药表型的关系,为开展耐药结核病快速诊断提供依据。方法通过基因测序技术,分析结核分枝杆菌利福平(rifampin,RFP)耐药相关基因rpoB和异烟肼(isoniazid,INH)耐药相关基因katG不同位点的突变频率,探讨基因型与耐药表型的关系。结果共收集新登记涂阳病人菌株283株,其中255株结核分枝杆菌成功测序,包括38株RFP耐药株,50株INH耐药株,48株链霉素耐药菌株,21株乙胺丁醇耐药株,34株耐多药菌株。28株(11.0%)在rpoB 81bp的基因核心区发生了点突变,21株出现单个位点突变外,7株出现两位点突变,突变形式主要为rpoB531 TCG→TTG单个位点突变。30株(11.8%)发生了katG基因区的突变,所有突变形式为katG315AGC→ACC。rpoB基因突变全部发生于RFP耐药菌株中,katG基因突变全部发生于INH耐药菌株中。结论检测rpoB与katG基因位点的突变对判断江苏省地区耐药结核以及耐多药结核有重要的价值,可以为开展耐药结核病早期诊断提供科学依据。     

结核分枝杆菌inhA基因突变的研究

目的：了解我国结核分枝杆菌耐异烟肼（INH）临床分离株inhA基因突变情况,探讨快速检测结核分枝杆菌耐药基因型的分子药敏检测方法。：方法：用PCR单链构象多态性（PCR－SSCP）和PCR直接测序法（PCR－DS）分析30 结核分枝杆菌临床分离株inhA基因。结果：以结核分枝杆菌H37Rv标准株对照观察所有INH敏感株的PCR－SSCP和PCR－DS图谱,均未发现inhA基因突变,在12株INH耐药株中,有5株无PCR－SSCP和PCR－DS图谱异常,占INH耐药株的41．7％,另有5株和2株分别发生核苷酸错义突变和同义突变,共占INH耐药株的58．3％,结果：多数结核分枝杆菌耐INH与inhA基因突变密切相关,但检测inhA基因突变不宜作为临床分离株耐药性的快速检测指标。     

2017—2022年乐山市311例耐药结核分枝杆菌相关耐药基因变异特征分析

目的 分析乐山市2017—2022年收集得到的311例耐药结核分枝杆菌相关耐药基因突变位点特征，为本地区耐药结核病防治提供数据支持。方法 采用线性杂交酶显色技术对结核分枝杆菌进行耐药检测，对RFP和INH耐药基因的突变位点与不同耐药类型的病例特征进行分析，了解耐药基因突变位点频率的分布特点。结果 被纳入分析的311例耐药结核分枝杆菌，其中单耐RFP 63例(20.26%)，单耐INH 126例(40.51%)，耐多药122例(39.23%)，按单耐RFP、单耐INH、耐多药3种类型分类后发现不同年龄组(χ²=20.336,P=0.002)、不同患者类型(χ²=15.496,P=0.004)、不同民族(χ²=7.852,P=0.020)的耐药情况差异均有统计学意义，单耐RFP相关rpoB基因突变位点主要发生在S531L、H526Y位点，单耐INH相关katG/inhA基因突变位点主要发生在S315T1、C-15T位点，耐多药中rpoB基因和katG/inhA基因位点突变组合以S531L+S315T1为主。结论 乐山地区耐药...     

福建省耐多药结核分枝杆菌耐药相关基因突变特征

目的初步分析福建耐多药结核病(multi-resistant tuberculosis,MDR-TB)临床分离结核分枝杆菌利福平和异烟肼的耐药相关基因突变情况。方法自福建福州肺科医院收集耐多药结核分枝杆菌临床分离菌株,采用PCR测序技术测定利福平和异烟肼耐药相关基因,包括rpoB、katG、inhA和mabA-inhA,并与标准菌株基因序列比对,分析基因突变特点。结果共对67株MDR-TB菌株进行了分析,91.04%的菌株在rpoB81 bp RRDR区发生突变,其中,88.06%(59/67)的MDR-TB菌株在rpoB531、526和516位发生突变;79.10%的菌株在katG、inhA或mabA-inhA上发生突变,59.70%(40/67)的菌株在katG315或者mabA-inhA(-15)位发生突变,没有检测到同时在inhA结构基因和基因调节区发生突变的菌株。结论 PCR-DNA测序分析技术可以用于检测MDR-TB临床分离菌株对RFP和INH的药物敏感性。     

反向斑点杂交技术在结核分枝杆菌耐药性检测中的应用研究

目的利用反向斑点杂交技术，建立结核分枝杆菌对利福平（RFP）、异烟肼（INH）、链霉素（SM）和乙胺丁醇（EMB）耐药相关基因突变的快速检测方法。方法根据结核分枝杆菌标准株H37Rv序列，自行设计针对rpoB、katG、inhA、rpsL和embB基因中常见耐药突变区的系列寡核苷酸探针，制成膜芯片，并对64例结核分枝杆菌临床株的基因突变情况进行检测。结果在36株RFP耐药菌中，有32株被检出在rpoB基因上发生突变，突变检出率为88．89％（32／36）；在39株INH耐药菌中，有30株被检出在katG或inhA基因上发生基因突变或缺失，检出率为76．92％（30／39）；在34株SM耐药菌中，有25株被检出在rpsL基因分析部位发生突变，检出率为73．5％（25／34）；在32株EMB耐’药菌中，有19株在embB基因分析部位发生突变，检出率为59．4％（19／32）。膜芯片检出的突变与基因测序结果一致。结论用膜芯片检测结核分枝杆菌对利福平（RFP）、异烟肼（INH）、链霉素（SM）和乙胺丁醇（EMB）四种主要一线抗结核药的耐药性，具有较高的特异性和敏感性，可作为常规药敏方法的补充，用于指导开展早期、有效的临床化疗。     

浙江地区耐多药结核分枝杆菌基因突变特征分析

目的 分析浙江地区耐多药结核分枝杆菌(M.tuberculosis complex,MTBC)异烟肼(isoniazid,INH)和利福平(rifampicin,RIF)耐药相关基因突变特征.方法 对患者痰标本阳性培养物进行菌种鉴定,提取耐多药菌株DNA,应用PCR法对inhA、katG和rpoB RRDR区进行扩增,...     

应用基因芯片技术检测结核分枝杆菌耐药基因

目的应用基因芯片快速检测结核分枝杆菌耐利福平rpoB基因突变和耐异烟肼katG、inhA基因突变,建立一种新的分子药敏试验方法。方法根据结核分枝杆菌rpoB、katG、inhA基因序列设计探针并制作DNA芯片,PCR掺入法荧光标记,结核分枝杆菌基因突变位点的目的片断与DNA芯片杂交,同时以传统药敏试验和DNA测序法为对照。结果 70株结核分枝杆菌临床分离株中,20株药物敏感株芯片杂交结果与标准株完全相同;30株耐RIF临床分离株均检测到rpoB基因突变;50株异烟肼耐药株中有41株检测到katG基因突变,9株检测到inhA基因突变,与测序结果完全一致。结论用DNA芯片可快速、特异地检测出大多数结核分枝杆菌分离株的rpoB、katG、inhA基因突变,可用于临床耐药性的检测,指导临床用药。     

保定市结核分枝杆菌多种耐药基因突变流行病学调查

目的：调查保定市人群结核分枝杆菌对利福平、异烟肼、乙胺丁醇、链霉素、吡嗪酰胺耐药基因突变类及发生率，为保定市结核病的防治工作提供分子生物学依据。方法：对440株临床分离出的结核分枝杆菌进行培养和药物敏感试验，应用聚合酶链单链构象多态性分析（PCR—SSCP）方法对rpoB、katG、embB、inhA、rrs、rpsL、pncA基因进行突变分析。结果：440株临床分离结核分枝杆菌RFP、INH、SM、EMB、PZA耐药率分别为43．6％、37．5％、43．18％、20％、5％。耐药菌株基因突变率为耐RFP：rpoB92．6％（176／190）；耐INH：katG65．4％（108／165）；耐EMB：embB45％（40／88）；耐INH：inhA39．3％（65／165）；耐SM：rrs20％（38／190）；耐SM：rpsL 65％（124／190）；耐PZA：pncA 36．3％（8／22）。结论：保定市结核分枝杆菌耐药基因突变率与药物敏感性试验结果之间有明显相关性。应用PCR—SSCP进行耐药基因分析。可以快速、准确地分析结核分枝杆菌耐药情况。同时本研究也为保定市结核病的预防提供了分子生物学依据。     

Self-reported health problems among Swedish miners one year after unemployment

Unemployment is considered to be a public health concern sincedeterioration in the health of the unemployed is often anticipated.However, for some groups, such as miners, unemployment mightimprove health due to a cessation of potentially harmful occupationalexposures. This study evaluates the health of 79 miners in oneSwedish iron-ore mine, and 226 age-matched controls from thegeneral population, during one year after the closure of themine. The participants received a questionnaire regarding medicalhistory and subjective symptoms at the beginning of the studyperiod, and after one year. Statistically significant negativeeffects on self-reported health attributable to unemploymentwere not found, although neuropsychiatric symptoms were morecommon among the unemployed miners. The miners reported a statisticallysignificant improvement in grip force (p=0.031). They had asignificantly higher prevalence of symptoms associated withmining related exposures when compared with the population controls;pain in the upper extremities [relative risk (RR)=2.27, 95%confidence interval (Cl)=1.44–3.59), back pain (RR=1.84;Cl=1.237–2.75), vasospastic disease of the fingers (RR=2.05;Cl=1.18–3.57) and obstructive respiratory symptoms (attacksof dyspnea and wheezing: RR=3.67; Cl=1.167–11.6).     

Excès de cas humains et animaux de tularémie en France au cours de l’hiver 2007–2008 : émergence ou phénomène isolé ?

Context

Tularemia is a zoonosis affecting humans and hares in France. We describe the results of surveillance in both species, in 2007 and 2008.

Methods

Human tularemia cases are mandatorily notifiable in France since 2003. In hares, surveillance relies on volunteer hunter associations in all districts of the country. Data from mandatory reports and volunteer surveillance in 2007/2008 were analyzed and compared with previous results.

Results

In 2007/2008, 144 cases were reported in humans and 117 cases in hares. This was a 100% increase compared to previous years. Human cases differed from those of previous years only by the frequency of contact with breeding animals. Human cases without any documented risk exposure were also more frequent.

Conclusion

An increase of tularemia cases occurred in 2007/2008 in both species. Complementary studies are needed to identify the species reservoir in France to understand the causes of this peak of cases.     

Occupational health hazards in mining: an overview

This review article outlines the physical, chemical, biological, ergonomic and psychosocial occupational health hazards of mining and associated metallurgical processes. Mining remains an important industrial sector in many parts of the world and although substantial progress has been made in the control of occupational health hazards, there remains room for further risk reduction. This applies particularly to traumatic injury hazards, ergonomic hazards and noise. Vigilance is also required to ensure exposures to coal dust and crystalline silica remain effectively controlled.     

Manufacture and use of nanomaterials: current status in the UK and global trends

This paper provides an overview of the production and use of nanomaterials (NMs), particularly in the UK. Currently, relatively few companies in the UK are identifiable as NM manufacturers, the main emphasis being the bulk markets in metals and metal oxides, and some niche markets such as carbon nanotubes and quantum dots. NM manufacturing in the UK does not reflect the global emphasis on fullerenes, nanotubes and fibres. Some assumptions have been made about the types of NM that are likely to be imported into the UK, which currently include fullerenes, modified fullerenes and other carbon-based NMs including nanotubes. Many university departments, spin-offs and private companies have developed processes for the manufacture of NMs but may only be producing small quantities for research and development (R&D) purposes. However, some have the potential to scale up to produce large quantities. The nanotechnology industry in the UK has strong R&D backup from universities and related institutions. This review has covered R&D trends at such institutions, and appropriate information has been added to a searchable database. While several companies are including NMs in their products, only a few (e.g. manufacturers of paints, coatings, cosmetics, catalysts, polymer composites) are using nanoparticles (NPs) in any significant quantities. However, this situation is likely to change rapidly. There is a need to collect more information about exposure to NPs in both manufacturing and user scenarios. As the market grows, and as manufacturers switch from the micro- to the nanoscale, the potential for exposure will increase. More research is required to quantify any risks to workers and consumers.     

Investigating clusters in the workplace and beyond

Clusters of disease are common and occur in the workplace and in the general community. They often arouse considerable concern among the population. Investigations have sometimes lead to exciting new knowledge, but in general the investigation of clusters is difficult and often unrewarding, especially for community clusters. In the workplace, investigations are more likely to find associations and even new causes, but still many clusters remain enigmatic. Despite this, there are many reasons for investigating clusters, including allaying community concern and identifying uncontrolled exposures. A structure for investigating clusters in the workplace is suggested.     

Assessing occupational and environmental exposure

Exposure assessment is a poorly understood component of the science of epidemiology. The relationship between exposure to chemicals and ill-health outcomes is often calculated using crude exposure measures such as ever/never exposed or duration. When investigating subtle effects, exposures need to be characterized much more fully in terms of intensity, frequency, duration and route. While occupational exposures tend to be much greater than those experienced from the wider environment there is a need to remember that, for many chemicals, exposure can occur occupationally, environmentally and through consumer use of products containing the material of interest. Inhalation exposure has generally been the traditional focus for most epidemiological investigations but there is now growing awareness of the importance of the dermal and ingested routes of contact and internalization. Quantification of the exposure also needs to be related to a biological mechanism of action and exposure metrics need to be selected accordingly. Occupational exposures can generally be measured using simple well-validated techniques. Environmental exposures require much more sensitive instruments and are more difficult to assess. Exposure modelling, particularly for the environmental fate of chemicals has undergone many recent developments and Monte Carlo techniques can be used to characterize model uncertainty and variability. This approach to exposure assessment can now be used in the setting of the wider environment and will enable a far better understanding of the relationship between exposure and disease.     

Mercury toxicity due to the smelting of placer gold recovered by mercury amalgam

A 19-year-old man developed tremor in both hands and fatigue after starting work at a placer gold mine where he was exposed to mercury-gold amalgam. Examination revealed an intention tremor, dysdiadochokinesis and mild rigidity. The 24-h urinary mercury concentration reached a peak of 715 nmol/l (143 ug/l) shortly before the clinical examination, after which he was removed from working in the gold room [Mercury No. Adverse Effect Level: 250 nmol/l (50 ug/l)]. On review 7 weeks later his tremor had almost resolved and the dysdiadochokinesis and rigidity had gone. The 24-h urinary mercury concentration had fallen to 160 nmol/l (32 ug/l). The principal exposure to mercury was considered to be the smelting of retorted gold with previously unrecognized residual mercury in it. The peak air concentration of mercury vapour during gold smelting was 0.533 mg/m3 (Mercury Vapour ACGIH TLV: 0.05 mg/m3 TWA). Several engineering and procedural controls were instituted. This episode occurred at another mine site, unrelated to Mount Isa Mines Limited.     

How Adults with Acquired Brain Damage Perceive Computer Training as a Rehabilitation Tool: A Focus-group Study

The aim of this study was to explore and describe how adult outpatients with acquired brain damage and referred to occupational therapy perceive computer training with the RehaCom programs, in order to evaluate the method of treatment as a tool in the rehabilitation of persons with cognitive disorders. By using focus-group discussions as a qualitative method of research when analysing the result, five themes with corresponding categories emerged, describing a development of understanding and learning about capacities. Themes describing how the participants could apply strategies to overcome shortcomings in daily occupations and the therapeutic role of the occupational therapist were identified as well. The result shows that a computer training program such as RehaCom can be used as an educational tool, for example, to guide a person who is trying to adopt compensatory strategies to avoid overload by taking pauses. It was found that anything the participants learned was also applicable to occupational performance in daily life.