糖尿病流行病学研究策略及分子遗传学研究进展

流行病学是现代医学的一门重要的基础学科,也是一门应用广泛的应用学科。流行病学作为方法学在复杂疾病研究中有不可替代的作用。糖尿病具有复杂疾病属性,应该以系统的多层次的流行病学方法为研究策略。本文从流行病学与临床医学、遗传学及分子生物学交叉所形成的分支学科一临床流行病学、遗传流行病学及分子流行病学三个方面对糖尿病的研究进展作一综述,并从分子遗传学角度列举了部分糖尿病的候选基因。提出糖尿病的研究应该从宏观流行病学（如社会环境等因素的影响）和微观流行病学（如分子遗传等）结合系统地进行研究。     

糖尿病流行病学研究策略及分子遗传学研究进展

流行病学是现代医学的一门重要的基础学科,也是一门应用广泛的应用学科。流行病学作为方法学在复杂疾病研究中有不可替代的作用。糖尿病具有复杂疾病属性,应该以系统的多层次的流行病学方法为研究策略。本文从流行病学与临床医学、遗传学及分子生物学交叉所形成的分支学科--临床流行病学、遗传流行病学及分子流行病学三个方面对糖尿病的研究进展作一综述,并从分子遗传学角度列举了部分糖尿病的候选基因。提出糖尿病的研究应该从宏观流行病学(如社会环境等因素的影响)和微观流行病学(如分子遗传等)结合系统地进行研究。     

Occupational risk of tuberculosis transmission in a low incidence area

Background

To investigate the occupational risk of tuberculosis (TB) infection in a low-incidence setting, data from a prospective study of patients with culture-confirmed TB conducted in Hamburg, Germany, from 1997 to 2002 were evaluated.

Methods

M. tuberculosis isolates were genotyped by IS6110 RFLP analysis. Results of contact tracing and additional patient interviews were used for further epidemiological analyses.

Results

Out of 848 cases included in the cluster analysis, 286 (33.7%) were classified into 76 clusters comprising 2 to 39 patients. In total, two patients in the non-cluster and eight patients in the cluster group were health-care workers. Logistic regression analysis confirmed work in the health-care sector as the strongest predictor for clustering (OR 17.9). However, only two of the eight transmission links among the eight clusters involving health-care workers had been detected previously. Overall, conventional contact tracing performed before genotyping had identified only 26 (25.2%) of the 103 contact persons with the disease among the clustered cases whose transmission links were epidemiologically verified.

Conclusion

Recent transmission was found to be strongly associated with health-care work in a setting with low incidence of TB. Conventional contact tracing alone was shown to be insufficient to discover recent transmission chains. The data presented also indicate the need for establishing improved TB control strategies in health-care settings.     

Prevalence of Human Melioidosis on Hainan Island in China

Eight human cases of melioidosis were diagnosed at Hainan People's Hospital over a period of one year. Four of the cases were of septicemia form, while the rest were of chronic form with abscesses in different organs. All the isolates were intrinsically resistant to cefazolin, cefuroxime, and gentamicin, while being rather sensitive to ampicillin/sulbactam, ticarcillin/clavulanic acid, and imipenem. A serological survey of exotoxin antibodies at different farms showed that Xinglong was a farm seriously devastated by Burkholderia pseudomallei, while the mountainous farm of Licai had the lowest prevalence (P < 0.01). From the results of serological survey and melioidosis case distribution, it could be clearly seen that melioidosis predominantly exists in coastal plain regions around this island, where the altitude above sea-level is below 100 m, the annual rainfall is up to 2,300 mm and a rather warm climate in coldest months of December and January.     

Use of genetic markers and gene-diet interactions for interrogating population-level causal influences of diet on health

Differences in diet appear to contribute substantially to the burden of disease in populations, and therefore changes in diet could lead to major improvements in public health. This is predicated on the reliable identification of causal effects of nutrition on health, and unfortunately nutritional epidemiology has deficiencies in terms of identifying these. This is reflected in the many cases where observational studies have suggested that a nutritional factor is protective against disease, and randomized controlled trials have failed to verify this. The use of genetic variants as proxy measures of nutritional exposure-an application of the Mendelian randomization principle-can contribute to strengthening causal inference in this field. Genetic variants are not subject to bias due to reverse causation (disease processes influencing exposure, rather than vice versa) or recall bias, and if obvious precautions are applied are not influenced by confounding or attenuation by errors. This is illustrated in the case of epidemiological studies of alcohol intake and various health outcomes, through the use of genetic variants related to alcohol metabolism (in ALDH2 and ADH1B). Examples from other areas of nutritional epidemiology and of the informative nature of gene-environment interactions interpreted within the Mendelian randomization framework are presented, and the potential limitations of the approach addressed.     

The dispersion of age differences between partners and the asymptotic dynamics of the HIV epidemic

In this paper, the effect of a change in the distribution of age differences between sexual partners on the dynamics of the HIV epidemic is studied. In a gender- and age-structured compartmental model, it is shown that if the variance of the distribution is small enough, an increase in this variance strongly increases the basic reproduction number. Moreover, if the variance is large enough, the mean age difference barely affects the basic reproduction number. We, therefore, conclude that the local stability of the disease-free equilibrium relies more on the variance than on the mean.     

Epidemic progression on networks based on disease generation time

We investigate the time evolution of disease spread on a network and present an analytical framework using the concept of disease generation time. Assuming a susceptible–infected–recovered epidemic process, this network-based framework enables us to calculate in detail the number of links (edges) within the network that are capable of producing new infectious nodes (individuals), the number of links that are not transmitting the infection further (non-transmitting links), as well as the number of contacts that individuals have with their neighbours (also known as degree distribution) within each epidemiological class, for each generation period. Using several examples, we demonstrate very good agreement between our analytical calculations and the results of computer simulations.     

Treatment design,health outcomes,and demographic categories in the literature on minimum wages and health

This literature review analyzes studies from the US, Canada, the UK, and Europe from inception to April 1, 2021 and focuses on treatment designs, health outcomes, demographic categories and data issues. Study designs are classified as treatment-effect-on-the-treated (7 studies), intent-to-treat (37), and what may be called possible-effects-on-anyone (10). Treatment-effects-on-the-treated designs are best for addressing the longstanding question: does income affect health or vice versa? I argue that they are also better for estimating the overall effect of minimum wages on health. Health outcomes are grouped into seven broad categories, such as overall physiological health and behavior, and 33 narrow categories, such as self-rated health and smoking. Demographic categories include gender, race/ethnicity, and age. The preponderance of evidence suggests that studies relying on the treatment-effect-on-the-treated and possible-effects-on-anyone designs find minimum wages improve health; there is no preponderance of evidence for overall health within intent-to-treat designs. With respect to specific health outcomes and demographic categories, there is no preponderance of evidence, except for improving infant and child health. One data issue concerns whether either intent-to-treat or possible-effects-on-everyone studies are reliable given that likely more than 70 % of people in their samples earn substantially above minimum wages thereby favoring the null hypothesis. Treatment-effect-on-the-treated designs are likely the best designs, and findings are largely consistent in showing that minimum wages improve some measures of health, for example, financial anxiety.     

Correlations among indices of electric and magnetic field exposure in electric utility workers

Power-frequency electric and magnetic fields are known to exhibit marked temporal variation, yet in the absence of clear biological indications, the most appropriate summary indices for use in epidemiologic studies are unknown. In order to assess the statistical patterns among candidate indices, data on 4383 worker-days for magnetic fields and 2082 worker-days for electric fields collected for the Electric and Magnetic Field Project for Electric Utilities using the EMDEX meter [Bracken (1990): Palo Alto, CA: Electric Power Research Institute] were analyzed. We examined correlations at the individual and job title group levels among indices of exposure to both electric and magnetic fields, including the arithmetic mean, geometric mean, median, 20th and 90th percentiles, time above lower cutoffs of 20 V/m and 0.2 μT, and time above higher cutoffs of 100 V/m and 2.0 μT. For both electric and magnetic fields, the arithmetic mean was highly correlated with the 90th percentile; moderately correlated with the geometric mean, median, and lower and higher cutoff scores; and weakly correlated with the 20th percentile. Electric and magnetic field indices were generally weakly correlated with one another. Rank-order correlation coefficients were consistently greater than product-moment correlation coefficients. Job title group summary scores showed higher correlations among electric field indices and magnetic field indices and between electric and magnetic field indices than was found for individual worker-days, with only the 20th percentile clearly independent of the others. These results suggest that individuals' exposures are adequately characterized by a measure of central tendency for electric and magnetic fields, such as the arithmetic or geometric mean, and an indicator of a lower threshold or cutoff for each field type, such as the 20th percentile or proportion of time above 20 V/m or 0.2 μT. A single measure of central tendency for each type of field appears to be adequate when exposures are assessed at the job title level. © 1994 Wiley-Liss, Inc.     

Yersinia pseudotubetculosis in Italy. Attempted Recovery from 37,666 Samples

From 1981 to 1991, 37,666 human, animal, food and environmental samples were cultured for Yersinia pseudotuberculosis using direct plating methods and/or cold enhancement techniques. Despite an intensive surveillance and adequate culture methods, Y. pseudotuberculosis was isolated from stools of 0.05% (5/9,720) of patients with acute enteritis, and alimentary tracts of 0.1% (10/6,849) of apparently healthy animals. No Y. pseudotuberculosis strains were recovered from stools of 4,726 healthy controls nor from the appendices (656), mesenteric lymph nodes (84), and stools (421) of 656 patients operated for suspected appendicitis. Of the 10,842 food and 4,368 environmental samples, none yielded positive cultures for Y. pseudotuberculosis.     

湖北鹤峰县蛇伤流行病学研究

为摸清我县蛇伤发病情况,对全县进行了初步调查.调查时间是1989年至1991年三年;调查人口20.3万人.蛇伤数213人,平均年发病率为0.35‰.其中男性161例占75.59%.死亡2例,死亡率0.94%.蛇伤高峰在5至8月.受伤者绝大多数是农民(97.65%).受伤部位多为下肢(78.40%).受伤地点多在山林中(40.85%)和山间小路上(38.03%),致伤蛇种主要是蝮蛇(40.85%)和烙铁头蛇(33.80%),其次是竹叶青蛇(13.62%)和五步蛇(8.45%).本地对人危害最大的是五步蛇。     

Static behavioral effects on gonorrhea transmission dynamics in a MSM population

An SIS/SAS model of gonorrhea transmission in a population of highly active men-having-sex-with-men (MSM) is presented in this paper to study the impact of safe behavior on the dynamics of gonorrhea prevalence. Safe behaviors may fall into two categories—prevention and self-awareness. Prevention will be modeled via consistent condom use and self-awareness via STD testing frequency. Stability conditions for the disease free equilibrium and endemic equilibrium are determined along with a complete analysis of global dynamics. The control reproductive number is used as a means for measuring the effect of changes to model parameters on the prevalence of the disease. We also find that appropriate intervention would be in the form of a multifaceted approach at overall risk reduction rather than tackling one specific control individually.     

Evolutionary analysis of hepatitis C virus gene sequences from 1953

Reconstructing the transmission history of infectious diseases in the absence of medical or epidemiological records often relies on the evolutionary analysis of pathogen genetic sequences. The precision of evolutionary estimates of epidemic history can be increased by the inclusion of sequences derived from ‘archived’ samples that are genetically distinct from contemporary strains. Historical sequences are especially valuable for viral pathogens that circulated for many years before being formally identified, including HIV and the hepatitis C virus (HCV). However, surprisingly few HCV isolates sampled before discovery of the virus in 1989 are currently available. Here, we report and analyse two HCV subgenomic sequences obtained from infected individuals in 1953, which represent the oldest genetic evidence of HCV infection. The pairwise genetic diversity between the two sequences indicates a substantial period of HCV transmission prior to the 1950s, and their inclusion in evolutionary analyses provides new estimates of the common ancestor of HCV in the USA. To explore and validate the evolutionary information provided by these sequences, we used a new phylogenetic molecular clock method to estimate the date of sampling of the archived strains, plus the dates of four more contemporary reference genomes. Despite the short fragments available, we conclude that the archived sequences are consistent with a proposed sampling date of 1953, although statistical uncertainty is large. Our cross-validation analyses suggest that the bias and low statistical power observed here likely arise from a combination of high evolutionary rate heterogeneity and an unstructured, star-like phylogeny. We expect that attempts to date other historical viruses under similar circumstances will meet similar problems.     

兰州地区腹泻患者艰难梭菌的感染状况调查

目的调查兰州地区腹泻患者中艰难梭菌的流行特点,揭示国内艰难梭菌感染的现况。方法通过细胞毒检测试验和酶联免疫吸附试验对206份临床粪便样品进行毒素检测。结果 206份粪便滤液经细胞毒检测有26份样品使非洲绿猴肾细胞（vero细胞）圆缩化,确认含有艰难梭菌毒素;经酶联免疫吸附试验有28份为阳性,其中23份与细胞毒检测结果一致,与细胞毒试验的符合率为88.5%。结论兰州地区住院腹泻患者中艰难梭菌感染率约为12.62%。     

Health-exposure modeling and the ecological fallacy

Recently, there has been an increased interest in modeling the association between aggregate disease counts and environmental exposures measured, for example via air pollution monitors, at point locations. This paper has two aims: first, we develop a model for such data in order to avoid ecological bias; second, we illustrate that modeling the exposure surface and estimating exposures may lead to bias in estimation of health effects. Design issues are also briefly considered, in particular the loss of information in moving from individual to ecological data, and the at-risk populations to consider in relation to the pollution monitor locations. The approach is investigated initially through simulations, and is then applied to a study of the association between mortality in those over 65 in the year 2000 and the previous year's SO2, in London. We conclude that the use of the proposed model can provide valid inference, but the use of estimated exposures should be carried out with great caution.     

The antigenic evolution of influenza: drift or thrift?

It is commonly assumed that antibody responses against the influenza virus are polarized in the following manner: strong antibody responses are directed at highly variable antigenic epitopes, which consequently undergo ‘antigenic drift’, while weak antibody responses develop against conserved epitopes. As the highly variable epitopes are in a constant state of flux, current antibody-based vaccine strategies are focused on the conserved epitopes in the expectation that they will provide some level of clinical protection after appropriate boosting. Here, we use a theoretical model to suggest the existence of epitopes of low variability, which elicit a high degree of both clinical and transmission-blocking immunity. We show that several epidemiological features of influenza and its serological and molecular profiles are consistent with this model of ‘antigenic thrift’, and that identifying the protective epitopes of low variability predicted by this model could offer a more viable alternative to regularly update the influenza vaccine than exploiting responses to weakly immunogenic conserved regions.     

Alcohol consumption and type 2 diabetes among older adults: the Cardiovascular Health Study

Objective: The objective was to examine the role of total and beverage‐specific alcohol consumption on the incidence of type 2 diabetes mellitus (DM) among elderly men and women. Research Methods and Procedures: We studied prospectively 4655 participants of the Cardiovascular Health Study who were free of DM at baseline. Alcohol consumption was obtained at baseline and during follow‐up examinations. DM was defined using fasting glucose and/or use of hypoglycemic medications. We used Cox proportional hazard models to estimate adjusted relative risks of diabetes across alcohol categories. Results: During a mean follow‐up of 6.3 years, 234 incident cases of DM were documented. Compared with never drinkers, hazard ratios [95% confidence interval (CI)] for DM were 0.7 (0.3 to 1.4), 0.5 (0.3 to 0.9), 0.6 (0.4 to 1.1), and 0.8 (0.4 to 1.3) for former drinkers and current drinkers of <1, 1 to 6, and 7+ drinks per week, respectively, for men after adjustment for age, BMI, education, and smoking. Corresponding values for women were 1.2 (0.6 to 2.3), 0.7 (0.4 to 1.1), 0.6 (0.3 to 1.1), and 0.4 (0.2 to 1.0), respectively. A reduced risk of DM was observed with all types of beverage consumed. Similar findings were observed when we repeated the above analyses using simple or weighted cumulative alcohol update and covariates over time. Discussion: Light to moderate alcohol consumption was associated with a lower incidence of DM among elderly people, irrespective of the type of beverage consumed.     

湖南省长株潭地区儿童烧伤流行病学调查研究

目的：总结分析湖南省长株潭地区儿童烧伤的流行病学特征。方法：采用分层随机抽样法抽取湖南省长株潭地区3所医院,收集其2010年1月至2010年12月间收治的0—14岁烧伤患儿病历资料,并对烧伤患儿或其家长进行问卷调查。、结果：各年龄段患儿烧伤构成比依次为0-3岁（62．1％）、4-6岁（24．2％）以及7—14岁（13．6％）。致伤原因构成比依次为热液烧伤（56．1％）、火焰烧伤（31．8％）、其他原因烧伤（12．1％）。83．3％的烧伤发生在室内,客厅为最主要的烧伤发生场所占47．3％。75．8％的患儿烧伤发生在白天（6：00-18：00）。62．5％的患儿烧伤发生在夏、秋两季（6月-11月）。结论：在长株潭地区,婴幼儿时期（0-3岁）为儿童烧伤的易发年龄段;热液／热蒸汽造成的烧烫伤是儿童烧伤最常见的类型;室内特别是客厅为儿童烧伤最容易发生的地点。白天和夏、秋两季为儿童烧伤的好发时段和季节。     

Fungemia in cancer patients in Brazil: Predominance of non-albicans species

The objective of this study was to characterize the epidemiology of candidemia in cancer patients in the city of Rio de Janeiro, Brazil. An 18-month survey of fungemia in patients with cancer was undertaken in three Hospitals in Rio de Janeiro. Forty-three episodes of candidemia were identified in 43 patients, 43 of which were episodes of candidemia; in ten cases the strains were not available for further identification of species and were excluded from this analysis. The overall distribution of fungi causing fungemia was: Candida albicans (5), Candida tropicalis (16), Candida parapsilosis (6), Candida guilliermondii (4), Candida lusitaniae (1) and Candida stellatoidea (1). Antifungal prophylaxis had been administered before the episode of fungemia in only six patients (18.2%): oral itraconazole in three patients and oral nistatin, low dose intravenous amphotericin B and oral fluconazole in one patient each. There was no difference in the presence of risk factors, clinical characteristics or in the outcome between albicans and non-albicans species, nor between Candida tropicalis and other non-albicans species. There was a clear predominance of non-albicans species, regardless of the underlying disease, antifungal prophylaxis or the presence of neutropenia. This revised version was published online in June 2006 with corrections to the Cover Date.     

Chromoblastomycosis: a retrospective study of 325 cases on Amazonic Region (Brazil)

A retrospective study of 325 cases of chromoblastomycosis diagnosed in the last 55 years in the Amazon region was carried out by the main Mycology services of the state of Pará, Brazil (Department of Tropical Pathology – UFPA and Mycology Department of the Evandro Chagas Institute/FNS). The data obtained showed that: (a) the main age group affected by the diseases range from 41 to 70 years-old, (b) 86.1% of the patients were agricultural-workers, (c) 93.2% of them were males and (d) 80.7% showed lesions on the lower limbs (feet and legs). The diagnosis of 62% of the cases was confirmed by laboratory studies considering the tissue form in histopathological analysis. In 24% of patients (78 cases), the etiological agent was isolated and identified through culture. Fonsecaea pedrosoi was present in 77 cases and Phialophora verucosa in only one case. This revised version was published online in June 2006 with corrections to the Cover Date.