Undertreatment of hypertension and the risk of stroke in the oldest old

The benefit of pharmacological treatment of hypertension in the prevention of cardiovascular diseases has been established mainly in subjects younger than 80 years of age. The consequences of undertreatment of hypertension with regard to the occurrence of stroke was studied in the Netherlands. About 33% of the hypertensives younger than 80 years and 55% of the hypertensives older than 80 years were not pharmacologically treated, although they were 'candidates' for pharmacological treatment of hypertension. About 19% (n = 1350) of all strokes that occurred in the Netherlands in 1994 among hypertensives younger than 80 years may be attributable to untreated hypertension. Among hypertensives older than 80 years this percentage was 32% (n = 1345). Although the benefit of pharmacological treatment of hypertension in persons older than 80 years has not been established experimentally, the results suggest that a considerable proportion of the strokes among this group of hypertensives may be prevented.     

Statin Use and Markers of Immunity in the Doetinchem Cohort Study

It has been suggested that statins can both stimulate and suppress the immune system, and thereby, may influence autoimmune diseases. Therefore, we studied effects of statins on innate and adaptive immunity, and self-tolerance by measuring serological levels of C-reactive protein (CRP), neopterin, immunoglobulin E (IgE) antibodies and the presence of autoantibodies (antinuclear antibodies (ANA) and IgM rheumatoid factor (RF)) in the general population. We conducted a nested case-control study within the population-based Doetinchem cohort. Data from health questionnaires, serological measurements and information on medication from linkage to pharmacy-dispensing records were available. We selected 332 statin users (cases) and 331 non-users (controls), matched by age, sex, date of serum collection, history of cardiovascular diseases, diabetes mellitus type II and stroke. Multivariate regression analyses were performed to estimate effect of statins on the immune system. The median level of CRP in statin users (1.28 mg/L, interquartile range (IQR): 0.59-2.79) was lower than in non-users (1.62 mg/L, IQR: 0.79-3.35), which after adjustment was estimated to be a 28% lower level. We observed an inverse association between duration of statin use and CRP levels. Elevated levels of IgE (>100 IU/mL) were more prevalent in statin users compared to non-users. A trend towards increased levels of IgE antibodies in statin users was observed, whereas no associations were found between statin use and levels of neopterin or the presence of autoantibodies. In this general population sub-sample, we observed an anti-inflammatory effect of statin use and a trend towards an increase of IgE levels, an surrogate marker for Th (helper) 2 responses without a decrease in neopterin levels, a surrogate marker for Th1 response and/or self-tolerance. We postulate that the observed decreased inflammatory response during statin therapy may be important but is insufficient to induce loss of self-tolerance.     

Common variants in the type 2 diabetes KCNQ1 gene are associated with impairments in insulin secretion during hyperglycaemic glucose clamp

Background

Genome-wide association studies in Japanese populations recently identified common variants in the KCNQ1 gene to be associated with type 2 diabetes. We examined the association of these variants within KCNQ1 with type 2 diabetes in a Dutch population, investigated their effects on insulin secretion and metabolic traits and on the risk of developing complications in type 2 diabetes patients.

Methodology

The KCNQ1 variants rs151290, rs2237892, and rs2237895 were genotyped in a total of 4620 type 2 diabetes patients and 5285 healthy controls from the Netherlands. Data on macrovascular complications, nephropathy and retinopathy were available in a subset of diabetic patients. Association between genotype and insulin secretion/action was assessed in the additional sample of 335 individuals who underwent a hyperglycaemic clamp.

Principal Findings

We found that all the genotyped KCNQ1 variants were significantly associated with type 2 diabetes in our Dutch population, and the association of rs151290 was the strongest (OR 1.20, 95% CI 1.07–1.35, p = 0.002). The risk C-allele of rs151290 was nominally associated with reduced first-phase glucose-stimulated insulin secretion, while the non-risk T-allele of rs2237892 was significantly correlated with increased second-phase glucose-stimulated insulin secretion (p = 0.025 and 0.0016, respectively). In addition, the risk C-allele of rs2237892 was associated with higher LDL and total cholesterol levels (p = 0.015 and 0.003, respectively). We found no evidence for an association of KCNQ1 with diabetic complications.

Conclusions

Common variants in the KCNQ1 gene are associated with type 2 diabetes in a Dutch population, which can be explained at least in part by an effect on insulin secretion. Furthermore, our data suggest that KCNQ1 is also associated with lipid metabolism.     

Pygo基因的细胞定位及其在果蝇发育过程中的表达(英文)

Wingless信号传导是果蝇胚胎和幼虫发育过程中的一个关键性的信号传导通路。已鉴定出来许多参与Wg Wnt信号传导的Wg或其脊椎动物同源基因Wnt下游传导通路的基因。Wg下游的Wg信号传导是由核TCF LEF 1通过Armadillo (Arm) β catenin介导的。pygopus (pygo)是一个最近发现的Wg Wnt信号传导通路新成员。通过细胞定位实验发现pygo专一性的表达在细胞核中。运用反义mRNA作探针的原位杂交技术 ,观察到了pygo基因在果蝇胚胎中的表达特性。虽然pygo普遍表达于果蝇胚胎发生全过程 ,但pygo在前囊胚层 (pre blastoderm)中的表达水平相对较高 ,这说明胚胎发生过程中来自母方的贡献较高。在幼虫组织 (包括翅成虫盘 ,眼成虫盘和腿成虫盘 )的发育过程中 ,pygo的表达水平总的来说比较低。然而 ,比较翅成虫盘 ,眼成虫盘和腿成虫盘的pygo表达水平 ,则在翅成虫盘和腿成虫盘pygo的表达水平相对较高。     

云南茶树上的附生地衣

对云南茶叶农场中的附生地衣进行调查发现: 附生在茶树上的地衣有25 属, 51 种; 其中, 45 种是首次报道附生在茶树上, 包括2 个中国新记录种: 癞屑衣( Lepraria lobificans) 和阿曼原胚衣( Protoblastenia amagiensis) , 以及20 个云南新分布种。壳状地衣的共生菌丝侵入茶叶树干外皮层组织, 在生长过程中产生地衣酸, 一定程度的加速了农场中茶树的老化; 靠近茶树发芽点生长的壳状地衣和叶状地衣, 造成芽体发育不良, 对茶叶的产量和品质有一定影响。     

宁夏沙坡头地区中国新记录地衣（英文）

报道了宁夏沙坡头沙漠地区地衣3个中国新记录种:Fulgensia desertorum,Rinodina bischoffii和Seirophora orientalis,描述了3种地衣的表型特征,生态学特征及分布情况。     

Room for improvement in conducting and reporting non-inferiority randomized controlled trials on drugs: a systematic review

Background

A non-inferiority (NI) trial is intended to show that the effect of a new treatment is not worse than the comparator. We conducted a review to identify how NI trials were conducted and reported, and whether the standard requirements from the guidelines were followed.

Methodology and Principal Findings

From 300 randomly selected articles on NI trials registered in PubMed at 5 February 2009, we included 227 NI articles that referred to 232 trials. We excluded studies on bioequivalence, trials on healthy volunteers, non-drug trials, and articles of which the full-text version could not be retrieved. A large proportion of trials (34.0%) did not use blinding. The NI margin was reported in 97.8% of the trials, but only 45.7% of the trials reported the method to determine the margin. Most of the trials used either intention to treat (ITT) (34.9%) or per-protocol (PP) analysis (19.4%), while 41.8% of the trials used both methods. Less than 10% of the trials included a placebo arm to confirm the efficacy of the new drug and active comparator against placebo, and less than 5.0% were reporting the similarity of the current trial with the previous comparator''s trials. In general, no difference was seen in the quality of reporting before and after the release of the CONSORT statement extension 2006 or between the high-impact and low-impact journals.

Conclusion

The conduct and reporting of NI trials can be improved, particularly in terms of maximizing the use of blinding, the use of both ITT and PP analysis, reporting the similarity with the previous comparator''s trials to guarantee a valid constancy assumption, and most importantly reporting the method to determine the NI margin.