Economic Costs of Childhood Diseases and Disabilities Attributable to Environmental Contaminants in Washington State, USA

This study estimates the economic costs associated with childhood diseases and disabilities attributable to environmental contaminants in Washington State, USA, including asthma, cancer, lead exposure, birth defects, and neurobehavioral disorders. The estimates are based on “cost of illness” models that include direct healthcare costs and indirect costs. The estimates are also based on an “environmentally attributable fraction” model which quantifies the proportions of each disease or disability that can reasonably be attributed to environmental contaminants. The study concludes that the annual cost of selected childhood diseases and disabilities attributable to environmental contaminants in Washington State is $1875 million in 2004 $, comprising $310.6 million in direct healthcare costs and $1565 million in indirect costs, and with a range of $1600–$2200 million a year. These estimates are consistent with other studies. Like the previous studies, a significant proportion of the estimated costs can be attributed to lead exposure. This estimate is equivalent to about 0.7% of the total Washington Gross State Product, and the estimated direct healthcare costs are equivalent to at least 0.2% of the total Washington State health expenditures. These costs could be lessened or prevented if exposures to environmental contaminants were reduced or eliminated. This study argues for the need for an ecosystem approach to human health in which the condition of the environment, in terms of exposures to environmental contaminants, must be addressed taking a systemic perspective.     

Remote sensing and geographic information systems in the spatial temporal dynamics modeling of infectious diseases

Similar to species immigration or exotic species invasion,infectious disease transmis-sion is strengthened due to the globalization of human activities. Using schistosomiasis as an exam-ple,we propose a conceptual model simulating the spatio-temporal dynamics of infectious diseases. We base the model on the knowledge of the interrelationship among the source,media,and the hosts of the disease. With the endemics data of schistosomiasis in Xichang,China,we demonstrate that the conceptual model is feasible; we introduce how remote sensing and geographic information systems techniques can be used in support of spatio-temporal modeling; we compare the different effects caused to the entire population when selecting different groups of people for schistosomiasis control. Our work illustrates the importance of such a modeling tool in supporting spatial decisions. Our mod-eling method can be directly applied to such infectious diseases as the plague,lyme disease,and hemorrhagic fever with renal syndrome. The application of remote sensing and geographic informa-tion systems can shed light on the modeling of other infectious disease and invasive species studies.     

健康教育对心脑血管疾病终点事件发生的干预效应

通过健康教育干预探讨对心脑血管疾病发生之影响,为心脑血管疾病的防治工作提供理论依据。方法：从2000年到我院集中体检的大于50岁以上的在职和离退休干部4000人中,抽出资料完整并符合本次研究纳入标准者2000人,随机分为健康干预组和一般治疗对照组各1000人。其中干预组1000人中,高血压480人,高脂血症413人,高血压合并高脂血症107人;对照组1000人中,高血压478人,高脂血症423人．高血压合并高脂血症100人。两组均以高血压、高脂血症作为最主要的危险因素进行健康教育干预。健康教育干预组患者分别建立健康档案,制定系统的健康教育干预措施并组织实施,定期随访：一般治疗对照组患者将体检结果通知本人后,由其在门诊接受健康教育和治疗,对健康教育和治疗方法不作强制性规定。连续观察五年,比较两组五年间心脑血管疾病的发生情况（即以发生AMI／心绞痛、脑出血、脑血栓形成等心脑血管疾病的终点事件为评价标准）。结果：健康教育干预组病情控制良好,发生上述心脑血管疾病终点事件比危险因素对照组明显减少（急性心肌梗塞发生率为2．0％比3．4％,脑血栓发生率为4．3％比7．5％,TIA为2．1％比2．9％）,P〈0．01。结论：对存在心脑血管疾病危险因素者积极开展健康教育干预,可起到控制疾病进一步发展,减少心脑血管疾病终点事件的发生。     

Using budding yeast to screen for anti-prion drugs

Prions are misfolded proteins capable of propagating their altered conformation which are commonly considered as the causative agent of transmissible spongiform encephalopathies, a class of fatal neurodegenerative diseases. Currently, no treatment for prion-based diseases is available. Recently we have developed a rapid, yeast-based, two-step assay to screen for anti-prion drugs [1]. This new method allowed us to identify several compounds that are effective in vivo against budding yeast [PSI+] and [URE3] prions but also able to promote mammalian prion clearance in three different cell culture-based assays. Taken together, these results validate our method as an economic and efficient high-throughput screening approach to identify novel prion inhibitors or to carry on comprehensive structure-activity studies for already isolated anti-mammalian prion drugs. These results suggest furthermore that biochemical pathways controlling prion formation and/or maintenance are conserved from yeast to human and thus amenable to pharmacological and genetic analysis. Finally, it would be very interesting to test active drugs isolated using the yeast-based assay in models for other diseases (neurodegenerative or not) involving amyloid fibers like Huntington's, Parkinson's or Alzheimer's diseases.     

Central obesity as a risk factor for prostatic hyperplasia

Objective: Obesity‐related metabolic diseases may influence prostatic hyperplasia. This study examined the impact of obesity on prostate volume in men without overt obesity‐related metabolic diseases. Research Methods and Procedures: We recruited 146 men over the age of 40 years who did not have overt obesity‐related diseases, such as diabetes, impaired fasting glucose, hypertension, or dyslipidemia. Transrectal ultrasonography was performed on all subjects. The subjects were divided into three groups according to their BMI: normal (18.5 to 22.9 kg/m²), overweight (23 to 24.9 kg/m²), and obese (≥25 kg/m²), and two groups according to their waist circumference: normal waist (≤90 cm) and central obesity (>90 cm). The classification of the subgroups was based on the Asia‐Pacific criteria of obesity. We compared the prostate volume among subgroups and assessed factors related to prostatic hyperplasia. Results: Mean prostate volume was 18.8 ± 5.0, 21.8 ± 7.2, and 21.8 ± 5.6 mL in the normal, overweight, and obese groups, respectively, and was 20.0 ± 5.9 and 23.7 ± 5.3 mL in the normal waist and central obesity group, respectively. Prostate volume was significantly greater in the obese group than in the normal group (P = 0.03) and in the central obesity group compared with the normal waist group (P = 0.002). Prostate volume was positively correlated with BMI and waist circumference after adjustment for age. After adjusting for confounding factors, central obesity was an independent factor affecting prostatic hyperplasia, which was defined as a prostate volume >20 mL (odds ratio = 3.37, p = 0.037). Relative to men with both low BMI (18.5 to 22.9 kg/m²) and normal waist circumference, those with high BMI (≥25 kg/m²) and central obesity were at significantly increased risk of prostatic hyperplasia (odds ratio = 4.88, p = 0.008). However, those with high BMI (≥25 kg/m²) and normal waist circumference were not at significantly increased risk. Discussion: Prostate volume was greater in the obese and central obesity groups than in the normal group after patients with overt obesity‐related metabolic diseases were excluded. Although both BMI and waist circumference were positively correlated with prostate volume, central obesity was the only independent factor affecting prostate hyperplasia. We suggest that central obesity is an important risk factor for prostatic hyperplasia.     

线粒体融合蛋白2与心血管疾病

线粒体融合蛋白2(mitofusin2,Mfn2)不仅是一种不可或缺的调控线粒体形态和功能的动力素(dynamin)相关蛋白,还是一个重要的细胞内信号分子,参与调控细胞增殖、分化、凋亡等生命过程。Mfn2与高血压、冠状动脉腔内成形术后再狭窄、动脉粥样硬化、心肌肥厚、心肌氧化损伤等多种心血管疾病的病理生理过程密切相关,并通过调节物质代谢影响糖尿病和胰岛素抵抗等的发病。此外,Mfn2还可能是心血管疾病的一个重要的分子标志和治疗靶分子。     

CDK5 phosphorylates eNOS at Ser‐113 and regulates NO production

Phosphorylation of endothelial nitric oxide synthase (eNOS) is key mechanism in response to various forms of cellular stimulation. Through protein nitration by peroxynitrite, eNOS is believed to be responsible for the major abnormalities in several important neurodegenerative diseases including Alzheimer's (AD) and Parkinson's diseases (PD). Recent studies provide important in vivo evidence that hyperactivation of Cdk5 by p25 plays an essential role in the cell death of neurons in experimental models of AD and PD. This study focuses on the functional regulation of eNOS by Cdk5/p35 complex in a phosphorylation dependent manner. Our results showed that Cdk5 can phosphorylate eNOS both in vitro and in vivo. In vitro kinase assay together with the bioinformatic analysis and site direct mutagenesis revealed that Ser‐113 is the major phosphorylation site for Cdk5. Most interestingly, the nitrite production was significantly reduced in eNOS and Cdk5/p35 co‐transfected SH‐SY5Y cells when compared with co‐transfection of Cdk5/p35 and S113A. Together, our data suggest that Cdk5 can phosphorylate eNOS at the Ser‐113 site and down‐regulate eNOS‐derived NO levels. J. Cell. Biochem. 110: 112–117, 2010. © 2010 Wiley‐Liss, Inc.     

Chemical synthesis and characterization of wild‐type and biotinylated N‐terminal domain 1–64 of β2‐glycoprotein I

The antiphospholipid syndrome (APS) is a severe autoimmune disease associated with recurrent thrombosis and fetal loss and characterized by the presence of circulating autoantibodies (aAbs) mainly recognizing the N‐terminal domain (DmI) of β2‐glycoprotein I (β2GpI). To possibly block anti‐β2GpI Abs activity, we synthesized the entire DmI comprising residues 1–64 of β2GpI by chemical methods. Oxidative disulfide renaturation of DmI was achieved in the presence of reduced and oxidized glutathione. The folded DmI (N‐DmI) was purified by RP‐HPLC, and its chemical identity and correct disulfide pairing (Cys4‐Cys47 and Cys32‐Cys60) were established by enzymatic peptide mass fingerprint analysis. The results of the conformational characterization, conducted by far‐ and near‐UV CD and fluorescence spectroscopy, provided strong evidence for the native‐like structure of DmI, which is also quite resistant to both Gdn‐HCl and thermal denaturation. However, the thermodynamic stability of N‐DmI at 37°C was remarkably low, in agreement with the unfolding energetics of small proteins. Of note, aAbs failed to bind to plates coated with N‐DmI in direct binding experiments. From ELISA competition experiments with plate‐immobilized β2GpI, a mean IC₅₀ value of 8.8 μM could be estimated for N‐DmI, similar to that of the full‐length protein, IC₅₀(β2GpI) = 6.4 μM, whereas the cysteine‐reduced and carboxamidomethylated DmI, RC‐DmI, failed to bind to anti‐β2GpI Abs. The versatility of chemical synthesis was also exploited to produce an N‐terminally biotin‐(PEG)₂‐derivative of N‐DmI (Biotin‐N‐DmI) to be possibly used as a new tool in APS diagnosis. Strikingly, Biotin‐N‐DmI loaded onto a streptavidin‐coated plate selectively recognized aAbs from APS patients.     

雌激素受体与神经系统疾病

雌激素受体是类固醇激素受体超家族成员之一,是一种配体依赖性转录因子,具有广泛的生物学功能。雌激素受体在脑内具有广泛的分布,且与一些神经系统疾病的发生发展相关。就雌激素受体在脑内的分布及其与神经系统疾病的关系进行论述。     

Studies on the structural stability of rabbit prion probed by molecular dynamics simulations of its wild-type and mutants

Prion diseases are invariably fatal and highly infectious neurodegenerative diseases that affect humans and animals. Rabbits are the only mammalian species reported to be resistant to infection from prion diseases isolated from other species (Vorberg et al., 2003). Fortunately, the NMR structure of rabbit prion (124-228) (PDB entry 2FJ3), the NMR structure of rabbit prion protein mutation S173N (PDB entry 2JOH) and the NMR structure of rabbit prion protein mutation I214V (PDB entry 2JOM) were released recently. This paper studies these NMR structures by molecular dynamics simulations. Simulation results confirm the structural stability of wild-type rabbit prion, and show that the salt bridge between D177 and R163 greatly contributes to the structural stability of rabbit prion protein.