黄热病的再流行与世界卫生组织的消除黄热病流行战略

近年来,蚊虫传播的黄热病在非洲和南美洲地区大面积“再流行”,仅南美洲的巴西在一年时间就发现数千例黄热病确诊病例,黄热病已经在非洲和南美洲地区造成巨大的公共卫生负担。此外,在黄热病非流行国家和地区发现大量输入性病例,使得黄热病有可能在非洲和南美洲以外的地区成为“新发传染病”而在世界更大范围流行。为此,世界卫生组织制定了“消除黄热病流行（EYE）”战略,预计利用10年时间在黄热病流行地区接种13.8亿剂量黄热疫苗,以降低黄热病对国际公共卫生健康的危害。     

Molecular characterization of the 17D-204 yellow fever vaccine

IntroductionThe worldwide use of yellow fever (YF) live attenuated vaccines came recently under close scrutiny as rare but serious adverse events have been reported. The population identified at major risk for these safety issues were extreme ages and immunocompromised subjects. Study NCT01426243 conducted by the French National Agency for AIDS research is an ongoing interventional study to evaluate the safety of the vaccine and the specific immune responses in HIV-infected patients following 17D-204 vaccination. As a preliminary study, we characterized the molecular diversity from E gene of the single 17D-204 vaccine batch used in this clinical study.Materials and methodsEight vials of lyophilized 17D-204 vaccine (Stamaril^®, Sanofi-Pasteur, Lyon, France) of the E5499 batch were reconstituted for viral quantification, cloning and sequencing of C/prM/E region.ResultsThe average rate of virions per vial was 8.68 ± 0.07 log₁₀ genome equivalents with a low coefficient of variation (0.81%). 246 sequences of the C/prM/E region (29–33 per vials) were generated and analyzed for the eight vials, 25 (10%) being defective and excluded from analyses. 95% of sequences had at least one nucleotide mutation. The mutations were observed on 662 variant sites distributed through all over the 1995 nucleotides sequence and were mainly non-synonymous (66%). Genome variability between vaccine vials was highly homogeneous with a nucleotide distance ranging from 0.29% to 0.41%. Average p-distances observed for each vial were also homogeneous, ranging from 0.15% to 0.31%.ConclusionThis study showed a homogenous YF virus RNA quantity in vaccine vials within a single lot and a low clonal diversity inter and intra vaccine vials. These results are consistent with a recent study showing that the main mechanism of attenuation resulted in the loss of diversity in the YF virus quasi-species.     

How Frequent Are Asthma Exacerbations in a Pediatric Primary Care Setting and Do Written Asthma Action Plans Help in Their Management?

Purpose. In the National Heart, Lung, and Blood Institute Guidelines for the Diagnosis and Management of Asthma, the expert panel recommends that a written asthma action plan be provided for all patients with asthma. Studies evaluating the usefulness of the asthma action plan in children are limited. We aim to determine exacerbation frequency and usefulness of the asthma action plan in managing exacerbations that occur in a pediatric primary care setting. Methods. Caretakers of asthmatic children attending the general pediatric clinic in an inner-city hospital completed a one-page questionnaire covering topics such as asthma severity, frequency of exacerbations, and possession/usefulness of an asthma action plan. Although controversy exists over the definition of yellow and red zone exacerbations, we defined the yellow zone as symptoms that require albuterol more than three times a day or more than two nights in succession. The red zone was defined as symptoms requiring systemic corticosteroids and/or an urgent physician visit. Results. Seventy of 75 subjects completed the survey. Almost 80% of respondents carried the diagnosis of persistent asthma, whereas the remainder had intermittent asthma. Exacerbation frequency over a 3-month period was determined. Approximately 80% of children experienced at least one yellow zone episode: 42% had one or two yellow zone episodes, and 39.6% had between three and five episodes. Sixty-three percent of patients did not experience a single red zone exacerbation. Almost 75% (44 of 59) of subjects possessed an asthma action plan. Ninety percent (37 of 41) of respondents with action plans found the plan to be useful in managing exacerbations. Conclusion. Approximately four of every five asthmatic children seen in this primary care setting experienced a yellow zone exacerbation at least once during a 3-month period. One third experienced at least one red zone episode. Nine of every 10 caretakers with an action plan reported the asthma action plan to be of value in managing exacerbations.     

水前房角镜学的使命

水前房角镜学是新建的眼科学的一个分野,为眼科疾患病人服务是她的使命。水前房角镜学的最大优点是其含金量能百分之百地转化为读者的受益。     

51例黄磷烧伤临床分析

对５１例黄磷烧伤病人进行临床分析。结果表明：黄磷对人体毒性大，即使烧伤面积不大，亦可因磷中毒而丧。磷中毒易造成肾、肝等裨性器官的损害。硫酸铜用于烧伤创面用量过大易引起铜中毒致急性溶血性贫血，不可作为黄磷 伤的创面用工。     

Yellow fever virus strains Asibi and 17D-204 infect human umbilical cord endothelial cells and induce novel changes in gene expression

Yellow fever (YF) is a zoonotic infection with more than 200,000 cases reported annually. Relatively little is known about YF pathogenesis in humans. In this study, we demonstrate that human vascular endothelial cells are susceptible to infection with wild-type and vaccine strains of the YFV and that these infections lead to a differential cellular response to infection. The infection of endothelial cells with either virus resulted in a significant induction of interferon-inducible genes p 78 and Cig 5 while wild-type virus induced a much more pronounced IL 6 and Bc l2 response than did the vaccine strain. Both viruses induced RANTES gene expression, but only the wild-type virus had corresponding increases in RANTES protein expression. The results demonstrate that the wild-type and vaccine strains of YFV elicit significantly different responses to infection in endothelial cells, despite being nearly identical genetically. These differences may account for the attenuated phenotype of the YFV vaccine strain, though the mechanism remains unclear. These data also point to a role for vascular endothelial cells in YF hemorrhagic fever and also suggest that IL 6 may play a role in increased viral pathogenesis, perhaps by influencing coagulation via release of coagulation co-factors such as fibrin or fibrinogen.     

大鼠运动皮层投射神经元与Parvalbumin免疫阳性神经纤维终末的关系──免疫荧光、Confocal显微镜观察

Parvalburnin是细胞内一种钙结合蛋白。同时又可作为中枢神经系统内与GABA共存的神经元亚群的特异标记物，主要标记篮状及苔烛细胞。用PAP方谈染色可见大鼠Parvalbumin免疫阳性神经终末在运动皮层锥体神经元胞体周围形成包篮现象，但因该方法的局限性．较难明确二者的关系。为进一步了解Parvalbumin阳性终未在锥体神经元脑体、树突与轴突整体上的分布状况以及运幼皮层内不同传出神经元是否均接受同样的支配，本实验利用FastBlue送行标记、固定脑片细胞内注入LueiferYellow结合免疫荧光、Confocal显微镜观察，研究运动皮层内皮质丘脑（束旁核）、皮质效状体及皮质脊髓三种投射神经元与Parvalbumin阳性终末的关系。通过1．μ连续扫描图像的分析及立体对观察，Parvalbumin阳性终末清晰可见，与LuciferYellow标记的锥体细胞的关系也容易辨别．在三种投射神经元胞体上均可见Parvalbumin阳性终末包绕，形成明显包篮现象，但三种神经元上的终末数未见明显区别·阳性终未还分布于近端树突上，距胞体越远越稀疏：但在距脑体50μm以上的顶树突、30μm以上的基树突及其二、三级分枝的远端树突上仍偶有终末分布．此外，三种神经元轴突起始段上也有少量终末接触，但未形成明显的cartridge现象．这一结果揭示，Parvalb     

The RNA helicase, nucleotide 5'-triphosphatase, and RNA 5'-triphosphatase activities of Dengue virus protein NS3 are Mg2+-dependent and require a functional Walker B motif in the helicase catalytic core

The nonstructural protein 3 (NS3) of Dengue virus (DV) is a multifunctional enzyme carrying activities involved in viral RNA replication and capping: helicase, nucleoside 5'-triphosphatase (NTPase), and RNA 5'-triphosphatase (RTPase). Here, a 54-kDa C-terminal domain of NS3 (DeltaNS3) bearing all three activities was expressed as a recombinant protein. Structure-based sequence analysis in comparison with Hepatitis C virus (HCV) helicase indicates the presence of a HCV-helicase-like catalytic core domain in the N-terminal part of DeltaNS3, whereas the C-terminal part seems to be different. In this report, we show that the RTPase activity of DeltaNS3 is Mg2+-dependent as are both helicase and NTPase activities. Mutational analysis shows that the RTPase activity requires an intact NTPase/helicase Walker B motif in the helicase core, consistent with the fact that such motifs are involved in the coordination of Mg2+. The R513A substitution in the C-terminal domain of DeltaNS3 abrogates helicase activity and strongly diminishes RTPase activity, indicating that both activities are functionally coupled. DV RTPase seems to belong to a new class of Mg2+-dependent RTPases, which use the active center of the helicase/NTPase catalytic core in conjunction with elements in the C-terminal domain.     

Dye-coupled magnocellular peptidergic neurons of the rat paraventricular nucleus show homotypic immunoreactivity

Magnocellular neurons in rat hypothalamic slices are known to exhibit dye coupling: the transfer of the fluorescent dye, Lucifer Yellow, from an intracellularly-injected neuron to one or more nearby neurons. The question of the hormonal identity of coupled cells and the possibility of dye coupling as an artefact led us to determine the immunoreactivity of dye-coupled magnocellular neurons in the paraventricular nucleus of the rat hypothalamus using antisera to oxytocin- and vasopressin-associated neurophysins. In 23 pairs, one triplet, and one quadruplet, immunoreactivity to one or the other antiserum was always exclusive, and dye coupling was always homotypic, that is, coupled neurons in each instance were reactive to the same antiserum. The quadruplet, triplet and 17 pairs were immunoreactive to vasopressin-associated neurophysin, and oxytoxin-associated neurophysin immunoreactivity was observed in the remaining pairs. Immunoreactivity to each antiserum was found for somasomatic and non somasomatic modes of coupling and for coupled neurons in the three magnocellular areas of the nucleus. A relationship between mode of coupling and hormone content was not detected. The data support the hypothesis that coupling is a real, functionally significant mechanism for coordinating neuronal activity in this nucleus, particularly under conditions of high hormone demand. They do not support the idea that coupling is artefact. The possibility of a relationship between hormone content and mode of coupling, and the projection pathway(s) of the coupled neurons of each type require further study.