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.     

构建数字化、可视化教学平台实现妇产科学教学手段多元化

介绍了构建数字化、可视化教学平台,实现妇产科教学手段多元化的做法。内容包括多媒体课件开发制作,利用医学视听教材,建设妇产科图片数据库,建设妇产科标本库(馆),利用模型、模块进行模拟操作,加强实践技能培养和通过临床见习、实习将理论应用于实践等问题。     

The Impact of Community Diversity and Consolidated Inequality on Dropping Out of High School

Abstract: Data from the National Education Longitudinal Study were combined with census data at the zip code level to examine the impact of neighborhood racial and ethnic diversity and consolidated inequality, in addition to individual, family, and school factors, on the likelihood of dropping out of high school. Results indicate that while the effects for diversity and consolidated inequality did not support the stated hypotheses, main effects for family risk and prior academic achievement were significant and in the stated direction. Also, when controlling for individual, family, school, and neighborhood characteristics, African Americans were less likely than White students to drop out of school. Implications for contextual effects research and educational outcomes are discussed.     

COPD机械通气病人下呼吸道感染致病菌分布特点

①目的 探讨慢性阻塞性肺病(COPD)病人机械通气后下呼吸道感染致病菌的特点。②方法 取32例COPD并发呼吸衰竭行机械通气病人下呼吸道分泌物做痰细菌学培养，同时做药物敏感试验。③结果 32例病人共分离出菌株76株，阳性率71．7％，其中混合感染10例次。其中革兰阴性杆菌(GNB)58株，占76．3％；阳性球菌10株，占13．2％；真菌8株，占10．5％。常见致病菌以铜绿假单胞菌、鲍曼不动杆菌和肺炎杆菌为主，GNB中铜绿假单胞菌和不动杆菌的耐药率高。④结论 COPD应用机械通气病人下呼吸道感染以革兰阴性杆菌为主，耐药性高。     

The nature of polymorphism of the HLA-DRB intron sequences is lineage specific

Abstract: The sequence database of HLA-DRB genes is mainly derived from mRNA analysis or has focused exclusively on the polymorphism of the 2nd exon. Little is known about the non-coding sequences of the different DRB alleles which represent about 94% of the genes. In this study we have determined the sequence of the 3' 500 bp intron 1 fragment adjacent to exon 2 in all serologically defined HLA-DRB genes and their most frequent allelic subtypes. The intron sequences turned out to be highly polymorphic. Similar to the class I introns, this variability was not characterized by random point mutations but by a highly systematic diversity reflecting the lineage-specific relationship of the HLA-DR alleles. With a few exceptions in DRB1*15, 13 and 08 as well as DRB 4 and 5, the variability mirrors the serological diversity. As well as delivering insight into the genetic relationship between the different DRB alleles, these sequences will provide an extremely valuable basis for developing advanced DRB sequencing strategies for clinical purposes.     

Hepatitis B virus genetic diversity and its impact on diagnostic assays

Summary.  Hepatitis B virus (HBV) circulates in blood as closely related, but genetically diverse molecules called quasispecies. During replication, HBV production may approach 10¹¹ molecules/day, although during peak activity this rate may increase 100–1000 times. Generally, DNA polymerases have excellent fidelity in reading DNA templates because they are associated with an exonuclease which removes incorrectly added nucleotides. However, the HBV-DNA polymerase lacks fidelity and proofreading function partly because exonuclease activity is either absent or deficient. Thus, the HBV genome and especially the envelope gene, is mutated with unusually high frequency. These mutations can affect more than one open reading frame because of overlapping genes. The S gene contains an exposed major hydrophilic region (residues 110–155), which encompasses the 'a' determinant that is important for inducing immunity. Nucleotide substitutions in this region are common and result in reduced binding or failure to detect hepatitis B surface antigen (HBsAg) in diagnostic assays. Adaptive immunity also depends on the recognition of HBsAg by specific antibody and variants pose a threat if they interfere with binding to antibody. Finally, genomic hypervariability allows HBV to escape selection pressures imposed by antiviral therapies, vaccines and the host immune system, and is responsible for creating genotypes, subgenotypes and subtypes.     

Microbial aspects of home enteral nutrition–a discussion

Factors that might contribute to the microbial contamination of enteral feeds prepared and administered in the home are reviewed and the significance of this contamination discussed. Numbers, types and sources of micro-organisms, and possible routes for contamination of home enteral feeds, are outlined and the role of cleaning and disinfection in reducing the microbial load is discussed. Some preliminary guidelines are suggested for the handling of enteral feeds in the home.     

Ethnic Minorities, Migration and Risk of Undernutrition in Children

Well-controlled, comparative studies suggest that in "food rich" or "resource rich" environments, ethnic minority status is not an independent risk factor for malnutrition. In England, Australia, and the United States, nutrient intake, nutritional status measures and growth are comparable between children of ethnic minorities and non-minority children of similar economic status. Children of recent immigrants are an exception to this generalization, suggesting that recent arrival in a new environment is a risk factor for malnutrition. Family-level studies of intraethnic diversity are required to develop more sensitive and specific profiles of risk factors for malnutrition.     

Multicultural Health Care in Practice

This study presents a first assessment of the challenges faced by Dutch health care providers dealing with the increasing cultural diversity in Dutch society. Qualitative interviews with 24 Dutch caregivers and policy-makers point to a number of important difficulties encountered when confronted with the growing diversity of patient populations. The study focuses explicitly on the challenges health care providers perceive in their direct interactions with patients. On the basis of the observations of the 24 respondents five strategies were formulated to improve the delivery of care in a multicultural environment. Their findings were further evaluated by confronting the empirical data with care-ethical notions (attentiveness, responsibility, competence, and responsiveness) and intercultural communication-theory.