Development of a high-growth enterovirus 71 vaccine candidate inducing cross-reactive neutralizing antibody responses

Although Enterovirus 71 (EV71) has only one serotype based on serum neutralization tests using hyperimmune animal antisera, three major genogroups (A, B and C) including eleven genotypes (A, B1-B2, and C1-C5) can be well classified based on phylogenetic analysis. Since 1997, large-scale EV71 epidemics occurred cyclically with different genotypes in the Asia-Pacific region. Therefore, development of EV71 vaccines is a national priority in several Asian countries. Currently, five vaccine candidates have been evaluated in clinical trials in China (three C4 candidates), Singapore (one B2 candidate), and Taiwan (one B4 candidate). Overall, the peak viral titers of these 5 vaccine candidates could only reach about 10⁷ TCID₅₀/mL. Moreover, genotypes of these 5 candidates are different from the current predominant genotype B5 in Taiwan and South-Eastern Asia. We adapted a high-growth EV71 genotype B5 (HG-B5) virus after multiple passages and plaque selections in Vero cells and the HG-B5 virus could reach high titers (>10⁸ TCID₅₀/mL) in a microcarrier-based cell culture system. The viral particles were further purified and formulated with alum adjuvant. After two doses of intramuscular immunization in rabbits, the HG-B5 vaccine candidate could induce cross-reactive neutralizing antibodies against the three major EV71 genogroups. In conclusion, a high-growth EV71 virus was successfully adapted in Vero cells and could induce broad spectrum neutralizing antibody titers against three (A, B5, and C4) genotypes in rabbits.     

Population structure and drug resistance patterns of emerging non-PCV-13 Streptococcus pneumoniae serotypes 22F, 15A,and 8 isolated from adults in Ontario,Canada

The introduction of pneumococcal conjugate vaccines has led to the emergence of non-vaccine serotypes, which contributed to invasive pneumococcal disease in Canada and worldwide. A significant increase in the prevalence of non-13-valent pneumococcal conjugate vaccine (PCV-13)-included serotypes 22F, 15A, and 8 was observed from 2009 to 2013 in Ontario (all p values < 0.01). In this study, whole genome sequencing was conducted on the 25 isolates of serotype 22F, seven of 15A and 10 of 8 to investigate the population structure and antibiotic resistance. All seven serotype 15A isolates were found to be multidrug resistant. From whole genome analysis, we observed recombination events among serotypes 22F, 15A and 8 populations. Serotype 22F (ST433) has emerged into two sub-populations, with 28% (7/25) exhibiting recombination events, and five also acquiring macrolide resistance as a result of recombination. This study enhances the knowledge on the molecular evolution of emerging non-PCV-13 vaccine serotype 22F, including acquisition of resistance genes through recombination events. It underpins the importance of whole genome sequencing in studying Streptococcus pneumoniae population structures and dynamics, and its utility in molecular surveillance.     

Potential Overtreatment and Undertreatment of Type 2 Diabetes Mellitus in Long-Term Care Facilities: A Systematic Review

ObjectiveTo investigate the prevalence, outcomes, and factors associated with potential glycemic overtreatment and undertreatment of type 2 diabetes mellitus (T2DM) in long-term care facilities (LTCFs).DesignSystematic review.Setting and ParticipantsResidents with T2DM and aged ≥60 years living in LTCFs.MeasuresArticles published between January 2000 and September 2020 were retrieved following a systematic search of MEDLINE, EMBASE, Cochrane Library, CINAHL plus, and gray literature. Inclusion criteria were the reporting of (1) potential overtreatment and undertreatment quantitatively defined (implicitly or explicitly) based on hemoglobin A1c (HbA1c) and/or blood glucose; (2) prevalence, outcomes, and associated factors of potential glycemic overtreatment and undertreatment; and (3) the study involved residents of LTCFs.ResultsFifteen studies were included. Prevalence of potential overtreatment (5%–86%, n = 15 studies) and undertreatment (1.4%–35%, n = 8 studies) varied widely among facilities and geographical locations, and according to definitions used. Prevalence of potential overtreatment was 16%–74% when defined as treatment with a glucose-lowering medication in a resident with ≥1 hypoglycemia risk factor or serious comorbidity, together with a HbA1c <7% (n = 10 studies). Potential undertreatment was commonly defined as residents on glucose-lowering medication having HbA1c >8.5% and the prevalence 1.4%–14.8% (n = 6 studies). No studies prospectively measured resident health outcomes from overtreatment and undertreatment. Potential overtreatment was positively associated with use of oral glucose-lowering medications, dementia diagnosis or dementia severity, and/or need for assistance with activities of daily living (n = 2 studies). Negative association was found between potential overtreatment and use of insulin/combined insulin and oral glucose-lowering medication. No studies reported factors associated with potential undertreatment.Conclusions and ImplicationsThe prevalence of potential glycemic overtreatment and undertreatment varied widely among residents with T2DM depending on the definition(s) used in each study. Longitudinal studies examining associations between glycemic management and health outcomes, and the use of consensus definitions of overtreatment and undertreatment are required to establish findings about actual glycemic overtreatment and undertreatment in LTCFs.     

Safety evaluation of metal exposure from commonly used moisturizing and skin-lightening creams in Nigeria

The concentrations of ten metals (Cd, Pb, Ni, Cr, Cu, Co, Fe, Mn, Zn and Al) were measured in some commonly used moisturizing and skin-lightening creams in Nigeria with a view to providing information on the risk of exposure to metals from the use of these products. The metal concentrations in these products were measured by atomic absorption spectrometry after acid digestion of the samples. The measured concentrations of metals in the skin moisturizing creams ranged from <0.15 to 6.3 μg/g Cd, <0.02 to 17.5 μg/g Cu, 2.25 to 6.25 μg/g Cr, <0.25 to 124.3 μg/g Al, 0.2 to 7.3 μg/g Pb, <0.03 to 10.7 μg/g Ni, 17.3 to 372.0 μg/g Zn, <0.02 to 1.0 μg/g Co, 17.75 to 28.8 μg/g Mn, <0.1 to 89.8 μg/g Fe while the concentrations of metals in the skin-lightening products ranged from <0.15 to 16.5 μg/g Cd, <0.02 to 10.0 μg/g Cu, 4.25 to 8.0 μg/g Cr, <0.25 to 128.0 μg/g Al, 0.5 to 4.5 μg/g Pb, <0.03 to 1.65 μg/g Ni, 24.7 to 267.5 μg/g Zn, <0.02 to 2.5 μg/g for Co, 19.3 to 31.8 μg/g Mn, 9.5 to 211.63 μg/g Fe. In a significant number (>93%) of the samples investigated the concentrations of Pb, Cd, Ni and Co were below the specified limit, or the maximal limit for impurities in colour additives in cosmetics for external use. However, Cr was found at concentrations above the allergenic limit of 1 μg/g. The results also showed that skin-lightening creams contained higher concentrations of the studied metals than the moisturizing creams, except for Ni, which indicates that persons who uses skin-lightening creams in preference to moisturizing ones, are exposed to higher concentrations of metals.     

上海市闵行区2013年HIV-1分子流行病学研究

目的了解上海市闵行区艾滋病病毒(HIV)感染者特征和HIV基因亚型情况。方法上海市闵行区2013年首次确诊为HIV阳性的感染者血清,应用巢氏PCR扩增pol基因,使用HIV-Blast软件判定亚型;Mega 5.1软件将待分析序列与国际参考株序列比对,采用Neighbor-Joining(N-J)法构建系统进化树。应用SPSS 17.0软件,对计数数据采用χ2检验和Fisher′s精确概率计算法进行比较,P0.05为差异有统计学意义。结果有101例感染者纳入研究,成功扩增86例(85.15%)患者的pol基因。共发现6种亚型:CRF01_AE、CRF07_BC、RF08_BC、B、CC和CRF01_AE/B。CRF01_AE是最主要的亚型(60.47%,52/86),其次是CRF07_BC(27.91%,24/86)。感染者均由性途径传播,其中同性传播占63.95%(55/86),异性传播占36.05%(31/86)。结论同性传播是闵行区HIV感染的主要传播途径。流动人口聚集,带来的流行毒株多样化已经成为闵行区HIV的流行特点,应加强对HIV亚型变异的监测。     

The diffusion of autism spectrum disorder in Costa Rica: Evidence of information spread or environmental effects?

In the U.S., children with autism spectrum disorder (ASD) have been found to live in spatial clusters. Studies have suggested that the clustering is caused by social or environmental factors, but determining the cause of the clustering is difficult in the U.S. setting because of unmeasured variation in healthcare access and diagnostic practices. The present study explores the diffusion of ASD in a small setting in which the diagnosis is not widely publicised and there is no variation in healthcare access or diagnostic practices. Costa Rica provides universal healthcare and only has one diagnosing clinic for young children, and the diagnosis is relatively new and little known among clinicians and parents. In addition, the potential for mercury exposure from the source that has been associated with ASD is absent, and areas with high levels of air pollution are spatially concentrated. Focusing on all young children who underwent an ASD assessment from 2010 to 2013, we identify spatial clusters that suggest a mechanism that does not depend on information about ASD, healthcare access, diagnostic practices, or environmental toxicants. These findings provide details of the “contextual drivers” of the increasing worldwide prevalence of ASD.     

应用气-液界面染毒技术研究柴油机尾气对16HBE细胞的毒性作用

[目的]应用气-液界面染毒技术探索柴油机尾气对人支气管上皮(16HBE)细胞急性毒性作用. [方法]在流速为20 mL/min,37℃的条件下,用柴油机尾气分别对生长在多孔膜上的16HBE细胞持续染毒5、10、15、20、30 min,分别使用CCK-8(Cell Counting Kit-8)检测法、乳酸脱氢酶(LDH)释放法、中性红摄入法(NRU)检测柴油机尾气对细胞存活率的影响;对细胞存活率约50％以上的染毒组用流式细胞术检测柴油机尾气对细胞凋亡率的影响;同时对每个染毒组分别设置用滤膜过滤的洁净空气作为对照组,暴露时间和检测方法均与染毒组-致. [结果]3种存活率检测方法的结果表明,染毒组与对照组相比,柴油机尾气持续染毒15 min及更长时间以后,细胞存活率降低,差异有统计学意义(P＜ 0.05),且呈随染毒时间延长而逐渐降低的趋势.3种方法比较表明,低流速短时间柴油机尾气对16HBE细胞的损伤作用以细胞膜损伤最为显著,其次是线粒体损伤.用柴油机尾气持续染毒10、15 min,染毒组细胞早期凋亡率、晚期凋亡及坏死率较对照组均升高,差异均有统计学意义(P＜ 0.05).10、15 min染毒组的晚期凋亡及坏死细胞多于早期凋亡细胞(P＜0.05). [结论]气-液界面染毒技术可以应用于柴油机尾气等气溶胶有害物质的体外毒性研究;同时发现柴油机尾气导致的16HBE细胞急性毒性为细胞膜损伤、线粒体损伤及细胞凋亡.     

百草枯致神经发育毒性的研究进展

百草枯是目前世界上使用最广泛的除草剂之一.它的急性毒性和长期低剂量接触所致的神经毒性一直被人们关注,对机体神经发育产生的影响也不容忽视.本文以近年来国内外有关百草枯神经发育毒性的研究为基础,综述其流行病学研究、实验动物研究以及可能的毒性机制等方面研究进展;结合本课题组的已有研究,提示百草枯的神经发育毒性可能与帕金森病发展密切相关,应予以广泛关注.