The Influence of the Incubation Period on Qualitative Aspects of the Spread of AIDS

Based on a simple stochastic model the influence of the incubation period of the HIV-infection on some qualitative aspects of the spread of AIDS is studied. A critical ‘nfection rat’ is calculated in dependence on parameters of the incubation period density function.     

罗哌卡因复合舒芬太尼在潜伏期分娩镇痛中的应用效果

目的:探讨罗哌卡因复合舒芬太尼在潜伏期分娩镇痛中的应用效果。方法:择取2015年1月~2016年1月我院收治的产妇102例,随机分为A、B、C组,各组34例,A组产妇宫口开至1 cm时采取罗哌卡因复合舒芬太尼硬膜外自控分娩镇痛,B组产妇宫口开至3 cm时采取罗哌卡因复合舒芬太尼硬膜外自控分娩镇痛,C组产妇未采取分娩镇痛,比较两组第一产程潜伏期、活跃期及第二产程持续时间及宫缩时视觉模拟评分(VAS)评分,比较各组产妇出血量、新生儿体质量及胎儿娩出后1 min、5 min Apgar评分,记录各组治疗30 d后不良反应。结果:A组、B组第一产程潜伏期持续时间明显较C组延长,活跃期持续时间较C组明显缩短,差异有统计学意义(P0.05);A组产妇宫颈口开至2 cm和cm时VAS评分低于B组和C组,差异有统计学意义(P0.05);A组、B组产妇在活跃期、第二产程时VAS评分低于C组,差异有统计学意义(P0.05);各组产妇出血量、新生儿体质量、Apgar评分比较均无统计学意义(P0.05);C组抑郁症发生率均高于较A组和B组,差异有统计学意义(P0.05)。结论:从产妇潜伏期开始应用罗哌卡因复合舒芬太尼进行分娩镇痛的效果较好,具有良好的应用价值。     

高寒草甸常见雀形目鸟类的卵壳特征

作为胚胎发育的屏障,卵壳特征如卵壳厚度和气孔密度具有重要的生态学意义。本文研究了高寒草甸繁殖的7种代表性雀形目鸟类角百灵（Eremophila alpestris）、小云雀（Alauda gulgula）、黄头鹡鸰（Motacilla citreola）、树麻雀（Passer montanus）、粉红胸鹨（Anthus roseatus）、黄嘴朱顶雀（Carduelis flavirostris）、赭红尾鸲（Phoenicurus ochruros）的卵与卵壳特征,以探索在高寒缺氧环境下,不同科鸟类的适应性调节。结果发现,7种鸟类中,除小云雀和角百灵之外,其他鸟类的卵与卵壳特征均有显著的种间差异（除卵壳厚度和气孔直径之外）;对7种鸟类卵壳厚度、气孔密度、卵体积、卵重之间的线性拟合显示,卵壳厚度、卵体积与气孔密度均无显著相关性（卵壳厚度：P = 0.11,卵体积：P = 0.09）,卵重、卵体积与卵壳厚度呈显著正相关（卵重：r2 = 0.46,P ＜ 0.001;卵体积：r2 = 0.44,P ＜ 0.001）;对7种鸟类卵的数据与繁殖期雌鸟平均体重的线性拟合结果显示：平均卵重、卵壳厚度的差异与雌鸟体重成正相关（卵重：r2 = 0.66,P = 0.03;卵壳厚度：r2 = 0.92,P ＜ 0.01）;对6种鸟类（缺乏粉红胸鹨窝卵数数据）卵的数据与孵卵相关变量的线性拟合结果显示：卵壳厚度及气孔率与窝卵数成负相关（卵壳厚度：r2 = 0.64,P = 0.056;气孔率：r2 = 0.87,P ＜ 0.01）,6种鸟类（缺乏树麻雀巢杯指数数据）气孔率与巢杯指数或巢型无显著相关性（巢杯指数：P = 0.49,巢型：P = 0.435）。卵表面积和总气孔数解释了大部分气孔率差异（87%）,卵重和气孔率与孵卵期无显著相关（P = 0.77）,气孔率显著低于预期气孔率（P＜0.001）。这些结果表明,种间的遗传性（如成鸟的形态、窝卵数等）决定了大部分卵与卵壳特性的差异,但是为适应高寒低氧的气候特征,不同种的鸟都具有相对厚的卵壳和低的气孔率特征,说明环境因素同样影响卵的进化。另外,单纯的卵特性（卵体积和气孔率）并不能决定孵卵期的长短,亲鸟的孵卵行为同样具有重要的影响,角百灵虽然离巢频率相对较高,但是孵卵期却相对较短,这可能与其较高的气孔率有关。     

The correlation between infectivity and incubation period of measles, estimated from households with two cases

The generation time of an infectious disease is the time between infection of a primary case and infection of a secondary case by the primary case. Its distribution plays a key role in understanding the dynamics of infectious diseases in populations, e.g. in estimating the basic reproduction number. Moreover, the generation time and incubation period distributions together characterize the effectiveness of control by isolation and quarantine. In modelling studies, a relation between the two is often not made specific, but a correlation is biologically plausible. However, it is difficult to establish such correlation, because of the unobservable nature of infection events. We have quantified a joint distribution of generation time and incubation period by a novel estimation method for household data with two susceptible individuals, consisting of time intervals between disease onsets of two measles cases. We used two such datasets, and a separate incubation period dataset. Results indicate that the mean incubation period and the generation time of measles are positively correlated, and that both lie in the range of 11-12 days, suggesting that infectiousness of measles cases increases significantly around the time of symptom onset. The correlation between times from infection to secondary transmission and to symptom onset could critically affect the predicted effectiveness of isolation and quarantine.     

2020年江苏省稻飞虱虫源地及暴发成因分析

为了明确江苏省稻飞虱(白背飞虱Sogatella furcifera Horváth和褐飞虱Nilaparvata lugens St?l)在沉寂近10年后再次暴发的成因,通过分析江苏2020年白背飞虱和褐飞虱的田间调查及灯诱数据,并结合气象条件,研究了江苏省稻飞虱暴发的主要影响因素。结果表明：(1)2020年,江苏省白背飞虱虫源主要来自于江西中、北部,湖南东部以及湖北东部;褐飞虱虫源主要来自于安徽南部、浙江北部、本省南部以及江西省中北部。(2)江淮地区自6月中旬至7月下旬的超长降雨期有利于江苏省早期迁入虫源大量降落。(3)9月初,田间已存在大量褐飞虱短翅型成虫,适宜的秋季温度促使田间短翅型褐飞虱大量繁殖,导致后期田间褐飞虱大暴发。总而言之,超长降雨期有利于早期稻飞虱的迁入降落,而秋季的适宜温度引发短翅型成虫大量繁殖,是导致江苏省稻飞虱在沉寂近10年后再次暴发的主要因素。这些结果为稻飞虱暴发规律的阐明及可持续治理提供了理论依据和参考价值。     

听性脑干反应在脑外伤后听力患者的早期诊断及预后中的意义

目的:探讨脑外伤后伴发听力损伤的患者听性脑干反应的特点及其和预后的相关性。方法:纳入颅脑外伤伴发听力障碍的患者50例,其中男34例,女16例,为观察组,选健康正常成年人50例为对照组,其中男30例,女20例。对观察组受伤后2周内及6个月后进行听性脑干反应检查,对比分析两组患者听性脑干反应波特点及其和预后的相关性。结果:正常人听觉阈值的95%置信区间是[10.24-19.33]d BHL。观察组和对照组的听觉阈值分别为52.24±21.75(d Bn HL)、11.36±3.02(d Bn HL),差异有统计学意义(p0.05)。对照组主波Ⅰ、Ⅲ、Ⅴ出现率为100%,观察组的出现率分别为78.00%、66.00%、88.00%,差异有统计学意义(P0.05)。病例组和对照组相比,Ⅰ、Ⅱ、Ⅲ、Ⅳ、Ⅴ潜伏期均延长,差异存在统计学意义(P0.05)。预后良好组患者受伤2周内和6个月后Ⅰ、Ⅲ、Ⅴ出现率明显增加,潜伏期缩小,差异有统计学意义(P0.05)。而无改善组患者Ⅰ、Ⅲ、Ⅴ出现率略有增加,潜伏期缩小不明显,差异无统计学意义(P0.05)。结论:脑外伤患者听性脑干反应主波Ⅰ、Ⅲ、Ⅴ缺失,潜伏期缩小,若此种变化持续不改善,预示着听力损伤预后较差。     

菲牛蛭交配及卵茧人工孵化初步研究

人工饲养条件下,比较观察了不同养殖模式(水体、土壤)和不同温度(24℃、26℃、28℃、30℃、32℃和34℃)对菲牛蛭(Hirudinaria manillensis)交配率的影响,并进行了不同卵茧质量(＜0.6 g、0.6～1.0 g、1.0～1.5g、1.5～2.0 g、＞2.0 g)及不同温度(22℃、24℃、...     

CMG2-Fc 融合蛋白突变体筛选及中和炭疽毒素活性分析

目的:筛选能有效中和炭疽毒素和抵抗炭疽毒素损伤细胞的CMG2-Fc(炭疽毒素受体II-人免疫球蛋白Fc段融合蛋白)突变体。方法:运用FoldX等计算软件分析CMG2与PA晶体学结构,设计能提高CMG2-PA亲和力的突变体分子,并与人IgG1Fc片段构成融合基因,转染CHO-S细胞并通过亲和层析获得CMG2-Fc突变体蛋白,通过亲和力检测和细胞保护实验分析各突变体中和炭疽毒素能力。结果:筛选并表达了8个CMG2-Fc突变体分子,亲和力实验显示其中E117Q突变可明显提高CMG2-Fc与PA的亲和力(KD=1.35×10-11 mol/L),细胞保护实验提示E117Q突变能有效提高CMG2-Fc中和炭疽毒素能力(CMG2-Fc(E117Q)的IC50为15 ng/μL,而wt CMG2-Fc的IC50为50ng/μL)。结论:CMG2-Fc(E117Q)突变体分子可作为拮抗炭疽毒素损伤的炭疽治疗药物分子,进行进一步研究。     

Epidemic modelling: Aspects where stochasticity matters

Epidemic models are always simplifications of real world epidemics. Which real world features to include, and which simplifications to make, depend both on the disease of interest and on the purpose of the modelling. In the present paper we discuss some such purposes for which a stochastic model is preferable to a deterministic counterpart. The two main examples illustrate the importance of allowing the infectious and latent periods to be random when focus lies on the probability of a large epidemic outbreak and/or on the initial speed, or growth rate, of the epidemic. A consequence of the latter is that estimation of the basic reproduction number R₀ is sensitive to assumptions about the distributions of the infectious and latent periods when using data from the early stages of an outbreak, which we illustrate with data from the H1N1 influenza A pandemic. Some further examples are also discussed as are some practical consequences related to these stochastic aspects.     

Effects of early incubation constancy on embryonic development: An experimental study in the herring gull Larus argentatus

1.

In many birds, parental nest attendance in early incubation is variable, with eggs incubated only intermittently. The effect of this on chick hatching success is unknown.     

A modeled time-varying density function for the incubation period of AIDS

Building on the Weibull distribution, we develop a modeled time-varying density function of the incubation time between exposure to HIV infection and full-blown AIDS. This approach leads to a series of cohort-specific density functions that take into account the increasing impact of new therapies such as zidovudine (AZT). The resulting modeled density functions are studied in detail, particularly with regard to their modes and medians. The mode is sensitive to changes in the period incubation time distribution, with even a possibility of a bimodal distribution for certain combinations of the parameters that determine the rate at which the period median incubation time changes. An important substantive result is that when a period median incubation period slowly increases to some leveling off value, say m(x _c ), then it is surprisingly early on that cohorts of infected individuals have a median incubation period very close to that ultimate value m(x _c ).     

炭疽灭活和裂解芽胞抗原免疫家兔后血清中的IgG抗体应答

炭疽杆菌芽胞在炭疽免疫中发挥基本作用。实验中以炭疽活芽胞疫苗为原形,建立了制备灭活和裂解炭疽芽胞的方法,研究了各种灭活和裂解炭疽芽胞疫苗不同浓度、不同剂次免疫家兔的抗芽胞和毒素IgG应答,总结分析了各种灭活和裂解炭疽芽胞疫苗用于新疫苗成分之一的可能性。甲醛灭活炭疽芽胞疫苗设芽胞浓度2.5×108剂量组、5×108剂量组、1×109剂量组,于0、4、8周时3次免疫。在3剂免疫后血清抗炭疽芽胞IgG水平持续升高,首次免疫后4、8、12周时家兔血清中抗芽胞IgG几何平均滴度可达到600～16000。裂解炭疽芽胞疫苗的制备和动物免疫中,只采取了2.5×108芽胞浓度,两剂免疫,免疫时间为0、4周。在首次免疫后4、8、12周时家兔血清中抗芽胞IgG几何平均滴度分别为362、776和388。各时间点采集的家兔血清未能测出或只测出极微量的抗炭疽毒素IgG。通过上述研究认为,以裂解炭疽芽胞抗原作为炭疽疫苗成分之一,其抗原性和免疫原性是适宜的;免疫剂量可以设定为2.5×108芽胞浓度上下;免疫次数可定为2剂间隔1个月。     

Termination of parental care due to small clutch size in the temperate damselfish,Chromis notata

Synopsis Reproductive behavior of the temperate damselfish, Chromis notata, was investigated on the island of Mukaishima, Japan, almost daily during the breeding season in 1982. Both males and females repeated reproductive cycles many times during the breeding season. Females had a strong tendency to spawn a whole clutch on one nest during a few hours. The average number of eggs which a male gained per reproductive cycle was estimated at 38560 (480–131100 eggs). Males ordinarily cared for eggs until just prior to hatching, but abandoned more than half of the nests with the eggs numbering less than 11568. Contribution 207 from the Mukaishima Marine Biological Station.     

Molecular Dynamics Simulations of Complexes Between Wild-Type and Mutant Anthrax Protective Antigen Variants and a Model Anthrax Toxin Receptor

Abstract

Bacillus anthracis, a spore-forming infectious bacterium, produces a toxin consisting of three proteins: lethal factor (LF), edema factor (EF), and protective antigen (PA). LF and EF possess intracellular enzymatic functions, the net effect of which is to severely compromise host innate immunity. During an anthrax infection PA plays the critical role of facilitating entry of both EF and LF toxins into host cell cytoplasm. Crystal structures of all three of the anthrax toxins have been determined, as well as the crystal structure of the (human) von Willebrand factor A (integrin VWA/I domain)—an anthrax toxin receptor. A theoretical structure of the complex between VWA/I and PA has also been reported. Here we report on the results of 1,000 psec molecular dynamics (MD) simulations carried out on complexes between the Anthrax Protective Antigen Domain 4 (PA-D4) and the von Willebrand Factor A (VWA/I). MD simulations (using Insight II software) were carried out for complexes containing wildtype (WT) PA-D4, as well as for complexes containing three different mutants of PA-D4, one containing three substitutions in the PA-D4 “small loop” (residues 679–693) (D683A/L685E/Y688C), one containing a single substitution at a key site at the PA-D4—receptor interface (K679A) and another containing a deletion of eleven residues at the C-terminus of PA (A724–735). All three sets of PA mutations have been shown experimentally to result in serious deficiencies in PA function. Our MD results are consistent with these findings. Major disruptions in interactions were observed between the mutant PA-D4 domains and the anthrax receptor during the MD simulations. Many secondary structural features in PA-D4 are also severely compromised when VWA complexes with mutant variants of PA-D4 are subjected to MD simulations. These MD simulation results clearly indicate the importance of the mutated PA-D4 residues in both the “small loop” and at the carboxyl terminus in maintaining a PA conformation that is capable of effective interaction with the anthrax toxin receptor.     

Thermostabilization of protective antigen—the binding component of anthrax lethal toxin

Protective antigen (PA) is the binding component of anthrax lethal toxin produced by Bacillus anthracis, and constitutes a major ingredient of the vaccine against anthrax. PA and lethal factor when added together are cytolytic to mouse macrophages and J774G8 macrophage cell line. This in vitro lethal toxicity assay is very useful in understanding the molecular mechanism of action of lethal toxin. Effective utilization of PA is, however, hampered due to its thermolability. On prolonged storage at 37 ° C, PA was found to lose its activity almost completely. The effect of solvent additives like trehalose, sorbitol, xylitol, sodium citrate and magnesium sulphate on the thermal stabilization of PA was examined. The results indicated an increase in the stability of PA when the incubation at 37 ° C was carried out in the presence of solvent additives used in the 1–3 M range. Magnesium sulphate helped retain the activity up to 82.7% against the control in which no additive was used, as judged by cytolytic assay using J774G8 macrophage cell line. Trehalose or sodium citrate also showed an appreciable protection of PA activity, while sorbitol or xylitol were not very effective. Competitive binding assay using radiolabeled PA showed that PA had lost capacity of binding to macrophage cells on prolonged incubation at 37 ° C. Circular dichroism results at 4, 18 and 37 ° C indicated an increase in secondary structure at 37 ° C relative to that at 4 or 18 ° C, supporting the activity data.     

Incubation temperature fluctuation does not affect incubation length and hatchling phenotype in the Chinese skink Plestiodon chinensis

Studies examining the effects of incubation temperature fluctuation on the phenotype of hatchling reptiles have shown species variation. To examine whether incubation temperature fluctuation has a key role in influencing the phenotype of hatchling Chinese skinks (Plestiodon chinensis), we incubated eggs produced by 20 females under five thermal regimes (treatments). Eggs in three treatments were incubated in three incubators, one set constant at 27 °C and two ramp-programmed at 27±3 °C and 27±5 °C on a cycle of 12 h (+) and 12 h (−). The remaining eggs were incubated in two chambers: one inside a room where temperatures varied from 23.0 to 31.1 °C, with a mean of 27.0 °C; the other outside the room where temperatures varied from 20.2 to 35.3 °C, with a mean of 26.1 °C. We found that: (1) for eggs at a given embryonic stage at ovipositon, the mean rather than the variance of incubation temperatures determined the length of incubation; (2) most (egg mass, embryonic stage at oviposition, incubation length and all examined hatchling traits except tail length and locomotor performance) of the examined variables were affected by clutch; and (3) body mass was the only hatchling trait that differed among the five treatments, but the differences were tiny. These findings suggest that incubation temperature fluctuation has no direct role in influencing incubation length and hatchling phenotype in P. chinensis.     

炭疽活疫苗家兔免疫力与血清抗芽胞IgG关系的研究

炭疽疫苗是预防炭疽流行和炭疽生物恐怖的重要手段。已有动物实验表明,炭疽活疫苗的保护力优于以保护性抗原为主要成份的无细胞疫苗,但两类现行疫苗都有待重新评价和改进。炭疽疫苗的效力必须用适当的实验室方法进行检测与分析才能了解其性质和细节。试验中力图探寻炭疽活疫苗家兔免疫力与血清抗芽胞抗体水平的关系。用“皮上划痕人用炭疽活疫苗”免疫家兔,以特定制备的炭疽芽胞抗原用ELISA法检测血清抗炭疽芽胞IgG抗体水平,并用强毒炭疽杆菌攻击进行效力试验。免疫家兔血清几何平均抗芽胞IgG滴度在免疫后一个月内持续升高,14d达到206,28d时达到776,这时其抵抗20MLD毒菌攻击的保护率为80％,符合中国生物制品规程要求的保护力。一个月后抗体水平开始下降,42d时滴度降至223。实验所揭示的炭疽减毒活疫苗诱导的家兔抗芽胞IgG抗体与抗炭疽保护力之间的关系,既为评价现行疫苗提供了资料,也为研制新型疫苗建立了参考性指标。     

Determination of benzethonium chloride in anthrax vaccine adsorbed by HPLC

A novel and sensitive HPLC method for the determination of benzethonium chloride (BZC) in anthrax vaccine was developed. Adjuvant Alhydrogel was removed by syringe filter after a simple sample pretreatment - acidification prior to injection. Chromatography was performed by isocratic reverse phase separation with methanol/262 mM ammonium acetate (80/20, v/v) on an endcapped C18 column with diode array detector (DAD). The method showed excellent recovery (100+/-1.5%). The results indicated that this method could accurately determine BZC at the limit of detection (LOD) of 0.5 ppm and the limit of quantitation (LOQ) of 1.5 ppm with dynamic range up to 100 ppm. The comparison of analysis between new HPLC and old titrimetric methods is also reported. The HPLC method is proven to be more accurate and precise with much less vaccine sample and human labor required.