Pharmacokinetics of poly(hydroxyethyl-l-asparagine)-coated liposomes is superior over that of PEG-coated liposomes at low lipid dose and upon repeated administration

‘Stealth’ liposomes with a poly(ethylene glycol) (PEG) coating are frequently studied for drug delivery and diagnostic purposes because of their prolonged blood circulation kinetics. However, several recent reports have demonstrated that PEG-liposomes are rapidly cleared at single low lipid doses (< 1 μmol/kg) and upon repeated administration (time interval between the injections 5 days-4 weeks). Recently, poly(amino acid)-based stealth liposome coatings have been developed as alternative to the PEG-coating. In this study, the pharmacokinetic behavior of liposomes coated with the poly(amino acid) poly(hydroxyethyl-l-asparagine) (PHEA) was evaluated at low lipid doses and upon repeated administration in rats. Blood circulation times and hepatosplenic localization of PHEA-liposomes were assessed after intravenous injection. When administered at a dose of 0.25 μmol/kg or less, PHEA-liposomes showed significantly longer blood circulation times than PEG-liposomes. A second dose of PHEA-liposomes 1 week after the first injection was less rapidly cleared from the circulation than a second dose of PEG-liposomes. Although the mechanisms behind these observations are still not clear yet, the use of PHEA-liposomes appears beneficial when single low lipid doses and/or repeated dosing schedules are being applied.     

A Variance Components Model for Analyzing Repeated Measures Designs with Non-Stationary Error Structure

When data are collected in the form of multiple measurements on several subjects, they are often analyzed as repeated measures data with some stationary error structure assumed for the errors. For data with non-stationary error structure, the multivariate model is often used. The multivariate model imposes restrictions that are often not met in practice by data of such type. At the same time, they ignore valuable information in the data that are related to time dependencies and time relations. In this paper, we propose a model that is a reparametrization of the multivariate model and is suitable to analyze general repeated measures designs with non-stationary error structure. The model is shown to be a variance components model whose components are estimated using the method of maximum likelihood. Several other properties of the model are derived and discussed including tests of significance. Finally, an example on neurological data is included to demonstrate its application in biological sciences.     

Interval Estimation of Simple Difference in Dichotomous Data with Repeated Measurements

When comparing two treatments, we often use the simple difference between the probabilities of response to measure the efficacy of one treatment over the other. When the measurement of outcome is unreliable or the cost of obtaining additional subjects is high relative to that of additional measurements from the obtained subjects, we may often consider taking more than one measurement per subject to increase the precision of an interval estimator. This paper focuses discussion on interval estimation of simple difference when we take repeated measurements per subject. This paper develops four asymptotic interval estimators of simple difference for any finite number of measurements per subject. This paper further applies Monte Carlo simulation to evaluate the finite‐sample performance of these estimators in a variety of situations. Finally, this paper includes a discussion on sample size determination on the basis of both the average length and the probability of controlling the length of the resulting interval estimate proposed elsewhere.     

Asymmetric crossing over in the spontaneous formation of large deletions in the tonB-trp region of the Escherichia coli K-12 chromosome.

The chromosomal tonB gene of Escherichia coli was used as a target for the detection of spontaneous deletion mutations. The deletions were isolated in both recA ⁺ and recA ⁻ cells, and mutants carrying large deletions were identified because they also lacked part or all of the trp operon. The frequencies of tonB-trp deletion were 1.79 × 10⁻⁹ and 1.09 × 10⁻⁹ for recA ⁺ and recA ⁻ cells, respectively. We analyzed 12 deletions from recA ⁺ and 10 from recA ⁻ cells by cloning and direct sequencing. The deletions ranged in size from 5612 bp to 15142 bp for recA ⁺ and from 5428 bp to 13289 for recA ⁻ cells. Three deletions from recA ⁺ cells and five deletions from recA ⁻ cells were found to have occurred between short sequence repeats at the termini of the deletion, leaving one copy of the repeat in the mutant sequence. Seven deletions from recA ⁺ cells and three deletions from recA ⁻ cells did not have repeats at their termini; in these cases, the DNA sequences that are adjacent to the deletion termini in the wild-type are characterized by short (2–4 bp) repeats. From these results, a model is presented for the generation of deletion mutations which involves formation of an asymmetric crossover mediated by repeated sequences of 2- to 4-bp. Received: 14 September 1998 / Accepted: 22 December 1998     

Inference of global HIV-1 sequence patterns and preliminary feature analysis

The epidemiology of HIV-1 varies in different areas of the world, and it is possible that this complexity may leave unique footprints in the viral genome. Thus, we attempted to find significant patterns in global HIV-1 genome sequences. By applying the rule inference algorithm RIPPER (Repeated Incremental Pruning to Produce Error Reduction) to multiple sequence alignments of Env sequences from four classes of compiled datasets, we generated four sets of signature patterns. We found that these patterns were able to distinguish southeastern Asian from nonsoutheastern Asian sequences with 97.5% accuracy, Chinese from non-Chinese sequences with 98.3% accuracy, African from non-African sequences with 88.4% accuracy, and southern African from non-southern African sequences with 91.2% accuracy. These patterns showed different associations with subtypes and with amino acid positions. In addition, some signature patterns were characteristic of the geographic area from which the sample was taken. Amino acid features corresponding to the phylogenetic clustering of HIV-1 sequences were consistent with some of the deduced patterns. Using a combination of patterns inferred from subtypes B, C, and all subtypes chimeric with CRF01_AE worldwide, we found that signature patterns of subtype C were extremely common in some sampled countries (for example, Zambia in southern Africa), which may hint at the origin of this HIV-1 subtype and the need to pay special attention to this area of Africa. Signature patterns of subtype B sequences were associated with different countries. Even more, there are distinct patterns at single position 21 with glycine, leucine and isoleucine corresponding to subtype C, B and all possible recombination forms chimeric with CRF01_AE, which also indicate distinct geographic features. Our method widens the scope of inference of signature from geographic, genetic, and genomic viewpoints. These findings may provide a valuable reference for epidemiological research or vaccine design.     

黑线仓鼠殴斗行为模式及其与生理状态的关系

本文以分布于鲁西南山区的黑线仓鼠雄体为对象,通过测定重复遭遇战(repeated encounters)对黑线仓
鼠体重、生理指标等参数的作用,以期阐明社群冲突(social conflict)对黑线仓鼠生理状态的影响。研究结果表
明:在4 周的重复遭遇战过程中,参与冲突个体的体重增长率略有降低,但未达到显著水平;粪便肾上腺皮质
激素(GCs)含量呈现波动性变化,在整个遭遇战过程中,优势个体与从属个体的GCs 含量交替显著升高,与
冲突时间及个体社群地位均有关;优势个体保持较高的睾酮水平,利于其增强攻击行为和获得优势地位;从属
组雄体的肾上腺显著增大,但生殖腺间差异不显著;HPA 轴对HPG 轴具有显著的抑制效应,肾上腺分泌的皮质
醇可显著抑制个体的睾酮分泌,二者呈显著的负相关关系。这些数据表明,黑线仓鼠雄体可通过斗殴行为建立
明确的优势- 从属关系,睾酮可促进个体优势地位的形成并受到肾上腺皮质醇抑制;HPA 轴对HPG 轴的抑制未
能在器官指数方面得到证实。从属个体受到胁迫,对优势雄性黑线仓鼠野外生存和繁殖有重要意义。     

乳酸菌阴道胶囊辅助治疗在行ART反复着床失败患者中的应用

探究行辅助生殖技术（ART）反复着床失败患者应用乳酸菌阴道胶囊辅助治疗对子宫内膜容受性（ER）和阴道微生物的影响。

选取2020年5月至2022年5月本院收治ART反复着床失败患者100例,根据治疗方式分为观察组（n = 50）和对照组（n = 50）。对照组采用常规治疗,观察组采用常规治疗联合乳酸菌阴道胶囊。比较两组的性激素水平（雌二醇、孕酮）,内膜容积、子宫内膜厚度、血管血流指数（VFI）、内膜血流指数（FI）和阻力指数（RI）等子宫内膜容受性指标,阴道pH值、阴道菌群检出率和乳酸菌数量。

两组治疗前后血清雌二醇、孕酮水平比较,差异无统计学意义（P＞0.05）。两组治疗前子宫内膜厚度、内膜容积、血管血流指数、内膜血流指数和阻力指数比较,差异无统计学意义（P＞0.05）。治疗后观察组子宫内膜厚度、内膜容积和血管血流指数均高于治疗前（P＜0.01）和对照组（P＜0.05）。治疗前两组菌群检出率差异无统计学意义（P＞0.05）,治疗后两组菌群检出率均低于治疗前（P＜0.05）,治疗后观察组菌群检出率低于对照组（P＜0.05）。两组阴道pH值均低于治疗前（P＜0.001）,治疗后观察组阴道pH值低于对照组（P＜0.001）。两组阴道乳杆菌正常率均高于治疗前（P＜0.05）,治疗后观察组高于对照组（P＜0.05）。两组胚胎着床率、临床妊娠率、早期流产率和持续妊娠率差异无统计学意义（P＞0.05）。

乳酸菌阴道胶囊治疗ART反复着床失败患者可以改善子宫内膜容受性和阴道菌群。

     

Does sex matter? Differential responses to corticosterone administration in the zebra finch

Because of potentially deleterious effects of chronic stress, physiological measurements of stress hormones (in birds, corticosterone (CORT)) are often used to determine the consequences of natural or human-induced change. Often, it is assumed that CORT levels will be similar between the sexes and the results are pooled. However, recent studies have reported sex differences in CORT concentrations in avian species. As zebra finches (Taeniopygia guttata) are one of the most widely used bird species in laboratory studies worldwide, potential sex-specific differences in hormone metabolism, as well as the clearance rate of oral doses of exogenous CORT, are highly relevant. The results of this study show that female zebra finches have a significantly higher baseline CORT than males, which could partially be a product of differential responses to semi-isolation. In addition, a single dose of exogenous CORT resulted in different blood profiles between the sexes over time, though exogenous CORT was cleared from blood within 90 min following treatment in both sexes. Interestingly, exposure to multiple doses of exogenous CORT resulted in elevated CORT levels 24 h after treatment in both sexes. These results highlight the need for further investigations into potential sex differences in hormone metabolism, as well as possible cumulative effects of repeated stress.