Recent advances in preclinical in vitro approaches towards quantitative prediction of hepatic clearance and drug-drug interactions involving organic anion transporting polypeptide (OATP) 1B transporters

Hepatic uptake mediated by organic anion transporting polypeptide (OATP) 1B1 and 1B3 can serve as a major elimination pathway for various anionic drugs and as a site of drug-drug interactions (DDIs). This article provides an overview of the in vitro approaches used to predict human hepatic clearance (CL_h) and the risk of DDIs involving OATP1Bs. On the basis of the so-called extended clearance concept, in vitro–in vivo extrapolation methods using human hepatocytes as in vitro systems have been used to predict the CL_h involving OATP1B-mediated hepatic uptake. CL_h can be quantitatively predicted using human donor lots possessing adequate OATP1B activities. The contribution of OATP1Bs to hepatic uptake can be estimated by the relative activity factor, the relative expression factor, or selective inhibitor approaches, which offer generally consistent outcomes. In OATP1B1 inhibition assays, substantial substrate dependency was observed. The time-dependent inhibition of OATP1B1 was also noted and may be a mechanism underlying the in vitro–in vivo differences in the inhibition constant of cyclosporine A. Although it is still challenging to quantitatively predict CL_h and DDIs involving OATP1Bs from only preclinical data, understanding the utility and limitation of the current in vitro methods will pave the way for better prediction.     

Self‐objectification in the context of breastfeeding: A concept analysis

To increase the overall rate of breastfeeding initiation and duration, factors involved in a mother's decision to breastfeed must be identified. Self‐objectification in the context of breastfeeding was a concept selected for exploring factors associated with negative views of breastfeeding. A concept analysis following the eight‐step Walker & Avant method provides clarity and context to the concept of self‐objectification in the context of breastfeeding. The antecedents of self‐objectification in the context of breastfeeding include living in a culture of sexualization and objectification of women and the internalization of the values of objectification. Attributes of self‐objectification in the context of breastfeeding are a prioritization of physical appearance attributes of the breast over the health benefits of breastfeeding and a preoccupation with physical appearance. Consequences include negative views toward breastfeeding initiation, duration, and public breastfeeding. A concept analysis on self‐objectification in the context of breastfeeding will provide definition and clarity to this phenomenon, lend to theory and measurement, and add literature to the sociocultural factors impacting breastfeeding decisions.     

快速康复内窥镜椎间盘切除术治疗腰椎间盘突出症的临床观察

目的:探讨快速康复外科理念联合内窥镜椎间盘切除术治疗腰椎间盘突出症的疗效。方法:选取2018年4月—2019年4月本院收治的86例腰椎间盘突出症患者,随机分为两组,每组43例,对照组通过内窥镜椎间盘切除术治疗,观察组予以快速康复外科理念联合内窥镜椎间盘切除术治疗,对比两组疗效和并发症发生情况。结果:观察组并发症发生率(4.65%)较对照组(18.60%)低,差异有统计学意义(P 0.05);观察组下床活动时间、住院时间较对照组短,术后7天的疼痛评分较对照组低,差异有统计学意义(P 0.05);术后3个月,观察组的Oswestry功能障碍指数问卷表评分较对照组低,日本骨科协会评估治疗分数较对照组高,差异有统计学意义(P 0.05)。结论:探讨快速康复外科理念联合内窥镜椎间盘切除术治疗腰椎间盘突出症可减少并发症,缩短术后恢复时间,进而促进患者功能有效康复。     

去势后大鼠海马结构一氧化氮合酶阳性神经元的变化

目的：观察去势后大鼠海马结构一氧化氮合酶（NOS）阳性神经元的变化。方法：用黄递酶组织化学染色方法观察切除双侧卵巢后雌后SD大鼠海马结构NOS阳性神经元的形态，分布的变化，并进行计算机图像分析。结果：去势后海马结构NOS阳性神经元分布变化有区域差异性；NOS阳性神经元在下托、海马（CA）一区邻近下托的部分、CA三区、CA四区（CA4）和齿状回（DG）数目明显减少，而在CA二区数目明显明显增多，CA4和DG的NOS阳性神经元平均密度降低，胞体的平均周长和平均截面积都明显减少。结论：雌激素可能通过影响海马结构NOS的表达来影响学习和记忆。     

Development of the blood-testis barrier in the domestic fowl (Gallus domesticus)

The formation of the blood-testis barrier (BTB) in the domestic fowl was studied at the electronmicroscopic level employing lanthanum as a tracer. No effective barrier could be demonstrated in testes before puberty, although several components of the Sertoli junctional complex such as focal tight junctions and desmosomes were already existent. The time of onset of meiosis after hatching showed great individual variation and meiosis did not occur synchronously in the tubules of a given testis. An effective barrier could first be detected in tubules containing early spermatids, and in which spermatogonia and primary spermatocytes at the leptotene stage were still within the open compartment. Thus, barrier formation was correlated with the occurrence of haploid germ cells. Complete compartmentation of seminiferous tubules, leaving only spermatogonia within the open compartment, was attained in tubules containing elongated spermatids of the maturation phase. In these tubules, primary spermatocytes at the leptotene stage were situated in an intermediate compartment.     

Balance and gait improved in patients with MS after physiotherapy based on the Bobath concept

Background and Purpose . Patients with multiple sclerosis (MS) tend to have movement difficulties, and the effect of physiotherapy for this group of patients has been subjected to limited systematic research. In the present study physiotherapy based on the Bobath concept, applied to MS patients with balance and gait problems, was evaluated. The ability of different functional tests to demonstrate change was evaluated. Method . A single‐subject experimental study design with ABAA phases was used, and two patients with relapsing–remitting MS in stable phase were treated. Tests were performed 12 times, three at each phase: A (at baseline); B (during treatment); A (immediately after treatment); and A (after two months). The key feature of treatment was facilitation of postural activity and selective control of movement. Several performance and self‐report measures and interviews were used. Results . After intervention, improved balance was shown by the Berg Balance Scale (BBS) in both patients, and improved quality of gait was indicated by the Rivermead Visual Gait Assessment (RVGA). The patients also reported improved balance and gait function in the interviews and scored their condition as ‘much improved’. Gait parameters, recorded by an electronic walkway, changed, but differently in the two patients. Among the physical performance tests the BBS and the RVGA demonstrated the highest change, while no or minimal change was demonstrated by the Rivermead Mobility Index (RMI) and Ratings of Perceived Exertion (RPE). Conclusion . The findings indicate that balance and gait can be improved after physiotherapy based on the Bobath concept, but this should be further evaluated in larger controlled trials of patients with MS. Copyright © 2006 John Wiley & Sons, Ltd.     

Kindergarten children's representation and understanding of written number symbols

Two samples of kindergarten children's representation and understanding of written number symbols were examined in two time points in one academic year. About 85% of Chinese five year olds (mean = 5 years 10 months) were able to use conventional number symbols to represent the quantity of 30 or larger. At the end of the kindergarten year, 94% of Chinese six year olds (mean = 6 years 4 months) were able to use conventional number symbols to represent the quantity of 100 or larger. Some Chinese six year olds had problems in representing written addition and subtraction tasks. Children's ability to represent written number symbols, ability to represent written addition and subtraction formula and their performance on written addition and subtraction were closely related. The performance of children in a university-affiliated childcare center was better than that of the center serving working-class families in Time 1, but the performance reversed at the end of the kindergarten year.     

Growth cones and axon trajectories of a sensory pathway in the amphibian spinal cord

Central axons of sensory ganglion (SG) neurons of the Xenopus tail enter the spinal cord via the ventral roots and travel dorsally and rostrally following a diagonal course within the lateral marginal zone (LMZ) to reach the dorsolateral fasciculus (DLF) (Nordlander et al.: Brain Res., 440:391-395, 1988). Axons are dispersed as they cross the cord. At the DLF they turn and travel together rostrally, sharing the fascicle with axons of primary sensory neurons (Rohon-Beard cells) already present in the tract. In this paper we analyze the growth patterns of the central projections of SG axons in the tail by using HRP applied to proximal branches of tail spinal nerves. Growth cones of the diagonal route are variable in configuration, often bearing processes that spread within the LMZ. Once the DLF, growth cones change shape, becoming distinctly linear. While growth cones navigating the diagonal part of the route never contact or fasciculate with other diagonal SG axons, SG growth cones and axons of the DLF are more closely associated with their fellows. Measurements of the slopes of SG axons in the diagonal route indicated a limited range with a mean of 23 degrees with respect to the cord axis. On the basis of these observations, we conclude that 1) navigational patterns for growth cones of this pathway differ for the diagonal versus the DLF part of its course, and 2) fasciculation is not a mechanism used by SG axons to reach the DLF, but that instead, each axon is able to find its way independently.