Early-life epileptiform discharges exert both rapid and long-lasting effects on AMPAR subunit composition and distribution in developing neurons

The perinatal period of brain is characterized by dynamic changes in structure and high propensity for epilepsy. Animal models have shown that alterations of AMPA receptor (AMPAR) assembly or function may be related to seizure-induced cell damage, long-lasting impairments in brain development and seizure threshold. However, effects of earlier epileptiform discharges on AMPAR composition and sub-cellular distribution remain understudied. In this study, we analyzed age-dependent variation of relative GluR1 and GluR2 protein levels in primary cultured rat cortical neurons at 7 DIV, 12 DIV, 17 DIV and 21 DIV. By inducing a single event of epileptiform activity at 6 DIV, we tested the effects of early-life seizure-like insults on AMPAR subunit distribution. We found a significant increase in synaptosomal membrane GluR1 expression in magnesium-free (MGF) medium-treated neurons at each time point detected (p < 0.05), while GluR2 expression increased at 7 DIV, and declined at 17 DIV and 21 DIV respectively (p < 0.05). That is, a trend of high GluR1 with much lower GluR2 expression on the surface membrane of epileptiform discharges experienced neurons over time in culture was presented. These findings in an in vitro model of early-life seizure may inform rodent models of epilepsy, as well as the cellular mechanism involved in epilepsy-associated brain dysfunction.     

阈值校正方式对PET脑显像统计参数图分析显示结果的影响

目的 探讨各种阈值校正方法对统计参数图(SPM)软件统计比较结果显示的影响.方法 利用Hoffman标准脑模型制作缺损模型PET成像与正常模型PET成像,进行统计参数图的统计比较.并选取脑梗死患者与健康检查者进行统计参数图的统计比较.结果 校正与非校正产生的结果有差异,其中族错误率(FWE)校正(P=5×10-2)得到的统计分析结果激活区最少及最小,其次是错误发现率(FDR)校正(P=5×10-2),非校正方式(P=1×10-3)得到的激活区最多及最大.但FDR校正效果不稳定,有时不如不校正.结论 统计参数图软件中FWE校正方法可明显降低假阳性,得到的结果可信度稳定地高于非校正方法.     

Increased fluidity of Plasmodium berghei-infected mouse red blood cell membranes detected by electron spin resonance spectroscopy

The fluidity of Plasmodium berghei-infected mouse red cell membranes is increased over that of uninfected cells at both 24°C and 37°C. This was demonstrated by electron spin resonance spectroscopy using the hydrocarbon spin labels 2-dodecyl-2′,5,5′-trimethyloxazolidine-N-oxyl and 2-heptyl-2′ -hexyl-5,5′-dimethyloxazolidine-N-oxyl to label regions of the bilayer near its surface, and deeper within the hydrocarbon region, respectively. Arrhenius plots of the ‘empirical motion parameter’ (R_i) obtained from 2-heptyl-2′-hexyl-5,5′-dimethyloxazolidine-N-oxyl-labeled cells versus temperature over the range from 0 to 45°C showed an hysteretic behavior of the spin labels in the membranes of both mature and immature uninfected cells. Such hysteretic behavior was consistently lacking in membranes of infected cells. These differences in membrane fluidity and spin label behavior are interpreted to reflect biochemical modifications of the red cell membrane which occur with infection by the malarial parasite.     

Hepatic elimination of drugs with concentration-dependent serum protein binding

For a drug with concentration-dependent serum protein binding, the unbound fraction of drug decreases during the drug elimination process. The clearance of the drug at a given blood flow rate is lower than would be expected from the observed unbound fraction in venous blood from a noneliminating organ. Based on both the well-stirred and parallel tube models, simulations demonstrated that consideration of concentration-dependent binding during drug elimination is important when the intrinsic clearance is higher than the blood flow and when the unbound drug concentration is much greater than the dissociation equilibrium constant of the binding complex.Supported in part by Grant GM 28423 from the National Institutes of General Medical Sciences, NIH.     

Evaluation of the effect of shift working and sleep quality on semen parameters in men attending infertility clinic

We aimed to evaluate the effect of shift work on semen parameters together with the effect of sleep quality in men attending infertility clinic. The participants were divided into two groups as follows: 104 shift worker men (Group 1) and 116 nonshift worker men (Group 2). Groups were compared in terms of semen parameters, Depression Anxiety Stress Scale-21 (DASS-21), and Pittsburg Sleep Quality Index (PSQI) scores. A higher rate of oligozoospermia and poor sleep quality and a lower mean normal morphology percentage was observed in shift workers than nonshift workers (p = .006, .039 and .036 respectively). In addition, a positive correlation was seen between sleep duration and sperm concentration, while a negative correlation was found between sleep latency and total sperm count. Shift working together with high PSQI score was also a significant association with oligozoospermia when controlling for the other variables of age, total testosterone, DASS-21 stress score, smoking and varicocele (OR = 2.11, 95% CI 1.03–4.34 and OR = 1.18, 95% CI 1.01–1.39 respectively). In this study, infertile shift workers had a lower percentage of normal morphology and higher rates of oligozoospermia and poor sleep quality. Considering that shift workers have lower sleep quality, it seems that shift working negatively affects the circadian rhythm.     

步枪立姿射击稳定性的力学特征

射击运动技术是衡量运动员水平的关键，它对运动员姿态控制的稳定性有相当高的要求。本文以步枪立姿运动为例，分析其姿态控制的力学特征，运用运动稳定性原理，求得人体上躯干最佳姿态控制角，并论证了人体躯干长度，前臂长度对稳定性的影响。最后将理论结果与对一些国内外著名运动员实测参数比较分析，证明了理论结论与实际基本相符。     

用双剂量实验数据分析药物的米氏消除参数的识别问题

本文分析了给药剂量对按一级过程吸收，米氏过程消除药物的血药浓度的峰值与达峰时间的影响。并据此讨论了利用较少的双剂量实验数据改善识别米氏参数的方法。     

不同年龄组正常人群影响最大胸椎后凸角的相关因素分析

目的：本研究通过对不同年龄组正常人群矢状位参数进行分析,旨在报道正常人群脊柱骨盆参数参考值范围,并探索不同年龄段引起最大胸椎后凸角改变的影响因素。 方法：本研究纳入自2015年1月至2018年月于两所医院健康体检中心的正常人群,收集人口统计学参数以及矢状位影像学参数。通过将人群分为≤40岁组与＞40岁组,对比分析不同年龄组人群的矢状位参数,并对不同年龄组影响最大胸椎后凸角max TK的因素进行相关性分析。结果：本研究共计纳入191例正常人群,其中≤40岁组94人,平均年龄为28.5±6.4岁;＞40岁组97人,平均年龄为53.9±8.3岁。不同年龄组人群在胸1椎体矢状位倾斜角T1 Tilt（18.6±6.5 vs. 20.6±5.5, P=0.023）, 胸椎后凸下端椎倾斜角TVA（15.3±5.3 vs. 17.5±6.6, P=0.013）,max TK（33.9±8.3 vs. 38.0±9.4, P<0.001）,max LL- max TK（14.9±8.9 vs. 12.3±9.4, P=0.048）及矢状面躯干偏移SVA（-2.5±21.8 vs. 6.1±20.9, P=0.006）上存在显著差异。在年龄≤40岁的人群中,T1 Tilt、TVA、max LL及骶骨倾斜角SS与max TK显著相关,而在年龄＞40岁的人群中,年龄、T1 Tilt、TVA、max LL及骨盆入射角PI与max TK显著相关。结论：max TK随着年龄增长呈现上下均匀增长趋势,在＞40岁的人群中,max TK与年龄呈现正相关关系。此外,不同年龄阶段,骨盆对于max TK改变的代偿呈现出不同的模式。     

不同致伤条件撞击对兔钝性胸部创伤伤情影响的实验研究

探讨不同致伤参数对兔钝性胸部创伤后胸部筘器官伤情的影响。方法采用兔钝性胸部创伤型,设置不同的致伤参数,观察其对胸部各器 伤情影响及其对死亡率的影响。结果驱动压力越大,胸部各器官伤情越重;撞击面积越大,对胸壁和肺的损伤较重,但心脏伤情并不随之加重;收缩末期撞击对心脏的损伤较重,舒张末期撞击大血管系统的影响较大,死亡率与驱动压力、撞击面积成正;舒张末期撞击死亡率上升。结论致伤参数不同,对钝化胸部创伤后     

Determination of microviscosity and location of 1,3-Di(1-pyrenyl)propane in brain membranes

We determined the microviscosity of synaptosomal plasma membrane vesicles (SPMV) isolated from bovine cerebral cortex and liposomes of total lipids (SPMTL) and phospholipids (SPMPL) extracted from SPMV. Changes in the microviscosity induced by the range and rate of lateral diffusion were measured by the intramolecular excimerization of 1,3-di(1-pyrenyl)-propane (Py-3-Py). The microviscosity values of the direct probe environment in SPMV, SPMTL and SPMPL were 38.17, 31.11 and 27.64 cP, respectively, at 37°C and the activation energies (E_a) of the excimer formation of Py-3-Py in SPMV, SPMTL and SPMPL were 8.236, 7.448 amd 7.025 kcal/mol, respectively. Probe location was measured by polarity and polarizability parameters of the probe Py-3-Py and probe analogues, pyrene, 1-pyrenenonanol and 1-pyrenemethyl-3β-hydroxy-22,23-bisnor-5-cholenate (PMC), incorporated into membranes or solubilized in reference solvents. There existed a good linear relationship between the first absorption peak of the¹L_a band and the polarizability parameter (n ²−1)/(2n ²+1). The calculated refractive index values for SPMV, SPMTL and SPMPL were close to 1.50, which is higher than that of liquid paraffin (n=1.475). The probe location was also determined by using a polarity parameter (f−1/2f¹). Here f=(ε−1)/(2ε+1) is the dielectric constant function and f'=(n ²−1)/(2n ²+1) is the refractive index function. A correlation existed between the monomer fluorescence intensity ratio and the solvent polarity parameter. The probes incorporated in SPMV, SPMTL, and SPMPL report a polarity value close to that of 1-hexanol (ε=13.29). In conclusion, Py-3-Py is located completely inside the membrane, not in the very hydrophobic core, but displaced toward the polar head groups of phospholipid molecules, e.g., central methylene region of aliphatic chains of phospholipid molecules.