Altered EphA5 mRNA expression in rat brain with a single methamphetamine treatment

Methamphetamine is a potent and indirect dopaminergic agonist which can cause chronic brain dysfunctions including drug abuse, drug dependence and drug-induced psychosis. Methamphetamine is known to trigger molecular mechanisms involved in associative learning and memory, and thereby alter patterns of synaptic connectivity. The persistent risk of relapse in methamphetamine abuse, dependence and psychosis may be caused by such alterations in synaptic connectivity. EphA5 receptors constitute large families of tyrosine kinase receptor and are expressed almost exclusively in the nervous system, especially in the limbic structures. Recent studies suggest EphA5 to be important in the topographic projection, development, and plasticity of limbic structures, and to be involved in dopaminergic neurotransmission. We used in situ hybridization to examine whether methamphetamine alters EphA5 mRNA expression in the brains of adult male Wister rats. EphA5 mRNA was widely distributed in the medial frontal cortex, cingulate cortex, piriform cortex, hippocampus, habenular nucleus and amygdala. Compared to baseline expression at 0 h, EphA5 mRNA was significantly decreased (by 20%) in the medial frontal cortex at 24 h, significantly increased (by 30%) in the amygdala at 9 and 24 h, significantly but transiently decreased (by 30%) in the habenular nucleus at 1 h after a single injection of methamphetamine. Methamphetamine did not change EphA5 mRNA expression in the cingulate cortex, piriform cortex or hippocampus. Our results that methamphetamine altered EphA5 mRNA expression in rat brain suggest methamphetamine could affect patterns of synaptic connectivity, which might be responsible for methamphetamine-induced chronic brain dysfunctions.     

慢性不完全性睡眠剥夺对幼鼠学习记忆的影响

目的：探讨慢性不完全性睡眠剥夺对幼鼠学习记忆能力的影响及其可能机制。方法：建立慢性不完全性睡眠剥夺动物模型，并测定其空间学习记忆能力，同时对幼鼠大脑前额皮质及海马神经元性一氧化氮合酶(nNOS)的表达进行分析。结果：睡眠剥夺组幼鼠完成预定任务所需的时间及发生错误的次数均超过正常对照组。睡眠剥夺组的nNOS在前额皮质区域阳性、强阳性表达面积及在海马区域强阳性表达面积均大于正常对照组。结论：慢性不完全性睡眠剥夺会影响幼鼠的学习记忆能力，而前额皮质及海马中nNOS表达水平的下降可能是慢性不完全性睡眠剥夺影响未成熟脑学习记忆能力的机制之一。     

Gustatory stimulus control and reversal learning in rats

Behavioral indices of taste discrimination have been used to study gustatory physiology and psychophysics though they are often biased by taste and position preferences and offer limited stimulus control. In the present experiment five rats were trained to discriminate distilled water from 0.9% NaCl using a discretetrials go-no go procedure. When two rats were further trained on a series of 0.1% saccharin/NaCl discrimination reversals, correct responding occurred more rapidly following saccharin presentations independent of its stimulus property (S^D or S^Δ). The results are discussed in the context of experimental methods and the usefulness of the present technique for studies of gustatory physiology.     

The development of goal-directed reaching in infants II. Learning to produce task-adequate patterns of joint torque

 Nine young infants were followed longitudinally from 4 to 15 months of age. They performed multijoint reaching movements to a stationary target presented at shoulder height. Time-position data of the hand, shoulder, and elbow were collected using an optoelectronic measurement system. In addition, we recorded electromyographic activity (EMG) from arm extensors and flexors. This paper documents how control problems of proximal torque generation may account for the segmented hand paths seen during early reaching. Our analysis revealed the following results: first, muscular impulse (integral of torque) increased significantly between the ages of 20 (reaching onset) and 64 weeks. That is, as infants got older they produced higher levels of mean muscular flexor torque during reaching. Data were normalized by body weight and movement time, so differences are not explained by anthropometric changes or systematic variations in movement time. Second, while adults produced solely flexor muscle torque to accomplish the task, infants generated flexor and extensor muscle torque at shoulder and elbow throughout a reach. At reaching onset more than half of the trials revealed this latter kinetic profile. Its frequency declined systematically as infants got older. Third, we examined the pattern of muscle coordination in those trials that exhibited elbow extensor muscle torque. We found that during elbow extension coactivation of flexor and extensor muscles was the predominant pattern in 67% of the trials. This pattern was notably absent in comparable adult reaching movements. Fourth, fluctuations in force generation, as measured by the rate of change of total torque (NET) and muscular torque (MUS), were more frequent in early reaching (20–28 weeks) than in the older cohort (52–64 weeks), indicating that muscular torque production became increasingly smoother and task-efficient. Our data demonstrate that young infants have problems in generating smooth profiles of proximal joint torques. One possible reason for this imprecision in infant force control is their inexperience in predicting the magnitude and direction of external forces. That infants learned to consider external forces is documented by their increasing reliance on these forces when performing voluntary elbow extensions. The patterns of muscle coordination underlying active elbow extensions were basically the same as during the prereaching phase, indicating that the formation of functional synergies is based on a basal repertoire of innervation patterns already observable in very early, spontaneous movements. Received: 5 January 1996 / Accepted: 19 August 1996     

Early coping experience and later aversive conditioning in cats

Kittens were given differential early experience in order to compare an objective coping behavior with the result of an inescapable aversive experience. Separate groups of kittens were treated in a shock motivated runway task at either 4 or 12 weeks of age, by allowing one member of a weight matched sibling pair to acquire an escape behavior, while the other member was confined; a third subject served as a handled control. Escape behavior was significantly different for 4 and 12 week old subjects, since the older kittens reached a running asymptote within the first few shock trials. At 6 months of age, the subjects were tested for effects of differential early treatment; heart rate, respiration rate and amplitude, and somatic activity were measured during classical conditioning. While all groups gave evidence of acquisition in one or more response measures, only a potentiated heart rate response in 4 week kittens could be related to early experience. Heart rate did not differentiate escaping kittens from confined ones. Rather, heart rate was related to early treatment with shock, perhaps reflecting an increased tendency to react with a passive defensive response.     

PBL教学在中学生艾滋病教育中的探索应用

目的 探讨问题导向式学习(PBL)教学法在中学生艾滋病健康教育的应用效果,为拓展青少年艾滋病健康教育提供科学性参考。方法 随机选取本地区某中学初一年级2个班102名中学生,分别设置对照组与干预组,对照组采用传统课堂讲授法,干预组采用PBL教学法。干预前后采用同一问卷进行调查。结果 干预后,对照组仅在“艾滋病全称”等6项知识(χ2=6.029～9.434,P=0.004～0.028)的知晓率与“应将艾滋病病人进行隔离(χ2=17.275,P＜0.001)”、“应对艾滋病病人关心同情(χ2=5.696,P=0.017)”2个条目的态度正向率较干预前有所提高;干预组在各项知识知晓率与态度正向率较干预前均有所提高(χ2=3.840～23.520,P均＜0.001～0.05)。干预前,两组在知识知晓率及态度正向率方面的差异无统计学意义(P均＞0.05);干预后,干预组在“艾滋病的全称”等9项知识的知晓率均高于对照组(χ2=4.943～10.183,P=0.026～0.001),仅在“对艾滋病病人具有恐惧感”的态度正向率高于对照组(χ2=11.330,P=0.001)。结论 中学生艾滋病健康教育中,PBL教学法具有更好的教学效果,可以在传统课堂教授法的基础上结合运用。     

新生儿败血症休克预测模型的构建——1 695例患儿回顾性研究

目的 筛选新生儿发生败血症休克的危险因素,建立新生儿败血症休克临床预测模型。方法 选取2016年1月1日—2019年12月31日重庆医科大学7家附属医疗机构中患有败血症的新生儿,根据是否发生败血症休克分为研究组和对照组。采用单因素分析、LASSO和logistic回归分析筛选危险因素。采用logistic、极端梯度提升（XGBoost）、随机森林（RF）、分类回归树（CART）和人工神经网络（ANN）建立新生儿败血症休克预测模型,根据灵敏度、特异度、曲线下面积等指标评估模型性能。结果 本研究中,共有339名败血症新生儿发生败血症休克,1 356名败血症新生儿未发生败血症休克。单因素分析筛选出31项差异指标,多因素分析筛选出12项独立危险因素。测试集中,logistic、XGBoost、RF、CART、ANN模型的曲线下面积分别为0.856 (0.809～0.903),0.861 (0.819～0.904),0.880 (0.838～0.922),0.835 (0.790～0.881),0.808 (0.756～0.860)。结论 本文构建的五种预测模型相对稳定,其中,RF模型的预测性能最佳,能为新生儿败血症休克提供较好的预测。     

A Framework for Using Real-World Data and Health Outcomes Modeling to Evaluate Machine Learning–Based Risk Prediction Models

ObjectivesWe propose a framework of health outcomes modeling with dynamic decision making and real-world data (RWD) to evaluate the potential utility of novel risk prediction models in clinical practice. Lung transplant (LTx) referral decisions in cystic fibrosis offer a complex case study.MethodsWe used longitudinal RWD for a cohort of adults (n = 4247) from the Cystic Fibrosis Foundation Patient Registry to compare outcomes of an LTx referral policy based on machine learning (ML) mortality risk predictions to referral based on (1) forced expiratory volume in 1 second (FEV₁) alone and (2) heterogenous usual care (UC). We then developed a patient-level simulation model to project number of patients referred for LTx and 5-year survival, accounting for transplant availability, organ allocation policy, and heterogenous treatment effects.ResultsOnly 12% of patients (95% confidence interval 11%-13%) were referred for LTx over 5 years under UC, compared with 19% (18%-20%) under FEV₁ and 20% (19%-22%) under ML. Of 309 patients who died before LTx referral under UC, 31% (27%-36%) would have been referred under FEV₁ and 40% (35%-45%) would have been referred under ML. Given a fixed supply of organs, differences in referral time did not lead to significant differences in transplants, pretransplant or post-transplant deaths, or overall survival in 5 years.ConclusionsHealth outcomes modeling with RWD may help to identify novel ML risk prediction models with high potential real-world clinical utility and rule out further investment in models that are unlikely to offer meaningful real-world benefits.     

Sleep following intense physical exercise stabilizes motor learning in typically developing boys

There is compelling evidence that sleep (N2, REM sleep, but also N3) supports the consolidation of motor memory in adults. Although children express higher levels of REM sleep and N3, it is still not understood why sleep does not benefit the consolidation of motor memory in children as in adults. Here, we aimed to manipulate sleep by daytime physical exercise in typically developing boys (N = 12; range 9–12 yrs) to test the impact on sleep and motor learning. The manipulation consisted of 1 h of intense ergometer exercise during the daytime before a night of restorative sleep. In a rest control condition, children were seated comfortably and listened to an audio drama. Motor learning was assessed with a visuomotor finger sequence tapping task; in both conditions learning took place before either exercise or rest. Prior to sleep in the sleep laboratory, motor memory was assessed as a baseline. Motor memory was again collected in the morning after a night of sleep in the lab. While there was no change in N3, we found prolonged REM sleep latency after physical activity compared to rest, corresponding to a prolonged first sleep cycle. With respect to motor learning, we found superior accuracy of motor performance after physical exercise compared to rest. Our findings suggest that physical exercise during the daytime stabilizes sleep-dependent motor learning.     

A Systematic Review of the Dietary Choline Impact on Cognition from a Psychobiological Approach: Insights from Animal Studies

The influence of dietary choline availability on cognition is currently being suggested by animal and human studies which have focused mainly on the early developmental stages. The aim of this review is to systematically search through the available rodent (rats and mice) research published during the last two decades that has assessed the effect of dietary choline interventions on cognition and related attentional and emotional processes for the entire life span. The review has been conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines covering peer-reviewed studies included in PubMed and Scopus databases. After excluding duplicates and applying the inclusion/exclusion criteria we have reviewed a total of 44 articles published in 25 journals with the contribution of 146 authors. The results are analyzed based on the timing and duration of the dietary intervention and the behavioral tests applied, amongst other variables. Overall, the available results provide compelling support for the relevance of dietary choline in cognition. The beneficial effects of choline supplementation is more evident in recognition rather than in spatial memory tasks when assessing nonpathological samples whilst these effects extend to other relational memory tasks in neuropathological models. However, the limited number of studies that have evaluated other cognitive functions suggest a wider range of potential effects. More research is needed to draw conclusions about the critical variables and the nature of the impact on specific cognitive processes. The results are discussed on the terms of the theoretical framework underlying the relationship between the brain systems and cognition.