早期强化步行基本功训练对脑卒中的预后分析

目的：分析早期强化步行基本功训练对脑卒中预后的影响。方法：选取我院2008年10月一2011年10月收治的176例恢复期脑卒中患者,按照随机数字表分为观察组及对照组,各88例,均接受常规药物治疗和康复训练,观察组在此基础上接受早期强化步行基本功训练,对比两组患者的预后。结果：两组患者治疗后FMA—LE、BBS及MBI评分均见上升,观察组较对照组上升程度更为明显（P〈0．05）,T2时期观察组评分亦见升高,而对照组评分与T1时期相比无明显统计学差异（P〉0．05）;两组患者治疗后步长、步宽及步速均见上升,观察组较对照组上升程度更为明显（P〈0．05）,T2时期观察组步态参数亦见升高,而对照组步态参数与T1时期相比无明显统计学差异（P〉0．05）。结论：早期强化步行基本功训练能够有效改善脑卒中患者下肢运动功能和平衡能力,保证治疗后步行功能,避免生活质量下降,该康复方法值得广泛推广。     

Recombinase-mediated cassette exchange (RMCE) — A rapidly-expanding toolbox for targeted genomic modifications

Starting in 1991, the advance of Tyr-recombinases Flp and Cre enabled superior strategies for the predictable insertion of transgenes into compatible target sites of mammalian cells. Early approaches suffered from the reversibility of integration routes and the fact that co-introduction of prokaryotic vector parts triggered uncontrolled heterochromatization. Shortcomings of this kind were overcome when Flp-Recombinase Mediated Cassette Exchange entered the field in 1994. RMCE enables enhanced tag-and-exchange strategies by precisely replacing a genomic target cassette by a compatible donor construct. After “gene swapping” the donor cassette is safely locked in, but can nevertheless be re-mobilized in case other compatible donor cassettes are provided (“serial RMCE”). These features considerably expand the options for systematic, stepwise genome modifications. The first decade was dominated by the systematic generation of cell lines for biotechnological purposes. Based on the reproducible expression capacity of the resulting strains, a comprehensive toolbox emerged to serve a multitude of purposes, which constitute the first part of this review. The concept per se did not, however, provide access to high-producer strains able to outcompete industrial multiple-copy cell lines. This fact gave rise to systematic improvements, among these certain accumulative site-specific integration pathways. The exceptional value of RMCE emerged after its entry into the stem cell field, where it started to contribute to the generation of induced pluripotent stem (iPS-) cells and their subsequent differentiation yielding a variety of cell types for diagnostic and therapeutic purposes. This topic firmly relies on the strategies developed in the first decade and can be seen as the major ambition of the present article. In this context an unanticipated, potent property of serial Flp-RMCE setups concerns the potential to re-open loci that have served to establish the iPS status before the site underwent the obligatory silencing process. Other relevant options relate to the introduction of composite Flp-recognition target sites (“heterospecific FRT-doublets”), into the LTRs of lentiviral vectors. These “twin sites” enhance the safety of iPS re-programming and -differentiation as they enable the subsequent quantitative excision of a transgene, leaving behind a single “FRT-twin”. Such a strategy combines the established expression potential of the common retro- and lentiviral systems with options to terminate the process at will. The remaining genomic tag serves to identify and characterize the insertion site with the goal to identify genomic “safe harbors” (GOIs) for re-use. This is enabled by the capacity of “FRT-twins” to accommodate any incoming RMCE-donor cassette with a compatible design.     

TIME-OF-DAY EFFECTS ON THE INTERNAL SIMULATION OF MOTOR ACTIONS: PSYCHOPHYSICAL EVIDENCE FROM POINTING MOVEMENTS WITH THE DOMINANT AND NON-DOMINANT ARM

It is well known that circadian rhythms modulate human physiology and behavior at various levels. However, chronobiological data concerning mental and sensorimotor states of motor actions are still lacking in the literature. In the present study, we examined the effects of time-of-day on two important aspects of the human motor behavior: prediction and laterality. Motor prediction was experimentally investigated by means of imagined movements and laterality by comparing the difference in temporal performance between right and left arm movements. Ten healthy participants had to actually perform or to imagine performing arm-pointing movements between two targets at different hours of the day (i.e., 08:00, 11:00, 14:00, 17:00, 20:00, and 23:00?h). Executed and imagined movements were accomplished with both the right and left arm. We found that both imagined and executed arm pointing movements significantly fluctuated through the day. Furthermore, the accuracy of motor prediction, investigated by the temporal discrepancy between executed and imagined movements, was significantly better in the afternoon (i.e., 14:00, 17:00, and 20:00?h) than morning (08:00 and 11:00?h) and evening (23:00?h). Our results also revealed that laterality was not stable throughout the day. Indeed, the smallest temporal differences between the two arms appeared at 08:00 and 23:00?h, whereas the largest ones occurred at the end of the morning (11:00?h). The daily variation of motor imagery may suggest that internal predictive models are flexible entities that are continuously updated throughout the day. Likewise, the variations in temporal performance between the right and the left arm during the day may indicate a relative independence of the two body sides in terms of circadian rhythms. In general, our findings suggest that cognitive (i.e., mental imagery) and motor (i.e., laterality) states of human behavior are modulated by circadian rhythms. (Author correspondence: charalambos.papaxanthis@u-bourgogne.fr)     

Seasonal Effect on Infants' Sleep Regulation: A Preliminary Study in a Mediterranean Climate

Infants' sleep-wake rhythms are influenced by multiple factors, including developmental and contextual aspects, as well as circadian cycles. Empirical studies that address the seasonal impact on infants' sleep are scarce. The present study examined aspects of sleep schedule and quality, comparing summer and winter months in a Mediterranean climate. This report is based on a convenience sample of 34 healthy 7-mo-olds, an age in which sleep is well consolidated and regulated compared with the first few months of life. Sleep was measured with actigraphy, in the home context. It was found that compared with winter, in the summer months, sleep onset occurred at a later hour, and more motor activity during sleep was detected. Although the overall sleep quality, as defined by sleep efficiency score, was similar in the two seasons, in the summer, more active sleep was observed. The authors discuss the finding in terms of circadian rhythms, developmental characteristics, as well as possible environmental factors and family routines, and call for more studies, in different climates and geographical zones, and in different developmental periods. (Author correspondence: cohen.dini@gmail.com or anats@edu.haifa.ac.il)     

Fused in Sarcoma (FUS) Protein Lacking Nuclear Localization Signal (NLS) and Major RNA Binding Motifs Triggers Proteinopathy and Severe Motor Phenotype in Transgenic Mice

Dysfunction of two structurally and functionally related proteins, FUS and TAR DNA-binding protein of 43 kDa (TDP-43), implicated in crucial steps of cellular RNA metabolism can cause amyotrophic lateral sclerosis (ALS) and certain other neurodegenerative diseases. The proteins are intrinsically aggregate-prone and form non-amyloid inclusions in the affected nervous tissues, but the role of these proteinaceous aggregates in disease onset and progression is still uncertain. To address this question, we designed a variant of FUS, FUS 1–359, which is predominantly cytoplasmic, highly aggregate-prone, and lacks a region responsible for RNA recognition and binding. Expression of FUS 1–359 in neurons of transgenic mice, at a level lower than that of endogenous FUS, triggers FUSopathy associated with severe damage of motor neurons and their axons, neuroinflammatory reaction, and eventual loss of selective motor neuron populations. These pathological changes cause abrupt development of a severe motor phenotype at the age of 2.5–4.5 months and death of affected animals within several days of onset. The pattern of pathology in transgenic FUS 1–359 mice recapitulates several key features of human ALS with the dynamics of the disease progression compressed in line with shorter mouse lifespan. Our data indicate that neuronal FUS aggregation is sufficient to cause ALS-like phenotype in transgenic mice.     

Blood,War, and Ritual: Religious Ecology, ‘Strong’ Culture,and Human Sacrifice in the Premodern World

What social factors predict human sacrifice in premodern societies? After summarising key insights from competing theoretical perspectives that seek to explain the presence of human sacrifice in premodern societies, we empirically assess the explanatory utility of each theory. We draw from Stark's ‘moral communities’ argument and Alexander and Smith's insights regarding cultural autonomy to highlight how the macro-level organisation of premodern societies impacted the practice of human sacrifice. Using data from Murdock and White's Standard Cross-Cultural Sample, logistic regression models suggest that premodern societies that expressed community ties through religious ceremonies were more likely to engage in human sacrifice, while beliefs in spirit aggression are correlated with lower likelihood of human sacrifice. In terms of non-religious factors, societies that experienced frequent famine were slightly less likely to activity in the ancient world are partly a function of societal complexity. We conclude by specifying the theoretical implications of these findings.     

脑电图检查对新生儿缺氧缺血性脑病的早期诊断及预后判断价值

目的:探讨脑电图检查对新生儿缺氧缺血性脑病早期诊断及预后判断的临床意价值。方法:本研究所选研究对象为我院2011年3月至2014年3月住院的91例出生后一天内的窒息新生儿,对其行脑电图检查,根据脑电图的检查结果将其分为四组,分别为正常组、轻度异常组、中度异常组、重度异常组。对上述四组患儿进行随访,时间点为出生后3个月、6个月,采用婴幼儿发育量表对患儿的智能发育进行测评,对各组智能发育的差异进行比较。结果:(1)91例患儿中,脑电图异常的有83例,异常率为91.21%,脑电图的异常程度与临床分度基本一致;(2)对患儿随访至3个月时,轻度、中度、重度异常组患儿的智力发育指数与运动发育指数的平均值与正常组患儿相比,具有显著差异(P0.05);(3)对患儿随访至6个月时,轻度异常组患儿的智力发育指数与运动发育指数的平均值与正常组患儿相比,无显著差异(P0.05)。中度、重度异常组患儿的智力发育指数与运动发育指数的平均值与正常组患儿相比,具有显著差异(P0.05)。结论:早期脑电图检查结果对新生儿缺氧缺血性脑病的早期诊断有利,为临床上早期干预提供了重要的参考依据。     

The effectiveness of the peer-delivered Thinking Healthy PLUS (THPP+) Program for maternal depression and child socioemotional development in Pakistan: study protocol for a randomized controlled trial

BackgroundThe negative effects of perinatal depression on the mother and child start early and persist throughout the lifecourse (Lancet 369(9556):145–57, 2007; Am J Psychiatry 159(1):43-7, 2002; Arch Dis Child 77(2):99–101, 1997; J Pak Med Assoc 60(4):329; J Psychosoma Res 49(3):207–16, 2000; Clin Child Fam Psychol Rev 14(1):1–27, 2011). Given that 10–35 % of children worldwide are exposed to perinatal depression in their first year of life (Int Rev Psychiatry 8(1):37–54, 1996), mitigating this intergenerational risk is a global public health priority (Perspect Public Health 129(5):221–7, 2009; Trop Med Int Health 13(4):579–83, 2008; Br Med Bull 101(1):57–79, 2012). However, it is not clear whether intervention with depressed women can have long-term benefits for the mother and/or her child. We describe a study of the effectiveness of a peer-delivered depression intervention delivered through 36 postnatal months, the Thinking Healthy Program Peer-delivered PLUS (THPP+) for women and their children in rural Pakistan.Methods/designThe THPP+ study aims are: (1) to evaluate the effects of an extended 36-month perinatal depression intervention on maternal and index child outcomes using a cluster randomized controlled trial (c-RCT) and (2) to determine whether outcomes among index children of perinatally depressed women in the intervention arm converge with those of index children born to perinatally nondepressed women. The trial is designed to recruit 560 pregnant women who screened positive for perinatal depression (PHQ-9 score ≥10) from 40 village clusters, of which 20 receive the THPP+ intervention. An additional reference group consists of 560 perinatally nondepressed women from the same 40 clusters as the THPP+ trial. The women in the nondepressed group are not targeted to receive the THPP+ intervention; but, by recruiting pregnant women from both intervention and control clusters, we are able to evaluate any carryover effects of the THPP+ intervention on the women and their children. Perinatally depressed women in the THPP+ intervention arm receive bimonthly group-based sessions. Primary outcomes are 3-year maternal depression and 3-year child development indicators. Analyses are intention-to-treat and account for the clustered design.DiscussionThis trial, together with the reference group, has the potential to further our understanding of the early developmental lifecourse of children of both perinatally depressed and perinatally nondepressed women in rural Pakistan and to determine whether intervening with women’s depression in the perinatal period can mitigate the negative effects of maternal depression on 36-month child development.

Trial registration

THPP-P ClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT02111915","term_id":"NCT02111915"}}NCT02111915 (registered on 9 April 2014).THPP+ ClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT02658994","term_id":"NCT02658994"}}NCT02658994 (registered on 21 January 2016).Sponsor: Human Development Research Foundation (HDRF).

Electronic supplementary material

The online version of this article (doi:10.1186/s13063-016-1530-y) contains supplementary material, which is available to authorized users.     

Cortical motor representation of the rectus femoris does not differ between the left and right hemisphere

Transcranial magnetic stimulation (TMS) involves non-invasive magnetic stimulation of the brain, and can be used to explore the corticomotor excitability and motor representations of skeletal muscles. However there is a lack of motor mapping studies in the lower limb and few conducted in healthy cohorts. The cortical motor representations of muscles can vary between individuals in terms of center position and area despite having a general localized region within the motor cortex. It is important to characterize the normal range for these variables in healthy cohorts to be able to evaluate changes in clinical populations. TMS was used in this cross-sectional study to assess the active motor threshold (AMT) and cortical representation area for rectus femoris in 15 healthy individuals (11 M/4F 27.3 ± 5.9 years). No differences were found between hemispheres (Left vs. Right P = 0.130) for AMT. In terms of y-axis center position no differences were found between hemispheres (Left vs. Right P = 0.539), or for the x-axis center position (Left vs. Right P = 0.076). Similarly, no differences in calculated area of the motor representation were found (Left vs. Right P = 0.699) indicating symmetry between hemispheres.     

体外反搏治疗小儿急性脑外伤的临床应用分析

目的:探讨以体外反搏为主的综合康复治疗对脑外伤后偏瘫患儿运动功能和日常生活活动能力(ADL)的影响。方法:选择2015年7月至2017年7月我院神经外科收治的脑外伤后偏瘫患儿46例,将其随机分为对照组和治疗组。两组患者均采用常规的康复治疗和护理,对照组采取常规的物理治疗(PT治疗),治疗组患者给予以体外反搏为主的综合康复治疗。于治疗1、3个月后,评价和比较两组患者粗大运动能力(GMFM)评分、精细运动能力(FMFM)评分和日常生活能力(ADL)评分的变化。结果:治疗1、3个月后,两组患儿GMFM、FMFM评分均较治疗前明显增加(均P0.01),而治疗组治疗后GMFM、FMFM评分均明显高于对照组(均P0.01)。两组治疗一个月后ADL总有效率(显效率与有效率之和)分别为90.48%和76.19%,治疗三个月后分别为95.24%和85.71%,治疗组均显著高于对照组(均P0.05)。结论:以体外反搏为主的综合康复治疗有利于促进脑外伤后偏瘫患者ADL及部分运动功能的提高。