基于ANSYS/LS-DYNA的神经电极植入脑组织过程数值仿真

目的 建立神经电极-脑组织数值仿真模型,研究神经电极在植入过程中对脑组织产生的植入损伤。方法 采用超黏弹性模型描述脑组织材料,基于单元删除法和最大主应变失效准则模拟组织破坏与分离,并通过平均等效应变量化组织植入损伤,考察神经电极楔形角、植入速度以及电极刚度对脑组织急性损伤的影响规律。结果 150°楔角所产生应变值较90°增加37.1%;100 μm/s慢速植入时电极植入路径上组织应变值较大（>57%）,500 μm/s较高速植入时植入路径上组织应变明显变小（<25%）;而电极刚度对组织损伤影响不明显,电极刚度从165 GPa下降至5 kPa时,组织应变仅增加1%~2%。结论 数值仿真模型可为神经电极与植入参数设计提供参考,从而减少组织植入损伤,提高电极工作寿命,满足长期临床应用。     

基于ANSYS/LS-DYNA的神经电极植入脑组织过程数值仿真

目的 建立神经电极-脑组织数值仿真模型,研究神经电极在植入过程中对脑组织产生的植入损伤。方法 采用超黏弹性模型描述脑组织材料,基于单元删除法和最大主应变失效准则模拟组织破坏与分离,并通过平均等效应变量化组织植入损伤,考察神经电极楔形角、植入速度以及电极刚度对脑组织急性损伤的影响规律。结果 150°楔角所产生应变值较90°增加37.1%;100 μm/s慢速植入时电极植入路径上组织应变值较大（>57%）,500 μm/s较高速植入时植入路径上组织应变明显变小（<25%）;而电极刚度对组织损伤影响不明显,电极刚度从165 GPa下降至5 kPa时,组织应变仅增加1%~2%。结论 数值仿真模型可为神经电极与植入参数设计提供参考,从而减少组织植入损伤,提高电极工作寿命,满足长期临床应用。     

基于硅基电极的脑组织微动损伤仿真

目的:为预测脑组织微动损伤和解决植入电极的长期寿命问题,本研究基于硅基微电极进行建模,并对神经电极-脑组织有限元模型进行数值仿真。 方法:采用超黏弹性模型描述脑组织材料,研究不同微动模式（纵向和横向）、不同物理耦合度下电极附近脑组织应变分布。 结果:纵向载荷分析显示当摩擦系数?增加时,脑组织最大von Mises应变呈降低趋势,并且电极尖端附近的组织应变最大,这表明电极与脑组织之间的物理耦合度对脑组织微动损伤有较大影响。增强电极和脑组织间的黏附程度,可以有效减小脑组织损伤。电极尖端的形状也极大地影响着组织的应变大小。横向载荷分析显示X轴方向的载荷产生的脑组织损伤区域大约为60 ?m,这表明电极之间的间距应大于60 ?m,否则不同电极产生的组织应变会发生重叠,这对于电极之间理想间距的设计和防止重叠应变形成多余的细胞鞘有着重要的意义。 结论:数值仿真模型可以为电极-脑组织界面参数和电极间距设计参数提供参考,从而减少组织损伤,提高电极工作寿命,满足临床应用。     

神经电极的水凝胶涂层及楔形角对组织损伤的影响

目的研究水凝胶涂层的厚度以及电极楔形角对植入损伤的影响。方法基于植入损伤评估系统,进行模拟神经电极植入过程的实验,评估电极植入造成的组织损伤。用浸涂次数(分别为0、1、2、3)控制水凝胶涂层的厚度,选用30°、40°、50°、60°为电极楔形角的变量。以最大组织应变和最大植入力为组织损伤的衡量标准。结果水凝胶涂层越厚,电极植入损伤越大。楔形角越小,植入损伤也越小。同时,减小针尖的楔形角可以减小涂层对组织损伤的影响程度。3次浸涂时,楔形角为30°时,最大组织应变与最大植入力分别增加3.4%和3.8%,而楔形角为60°时,两者分别增加11.3%和18.1%。结论神经电极的水凝胶涂层将增大植入电极对生物组织的损伤,然而减小电极尖端楔形角的方法可以降低水凝胶涂层厚度对植入损伤的影响程度。     

涂层修饰的柔性神经电极力学综合性能评估

目的对带有涂层修饰的柔性神经电极进行力学综合性能的评估,为电极及涂层参数的优化设计提供依据。方法对接触、植入以及微动阶段建立简化力学模型,以聚酰亚胺为电极材料,PEG为涂层材料,PDMS模具注塑法为涂层涂覆方法,设置40、80、120、160、200μm涂层厚度梯度,对3个因素(临界载荷、最大形变、脑组织最大应变)进行综合对比评估。结果厚度增加会引起临界载荷增大、最大形变减小以及脑组织最大应变减小,同时也会导致脑组织应变区域增大。均衡3个因素考虑,选择200μm作为涂层最佳厚度,在该厚度下,临界载荷为17.9 m N,最大形变为10.1μm,脑组织最大应变为0.011 4。结论涂层厚度对神经电极的力学性能有较大影响,在具体情况下可通过设置多个力学性能因素的影响因子选择最优参数。涂层的最优参数选择可提高电极的性能,对神经电极的临床应用具有重要意义。     

侵入式柔性神经电极的植入策略

侵入式神经电极将人类对神经科学的认识提升到微米与毫秒尺度.由于传统的刚性电极与柔软的脑组织间存在较大的机械不匹配性,柔性电极成为新一代神经电极的发展趋势.神经电极的柔性化更迭降低免疫反应的同时却失去植入刚度.分析神经电极的植入机制并总结目前研究中关于柔性电极的植入策略,旨在帮助解决柔性电极的植入能力丧失以及急性植入损伤...     

用束内电极进行肌肉复原

我们已研究了将聚四氟乙烯绝缘的直径为25μm的P_t-I_r束内电极植入支配猫腓肠肌和比目鱼肌的神经中所得到的肌肉复原。本项研究的目的在于测量包括刺激电极在内的经过优化设计的能最佳地记录周围神经单元活动的双极电极的性能。复原曲线确定了最佳刺激形状为一个相间距约为500μs和脉宽约为50μs的双相矩形脉冲。最大颤动收缩的一半所需的电流约为50μA。刺激所需的电流和电荷密度正好处在相关的组织和电极材料的安全水平以下。当我们用压碎神经的方法中断脊髓反射路径时,由一个给定的刺激所产生的力在某些情况下发生变化而在另一些情况下不变,     

Cuff电极长期植入性能初步研究

目的：研究Cuff电极长期植入性能。方法：在狗面神经颧支周围植入Cuff电极，通过这个植入电极，分别在14天、6月后提取自然发生的神经电信号，比较分析其信号的差异性；通过组织形态学的方法，在Cuff电极植人后6个月观察分析周围有电极植入的神经段落的组织形态学变化，以分析植入电极对神经的影响。结果：通过植入的Cuff电极，在电极植入后14天、6月均能提取出能反映眨眼动作发生的神经信号，所提取到的自然睁眼状态下的神经信号在幅值（RMS）和频率（MPF）方面没有明显的变化。长期植入Cuff电极的神经，未发现有明显的损伤性形态改变。结论：Cuff电极适合作为长期植入体使用。可以提取到稳定的神经电信号，对于所附着神经不会产生明显的损伤，提示这种植入电极的应用具有可逆性。     

经颅磁刺激和脑电联合作用时电磁场分布的仿真研究

目的：研究分析经颅磁刺激和脑电（TMS-EEG）联合作用时磁感应强度和感应电场强度的分布情况。方法：利用有限元多物理场仿真软件COMSOL，搭建3层同心球人头模型、TMS线圈模型和EEG电极模型，在TMS线圈的作用下，对比分析了有无脑电极时，人头模型当中磁感应强度和感应电场强度的不同。结果：取头部组织几个特殊位置点，放置脑电极后，各点处磁感应强度和感应电场强度均发生变化，磁感应强度最大变化达19.19%，感应电场强度最大变化达75.33%。添加脑电极后，人体头部组织YZ纵切面的最大磁感应强度降低7 mT，最大感应电场强度值降低0.6 V/m。大脑处的三维磁感应强度和感应电场强度均随着深度的增加而逐渐减小，放置脑电极后，脑组织中的最大磁感应强度值减少1.4 mT，最大感应电场强度值减少0.13 V/m。结论：经TMS-EEG联合作用时，在人头皮处放置脑电极会对电磁场的分布产生影响，间接影响TMS的治疗作用。     

螺旋袖套电极胞外刺激视神经的电场有限元分析

为了研究电极与神经作用机制,优化电极设计和指导假体的应用,有限元方法用于分析螺旋袖套电极刺激视神经产生的电场空间分布。建立了圆柱形的视神经模型,并考虑电极结构和脑脊液(CSF)厚度变化对刺激效果的影响。选择合适的网格剖分和边界条件,应用COMSOL Multiphysics有限元软件,计算电极的三维电场。结果表明,在相同的刺激条件下,纵向三电极结构比双电极结构(电极分别位于神经干对侧)的电流密度值要大,但双极结构所需引线少,植入简单,易于临床应用。应用参数扫描的方法仿真表明,由于CSF层的电导率比其他组织大,随着CSF层厚度增加,电极电场分布范围更大,但对电流的散射阻碍使神经刺激效果变差。     

Renal dysplasia and asplenia in two sibs

A family is reported in which two sibs, one male and the other female, both died within 24 hours of birth with enlarged polycystic kidneys. Postmortem histology in the second child showed gross renal dysplasia. In both children the pancreas was enlarged, nodular and cystic but the liver appeared macroscopically normal. In the second child, histological examination confirmed pancreatic fibrosis with cystic dilation of ducts, but showed portal fibrosis with bile duct proliferation in the liver.
This combination of findings is very reminiscent of those in a girl and her brother reported by Ivemark et al. (1959). The children reported here also showed absence or hypoplasia of the spleen, cardiac anomalies and other features of the Ivemark syndrome (Ivemark 1955), a quite different, usually sporadic, congenital disorder. It is suggested that the children described here have a distinct lethal congenital disorder, probably inherited in an autosomal recessive manner.     

Schizophrenia in a North Swedish geographical isolate, 1900–1977. Epidemiology, genetics and biochemistry

Over 200 schizophrenic patients belonging to three major and interrelated pedigree complexes have been investigated over the past 30 years in a North Swedish geographically isolated population, presently numbering about 6,000. An intensive investigation of a number of biochemical correlates and genetic markers in a few selected families belonging to one of the major pedigrees has indicated new strategies for the current research program.
Schizophrenia, as defined operationally, is significantly associated with decreased activities of two enzymes (1) blood platelet monoamine oxidase, (2) plasma dopamine-β-hydroxylase, and (3) with the genetic marker Gc² (group specific antigen). Both enzymes are subject to genetic variation. A positive score for linkage between schizophrenia and low plasma DBH activity has been calculated, but, so far, available data are insufficient for discrimination between linkage and partial contribution of genetically controlled low plasma DBH to the pathogenesis of the disease. Alternatively, both mechanisms could be involved.
As a model for continued research, schizophrenia is explained as based on a double dominant-recessive genotype (Aabb), representing a vulnerability which in about 50 % of cases develops into clinical schizophrenia. It is suggested that the dominant mutation (A) operates on or affects MAO activity, and that the recessive genotype (bb) is instrumental in low variates of DBH activity and very likely such variates within the normal range of physiological variation. Moreover, it is suggested that the combined effects of MAO- and DBH-reduced efficiency on the metabolism of e.g. dopamine could be an essential pathogenic mechanism for the schizophrenic illness which is segregating in this population.     

The dominant diseases of modernized societies as omega-3 essential fatty acid deficiency syndrome: Substrate beriberi

About 1900, modern food selection and processing caused widespread $\text{epidemics}$ of the B vitamin deficiency diseases of beriberi and pellagra which, for genetic reasons, often expressed as different diseases ranging from bowel and heart disease to dermatoses and psychoses. But the B vitamins merely help convert essential fatty acids (EFA) into the prostaglandin (PG) tissue regulators and it now turns out that, through hydrogenation, milling and selection of w3-poor southern foods, we have also been systematically depleting, by as much as 90%, a newly discovered trace Nordic EFA (w3) of special importance to primates and sole precursor of the PG3(4) series, even as a concurrent fiber deficiency increases body demand for EFA. Since substrate EFA is processed by many B vitamin catalysts, an EFA deficiency will mimic a $\text{panh}$ypovitaminosis B, i.e., a mixture of $\text{substrate}$ beriberi and $\text{substrate}$ pellagra resembling vitamin beriberi and pellagra but exhibiting as even more diverse $\text{endemic}$ disease. This would consitute a second stage of the Modern Malnutrition and explain why some workers now hold the dominant diseases of modermized societies to be new, nutritionally based, pellagraform yet lipid-related and to range, once again, from heart disease to psychosis. It is an assumption that our dominant diseases are unrelated to each other or are merely revealed by our diagnostic acumen and therapeutic success; and that hydrogenating millions of tons of food oils annually, to destroy the rancidity producing w3-EFA, is safe for $\text{primates}$. Extensive beriberiform disease is reported here in 32 typical cases taken from medical practice which responds strikingly to linseed oil supplements (60% w3-EFA) in confirmation of identical results in Capuchins.     

What will studies of Fulani individuals naturally exposed to malaria teach us about protective immunity to malaria?

There are an estimated over 200 million yearly cases of malaria worldwide. Despite concerted international effort to combat the disease, it still causes approximately half a million deaths every year, the majority of which are young children with Plasmodium falciparum infection in sub-Saharan Africa. Successes are largely attributed to malaria prevention strategies, such as insecticide-treated mosquito nets and indoor spraying, as well as improved access to existing treatments. One important hurdle to new approaches for the treatment and prevention of malaria is our limited understanding of the biology of Plasmodium infection and its complex interaction with the immune system of its human host. Therefore, the elimination of malaria in Africa not only relies on existing tools to reduce malaria burden, but also requires fundamental research to develop innovative approaches. Here, we summarize our discoveries from investigations of ethnic groups of West Africa who have different susceptibility to malaria.     

'Very sore nights and days': the child's experience of illness in early modern England, c.1580-1720

Sick children were ubiquitous in early modern England, and yet they have received very little attention from historians. Taking the elusive perspective of the child, this article explores the physical, emotional, and spiritual experience of illness in England between approximately 1580 and 1720. What was it like being ill and suffering pain? How did the young respond emotionally to the anticipation of death? It is argued that children’s experiences were characterised by profound ambivalence: illness could be terrifying and distressing, but also a source of emotional and spiritual fulfilment and joy. This interpretation challenges the common assumption amongst medical historians that the experiences of early modern patients were utterly miserable. It also sheds light on children’s emotional feelings for their parents, a subject often overlooked in the historiography of childhood. The primary sources used in this article include diaries, autobiographies, letters, the biographies of pious children, printed possession cases, doctors’ casebooks, and theological treatises concerning the afterlife.     

Guidelines for the Validation and Use of Immunoassays for Determination of Introduced Proteins in Biotechnology Enhanced Crops and Derived Food Ingredients

Recent advancements in agricultural biotechnology have created a need for analytical techniques to determine introduced proteins in crops enhanced through modern biotechnology techniques. These proteins are expressed in plant tissues and may be present in food ingredients. Immunoassays are ideally suited for protein detection and may be used as both quantitative and threshold methods. Microplate ELISA and lateral flow devices are two of the most commonly used immunoassay formats for agricultural biotechnology applications. This paper provides general background information and a discussion of criteria for the validation and application of immunochemical methods to the analysis of proteins introduced into plants and food ingredients using biotechnology methods. It is the result of a collaborative effort of members of the Analytical Environmental Immunochemical Consortium. This collaborative effort represents the combined expertise of several organizations to reach consensus on establishing guidelines for the validation and use of immunoassays. Further, the paper offers developers and users a consistent approach to adopting the technology as well as aid in producing accurate and meaningful results.     

Ultracryotomy: development and application (with examples from the yeast cytology) (author's transl)

The preparation steps usually necessary for obtaining ultrathin frozen sections of biological material (chemical prefixation, enclosing, cryoprotective treatment, freezing, sectioning, and post-staining the sections for transmission electron microscopy) are submitted to a critical analysis. The application of cryo-ultramicrotomy, in particularly for cytochemical purposes, is reviewed. Fundamental considerations of chemical prefixation and poststaining are supported by examples from yeast cytology. Furthermore, the efficiency of the cryo-ultramicrotomy (electron optical resolution of ultrastructural details) is demonstrated on yeast cells and protoplasts.     

HLA in North Colombia Chimila Amerindians

HLA-A,-B,-C,-DRB1 and -DQB1 alleles have been studied in Chimila Amerindians from Sabana de San Angel (North Colombian Coast) by using high resolution molecular typing. A frequent extended haplotype was found:HLA-A*24:02-B*51:10-C*15:02-BRB1*04:07-DQB1*03:02 (28.7%) which has also been described in Amerinndian Mayos Mexican population (Mexico, California Gulf, Pacific Ocean). Other haplotypes had already been found in Amerindians from Mexico (Pacific and Atlantic Coast), Peru (highlands and Amazon Basin), Bolivia and North USA. A geographic pattern according to HLA allele or haplotype frequencies is lacking in Amerindians, as already known. Also, five new extended haplotypes were found in Chimila Amerindians. Their HLA-A*24:02 high frequencies characteristic is shared with aboriginal populations of Taiwan; also, HLA-C*01:02 high frequencies are found in New Zealand Maoris, New Caledonians and Kimberly Aborigines from Australia. Finally, this study may show a model of evolutionary factors acting and rising one HLA allele frequency (-A*24:02), but not in others that belong to the same or different HLA loci.     

The case for allele‐specific recognition by the TCR

There is a sharp difference in how one views TCR structure–function–behaviour dependent on whether its recognition of major histocompatibility complex‐encoded restriction elements (R) is germline selected or somatically generated. The generally accepted or Standard model is built on the assumption that recognition of R is by the V regions of the αβ TCR, which is not driven by allele specificity, whereas the competing model posits that recognition of R is allele‐specific. The establishing of allele‐specific recognition of R by the TCR would rule out the Standard model and clear the road to a consideration of a competing construct, the Tritope model. Here, the case for allele‐specific recognition (germline selected) is detailed making it obvious that the Standard model is untenable.