双相障碍患者脑灰质体积变化性别差异性研究

目的:寻找不同性别双相障碍患者灰质体积减少脑区差异,探讨不同性别患者临床表现差异性的病理学机制。方法:以26位女性正常人、26例女性双相障碍患者、25位男性正常人、24例男性双相障碍患者作为研究对象,匹配年龄、受教育程度等。进行头部结构磁共振扫描,对平滑后的灰质图像进行双样本t检验,分析不同性别双相障碍患者灰质体积减少的脑区。结果:与女性对照组相比,女性双相障碍患者右侧舌回、右侧楔叶、右侧枕中回、右侧扣带回后部、右侧中央前后回脑区体积下降。与男性对照组相比,男性双相障碍患者体积下降的脑区包括右侧颞上回、右侧颞中回、右侧海马旁回、右侧额中回、右侧额下回、右侧楔前叶、右侧顶下小叶及右侧小脑后叶。结论:双相障碍患者体积下降脑区具有性别差异性,男性患者体积下降的脑区多在右侧颞叶皮层以及额叶及小脑后叶,而女性患者体积下降脑区多在右侧枕叶皮层以及扣带回后部及中央前后回脑区;这种差别可能与双相障碍患者临床表现的性别差异有关。     

多发性硬化和视神经脊髓炎的脑灰质结构分析

目的 利用基于体素的形态学测量(VBM)和基于皮层的脑形态学测量(SBM)方法对多发性硬化(MS)和视神经脊髓炎(NMO)患者脑灰质体积及皮层厚度进行比较分析,探讨这两种疾病的脑灰质结构变化的差异。方法 对21例MS患者,16例NMO患者以及19例健康对照者行磁共振常规序列扫描,基于Matlab2014a平台的统计参数工具SPM12以及SPM12下的小工具CAT12,对VBM和SBM方法处理的数据进行分析。结果 MS组与正常对照(NC)组相比,经高斯随机场(GRF)校正后,MS组在左侧枕上回、左侧楔叶、左侧距状皮质、左侧楔前叶、左侧中央后回、左侧中央旁小叶、右侧楔叶、左侧额中回、左侧额上回和左侧额内侧回灰质体积显著性减少(P<0.05);经族系错误(FWE)法校正后,MS组在左侧中央旁小叶、左侧额上回和左侧楔前叶皮层厚度显著性减少(P<0.05)。NMO组与NC组相比,经GRF校正后,NMO组在左侧中央后回、左侧中央前回、左侧顶下小叶、右侧中央前回和右侧额中回灰质体积显著性增加(P<0.05);NMO组在左侧枕中回、左侧枕上回、左侧颞下回、右侧枕中回、左侧额上回眶部、...     

6～18岁高功能孤独症患者脑灰质异常的磁共振成像研究

目的:探讨6~18岁高功能孤独症患者的灰质体积异常脑区以及异常脑区发育特点。方法:纳入19例6~18岁符合美国精神障碍诊断与统计手册第4版孤独症诊断标准且总智商≥70的高功能孤独症患者,以及年龄、总智商、性别组间匹配的16例正常对照,以磁共振成像检查收集被试的脑影像学资料,采用基于体素的形态学测量方法计算两组被试大脑各区域的灰质体积,在统计学参数图(SPM)软件SPM8中进行双样本t检验得出差异脑区,对结果进行错误率(FDR)多重比较校正(P0.05)。采用偏相关分析两组被试差异脑区灰质体积与年龄的相关性。结果:高功能孤独症组的右侧额下回眶额部灰质体积小于正常对照组(FDR校正,P0.05)。正常对照组右侧额下回眶额部灰质体积与年龄呈负相关(r=-0.592,P0.05),高功能孤独症患者右侧额下回眶额部灰质体积与年龄呈负相关(r=-0.696,P0.01)。结论:与正常人相比,6~18岁高功能孤独症患者右侧额下回眶额部发育异常,此脑区可能参与孤独症的病理机制。     

特发性全面性癫痫患者大脑结构异常改变的MRI研究

目的 基于深度学习脑龄预测方法和FreeSurfer图像分析软件,探讨特发性全面性癫痫（IGE）患者大脑形态结构的异常改变。方法 回顾性病例对照研究。纳入2020年1月—2021年12月山东省立医院及寿光市人民医院神经内科确诊的144例IGE患者。其中男84例、女60例,年龄10~70岁。基于公共脑成像数据库（人类连接组项目、中国人类连接组项目）建立正常人脑T₁加权像（T₁WI）MRI训练深度学习脑龄预测模型,并输入脑皮质及脑白质脑图。将IGE患者T₁WI MRI输入脑龄预测模型,获取预测脑龄。将27例未经治疗的早期IGE患者设为观察组,男18例、女9例,年龄（16.1±3.2）岁;招募与观察组年龄、性别匹配的29名健康志愿者作为对照组,男19例、女10例,年龄（16.4±4.5）岁,均行MR检查。观察项目：（1）比较IGE患者不同年龄段（10~20岁、>20~30岁、>30~40岁、>40~50岁、>50~60岁、>60~70岁）大脑的预测年龄与实际年龄的差异。（2）利用FreeSurfer软件,分析和比较观察组与对照组大脑皮质体积、厚度和表面积,以及局部形态的差异。结果 （1）IGE患者的不同年龄段中,除>30~40岁外（t=-1.58,P=0.138）,脑龄预测值均大于实际年龄,差异均有统计学意义（P值均<0.05）。（2）观察组与对照组的年龄、性别、教育程度等基线资料差异均无统计学意义（P值均>0.05）。与对照组比较,观察组大脑左、右半球皮质厚度略变薄,差异有统计学意义（t=3.91、3.40,P值均<0.01）;2组大脑半球皮质体积、表面积无明显变化,差异均无统计学意义（P值均>0.05）。与对照组相比,观察组脑区中右侧眶额皮质体积增大,无脑区皮质体积减小;右侧中央后回、左侧中央沟附近中央后回、右侧舌回后部分、左侧舌回及楔叶的皮质厚度均增加,右侧中央前回、双侧额上回（背侧）、右侧内嗅皮质的皮质厚度均减小;右侧海马旁回的皮质表面积增大,无脑区的皮质表面积减小。观察组左、右侧苍白球及右侧丘脑体积较对照组缩小,差异均有统计学意义（t=4.01、4.23、2.12,P值均<0.05）。2组左侧丘脑及双侧尾状核、壳核、海马及杏仁核体积比较,差异均无统计学意义（P值均>0.05）。结论 IGE患者在多个年龄段其脑结构都会发生异常改变。早期IGE患者的大脑皮质及皮质下核团仅发生细微结构的异常改变。     

基于ReHo方法的大学生网络成瘾静息功能磁共振成像研究

目的:探讨网络成瘾大学生静息状态脑功能特点。方法:采用ReHo分析方法 ,19名网络成瘾大学生及19名对照进行磁共振脑功能成像,比较两组平均脑ReHo图的差异。结果:IAD组ReHo值升高区域主要集中在小脑、脑干、扣带回(右侧)、双侧海马旁回、右侧额叶(直回,额中回及额下回)、左侧额上回、左侧楔前叶、右侧中央后回、右侧枕中回、右侧颞下回、左侧颞上回及颞中回;ReHo降低的区域仅表现在左侧顶叶的楔前叶。结论:网络成瘾大学生局域一致性存在异常,大部分脑区同步性增强,小脑、脑干、边缘叶、额顶叶同步性增强可能与网络成瘾奖赏通路有关。     

利用脑局部一致性方法对儿童全身强直发作性癫痫的研究

目的　应用静息态功能磁共振局部一致性方法研究儿童全身强直发作性癫痫患者脑区异常活动,探讨其发生的病理生理机制。 方法　对8例儿童全身强直发作性癫痫患者和30例正常儿童进行磁共振扫描,并计算全脑局部一致性的值,进行组间比较并研究局部一致性与病程的相关性。 结果　与对照组相比,癫痫组ReHo值增高的脑区为大脑深部核团（扣带回,丘脑,楔前叶等）,运动相关脑区,额下回,枕叶,颞叶和小脑;ReHo值降低的脑区为双侧额中回、右侧颞中回、左侧颞上回、双侧中央后回、左侧舌回。全身强直发作性癫痫与病程呈正相关的脑区为左侧楔前叶、左侧顶上小叶、右侧中央前回、右侧中央后回;与病程呈负相关的脑区为右侧楔前叶、右侧角回、中央旁小叶。 结论　局部一致性分析方法可以有效地反映癫痫患者异常的神经功能变化,有助于发现强直发作性癫痫发生的病理生理机制。     

正常人和精神分裂症患者脑灰质体积分析的性别效应

目的:通过比较男性和女性正常人、男性和女性精神分裂症患者之间的脑灰质体积差异,探讨脑结构分析中的性别效应。方法:采集60例正常人(30例男性)和96例精神分裂症患者(48例男性)的高分辨率三维脑结构磁共振图像,运用基于体素的形态测量法(VBM)进行分析,获得每一个体的脑灰质体积图像。采用两样本t检验分别比较男性和女性正常人,男性和女性精神分裂症患者之间的脑灰质体积差异。结果:与女性正常人相比,男性正常人左侧的颞中回和额中回、右侧的边缘叶和颞中回的灰质体积较大(P<0.001),而左侧尾状核和右侧海马的灰质体积较小(P<0.001)。与女性精神分裂症患者相比,男性患者双侧的颞下回和海马、左侧的颞上回和颞中回的灰质体积较大(P<0.001),而未发现灰质体积较小的脑区。结论:性别效应是影响正常人或精神分裂症患者脑结构分析的重要因素。     

阴性症状为主的精神分裂症男性患者认知功能及灰质密度改变

目的:运用基于体素的脑形态测量学方法(VBM),探讨以阴性症状为主的精神分裂症男性患者大脑结构形态学的改变,及其与精神病理学症状的关系。方法:15例阴性症状为主的成年男性精神分裂症患者和15例正常对照参与实验,所有研究对象均接受威斯康星卡片分类测验(WCST)与磁共振检查,获取磁共振T1加权像和高分辨率3D图像后进行VBM分析,比较患者组和正常对照组局部脑区灰质密度的差异性。结果:在威斯康星测验中,阴性症状为主的精神分裂症患者完成测查的总应答数、错误应答数和持续性错误数显著高于正常对照组,正确应答数和完成分类数与正常对照组没有显著差异。VBM分析显示患者右侧额上回,左侧额中回,左额内侧回,右侧楔叶,左侧颞中回的灰质密度较正常对照组低,未发现患者组灰质密度有明显增高的脑区。结论:以阴性症状为主的精神分裂症患者存在显著的额叶执行功能低下;双侧额叶灰质密度的下降可能是其执行功能损害的病理生理基础。     

精神分裂症及其健康同胞脑灰质体积异常的研究

目的:研究精神分裂症及其健康同胞的脑灰质体积的异常,为寻找精神分裂症大脑灰质异常内表型提供新的线索。方法:对27例精神分裂症、26例精神分裂症健康同胞以及27例年龄、性别及教育年限相匹配的健康对照进行结构磁共振扫描。运用基于体素的形态学分析方法比较各组的全脑灰质体积的差异。结果:与健康对照相比,健康同胞存在左侧枕中回、左侧楔前叶以及右侧丘脑的体积增大,精神分裂症存在左侧颞中回,左侧额上回,双侧颞下回的灰质体积下降以及右侧丘脑体积的增大;与其健康同胞相比,精神分裂症存在左侧额上回、双侧颞下回的灰质体积减小。其中,左侧额上回的灰质损失与精神分裂症的阳性症状总分以及阳性和阴性症状量表总分呈显著相关。结论:研究中发现精神分裂症患者主要表现为脑灰质体积下降,而精神分裂症健康同胞则存在脑灰质体积增大。健康同胞的脑灰质体积增大可能是使其免于罹患精神分裂症的代偿性改变,这些异常的改变可能反映了健康同胞对其遗传易感性相关的脑区灰质异常的代偿性保护作用。     

遭受多重侵害高职高专女生静息态脑功能局部一致性的研究

目的:探讨遭受多重侵害的高职高专女生静息态脑功能磁共振特点。方法:15名遭受多重侵害无创伤后应激症状被试(PV无PTSS组)、15名多重侵害有创伤后应激症状被试(PV有PTSS组)和15名正常对照接受静息态脑功能扫描。采用SPM8和静息态功能磁共振数据处理工具包分别进行数据预处理和ReHo分析。结果:静息状态下,与对照组相比,PV无PTSS组左侧额下回、左右额内侧回、右侧中央后回、左侧梭状回、左右海马旁回、右侧扣带回、左右豆状核和右侧岛叶的ReHo值降低;左右额上回、左右额中回、左右额下回、左右顶下小叶、左右楔前叶、左右颞上回、左侧颞横回、左右颞中回、右侧舌回和右侧扣带后回的ReHo值升高。与PV有PTSS组相比,PV无PTSS组在右侧额中回和额下回、左侧楔前叶、左侧舌回、左右海马旁回、左侧扣带回和左侧豆状核ReHo值降低;在左右额上回、左右额中回、左侧额内侧回、右侧中央后回、左侧缘上回、左右顶下小叶、左侧梭状回和左侧尾状核ReHo值升高。结论:遭受多重侵害但无创伤后应激症状的高职高专女生在静息状态下脑默认网络以及岛叶、基底神经节、海马旁回存在局部一致性信号异常,这些脑区异常可能为遭受多重侵害导致精神障碍的发病机制提供重要线索。     

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.     

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.     

'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.     

The universal muscular chamber. A basic unit of the genitourinary, cardiovascular, gastro-intestinal, skeletal, cutaneous, respiratory and other systems, endocameral hypertension; and spasm, the key to their idiopathic diseases and arthropathies

Starting with the integument, we see many organs are contractile sacs or multiples thereof, which tubes or bags constitute the major part of the entire body. Recognition of this basic unit and its characteristics sheds new light, individually and collectively, on many disorders previously considered unrelated. Muscular tears and perforations develop in the walls of these chambers, being no way peculiar to those organs, wherein, hydrochloric acid occurs. So, it is not necessary to explain the absence of excessive acid from patients who exhibit holes in the gastric, uterine, aortic, duodenal, rectal, pulmonary, retina, and other walls. Muscle, not acid is the great common factor relating idiopathic disorders in the gastrointestinal tract to each other and to similar diseases in other systems. When the units are linked together, the lesions tend to appear as arthropathies, i.e. at the joints. Rephrasing common-place observations, frees us from conventional, conceptual cul-de-sacs. An observation is only as good as its interpretation, so all possibilities must be considered, otherwise, we will remain blinded by our misconceptions.