RAC1 基因多态性对Rac1-GTP 蛋白表达水平的影响

目的:考察RAC1 基因多态性与Rac1-GTP 蛋白表达水平的相关性。方法:选择182 例健康汉族志愿者,经TaqMan-MGB 探针等位基因分型技术测定RAC1 基因中的4 个标签单核苷酸多态性(tag single nucleotide polymorphism,tag-SNPs)位点的基因型,采用酶联免疫吸附法测定其血浆中的Rac1-GTP 蛋白表达水平。分析Rac1-GTP 蛋白表达水平的分布特点;对RAC1 基因4 个tag-SNPs 不同基因型间Rac1-GTP 蛋白表达水平进行比较。结果:Rac1-GTP 蛋白表达水平在健康汉族人群中呈现正偏态分布,女性中的表达水平高于男性(P<0.05);随着年龄的增加有降低的趋势,但差异无统计学意义(P>0.05)。Rac1-GTP 蛋白表达水平在位点rs702482 和rs10951982 基因型间存在显著性差异(P<0.05),但在位点rs702483 和rs6954996 基因型间无统计学差异(P>0.05)。结论:在健康汉族人群中RAC1 基因多态性存在影响Rac1-GTP 蛋白表达水平的SNP 位点。     

孕酮受体基因多态性在宁夏回、汉族人群中的分布特征

目的:探讨孕酮受体基因(PGR基因)rs590688、rs1042838、rs11224592三个单核苷酸多态性(SNP)位点在宁夏回、汉族人群的分布特征并与1000Genomes网站上公布的其他群体分布频率进行比较分析。方法:采用TaqMan探针基因分型方法分析宁夏回、汉族人群867例(回族335例,汉族532例)PGR 3个SNPs位点rs590688、rs1042838、rs11224592基因型及等位基因频率的分布情况。结果:宁夏回、汉族人群PGR基因rs590688和rs1042838两个位点基因型及等位基因频率分布差异无统计学意义;rs11224592位点基因型及等位基因频率在宁夏回、汉族人群的分布差异有统计学意义;3个SNP位点的基因型及等位基因分布频率在男、女性别间差异无统计学意义。宁夏人群PGR基因rs590688、rs1042838、rs11224592位点基因型及等位基因分布频率与1000Genomes网站公布的其他群体相比较,rs590688位点与欧洲人群及非洲人群差异均有统计学意义;rs1042838位点与欧洲人群的差异有统计学意义;rs11224592位点与非洲人群的差异有统计学意义。结论:PGR基因rs590688、rs1042838、rs11224592位点基因型及等位基因频率在宁夏回、汉族人群的分布中,rs590688和rs1042838两个位点的分布无民族差异;rs11224592位点的分布具有民族差异;3个SNP位点的分布无性别差异。PGR 3个SNP位点基因型及等位基因频率在不同种族和地区的分布不同。     

湖北汉族健康人群肿瘤转移抑制基因Nm23基因多态性的测定及分布

目的:建立Nm23基因上10个单核苷酸多态性位点基因型的检测方法,并探讨这些位点在湖北武汉地区健康汉族人群中基因型分布特点,为研究Nm23基因多态性与相关疾病或药物不良反应关联性提供依据。方法:随机选取武汉地区健康体检人群200例,其中男性115例,女性85例。采用实时荧光Taq Man-MGB探针等位基因分型技术进行Nm23基因启动子及内含子区域共10个单核苷酸位点多态性检测。并采用分片段扩增直接测序方法对上述位点进行抽样验证。结果:建立的方法能够准确、快速地对Nm23基因单核苷酸多态性位点进行分型检测。所选Nm23基因上10个位点在湖北汉族人群中分布同国内其他地区研究及Hap Map数据库中北京地区汉族人群相近。且均符合Hardy-weinberg平衡,其中rs16949649与rs7207370、rs34214448,rs2159359与rs2302254、rs8075231、rs2041296、rs8071647位点间高度连锁不平衡,并运用Heploview软件筛选出4个Tag SNPs:rs34214448、rs2302254、rs11868380、rs2318785。结论:试验中建立的基因型测定方法可满足Nm23基因遗传多态性研究的需要,在Nm23基因多态性与相关疾病及药物不良反应关联性研究中可能具有重要应用价值。     

精氨酸加压素基因多态性在广西人群中的分布

目的探讨精氨酸加压素(AVP)基因单核苷酸多态性(SNP)位点rs2282018、rs3787482和rs1887854在303例广西人群中的分布,并对比不同族群间AVP基因型及等位基因频率分布的差别。方法采用单碱基延伸的聚合酶链反应(PCR)技术和DNA测序法,检测303例广西人AVP基因多态性,分析广西人群3个位点的基因型和等位基因的分布频率,并与人类基因组计划(Hap Map)公布的欧洲人、中国北京汉族人、日本人和非洲人的基因多态性分型数据比较,分析这5个人群人类的基因型及等位基因的分布频率。结果我国广西人群AVP基因rs2282018、rs3787482及rs1887854位点各自具有3种基因型,基因型和等位基因分布与性别无关。与人类基因组计划(Hap Map)公布的欧洲人、非洲人、日本人和中国北京人的单核苷酸多态性分型数据进行比较,广西人群AVP基因不同多态性位点的基因型和等位基因频率在不同地区人群的分布存在差异。结论广西地区人群中存在AVP基因多态性。广西人群AVP基因多态性的分布频率与其他不同地区种族人群比较存在差异。     

DVL2基因多态性与中国汉族人群先天性脊柱侧凸遗传易感性的关联研究

背景：近20年来小鼠的分子胚胎学研究进展获得了大量关于脊椎发育的分子信息,用同线性分析法确立先天性脊柱侧凸的候选基因已成为可能。 目的：通过候选基因DVL2上关键单核苷酸多态性位点的筛查,探索DVL2与中国汉族人群先天性脊柱侧凸及其不同临床表型之间的关联。 方法：采用病例-对照研究,入选127例中国汉族先天性脊柱侧凸患者和127例对照组。根据国际人类基因组单体型图计划提供的基因型数据,应用Haploview 4.1软件选取DVL2的标签和功能单核苷酸多态性。根据椎体畸形特点、畸形部位、畸形受累程度、有无合并肋骨畸形和椎管内畸形将病例组进一步分为不同临床表型。对所有样本应用SNPstream UHT Genotyping系统对所选单核苷酸多态性位点进行基因型鉴定;进一步进行基于基因型/等位基因频率的关联分析,并用Haploview 4.1软件分析对照组单核苷酸多态性位点间是否存在连锁不平衡。 结果与结论：共筛选5个位点：单核苷酸多态性1(rs2074222)、单核苷酸多态性2(rs222837)、单核苷酸多态性3(rs222835)、单核苷酸多态性4(rs10671352)和单核苷酸多态性5(rs222836),其基因型分布在病例和对照组中均符合Hardy-Weinberg平衡;5个位点处于完全连锁不平衡状态;5个位点的基因型/等位基因/单倍体型与先天性脊柱侧凸的发生风险之间不存在相关性。在进一步与先天性脊柱侧凸临床表型的关联分析中没有发现阳性位点。提示在中国汉族人群中DVL2基因可能不是引起先天性脊柱侧凸及其不同临床表型的主要因素,有待于进一步深入研究。     

新疆柯尔克孜族过氧化物酶体增殖物激活受体基因单核苷酸多态性

目的:分析柯尔克孜族健康人群过氧化物酶体增殖物激活受体基因(PPARG)的31个单核苷酸多态性(SNP)位点的遗传多态性;方法:利用Hap Map软件筛选31个SNPs位点,利用质谱检测技术进行多态性检测并根据质谱峰图判读样本目标位点基因型,利用χ~2检验确定筛选的SNP位点是否符合Hardy-Weinberg平衡定律并分析柯尔克孜族与其他民族间基因型和等位基因频率差异。结果:在31个SNP位点中,23个位点的最小等位基因频率MAF≥0.05具有多态性;在23个SNPs中rs1175540、rs17036242、rs2881654、rs2959273、rs2972162、rs4135275、rs709151、rs9310401、rs1801282位点在柯尔克孜族和维吾尔族人群间基因型和等位基因分布频率差异均有统计学意义;rs2292101、rs3856806、rs7626560位点在柯尔克孜族和北京汉族人群、犹他州居民、伊巴丹尼日利亚人群间基因型频率差异有统计学意义;rs3856806、rs4135275、rs6782475、rs7626560位点在柯尔克孜族和北京汉族人群、犹他州居民、伊巴丹尼日利亚人群间等位基因频率差异有统计学意义。结论:PPARG基因23个SNP位点多态性在新疆柯尔克孜人群和不同种族问差异具有统计学意义,这种差异可能是导致某些疾病在不同种族间的发现率和临床表现存在显著不同的因素之一。     

LMX1A基因多态性与中国汉族人群先天性脊柱侧凸遗传易感性的关联

背景：先天性脊柱侧凸是由于胚胎期脊柱椎体发育异常引起的脊柱侧凸,其遗传病因学假说开始引起许多学者的重视。 目的：通过候选基因LMX1A上关键单核苷酸多态性位点的筛查,探索LMX1A与中国汉族人群先天性脊柱侧凸及其不同临床表型之间的关联。 方法：入选127例中国汉族先天性脊柱侧凸患者,另选取外伤、感染、炎症性疾病等患者127例为对照组。根据国际人类基因组单体型图计划提供的基因型数据,应用Haploview 4.1软件选取LMX1A的标签和功能单核苷酸多态性位点。根据椎体畸形特点、畸形部位、畸形受累程度、有无合并肋骨畸形和椎管内畸形将病例组进一步分为不同临床表型。所有样本应用SNPstream UHT Genotyping系统对所选单核苷酸多态性位点进行基因型鉴定;进一步进行基于基因型/等位基因频率的关联分析,并用Haploview 4.1软件分析对照组单核苷酸多态性位点间是否存在连锁不平衡。 结果与结论：共筛选6个位点：SNP1(rs1819768)、SNP2(rs12023709)、SNP3(rs16841013)、SNP4(rs4656435)和SNP5(rs4657412)和SNP6(rs4657411),其基因型分布在病例组和对照组中均符合Hardy-Weinberg平衡;在基于基因型的关联分析中发现阳性位点SNP1和SNP2,单位点分析显示两位点基因型在病例组和对照组中的分布频率差异有显著性意义(P=0.026和P=0.026),在进一步非条件Logistic回归分析中发现这两个位点的基因型分布最符合Ressessive(OR=0.38;95%CI=0.15~0.94,P=0.029,AIC=354.9)遗传模型;SNP1、SNP2、SNP3和SNP6处于连锁不平衡状态,SNP4和SNP5也处于完全连锁不平衡状态,但单倍体型与先天性脊柱侧凸的发生风险之间不存在相关性;在进一步与先天性脊柱侧凸临床表型的关联分析中发现SNP1基因型AC型、SNP2基因型AG型、SNP3基因型CT型与有椎体形成障碍先天性脊柱侧凸的易感性升高有关。结果提示在中国汉族人群中LMX1A基因可能和先天性脊柱侧凸的发生、发展相关,是一个重要的易感基因。     

宁夏籍汉族大学生雌激素受体β基因多态性的分布特征*

目的：探讨雌激素受体β（ERβ）基因rs1256049、rs4986938 位点单核苷酸多态性在宁夏籍汉族大学生的 分布特征。方法：采用TaqMan 探针基因分型法,分析宁夏籍汉族1 156 名（ 男516 例,女640 例）大学生ERβ 基 因rs1256049、rs4986938 两位点多态性在不同性别间的分布特征,并与国内报道及1000 Genomes 网站上公布的 其他地区或种族健康人群进行比较。结果：宁夏籍汉族大学生ERβ 基因rs1256049、rs4986938 位点各基因型及等 位基因频率分布在不同性别间差异无统计学意义。与国内已报道结果相比,rs1256049 位点多态性与湖南、湖北、 成都和广西汉族及广西壮族人群间的分布均有显著性差异,与江苏汉族人群间差异无统计学意义;rs4986938 位 点多态性与湖南和成都汉族人群间的分布均有显著性差异,与江苏、湖北和广西汉族及广西壮族人群间差异无统 计学意义。与1000 Genomes 网站结果相比,rs1256049、rs4986938 两位点多态性与中国南方人群、欧洲人群和 非洲人群的分布差异均有显著统计学意义,与北京汉族和日本人群差异均无统计学意义。结论：宁夏籍汉族大学 生ERβ 基因rs1256049、rs4986938 位点各基因型和等位基因频率分布在性别间无显著差异性,与国内不同地区及 国外不同种族人群间的差异性可能与遗传背景不同有关。     

IL-1、IL-10及TNF-β单核苷酸多态性与福建泉州地区汉族人群类风湿性关节炎的相关性研究

目的:探讨福建泉州地区汉族人群类风湿性关节炎(RA)患者炎症相关因子的单核苷酸多态性(SNP)位点的分布特征,并研究其与RA易感性的关系。方法:选取福建泉州地区汉族人群RA患者155例(RA组)和健康体检者170例(对照组)为研究对象,采用全血三引物等位基因特异性扩增(TRIP-ASPCR)技术对RA相关的SNP位点进行基因分型。运用SPSS 19.0统计分析软件,采用卡方检验和Logistic法分析Hardy-Weinberg遗传平衡吻合度、SNP位点等位基因与RA发病关联强度,并利用SHEsis软件对所选SNP位点进行连锁不平衡分析和单倍型分析。结果:对照组中有1个SNP位点符合Hardy-Weinberg平衡检验(P>0.05),RA组有1个SNP位点符合Hardy-Weinberg平衡检验(P>0.05);在对照组和RA组之间有4个SNP位点的等位基因频率差异存在统计学意义(P<0.05,OR>1),与RA呈正相关,且相关性明显。结论:RA患者中,存在4个SNP位点(IL-10 rs1800893、IL-1βrs16944、TNF-βrs2009658和...     

广西人群miRNA-107基因多态性分布特征及其与血脂的关系

目的探讨miR-107基因单核苷酸多态性(SNP)位点rs2296616 C/T在广西地区健康人群中的分布特点,对比其在不同种族间基因型及等位基因频率分布的差异,并进一步探讨rs2296616 C/T位点单核苷酸多态性(SNP)与血脂水平的相关性。方法采用多重单碱基延伸SNP分型技术(multiplex SNa Pshot)和DNA测序法,检测372例广西健康人rs2296616 C/T位点的多态性,用7600生化仪检测其血脂相关指标,并用统计学方法分别比较rs2296616C/T位点多态性在各种族人群间的分布差异及不同基因型间的血脂水平差异。结果广西人群miR-107基因rs2296616 C/T位点存在TT(91.1%)和CT(8.9%)两种基因型及T(95.6%)和C(4.4%)两种等位基因。该位点的基因型和等位基因型频率在广西人群不同性别间的比较,差异无统计学意义(P>0.05)。其基因型和等位基因频率与人类基因组单体型图(Hap Map)所公布的欧洲人、日本人、非洲人、印第安人和墨西哥人分型数据相比较,差异均有统计学意义(P<0.05),但与北京汉族人群比较,差异无统计学意义(P>0.05)。rs2296616 C/T位点两种基因型人群血脂之间比较,携带TT基因型人群的高密度脂蛋白胆固醇(HDL-C)与CT组比较,差异具有统计学意义(P<0.05)。结论广西人群miR-107基因rs2296616 C/T位点多态性与其他种族人群之间比较存在不同程度的差异;rs2296616 C/T位点多态性与HDL-C水平高低有关。     

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.     

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.     

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.