帕金森病患者NK细胞亚群及T淋巴细胞亚群变化的临床意义

目的:探讨帕金森病(PD)不同年龄、不同病期、伴随症状患者外周血NK细胞亚群及T淋巴细胞亚群的变化及其临床意义。方法:应用先进的流式细胞仪(FCM)直接免疫荧光染色法检测47例PD患者外周血NK细胞亚群及T淋巴细胞亚群,并与健康人组进行对照与相关分析。结果:PD组CD3+、CD4+、CD8+、CD4+/CD8+水平较对照组均明显降低(P<0.05),而CD16+56水平则较对照组明显增高(P<0.05)。高龄、病情重及伴痴呆和抑郁的PD患者CD3+、CD4+、CD8+、CD4+/CD8+水平降低更显著(P<0.05)。结论:PD发病过程中存在T细胞免疫功能低下及NK细胞免疫平衡失调,高龄、病情重及伴痴呆和抑郁的患者NK、T细胞免疫功能异常降低更明显,此为PD病理生理基础赋予新的内涵,亦为PD的免疫干预性治疗提供新的途径。     

α地中海贫血患儿免疫球蛋白与T淋巴细胞的价值与意义

目的探讨免疫球蛋白和T淋巴细胞在α地中海贫血患儿中的临床诊断意义。方法对来我院诊治的80例患者入院资料进行分析,将其随机分为两组。对照组为健康者,实验组为α地中海贫血患儿,采用免疫比浊法测定两组的免疫球蛋白M、A、G水平,并采用流式细胞仪检测对患者T淋巴细胞群进行检测。结果两组免疫球蛋白Ig A、Ig G、Ig M水平无统计学意义(P0.05);T淋巴细胞中,实验组CD3+水平为(47.6±4.13)%、CD4+为(34.1±3.18)%、CD4/CD8为(1.02±1.56),低于对照组(P0.05),两组CD8+差异不显著(P0.05);三组地贫患者免疫球蛋白Ig A、Ig G、Ig M水平无统计学意义(P0.05);中间型患儿T淋巴细胞CD3+、CD4+、CD4/CD8低于其他两组(P0.05),三组CD8+水平差异不显著(P0.05);且静止型与轻型之间差异不显著(P0.05)。结论α地中海贫血发病率较高,临床上测定免疫球蛋白和T淋巴细胞的水平可对该病的诊疗及预后有一定的作用。     

慢性髓系白血病患者外周血T淋巴细胞亚群和NK细胞检测的临床意义

目的 研究不同分期慢性髓系白血病患者外周血T淋巴细胞亚群、NK细胞的变化特点,以及应用伊马替尼治疗后获得完全细胞遗传学反应(complete cytogenetic reponse,CCyR)患者淋巴细胞亚群表达情况.方法 选取我院诊治40例慢性髓系白血病患者,其中急变期9例,慢性期31例.采用流式细胞术检测外周血T淋巴细胞亚群、NK细胞水平,并与正常对照组进行比较.结果 初治慢性期、急变期CML患者外周血CD3+、CD4+、CD8+T细胞百分率及CD4+/CD8+比值均低于正常对照组,且急变期CD3+、CD4+T细胞百分率及CD4 +/CD8+比值下降尤为突出(P＜0.01);初治慢性期患者NK细胞百分率与正常对照组相比无差异,而急变期患者低于正常对照组(P＜0.05).与正常组对比,伊马替尼治疗首次获得完全细胞遗传学反应患者仅CD4+T细胞百分率降低,差异具有统计学意义(P＜0.05);但获得完全细胞遗传学反应后应用伊马替尼治疗大于12月患者,CD3+、CD4+T细胞百分率及CD4 +/CD8+比值较正常对照组均有所下降(P＜0.05).与治疗前相比,治疗首次获得完全细胞遗传学反应患者CD3+、CD4+T细胞百分率升高(P＜0.05),而缓解后应用伊马替尼治疗大于12月患者T淋巴细胞亚群无改变(P＞0.05);各组的NK细胞百分比无差异(P＞0.05).初诊CML患者、急变期CD4+/CD8+的比值与BCR-ABLl/ABL1的比值呈负相关.结论 CML患者存在细胞免疫调节功能异常,且机体免疫功能与疾病分期密切相关.伊马替尼治疗初次获得完全细胞遗传学反应患者细胞免疫功能得到改善,但长期应用抑制患者细胞免疫功能.     

新辅助化疗对局部进展期乳腺癌患者T淋巴细胞亚群及NK细胞免疫功能的影响

目的:探讨局部进展期乳腺癌患者新辅助化疗前、后T淋巴细胞亚群及NK细胞免疫功能的变化。方法:采用流式细胞术检测54例局部进展期乳腺癌患者新辅助化疗前后的静脉血T淋巴细胞亚群及NK细胞免疫功能。美国癌症联合会(American Joint Commitree on Cancer,AJCC)肿瘤分期为Ⅱb期(仅T3N0M0)和Ⅲ期(不包括N3),静脉血于第1周期新辅助化疗治疗前及第3周期化疗后21日抽取,淋巴细胞亚群检测包括:T(CD3+,CD4+,CD8+),NK(CD56+,CD16+),经过3周期新辅助化疗CEF方案(表柔比星、环磷酰胺和5-氟尿嘧啶),根据新辅助化疗临床效果评价分为2组,化疗有效组38例(CR和PR),化疗无效组16例(SD和PD),并与正常体检健康者(40例)作比较。结果:乳腺癌患者治疗前CD4+、CD4+/CD8+明显低于对照组(P<0.01),NK细胞明显低于对照组(P<0.05),新辅助化疗后,有效组总CD3+、CD4+、CD4+/CD8+、NK细胞较治疗前均显著升高(P<0.05),CD8+降低(P<0.05);无效组CD3+、CD4+/CD8+及NK细胞较治疗前显著降低(P<0.05),而CD8+升高(P<0.05)。结论:局部进展期乳腺癌患者免疫功能低下,有效的辅助化疗能提高患者的免疫功能,定期监测免疫功能对指导临床治疗有意义。     

不同宫颈癌临床分期患者外周血中T淋巴细胞及NK细胞的表达分析

目的分析宫颈癌患者外周血中T淋巴细胞及其亚群以及NK细胞的表达情况。方法前瞻性分析145例在我院就诊的宫颈癌患者的临床资料,按照宫颈癌FIGO临床分期差别分为:宫颈癌Ⅰ期38例、宫颈癌Ⅱ期42例、宫颈癌Ⅲ期35例、宫颈癌Ⅳ期30例;同期选择体检正常女性30例作为对照组。应用流式细胞仪检测各组患者外周血CD3^+、CD4^+、CD8^+T细胞亚群、调节性T细胞(Treg)以及NK细胞数量,同时计算各亚群的比例以及Treg占CD4^+T细胞的比例。应用多元Logistic回归分析评估各细胞亚群数量及比例与宫颈癌临床分期的相关性。结果与对照组相比,宫颈癌患者CD3^+T细胞、CD4^+T细胞、NK细胞数量以及CD4^+/CD8^+比值均较低,Treg/CD4^+比值较高(均P <0.05),而CD8^+T细胞数量差异无统计学意义(均P>0. 05)。随宫颈癌病理严重程度递增,CD3^+T细胞、CD4^+T细胞、NK细胞数量以及CD4^+/CD8^+比值逐步降低,Treg/CD4^+比值逐步增高(均P <0.05),而CD8^+T细胞数量差异无统计学意义(均P>0.05)。多元Logistic回归分析显示,Treg/CD4^+比值是宫颈癌临床分期的危险因素,CD4^+T细胞、CD4^+/CD8^+比值及NK细胞是其保护性因素(均P<0.05)。结论宫颈癌患者细胞免疫功能均不同程度降低,晚期患者降低最显著。检测T淋巴细胞亚群及NK细胞可用于宫颈癌患者免疫监测,为临床治疗及预后评估提供参考。     

T淋巴细胞在不同类型白血病患者外周血中的变化

目的通过对不同类型白血病患者外周血T淋巴细胞亚群(CD3+、CD4+、CD8+)的检测以评价不同类型白血病患者的细胞免疫功能。方法采用流式细胞术检测200例不同类型白血病患者和52例健康志愿者外周血T细胞亚群的水平。结果与正常对照组相比,急性白血病和慢性白血病患者的CD4+/CD8+比值都是下调的(P<0.05);急性白血病患者(包括急淋和急粒)的CD3+、CD8+细胞水平是上升的,且急淋患者还伴随着CD4+细胞的降低(P<0.05);慢性白血病患者的CD3+、CD4+细胞水平是下调的,其中慢淋患者的CD3+细胞下调更为显著,而慢粒患者则是以CD8+细胞增高为主(P<0.05)。结论不同类型白血病患者外周血T淋巴细胞均存在免疫异常,且具有不同异常方式,对指导治疗及疗效观察有一定的临床意义。     

外周血T淋巴细胞亚群水平对胃癌辅助化疗患者预后的影响

目的:探讨外周血T淋巴细胞亚群水平对胃癌(GC)辅助化疗患者预后的影响.方法:选取2018年11月至2020年11月商丘市第一人民医院收治的100例GC患者为研究对象.均进行辅助化疗,治疗3个周期后,评估短期预后情况;并检测患者治疗前外周血T淋巴细胞亚群水平(CD3+、CD4+、CD8+、CD4+/CD8+),分析外周血T淋巴细胞亚群水平对GC辅助化疗患者预后的影响.结果:治疗3个周期后,预后良好为68例,占68.00％,预后不良32例,占32.00％;较预后良好组,预后不良组外周血CD3+、CD4+、CD4+/CD8+水平较低,CD8+水平较高(P<0.05);经Logistic回归分析结果显示,外周血CD3+、CD4+、CD4+/CD8+低表达,CD8+高表达可增加GC辅助化疗患者预后不良的风险(P<0.05);绘制受试者工作曲线(ROC)显示:CD3+、CD4+、CD8+、CD4+/CD8+水平预测GC辅助化疗患者短期预后不良的曲线下面积(AUC)分别为0.825、0.857、0.858、0.871,均具有一定的预测价值.结论:外周血T淋巴细胞亚群水平可影响GC辅助化疗患者预后情况,外周血CD3+、CD4+、CD4+/CD8+低水平,CD8+高水平可增加GC辅助化疗患者预后不良风险。     

恢复期SARS患者淋巴细胞亚群分布及其与T淋巴细胞Ag-NOR含量相关性的初步分析

目的　通过检测恢复期SARS患者外周血淋巴细胞亚群分布及其与T淋巴细胞核仁形成区嗜银蛋白 (Ag NOR)含量的相关性分析 ,探讨恢复期SARS患者的免疫状态及淋巴细胞亚群与活性状态改变的关系。方法　以流式细胞术检测患者外周血淋巴细胞亚群 ,用KL型免疫图像分析系统检测外周血T淋巴细胞Ag NOR ,对两者进行相关分析。结果　恢复期患者T淋巴细胞总数及CD4 +亚群基本正常 ,而CD8+亚群偏高 ,CD4 +/CD8+降低 ,CD4 +/CD8+<1的比例占 37.4 % ,激活T细胞中以CD8+细胞为主。B细胞比例正常。NK细胞明显低于对照组。重症患者CD4 +、CD4 +/CD8+、CD1 9+CD5+降低及CD8+、CD3+HLA DR+升高。 50岁以上及使用大剂量激素患者CD3+HLA DR+升高。淋巴细胞Ag NOR的含量 (IS % )在正常范围 ,但患者IS值呈偏态分布 ,低于正常范围者占 4 4.99%。淋巴细胞Ag NOR的含量与CD3+、NK、CD3+HLA DR+、CD3+CD2 5+在统计学上具有相关性。结论　恢复期SARS患者免疫功能趋于恢复正常 ,但部分患者的淋巴细胞亚群数量及淋巴细胞活性仍未恢复正常 ,这些病人在临床症状得到改善之后 ,尚需一定时间的观察随访 ,以了解SARS病毒对人体免疫机能的长期影响。     

支原体肺炎患儿免疫球蛋白、T淋巴细胞亚群细胞因子检测的临床意义

目的:观察支原体肺炎(MPP)患儿外周血免疫球蛋白、T淋巴细胞亚群以及细胞因子的含量变化,并探讨其在MPP发病机制中的作用。方法:采用流式细胞技术检测43例MPP患儿和30例正常对照组儿童外周血T淋巴细胞亚群CD3+、CD4+、CD8+,并用速率散射比浊法检测血清IgG、IgA和IgM含量,采用ELISA检测血清干扰素-γ(IFN-γ)、白介素(IL-2、IL-4和IL-6)水平。结果:MPP患儿外周血CD3+、CD4+T细胞百分率分别为61.45±6.75和33.52±5.81,较正常对照组68.28±7.34和38.71±6.29显著降低(P<0.05),CD8+T细胞和CD4+/CD8+比值较对照组无显著差别(P>0.05);MPP患儿血清免疫球蛋白与正常对照组比较,IgG和IgA均无明显差异,IgM较对照组增高(P<0.05);MPP患儿IFN-γ、IL-4、IL-6血清水平以及IFN-γ/IL-4比值较正常对照组明显增高(P<0.05),而IL-2水平低于正常对照组(P<0.05)。结论:MPP患儿存在免疫功能减低,免疫调节紊乱,辅助性T细胞亚群(Thl/Th2)失衡,并以Thl型细胞介导的免疫反应占相对优势状态。     

分泌性中耳炎患者外周血T淋巴细胞亚群及免疫球蛋白水平的变化

目的:探讨研究分泌性中耳炎患者外周血T淋巴细胞亚群及免疫球蛋白水平变化。方法:选取2008-12/2010-06进行治疗的50例分泌性中耳炎患者为研究对象,将其设为观察组,同时选取同期的50名健康人为对照组,分别检测两组人员外周血T淋巴细胞亚群及免疫球蛋白水平进行检测及比较。结果:经比较发现,观察组患者CD3+、CD4+及CD8+水平均明显低于对照组,CD4+/CD8+水平则高于对照组,同时血清IgA、IgG、IgM及C3、C4水平也一定程度上均高于对照组,且急性患者水平与慢性患者也有一定差异,经比较,有显著性差异或有非常显著性差异(P0.05或P0.01)。结论:分泌性中耳炎患者外周血T淋巴细胞亚群及免疫球蛋白水平均有一定的变化,对于了解患者的发展状况及严重程度等均有积极的意义,因此其水平检测值得临床进一步研究及探讨。     

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.     

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.     

The universal muscular chain reaction,muscle spasm,Torsions, ruptures and extravasations. Chameleons of pathology and some manifestations of simple muscular disorders

Most bodily functions require the coordinated actions of complementary and supplementary paired muscle groups. Where this essential muscular cooperation is lacking, hollow organs may burst and others become literally screwed up, giving rise to many similar spastic diseases such as Torticollis, Twisted ovarian cyst, Torsion of the Testis, Volvulus of the intestines, Varicose Veins, Megacolon, Aortamegaly, Scoliosis, Erb's Palsy, Peyronie's Disease, Main-en-Griffe, Undescended Foot (Pes Cavus), Talipes, Strabismus. Spasm is “panenepidemic” and unclassified examples of Torsion Dystonia and Dyskinesia really are as common as debt and taxes.     

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.     

Hypo- und Hypermagnesämie aus kardiologischer Sicht

Zusammenfassung Eine Reihe pathologischer Zustände bedingen Magnesiummangel. Zustände mit Hypermagnesämie sind ebenfalls bekannt, doch wesentlich seltener. Für den Kardiologen beachtenswert ist, daß unter Therapie mit bestimmten Diuretica bei Herzinsuffizienz, bei Herzinfarkt, Kardiomyopathie, Digitalisintoxikation und bestimmten Herzrhythmusstörungen Hypomagnesämie beobachtet wurde. Leider kann in der klinischen Routine nur ein extracelluläres Magnesiumdefizit durch Serumbestimmungen gemessen werden; über Magnesiummangel einzelner Organe kann nichts ausgesagt werden. Hinweise für Magnesiummangel geben aber neben der Messung des Serumspiegels Anamnese, klinischer Befund, bestimmte EKG-Veränderungen wie auch evtl. Hypokalämie, ein Zustand, bei dem sich oft — besonders bei Aldosteronismus — parallele Veränderungen zeigten.Tierexperimente deuten darauf hin, daß infarktähnliche Läsionen unter Magnesiummangel entstehen, doch ob Herzinfarkt beim Menschen durch Magnesiummangel ausgelöst werden kann, ist noch ungeklärt. In Leichenherzen zeigte sich im Infarktgebiet neben Calciumakkumulation signifikanter Magnesiumverlust, wobei unklar blieb, ob sich Ursache oder Folge des Infarktes widerspiegelten. Falls ein ursächlicher Zusammenhang besteht, ist er im Myokardstoffwechsel selbst zu suchen, wie bei der Alkoholkardiomyopathie, wo myokardialer Magnesiummangel zumindest als pathogenetischer Teilfaktor anerkannt wird. Andererseits versucht man aber auch Beziehungen zwischen Atherosklerose, Blutgerinnung und Hypomagnesämie herzustellen, in der Meinung, daß Magnesiummangel auch über den coronaren Pathomechanismus des Herzinfarktes wirken könnte. Sicher scheint, daß gewisse EKG-Veränderungen und Herzrhythmusstörungen durch einen irritierten Magnesiumhaushalt bedingt sein können, da sie bei Gabe bzw. Entzug von Magnesium verschwinden. Daß Magnesiummangel die Glykosidtoleranz verringert, wird tierexperimentell bestätigt. Unter Hypomagnesämie bewirkt Acetylstrophanthidin eher und länger Rhythmusstörungen als ohne, außerdem lassen diese sich durch Magnesiumgaben eliminieren. Da in gewissen Fällen spontane und digitalisinduzierte Herzrythmusstörungen durch Magnesiuminjektionen beseitigt wurden, scheint Magnesium als Therapeuticum angebracht. Einsatz verschiedener Magnesiumsalze bei Angina pectoris, degenerativen Herzerkrankungen und Herzinsuffizienz ohne geprüften und offensichtlich gestörten Magnesiumhaushalt ist fragwürdig, weil keine eindeutigen klinischen Erfolgsbeweise vorliegen. Immerhin mag es aber larvierte, durch Serumbestimmungen nicht erfaßbare Mangelzustände geben. Allgemein erscheint es aus kardiologischer Sicht ratsam, den Magnesiumhaushalt zu überwachen und in entsprechenden Fällen auszugleichen, um möglichen Myokardläsionen oder fatalen Herzrhythmusstörungen entgegenzuwirken.     

Environmental risk factors and their role in the management of atopic dermatitis

Introduction: The etiology of atopic dermatitis (AD) is multifactorial with interaction between genetics, immune and environmental factors.

Areas covered: We review the role of prenatal exposures, irritants and pruritogens, pathogens, climate factors, including temperature, humidity, ultraviolet radiation, outdoor and indoor air pollutants, tobacco smoke exposure, water hardness, urban vs. rural living, diet, breastfeeding, probiotics and prebiotics on AD.

Expert commentary: The increased global prevalence of AD cannot be attributed to genetics alone, suggesting that evolving environmental exposures may trigger and/or flare disease in predisposed individuals. There is a complex interplay between different environmental factors, including individual use of personal care products and exposure to climate, pollution, food and other exogenous factors. Understanding these complex risk factors is crucial to developing targeted interventions to prevent the disease in millions. Moreover, patients require counseling on optimal regimens for minimization of exposure to irritants and pruritogens and other harmful exposures.     

Class II HLA in Georgia Caucasus Tbilisi Georgians and their Mediterranean ancestry: The Usko Mediterranean languages

Georgia (or Sakartvelo in its own language) is a South Caucasus Mts. country with its easternmost part is enigmatically named Iberia, like the Iberian Peninsula, which may refer to rivers “Kura” and “Ebro” or their valleys respectively. Most of their inhabitants speak Georgian which is included within Dene-Caucasian group and Usko-Mediterranean subgroup of languages. The latter includes Basque, Berber, ancient Iberian-Tartessian, Etruscan, Hittite, Minoan Lineal A and others. In the present paper, HLA class II -DRB1 and -DQB1 alleles has been studied and extended haplotypes calculated. Most frequent haplotypes are also of Mediterranean origin (i. e.: (A*02-B*51)-DRB1*11:01-DQB1*03:01, (A*02-B*51)-DRB1*13:01-DQB1*06:03, or (A*24-B*35)-DRB1*01:01-DQB1*05:01) and DA genetic distances show that closest world populations to Georgians are Mediterraneans. Georgians also show common extended haplotypes ((A*02-B*51)-DRB1*11:01-DQB1*03:01, (A*02-B*13)-DRB1*07:01-DQB1*02:01 and (A*03-B*35)-DRB1*11:01-DQB1*03:01) with Svan people, a secluded population in North Georgia mountains. We can conclude that Georgians belong to a very old Mediterranean substratum according to both linguistics (Usko Mediterranean languages) and HLA genetics.     

'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.