Genetic aspects of animal reasoning

This paper reviews the investigations of Prof. L. V. Krushinsky and his colleagues into the genetics of complex behaviors in mammals. The ability of animals to extrapolate the direction of a food stimulus movement was investigated in wild and domesticated foxes (including different fur-color mutants), wild brown rats, and laboratory rats and mice. Wild animals (raised in the laboratory) were shown to be superior to their respective domesticated forms on performance of the extrapolation task, especially in their scores for the first presentation, in which no previous experience could be used. Laboratory rats and mice demonstrated a low level of extrapolation performance. This means that only a few laboratory animals were capable of solving the task, i.e., the percentage of correct solutions was equivalent to chance. The brain weight selection program resulted in two mice strains with a 20% (90-mg) difference in brain weight. Ability to solve the extrapolation task was present in low-brain weight mice in generations 7–11 but declined with further selection. Investigation of extrapolation ability in mice with different chromosomal anomalies demonstrated that animals with Robertsonian translocations Rb(8,17) 1lem and Rb(8,17) 6Sic were capable of solving this task in a statistically significant majority of cases, while mice with fusion of other chromosomes, as well as CBA normal karyotype mice, performed no better than expected by chance. Mice with two types of partial trisomies and animals homo- and heterozygous for translocations were also tested. Although mice with T6 trisomy performed no better than expected by chance, animals with trisomy for a chromosome 17 fragment solved the task successfully. Thus, a genetic component underlying the ability to solve the extrapolation task was demonstrated in three animal species. The extrapolation task in animals is considered to reveal a general capacity for elementary reasoning. The genetic basis of this capacity is very complex.     

通径分析在精神分裂症发病危险因素分析中的应用

本文对３０年前首次住院经ＣＣＭＤ－２再诊断的２０３例精神分裂症采用通径分析方法，进行了遗传流行病学对照研究。结果显示精神分裂症的发病与产次、性格、家族史有关。     

Polymorphisms in the human CYP1A1 gene as susceptibility factors for lung cancer: exon-7 mutation (4889 A to G), and a T to C mutation in the 3′-flanking region

Genetic differences in the metabolism of carcinogens may codetermine individual predisposition to cancer. Cytochrome P-4501A1 (CYP1A1) metabolically activates precarcinogens in cigarette smoke, such as benzo(a)pyrene, which is also an inducer of CYP1A1. Two point mutations have been reported, m1 in the 3-flanking region (6235T to C), and m2 within exon 7 (4889A to G), the latter leading to an isoleucine to valine exchange. In the Japanese population ml and m2 are correlated with lung cancer, suggesting an increased susceptibility to cigarette smoking related lung cancer. We studied 142 lung cancer and 171 reference patients in an ethnically homogeneous German group for m1 and m2 mutations by restriction fragment length polymorphism and allele-specific polymerase chain reaction, respectively. No statistically significant difference was found in the distribution of m1 alleles between lung cancer and controls; the frequency was 8.5% and 7.3% of the alleles, respectively (odds ratio = 1.17). A trend to an overrepresentation of ml alleles was observed among 52 squamous cell carcinoma patients (odds ratio = 1.65). In contrast, the frequency of m2 alleles in lung cancer patients was twofold higher (6.7%) than in the reference group (3.2%; odds ratio = 2.16; 95% confidence limits 0.96–5.11, P = 0.033); the odds ratio of m2 alleles in squamous cell carcinoma was 2.51 (95% confidence limits 0.85–7.05, P = 0.05). There was a close genetic linkage of m2 to m1 (10 of 11 reference patients), but a significantly higher number of cancer patients showed no linkage compared to the controls (odds ratio = 8.89, 95% confidence limits 0.83–433, P = 0.04). Thus no association was found between presence of ml alleles and lung cancer, but, in contrast, m2 alleles proved as a hereditary risk factor, especially if not linked with m1 alleles.Abbreviations Ah aryl hydrocarbon - CYP1A1 cytochrome P4501A1 - CYP1A1 CYP1A1 gene - PCR polymerase chain reaction - PY pack years - RFLP restriction fragment length polymorphism Correspondence to: N. Drakoulis     

An association of 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and common carotid atherosclerosis

Plasma homocysteine (Hcy) concentration has been shown to be influenced by a mutation in the gene coding methylenetetrahydrofolate reductase (MTHFR). Although plasma Hcy is related to atherosclerotic disorders, conflicting results have been reported about the association between MTHFR gene polymorphism and sclerotic lesions of the common carotid arteries. The effect of age–gene interaction on carotid arterial remodeling was investigated in elderly subjects with several risk factors for atherosclerosis. We evaluated sclerotic lesions of the common carotid arteries by ultrasonography in 326 patients (mean age ± standard deviation, 73 ± 12 years) and studied relations among the known risk factors for atherosclerosis, including MTHFR gene polymorphism and its interactions with age and sex. Of the 326 subjects studied, 136 had MTHFR genotype CC, 136 genotype CT, and 54 genotype TT. The three groups did not differ with respect to background factors such as age, history of cigarette smoking, blood pressure, lipids or uric acid, or in the incidence of atherosclerotic diseases. Spearman's rank correlation revealed a significant relationship between gender, age, Brinkman index, systolic blood pressure, triglycerides, HDL-cholesterol (HDL-C), uric acid, and MTHFR gene polymorphism. Multiple regression analysis using intima-media complex thickness (IMT) as a criterion variable and risk factors, including MTHFR gene polymorphism as explanatory variables showed that MTHFR gene polymorphism (P = 0.039) was a significant independent explanatory variable for IMT, along with gender (male) (P < 0.001), age (P < 0.001), systolic blood pressure (SBP) (P = 0.047), total cholesterol (T-C) (P < 0.001), and HDL-C (P < 0.001). Furthermore, a general linear model analysis revealed that interaction between age and MTHFR gene polymorphism was significantly associated with IMT, independently of age, SBP, T-C, and HDL-C in male subjects. However, age–gene interaction was not observed in female subjects. The findings of the present study confirm an association between MTHFR gene polymorphism and common carotid atherosclerosis in the Japanese population and further support the role of risk factor–gene interaction in common carotid atherosclerosis. Received: May 14, 2001 / Accepted: June 8, 2001     

Female specific risk factors for the development of Alzheimer’s disease neuropathology and cognitive impairment: Call for a precision medicine approach

Alzheimer's disease (AD) includes a long asymptomatic stage, which precedes the formal diagnosis of dementia. AD biomarker models provide a framework for precision medicine approaches during this stage. However, such approaches have ignored the possible influence of sex on cognition and brain health, despite female sex noted as a major risk factor. Since AD-related changes may emerge in midlife, intervention efforts are being redirected around this period. Midlife coincides with several endocrinological changes, such as the menopausal transition experienced by women. In this narrative review, we discuss evidence for sex-differences in AD neuropathological burden and outline key endocrinological mechanisms for both sexes, focussing on hormonal events throughout the lifespan that may influence female susceptibility to AD neuropathology and dementia onset. We further consider common non-modifiable (genetic) and modifiable (lifestyle and health) risk factors, highlighting possible sex-dependent differential effects for the AD disease course. Finally, we evaluate the studies selected for this review demonstrating sex-differences in cognitive, pathological and health factors, summarising the state of sex differences in AD risk factors. We further provide recommendations for targeted research on female-specific risk factors, to inform personalised strategies for AD-prevention and the promotion of female brain health.     

Hypertension risk factors and cardiovascular reactivity to mental stress in young men

Hypertension risk may be associated with increased pressor response to mental stress. However, studies using family history as a predictor of reactivity have obtained mixed results. We assessed cardiovascular responses to mental arithmetic stress (a 5-min serial subtraction task) in male medical students (n = 220) at three levels of hypertension risk based on parental history and the subject's systolic blood pressure (SBP): low (SBP < 125 mm Hg and 0 or 1 hypertensive parent), moderate (resting SBP ≥ 125 mm Hg or 2 hypertensive parents), or high (resting SBP ≥ 125 mm Hg and 1 or 2 hypertensive parents). High risk men showed the greatest blood pressure responses ( + 22/ + 16 mm Hg), while moderate and low-risk groups showed correspondingly smaller responses ( + 17/ + 13 and + 14/ + 11 mm Hg, p's < 0.02). Family history alone did not predict differential reactivity. This study replicates and extends our previous work suggesting the importance of using both family history and resting blood pressure level in determining future risk for hypertension in studies of cardiovascular reactivity in relation to hypertension risk in males.     

颅脑肿瘤术后并发静脉血栓栓塞症危险因素的Meta分析

目的明确颅脑肿瘤术后患者发生静脉血栓栓塞症(VTE)的危险因素。方法检索中国知网、万方、维普、中国生物医学文献、PubMed、The Cochrane Library、Web of Science、EMbase等数据库建库至2021年11月1日颅脑肿瘤术VTE危险因素的队列研究或病例对照研究。由两名研究人员独立进行文献筛选、资料提取以及文献质量评价。使用RevMan 5.4软件对纳入文献进行Meta分析。结果共纳入14篇文献,合计样本量40 552例,发生VTE1 801例。Meta分析结果显示,年龄＞45岁、术前D-二聚体升高、肥胖、女性、术前日常生活活动能力处于依赖状态、术前呼吸机依赖、术前曾患脓毒血症、高级神经胶质瘤、手术时间＞3.05 h、术后D-二聚体升高、术后下肢运动功能障碍、术后卧床不起、术后并发尿路感染为颅脑肿瘤术后患者发生VTE的危险因素。结论颅脑肿瘤术后VTE发生与多种因素有关。建议构建颅脑肿瘤术后VTE风险预测模型,关注高风险人群,落实规范化静脉血栓风险评估,注重血栓评估过程管控。     

基于波士顿矩阵的医疗纠纷管理研究

目的针对医疗纠纷赔款案件的危害性进行风险分类分析,为提升科室医疗安全管理水平提供参考。方法分析某院2016年-2019年125例医疗纠纷赔款案件,借鉴波士顿矩阵模型,将医疗纠纷发生科室及原因围绕损害性（均次损害量化值）、损失性［每床位（均次）赔款金额］、发生频次3个指标进行风险分类。结果医疗纠纷赔款案件高发科室主要是骨科（33.6%）和普外科（23.2%）,发生原因主要是责任心不强（22.4%）、手术不当（20.8%）、漏诊误诊（16.8%）。“高床位赔款,高损害风险”科室有心外科及普外科,“高床位赔款,低损害风险”科室有泌尿外科、骨科及神经外科;“高赔款,高损害风险”医疗纠纷原因有漏诊误诊、用药不合理、医疗并发症、手术不当,“低赔款,高损害风险”医疗纠纷原因有院内感染、责任心不强。结论波士顿矩阵模型能够为医疗纠纷防范提供风险评估工具,从而助力科室安全管理。管理者可结合风险评估结果,采取差异化管理策略。     

微观社会资本对农转非居民主客观健康认知一致性的影响研究

目的探讨微观社会资本对农转非居民自评健康与客观健康认知一致性的影响。方法两层logistic回归模型分析微观社会资本和人口学因素对健康认知一致性的影响。结果自评健康和客观健康的一致率为63.89%,个体社会资本和年龄对主客观健康一致性产生影响。结论使用自评健康作为健康指标时,应考虑个体社会资本的影响,提高自评健康的预测准确性。     

缺血性卒中相关性肺炎危险因素的病例对照研究

目的 探讨缺血性卒中相关性肺炎的危险因素。方法 回顾性纳入2018年1月—2020年12月期间唐山市协和医院神经内科住院的急性缺血性卒中(acute ischemic stroke, AIS)患者,收集人口统计学及临床资料。根据是否发生卒中相关性肺炎(stroke - associated pneumonia, SAP)分为非SAP组和SAP组,比较两组的各项临床资料,并采用多因素logistic回归分析SAP的独立影响因素。结果 共纳入721例患者,平均年龄(65.63±12.07)岁;SAP组年龄、入院美国国立卫生研究院卒中量表(National Institutes of Health Stroke Scale, NIHSS)评分,冠心病、心房颤动、卒中史、吞咽障碍和入院格拉斯哥昏迷评分≤10分的比例、同型半胱氨酸、纤维蛋白原和白细胞计数均高于非SAP组,而SAP组入院舒张压、高密度脂蛋白胆固醇、白蛋白、白蛋白与球蛋白比值、血红蛋白和红细胞计数均低于非SAP组,差异均有统计学意义;多因素logistic回归分析显示,年龄增高(OR = 1.055,95%CI:1.009～1.103)、入院NIHSS评分增加(OR = 1.290,95%CI:1.154～1.444)、白细胞计数升高(OR = 1.267,95%CI:1.101～1.457)是SAP发生的危险因素。结论 缺血性卒中相关性肺炎与高龄、入院NIHSS评分增加和白细胞计数升高相关。