维生素D及其受体在帕金森病中的作用

帕金森病(Parkinson's disease,PD)是一种常见的中枢神经系统退行性疾病,引起帕金森病的发病机制至今尚未明确。帕金森病患者及老年人普遍存在维生素D缺乏,这可能是帕金森病的重要发病机制之一。由于维生素D具有免疫调节,抗氧化,调节神经营养因子,降低神经毒性的功能,能同时针对几种导致神经退行性病变因素发挥作用,特别是老年人纠正维生素D缺乏可能会阻止神经元的损失和PD相关的认知功能下降。因此补充维生素D可能成为治疗PD的方法。近年来研究发现,维生素D受体基因多态性与帕金森病的发病有相关性。该文就维生素D及其受体在帕金森病中可能发生的保护作用及其机制作一综述。     

THE IMPAIRED DRIVER—A Review of the Facts

Traffic accidents have been subject to relatively little scientific study in California. A substantial barrier to adequate basic research in this field has been the assumption that more is known about the underlying causes of accidents than actually is. For example, within the medical profession, there is a tendency to assume that physical impairments of drivers are important in the causation of accidents, although little evidence has been collected to confirm or deny this assumption.Research into the underlying causes of accidents is a worthy but infinitely complex task. It must be accomplished before the driver''s contribution to accidents can be seen in proper perspective, its components identified and dealt with on a rational basis.     

Cardiac ultrasonography in structural abnormalities and arrhythmias. Recognition and treatment.

Fetal cardiac ultrasonography has become an important tool in the evaluation of fetuses at risk for cardiac anomalies. It can both guide prenatal treatment and assist the management and timing of delivery. We recommend that a fetal echocardiogram be done when there is a family history of congenital heart disease; maternal disease that may affect the fetus; a history of maternal drug use, either therapeutic or illegal; evidence of other fetal abnormalities; or evidence of fetal hydrops. The optimal timing of evaluation is 18 to 22 weeks'' gestation. An entire range of structural cardiac defects can be visualized prenatally, including atrioventricular septal defect, ventricular septal defect, cardiomyopathy, ventricular outlet obstruction, and complex cardiac defects. The outcome for a fetus with a recognized abnormality is unfavourable, with less than 50% surviving the neonatal period. Fetal cardiac arrhythmias are also a common occurrence, 15% in the series described here. Premature atrial or ventricular contractions are most commonly seen and usually require no treatment. Supraventricular tachycardia can result in hydrops and require in utero treatment to prevent fetal demise. Complete heart block, particularly in association with structural heart disease, has a poor prognosis for fetal survival.     

Coronary heart diseases: Assessment of risk associated with work exposure to ultralow-frequency magnetic fields

The present analysis was stimulated by previous findings on the possible influence of natural ultralow-frequency (ULF; 0.001–10 Hz) geomagnetic field variations on the cardiovascular system and indications of an effect of man-made ULF magnetic fields on the rate of myocardial infarction. In the present study, we considered the occupational health hazards of the strongest ULF magnetic fields in densely populated urban areas. Measurements of ULF magnetic field fluctuations produced by trains powered by DC electricity were performed by means of a computer-based, highly sensitive, three-component magnetometer. We found that the magnitude of magnetic field pulses inside the driver's cab of electric locomotives (ELs) could be ≥ 280 μT in the horizontal component perpendicular to the rails and up to approximately 130 μT in the vertical component, and, in the driver's compartment of electric motor unit (EMU) trains, they were approximately 50 and 35 μT, respectively. We have investigated the relationships between the occupational exposure to ULF magnetic field fluctuations produced by electric trains and cardiovascular diseases (CVDs) among railroad workers in the former Soviet Union. We have analyzed medical statistical data for a period of 3 years for approximately 45,000 railroad workers and 4,000 engine drivers. We have also analyzed 3 years of morbidity data for three subgroups of engine drivers (∼4,000 in each group) operating different types of trains. We find that EL drivers have a twofold increase in risk (2.00 ± 0.27) of coronary heart diseases (CHDs) compared with EMU drivers. Because our analysis of major CVDs shows that the examined subpopulations of drivers can be considered to have had equal exposure to all known risk factors, the elevated CHD risk among EL drivers could be attributed to the increased occupational exposure to ULF magnetic fields. © 1996 Wiley-Liss, Inc.     

Drinking and Driving

Alcohol misuse generates many health and social problems at a cost that society is increasingly unwilling to sustain. One of the most tragic consequences of alcohol misuse is the result of drinking and driving. Each week, impaired drivers kill 40 Canadian men, women and children and injure 1250 others. The Canadian Medical Association (CMA), in its campaign against drinking and driving, has recommended that a condition of obtaining or renewing a driver''s licence include the individual''s written consent to allow the taking of blood samples by qualified medical personnel when deemed necessary by law enforcement agencies. CMA has recommended to the provinces that the legal age for the purchase and public possession of alcohol be raised to 21. CMA also supports the ban of all alcohol advertising in the electronic media and emphasizes that since alcohol is a drug, all containers should be visibly labelled “Misuse of this Product can be Injurious to Health”. CMA continues to support and encourage the federal and provincial governments in their battle to prevent alcohol-related deaths and injuries through education, control of advertising, use of breathalyzer devices, mandatory blood alcohol testing and legislation enacting stiffer penalties for drinking and driving.     

Are problem drinkers dangerous drivers? An investigation of arrest for drinking and driving,serum gamma glutamyltranspeptidase activities,blood alcohol concentrations,and road traffic accidents: the Tayside Safe Driving Project.

Serum gamma glutamyltranspeptidase activity was measured in 440 drivers at the time of arrest for driving under the influence of alcohol. The results were compared with information gathered by the arresting police officer. One third of drivers over the age of 30 had abnormal gamma glutamyltranspeptidase activities at the time of arrest. Among drivers who required a driving license for their work, and older drivers, a disproportionately high number had raised gamma glutamyltranspeptidase activities indicating problem drinking. In drivers over the age of 30 a strong association was found between gamma glutamyltranspeptidase activities and road traffic accidents but not alcohol concentrations or previous convictions. These findings argue against the Department of Transport''s criteria for high risk offenders and indicate a clear need for new measures against problem drinkers among drinking and driving offenders.     

Protein interaction network for Alzheimer's disease using computational approach

Alzheimer''s disease (AD) is the most common form of dementia. It is the sixth leading cause of death in old age people. Despite recent advances in the field of drug design, the medical treatment for the disease is purely symptomatic and hardly effective. Thus there is a need to understand the molecular mechanism behind the disease in order to improve the drug aspects of the disease. We provided two contributions in the field of proteomics in drug design. First, we have constructed a protein-protein interaction network for Alzheimer''s disease reviewed proteins with 1412 interactions predicted among 969 proteins. Second, the disease proteins were given confidence scores to prioritize and then analyzed for their homology nature with respect to paralogs and homologs. The homology persisted with the mouse giving a basis for drug design phase. The method will create a new drug design technique in the field of bioinformatics by linking drug design process with protein-protein interactions via signal pathways. This method can be improvised for other diseases in future.     

Know Thy Neighbor: Costly Information Can Hurt Cooperation in Dynamic Networks

People need to rely on cooperation with other individuals in many aspects of everyday life, such as teamwork and economic exchange in anonymous markets. We study whether and how the ability to make or break links in social networks fosters cooperate, paying particular attention to whether information on an individual''s actions is freely available to potential partners. Studying the role of information is relevant as information on other people''s actions is often not available for free: a recruiting firm may need to call a job candidate''s references, a bank may need to find out about the credit history of a new client, etc. We find that people cooperate almost fully when information on their actions is freely available to their potential partners. Cooperation is less likely, however, if people have to pay about half of what they gain from cooperating with a cooperator. Cooperation declines even further if people have to pay a cost that is almost equivalent to the gain from cooperating with a cooperator. Thus, costly information on potential neighbors'' actions can undermine the incentive to cooperate in fluid networks.     

Genetic Factors in Hashimoto's Struma

It has previously been established that there is a significant history of thyroid disorders in families of patients with Hashimoto''s struma or chronic thyroiditis. In the present study, 99 relatives of 20 patients with Hashimoto''s struma or chronic thyroiditis were studied with regard to the incidence of circulating thyroid autoantibodies; 42 of these 99 relatives were found to have such antibodies. Twenty of the 99 relatives were shown to have thyroid abnormalities (chiefly goitre); of this group of 20, antibodies were found in 12. In the remaining 79 persons (who had no clinical evidence of thyroid disease), 30 were found to have circulating antithyroid antibodies. The incidence of such antibodies among these relatives is very significantly greater than in the general population.From these and other similar studies, there is strong evidence favouring a genetic predisposition for Hashimoto''s struma and chronic thyroiditis. The mode of inheritance is not yet established, and the pathogenesis of the disease has not yet been elucidated.     

Drowning deaths in people with epilepsy.

OBJECTIVE: To determine the demographic characteristics and risk factors associated with death from drowning among people with epilepsy. DESIGN: Retrospective review of medical examiner''s investigations into deaths from drowning from Jan. 1, 1981, to Dec. 31, 1990. SETTING: Alberta. MEASURES: Personal data, medical history, circumstances surrounding the death, autopsy findings and results of postmortem toxicologic analyses. RESULTS: Of 482 deaths from drowning in Alberta during the study period, 25 (5%) were considered by the medical examiner''s office to be directly related to seizures. Fifteen (60%) of the 25 deaths occurred while the person was taking a bath, unsupervised. Only one person (4%) died while taking a shower. The remaining deaths occurred on a river or lake (16%), in a private pool (8%), in a public pool (8%) and in a jacuzzi (4%). Two people fell out of moving boats while having a seizure; neither had been wearing a personal flotation device. Nineteen (83%) of 23 people who had been receiving anticonvulsant drug therapy had undetectable or subtherapeutic levels of one or more of the drugs at autopsy. Ethanol was not a factor in any of the deaths. CONCLUSIONS: Seizure-related drownings represent a small but potentially preventable proportion of all drownings. Enhanced seizure control and compliance with anticonvulsant drug therapy may prevent some of these deaths. In addition, all people with epilepsy, regardless of the level of control of their condition, should be encouraged to take showers while sitting instead of baths. The presence of people in the same house who are not directly supervising the person in the bathroom does not protect against drowning. Personal flotation devices should be worn at all times during boating activities.     

沙棘油对高脂小鼠诱发阿尔兹海默症的预防作用

目的:通过检测沙棘油作用高脂小鼠海马神经元内微管相关蛋白(Tau)及脑源性神经营养因子(BDNF)的表达水平,探讨沙棘油对高脂小鼠并发阿尔兹海默综合征的预防作用。方法:40只KM小鼠,随机取10只为正常对照组;30只以高脂饲料喂养建立高脂模型(HF),按10 mg/kg以生理盐水(阴性对照)、沙棘油(实验)、辛伐他丁(阳性对照)灌胃3 w。取小鼠海马组织进行HE染色、免疫组织化学检测和蛋白印迹分析,检测不同组别小鼠海马神经元内Tau蛋白及BDNF表达的变化。结果:高脂模型组与正常组比较,海马神经元结构在光镜下有明显差别;阴性对照组小鼠海马神经细胞数目减少,神经元内有黄色颗粒样沉淀;实验及阳性组海马损伤有改善,斑块状淀粉样蛋白减少;免疫组化及蛋白印迹显示各组间两种蛋白表达水平不同。结论:沙棘油对高脂小鼠海马体内Tau蛋白表达有抑制作用,加速淀粉样前体蛋白的代谢,降低了由β-淀粉样蛋白沉积诱发阿尔茨海默病的风险;而对BDNF表达有促进作用,能防止神经元受损伤死亡、改善神经元的病理状态、促进受损伤神经元再生。即沙棘油能有效预防高脂人群并发阿尔兹海默综合征。     

Apolipoprotein E genotype and association between smoking and early onset Alzheimer's disease.

OBJECTIVE--To investigate the hypothesis that differential survival between smokers and non-smokers leading to a decrease in the frequency of the e4 allele of the apolipoprotein E gene may explain the inverse relation between smoking history and early onset Alzheimer''s disease. DESIGN--A population based case-control study. SETTING--The four northern provinces of the Netherlands and metropolitan Rotterdam. SUBJECTS--175 patients with early onset Alzheimer''s disease and two independent control groups of 159 and 457 subjects. MAIN OUTCOME MEASURES--Frequencies of the apolipoprotein e4 allele and relative risk of early onset Alzheimer''s disease. RESULTS--The inverse association between smoking history and early onset Alzheimer''s disease could not be explained by a decrease in the frequency of the apolipoprotein e4 allele. Among carriers of this allele with a family history of dementia subjects with a history of smoking had a strongly reduced risk of early onset Alzheimer''s disease (odds ratio 0.10 (95% confidence interval 0.01 to 0.87)). CONCLUSIONS--The results suggest that the inverse relation between smoking history and early onset Alzheimer''s disease cannot be explained by an increased mortality in carriers of the apolipoprotein e4 allele who smoke. The association is strongly modified by the presence of the apolipoprotein e4 allele as well as by a family history of dementia.     

Single Molecule Force Spectroscopy on Titin Implicates Immunoglobulin Domain Stability as a Cardiac Disease Mechanism

Titin plays crucial roles in sarcomere organization and cardiac elasticity by acting as an intrasarcomeric molecular spring. A mutation in the tenth Ig-like domain of titin''s spring region is associated with arrhythmogenic cardiomyopathy, a disease characterized by ventricular arrhythmias leading to cardiac arrest and sudden death. Titin is the first sarcomeric protein linked to arrhythmogenic cardiomyopathy. To characterize the disease mechanism, we have used atomic force microscopy to directly measure the effects that the disease-linked point mutation (T16I) has on the mechanical and kinetic stability of Ig10 at the single molecule level. The mutation decreases the force needed to unfold Ig10 and increases its rate of unfolding 4-fold. We also found that T16I Ig10 is more prone to degradation, presumably due to compromised local protein structure. Overall, the disease-linked mutation weakens the structural integrity of titin''s Ig10 domain and suggests an Ig domain disease mechanism.     

A Case of Inappropriate Therapies for Atrial Flutter From a Subcutaneous ICD

Hypertrophic cardiomyopathy’s (HCM) association with sudden cardiac death is well recognised. The risk of sudden cardiac death is known to increase when there is a history of unexplained syncope, abnormal blood pressure response during exercise, severe left ventricular hypertrophy or a family history of unexplained death.Implantable Cardioverter Defibrillator (ICD) implantation has been widely used for primary and secondary prevention of sudden cardiac death (SCD) in people with HCM. Subcutaneous ICD (S-ICD) therapy has been developed to overcome some of the problems associated with the transvenous leads used in conventional ICDs.In this article, we report the use of S-ICD in a patient with HCM and multiple risk factors for sudden cardiac death, this device had to be extracted due to recurrent inappropriate shocks caused by over sensing of atrial flutter and failure to treat a VT episode. We are not aware of any reports of inappropriate shocks caused by atrial flutter in people with a S-ICD.     

The Leeuwenhoek Lecture, 1997. Marek's disease herpesvirus: oncogenesis and prevention.

There are a number of neoplasias for which a herpesvirus is an essential part of the aetiology. Of these, Marek''s disease is the most common and provides excellent opportunities for the study of a herpesvirus-induced tumour both experimentally and under natural conditions in the field. Marek''s disease is caused by an alpha herpesvirus; it differs from the other oncogenic herpesviruses which are gamma herpesviruses. It is a ubiquitous virus in poultry populations of the world and is highly cell-associated and contagious, yet only a proportion of infected fowl develop tumours. Evidence is presented to suggest that at least one of the reasons for a wide variation in the incidence of the disease is a temporal interplay between virulent viruses and viruses of low or no virulence. The viral genes associated with the oncogenicity of Marek''s disease virus (MDV) are discussed and it is concluded that it is likely that several genes are involved. Finally, a brief history of vaccination to control Marek''s disease is given and mode of action discussed. It is concluded that the mechanism of protection is mainly through an antiviral cell mediated immune response, resulting in a lowered challenge virus burden. Marek''s disease viruses over the past 40 years have been evolving greater oncogenicity, some of which are not adequately controlled by the vaccines that are currently available. It is suggested that for MDV to produce tumours, there is a need for the cytolytic infection phase and that infection must be with an MDV which possesses a functional gC, ICP4 for maintaining latency which allows the expression of at least the 1.8 kb family, pp38, meq, and possibly pp14 genes, for maintaining the tumour state and possibly initiating this state. Intervention in this process reduces the chance of tumour formation and incidence in a population which can occur through natural or man-mediated infection with non-pathogenic MDVs.     

Active Surveillance of Hansen's Disease (Leprosy): Importance for Case Finding among Extra-domiciliary Contacts

Hansen''s disease (leprosy) remains an important health problem in Brazil, where 34,894 new cases were diagnosed in 2010, corresponding to 15.3% of the world''s new cases detected in that year. The purpose of this study was to use home visits as a tool for surveillance of Hansen''s disease in a hyperendemic area in Brazil. A total of 258 residences were visited with 719 individuals examined. Of these, 82 individuals had had a previous history of Hansen''s disease, 209 were their household contacts and 428 lived in neighboring residences. Fifteen new Hansen''s disease cases were confirmed, yielding a detection rate of 2.0% of people examined. There was no difference in the detection rate between household and neighbor contacts (p = 0.615). The two groups had the same background in relation to education (p = 0.510), household income (p = 0.582), and the number of people living in the residence (p = 0.188). Spatial analysis showed clustering of newly diagnosed cases and association with residential coordinates of previously diagnosed multibacillary cases. Active case finding is an important tool for Hansen''s disease control in hyperendemic areas, enabling earlier diagnosis, treatment, decrease in disability from Hansen''s disease and potentially less spread of Mycobacterium leprae.     

'Positive biology' as a new paradigm for the medical sciences. Focusing on people who live long, happy, healthy lives might hold the key to improving human well-being

The nearly exclusive focus on understanding and treating chronic disease might not be the most efficient way to improve public health, especially as an effective alternative strategy exists.On 27 April 2009, during a speech at the National Academy of Sciences, US President Barack Obama pledged to invest more than 3% of US GDP in scientific research and development—the amount represented the largest ever investment in research and innovation. However, even a financial investment of such magnitude does not ensure that science is ''well-ordered'' [1], in the sense that the scientific research that is prioritized aspires to address the most significant challenges and problems for humanity.Among the many issues facing society that research must address, improving human health and tackling disease rank high, if not first, on the agenda. Accordingly, a huge fraction of research funding is spent on basic and applied research to further our understanding of the causes of disease and to find new cures and therapies. But is this focus on pathology the most efficient way to conduct research with the aim to improve human health and well-being?…a huge fraction of research funding is spent on basic and applied research to further our understanding of the causes of disease and to find new cures and therapiesMost of today''s medical research could be called ''negative biology''. It is conducted in an intellectual framework that presumes that the most important question to answer is: what causes pathology? Disease is its central focus and this explains why medical research and research funding is mainly concerned with trying to understand, prevent and treat specific diseases. The design of the US National Institutes of Health, which is largely composed of individual institutes dedicated to specific diseases such as cancer, mental illness or infectious diseases, reflects this prevalence of pathology-oriented negative biology.Positive biology, by contrast, focuses on a different set of questions and priorities. Rather than making pathology and disease the central focus of intellectual efforts and financial investments, positive biology seeks to understand positive phenotypes: why do some individuals live more than a century without ever suffering from the chronic diseases that afflict most humans much earlier in their lives? Why are some individuals more happy, optimistic, talented, or have a better memory than most people? The paradigm of positive biology is based on the insight that the process of evolution by natural selection does not create a perfect organism in terms of life expectancy, resistance to disease or other abilities. Observations of exceptional longevity or superior cognition therefore present fascinating puzzles for positive biology: which biological mechanisms would explain these exemplars of health and well-being? The goal of understanding positive phenotypes is that such knowledge might lead to new interventions that generally improve human well-being. This might be achieved by modulating the rate of ageing or by increasing opportunities for play and joy at all stages of the human lifespan, or by developing pharmaceuticals that safely enhance cognition or positive emotions, and so on.The goal of understanding positive phenotypes is that such knowledge might lead to new interventions that generally improve human well-beingThis is distinct from negative biology, which focuses on the proximate causes of specific diseases, rather than on the evolutionary causes of positive phenotypes. It presumes that health, survival and happiness are the default states and aims to explain the deviations: why do we develop cancer? Why do we suffer from depression? Why do we develop hypertension? Negative biology therefore faces the laudable but insurmountable task of trying to prevent or cure all disease. This is a costly and ultimately futile endeavour. Eliminating all types of cancer would increase life expectancy in the USA by approximately only three years [2]. Even eliminating cancer as a cause of death would not prevent any of the other chronic diseases of ageing—cardiovascular disease, Alzheimer and Parkinson disease, diabetes and so on—from afflicting the elderly. Moreover, the more than 40 years of ''war against cancer'' has not defeated a single type of cancer: we still have a long way to go before we can realistically expect to reap the three-year increase in life expectancy that eliminating all cancers could yield.In fact, negative biology has not yet developed a single cure for any one of the hundreds of chronic diseases that afflict millions of people living today. Of course, it has made significant advances to help prevent and treat chronic disease, but the fixation on pathology has meant that other potential avenues for research have been neglected.Indeed, a better understanding of exemplars of health and happiness—the goal of positive biology—could create more benefits for humans more quickly and more easily. A drug that would safely mimic the effects of caloric restriction, for instance, might delay, simultaneously, most diseases and afflictions of ageing. It would generate a much greater health dividend for ageing populations than defeating any one specific disease of ageing because slowing down the rate of ageing by seven years would reduce the age-specific risk of death, frailty and disability by about half at every age [3].Scientists are already making good progress on the project of positive biology, even if the intellectual framework is not yet clearly defined and their topics are rather piecemeal. Richard Miller, for example, a professor of pathology at Michigan University, USA, studies the genetics of ageing in mice and participates in the National Institute of Aging''s multi-institutional programme that evaluates the effects of drugs and nutriceuticals on the ageing process in mice. David Sinclair from Harvard University, USA, and others found that the plant compound resveratrol, which is found in the skin of grapes, can modulate the ageing process. Nir Barzilai and colleagues at the Albert Einstein School of Medicine in New York, USA, have conducted genetic research on more than 500 healthy elderly people between the ages of 95 and 112 years. Michael Rose from the University of California, Irvine, USA, has quadrupled the lifespan of fruit flies by delaying the age of reproduction. Finally, the biologist Cynthia Kenyon demonstrated that in Caenorhabditis elegans, a single gene can control the ageing process. Any of these research projects could eventually lead to the development of a new drug that retards the ageing process and diminishes the onslaught of chronic diseases that typically afflict humans after their sixth decade of life.Similarly, a lot of pioneering work is being undertaken in the burgeoning field of ''positive psychology''. Rather than studying why people suffer from mental illnesses such as depression, schizophrenia or ADHD (attention deficit hyperactivity disorder), positive psychology is primarily interested in how to improve the happiness of the ''average'' person. Martin Seligman, a psychologist at the University of Pennsylvania, USA, and a pioneer in the field of positive psychology, distinguishes different kinds and levels of happiness [4]. Hedonists who pursue immediate rewards such as the pleasure of buying something or receiving a compliment seek momentary happiness or what Seligman calls ''the pleasant life''. But these pleasures fade quickly and do not leave a lasting impact on subjective well-being. Enduring happiness, by contrast, is realized when we lead a meaningful life. After years spent studying what makes people happy, Seligman contends that it is rooted in attachment to something larger, and the larger the entity to which you attach yourself, the more meaning your life has [4].Eliminating all types of cancer would increase life expectancy in the USA by approximately only three yearsThis is clearly illustrated by the role of wealth. People often assume that being richer will mean being happier, yet surveys in many countries indicate that global levels of life satisfaction or happiness have not changed much during the past four decades despite large increases in real income per capita [5]. Most disposable income is spent on consumer goods that do little to actually enhance our well-being.In a recent study of the daily behaviour of happy people, researchers used an electronically activated recorder to record, and then later classify, participants'' daily conversations with others as either ''small talk'', that is banal conversations, and ''substantive talk'', where meaningful information was exchanged. They found that higher well-being was associated with less small talk and more substantive conversations [6]. While such a study does not establish the truth of Socrates'' famous claim that “the unexamined life is not worth living”, it does suggest that our need to feel attached to something larger is important to our happiness and well-being. This hypothesis is supported by recent studies on how people spend their money. Researchers from the University of British Columbia and Harvard Business School found that when individuals spend more money on prosocial goals, such as charity, they actually experience greater happiness than when they spend money on consumer products for themselves [7]. Similarly, the psychologist Barbara Fredrickson''s research on positive emotions—joy, serenity and gratitude—suggests that these expand cognition and behavioural tendencies [8].Finally, research on exemplars of resilience, that is, the ability of some people to cope and manage with tragic and traumatic events, could lead to the development of drugs that would increase people''s resilience. Avshalom Caspi and colleagues found that individuals with one or two copies of the short allele of the promoter of the 5-HTT serotonin receptor experience more depressive symptoms, diagnosable depression and suicidal thoughts in response to stressful events compared with individuals who are homozygous for the long allele [9].Cognitive functioning is another central topic of positive biology. What are the genetic and environmental determinants of high IQ, exceptional memory or social intelligence? Barbara Sahakian and colleagues found that the analeptic drug modafinil significantly enhanced performance tests of digit span, visual pattern recognition memory, spatial planning and stop-signal reaction time in healthy volunteers [10]. These findings of positive biology will eventually give us a better understanding of our human nature than the very limited focus on disease and pathology of negative biology and might then lead to new interventions, environments and attitudes that improve human well-being and happiness.Negative biology dominates medical research, from the questions research scientists tackle to the education of physicians and government regulation of health interventions. The dominance of this approach to the medical sciences presumes that the most important questions concern the causes of pathology rather than the causes of exemplar health and happiness. Positive biology takes a different approach: it does not limit the moral duty to apply knowledge and technology to improve human welfare to only treating specific diseases or impairments. Rather, it works under the assumption that if knowledge and research can improve people''s lives, there is a moral duty to advance that knowledge and promote well-being. Nor is positive biology predicated on a sharp distinction between therapy and enhancement. Instead, as the bioethicist John Harris has argued, “the overwhelming moral imperative for both therapy and enhancement is to prevent harm and confer benefit. Bathed in that moral light, it is unimportant whether the protection or benefit conferred is classified as enhancement or improvement, protection or therapy” [11].Generally, the medical system as a whole could be much more efficient if it concentrated its efforts on making people healthier and happier in the first place instead of its current focus on understanding and treating disease. Advancing the paradigm of positive biology should therefore help the medical sciences transcend the limited perspectives and aspirations of negative biology. Such a paradigm could help the world''s population to reap the benefits that new knowledge and technologies can offer in terms of making people healthier and happier. Societies and individuals already seek to achieve these goals: we educate our children to eat healthily and exercise and to develop their social goals to find fulfilment in life. The paradigm of positive biology simply encourages us to make use of the full range of options to realize these goals.…the medical system as a whole could be much more efficient if it concentrated its efforts on making people healthier and happier in the first place…In conclusion, positive biology is not contrary to the goals and aspirations of negative biology. Indeed the two paradigms are often complementary. For example, understanding why some high-risk individuals, such as sex workers, seem to have an intrinsic resistance to HIV-1 might spur the development of an HIV vaccine [12]. Similarly, understanding human brains with exceptional cognitive functioning might lead to new avenues for developing drugs and therapies against severe cognitive impairment. Understanding exemplars of health could create real benefits for those who are more vulnerable to disease and disability.     

轻度认知障碍的研究进展

老年性痴呆(阿尔茨海默病,Alzheimer disease,AD)是目前严重影响老年人生存质量的疾病,且疗效不佳。据推测到2050年阿尔茨海默病的患病率将是现今的三倍。轻度认知障碍(mild cognitive impairment,MCI)是介于阿尔茨海默病和正常衰老之间的一种认知功能损害状态,是发生阿尔茨海默病的高危因素。文献报道轻度认知障碍每年以8%-25%的比例进展为阿尔茨海默病,较正常人群阿尔茨海默病发病率高10倍。与阿尔茨海默病病理损害不可逆相比,轻度认知障碍患者通过早期干预治疗,可延缓或阻止病情发展为阿尔茨海默病。因此,对阿尔茨海默病早期出现的轻度认知功能障碍诊断及干预尤为重要。本文就认知功能早期阶段,轻度认知功能障碍的历年(2000年到2014年3月)研究进展从概念及分型、临床表现、诊断标准、病理生理及其影像学研究、危险因素及其预防、干预措施(药物和非药物)等方面的最新进展进行论述。     

Why Londoners have low death rates from ischaemic heart disease and stroke.

OBJECTIVE--To explain the low death rates from cardiovascular disease in London. SETTING--London and the other counties of England and Wales. SUBJECTS--Women living in London during 1901-10 and people in London dying during 1968-78. RESULTS--At the beginning of the twentieth century young women aged 15-34 in London had remarkably low death rates, largely because of low rates for tuberculosis and other infectious diseases and low mortality during childbirth. Their low death rates contrasted with the high rates in girls under 15 years. CONCLUSIONS--Large numbers of young women had migrated into London from agricultural counties in southern England and went into domestic service, where the diet was usually very good. Recent findings suggest that a mother''s nutrition and health has a major effect on the risk of cardiovascular disease in the next generation. The low cardiovascular mortality in London is consistent with this, and contrasts with the high mortality from other common diseases.