Genetic-Evidence That the Lewy Body Variant Is Indeed a Phenotypic Variant of Alzheimers-Disease

Lewy Body Variant (LBV) patients present as Alzheimers disease (AD) clinically; about two-thirds also have mild extrapyramidal features. At autopsy, neocortical and brain stem Lewy bodies are present in addition to changes diagnostic of AD. We have found that the Apolipoprotein E4 allele is a major genetic risk factor for LBV as it is for ′pure AD," in contrast to subjects with diffuse Lewy body disease or Parkinsons disease. This genetic evidence supports the concept that LBV-the second most common neurodegenerative form of dementia-is a phenotypic variant of AD.     

The effects of 'non-directive' questioning on an anticipated decision whether to undergo predictive testing for heart disease: an experimental study

This study investigates how individuals can be helped to make decisions about predictive genetic testing. Participants (n = 120) rated how likely they would be to opt for predictive testing for heart disease if it were available, and other variables such as anxiety about heart disease. They received information on predictive testing for heart disease and ratings were repeated. Participants were then randomly allocated to one of three groups and focused on the personal relevance of positive issues or negative issues which had been mentioned as part of the standardised information previously given. The third group focused on issues irrelevant to testing for heart disease. The form of questioning used in this focusing manipulation was intended to model the processes involved in non-directive questioning. Results showed a significant increase in likelihood of testing in the positive group, and a significant decrease in the negative group. There was also a significant decrease in rated anxiety about heart disease and perceived severity of an increased susceptibility to heart disease of the negative group relative to the positive and control groups. The results may have implications for the ways in which pre-test counselling is carried out.     

病例报告与临床科研思维

病例报告属于描述性研究方法,是通过记录非同寻常的临床现象,可能揭示新病种、特殊机制、新疗法等,为临床工作经验介绍、总结的初步形式。在医学科学探索的历程中,病例报告拥有特殊的地位和曾经的辉煌,目前仍是医学研究的一种重要体裁。"一个好的病例报告就是一个有教育意义的好故事",一个不同寻常的现象,可能是一个新的病种、一个特殊的机制或一种特殊的组织病变或生理功能紊乱所致。一篇好的病例报告为临床医生和科研工作者提供直接生动的第一手临床资料,能促进临床医生和医学生热爱临床工作,养成面对难题、独立思考、追根朔源、发现与解决问题的能力,值得重视。     

The effects of video feedback on running form

Correct running form is important for injury prevention; as such, correct form promotes continued engagement in running as a long-term form of exercise. Researchers have shown video feedback to be an effective strategy to improve athletic form for a variety of sports, but it has not been evaluated in any behavior analytic research as a method for improving running form. The purpose of this study is to evaluate the effectiveness of video feedback to improve running form for regular runners. During baseline, each participant was video recorded while running without any feedback (verbal or video). During intervention, the researcher recorded the participant, then showed them the video and provided feedback on correct or incorrect form, according to a 9-step task analysis. Results show that all three participants achieved 100% correct steps on the task analysis when video feedback was used to maintain their form during follow-up.     

An Anatomy of Illness

Because it focuses primarily on the sick body (disease), medicine ignores many of the concerns and needs of sick people. By listening to the stories of patients in the clinic, on the Internet, and in published book form, health care providers could gain a better understanding of the impact of disease on the person (illness), what it means to patients over and above their physical symptoms and what they might require over and above surgery or chemotherapy. Only by familiarizing themselves with the entire emotional landscape of illness, which includes fear, anger, shame, guilt, and above all loneliness, can the healthy--medicine as well as society in general--hope to heal in a comprehensive manner.     

Neuroprogressive disease of post-infectious origin: a review of a resurging subacute sclerosing panencephalitis (SSPE)

Subacute sclerosing panencephalitis (SSPE) is a progressive, essentially untreatable, disease of the nervous system. When first described in the 20th Century, it was characterized more for its neuropathological features than for its pathophysiology or cause. It was not until the 1960s that a clear relationship to the measles virus was established. It is now thought that this uncommon infectious encephalopathy is caused by a "slow," altered or persistent form of the wild measles virus which has harbored in the nervous system for years. Then a "breakout" occurs and the more lytic and virulent organisms produce the progressive and spreading inflammatory and destructive lesions which are confined to the nervous system. Epidemiological study of the disease confirms its relationship to measles. In the years since the development of national measles immunization programs, there has been a dramatic decline in the incidence of measles exanthem and until recently a corresponding decline in the incidence of SSPE. In recent years there has been a mild to moderate increase in cases of SSPE as reported to the USA/International SSPE Registry. As yet, there has not been a totally effective treatment. The purpose of this paper is to give an overall review on SSPE and its relationship to measles. This review will include a prospectus of its history, considerations as to its etiology, correlation of clinicopathological features, and thoughts on the past and present epidemiology and treatment.     

The Rise and Fall of Syphilis in Renaissance Europe

The rapid changes that syphilis underwent after the first major outbreak that occurred in Naples in the mid-1490s are believed to constitute the first well-documented example of a human disease. The new plague was of exceptional virulence, highly contagious and causing severe ulceration at the site of infection. According to medical and other historical sources, the ‘genius epidemics’ changed some years after this onset, and a slower-progressing form of syphilis seems to have replaced the initial severe form, as do many virulent epidemic infectious diseases that appear in devastating forms in a previously uninfected population. But what exactly were the features of the disease at the moment of its appearance in Europe at the end of the fifteenth century? How many years did it take for the early, virulent form to be replaced and become endemic? What was the pace of these changes through the decades following the onset of the epidemic? In this essay, I review these issues through an analysis of a large number of chronologically-ordered primary historical sources.     

The relationship between information processing style and information seeking,and its moderation by affect and perceived usefulness: Analysis vs. procrastination

We examined the relationship between information processing style and information seeking, and its moderation by anxiety and information utility. Information about Salmonella, a potentially commonplace disease, was presented to 2960 adults. Two types of information processing were examined: preferences for analytical or heuristic processing, and preferences for immediate or delayed processing. Information seeking was captured by measuring the number of additional pieces of information sought by participants. Preferences for analytical information processing were associated positively and directly with information seeking. Heuristic information processing was associated negatively and directly with information seeking. The positive relationship between preferences for delayed decision making and information seeking was moderated by anxiety and by information utility. Anxiety reduced the tendency to seek additional information. Information utility increased the likelihood of information seeking. The findings indicate that low levels of anxiety could prompt information seeking. However, information seeking occurred even when information was perceived as useful and sufficient, suggesting that it can be a form of procrastination rather than a useful contribution to effective decision making.     

术语和俗语对疾病风险认知的影响

本研究采用混合实验设计,探讨疾病术语和俗语对疾病风险认知的影响,结果发现:对疾病严重性和患病率估计存在锚定效应,疾病名称和熟悉度主效应显著,熟悉度和疾病名称存在交互作用。研究表明:对疾病严重性估计术语高于俗语,对患病率估计俗语高于术语。Bootstrap法分析表明,疾病名称可直接影响严重性估计,也可通过患病率估计影响严重性估计。术语导致严重性高估,但若通过患病率估计再评估严重性时,俗语导致患病率高估,进而对严重性高估。     

红斑性肢痛症合并周围神经损害1例诊治分析

红斑性肢痛症是一种罕见的临床综合征,以肢端皮肤间歇性皮温升高、发红、肿胀及烧灼样痛为特点,病变主要累及四肢末端,尤以下肢多见,多呈对称分布,较少见于面部和耳部.其症状常因运动和遇热而加重,休息和遇冷而减轻.临床上常分为原发性和继发性两大类,其中原发性红斑性肢痛症,多认为与编码Nav1.7亚单位的SCN9A基因突变有关.目前该病发病机制尚不明确,治疗上缺乏确切有效的治疗方案,临床易误诊误治.本文报道了红斑性肢痛症合并周围神经损害1例,以期提高对该病的认识.     

Cognitions related to anxiety: a pilot study of treatment

In general, where anxiety appears to have a specific external focus, such as the situations which are avoided by phobic patients, treatment involving systematic exposure to those situations seems to be effective. This is less appropriate, or even impossible, where anxiety is not dependent on any external circumstance, but is described by the patient as occurring at any time or place, either chronically over long periods, or acutely in the form of ‘panic attacks’. These patients with ‘generalised’ anxiety often describe internal cues for anxiety either in the form of thoughts (e.g. worry over a current problem) or somatic (e.g. chest sensations interpreted as possible heart disease). Beck et al. (1974) has suggested that on interview, all patients diagnosed as suffering from diffuse or generalised anxiety can report specific ideas or other cognitive cues which are associated with anxiety. These usually concern possible traumatic events, such as illness and death, or social rejection. Clearly Beck has in mind the possibility that these cognitions have the effect of inducing anxiety, although even if the validity of the subjective reports were to be accepted, the problem remains of whether the relationship between mood state and cognitions is causal and if so, in which direction it operates. Obviously a causal relationship may also operate in both directions simultaneously, to form a ‘vicious circle’ in which each exacerbates the other. To establish whether there is a sense in which particular cognitions contribute causally to anxious mood, it would be necessary to find a method of manipulating the type or frequency of cognitions thought to be operating in this way.

One obvious possibility is that of ‘thought-stopping’: that is, patients could be taught to identify thoughts which are associated with anxiety and stop them in the usual way (Wolpe, 1973, p. 211) e.g. by' shouting stop, and substituting an alternative thought. The present study was planned as a pilot experiment to determine (i) if appropriate anxiety related cognitions could be elicited from a series of patients with generalised anxiety, (ii) if the reported frequency of such thoughts could be modified by a thought-stopping technique, and (iii) if any changes in thought frequency were associated with improvements in mood.

Clearly there are many ‘non-specific’ features involved in thought-stopping which could also have therapeutic effects on mood. For this reason it was necessary to include an alternative procedure, not directed at reducing thought frequency, but having the same degree of plausibility to patients, and preferably to therapists. The control procedure chosen for this purpose was modelled on desensitisation, in which patients were encouraged to allow the supposedly anxiety-provoking thoughts into their mind and tolerate them, rather than attempt to stop them. In summary, the study employed a relaxation training phase as a base-line, followed by a cross-over design in which the two treatment phases of thought-stopping and ‘cognitive desensitisation’ were given to each patient, in balanced order.     

Intellectual, mnemonic, and frontal functions in dementia with Lewy bodies: A comparison with early and advanced Parkinson's disease

Both Parkinson's disease (PD) and dementia with Lewy bodies (DLB) share a common neuropathological marker, the presence of Lewy bodies in brain stem and basal forebrain nuclei. DLB, in addition, is associated with Lewy bodies in the neocortex, and, in it's more common form, with Alzheimer-type pathological markers, particularly amyloid plaques. Published neuropsychological studies have focused on the differential profiles of DLB and Alzheimer's disease (AD). However, it is presently unclear whether DLB should be classified as a variant of AD or PD. In the present study we compare a healthy age-matched control group with three groups of patients, one with DLB, and two with PD. One of the PD groups was early in the course (PD-E) and the second, more advanced group (PD-A), was matched on severity of cognitive impairment with the DLB group. The results show that DLB was associated with a different pattern of neuropsychological impairment than the PD-A group, particularly in tests believed to be mediated by prefrontal cortical regions.     

The picture superiority effect: support for the distinctiveness model

The form change paradigm was used to explore the basis for the picture superiority effect. Recognition memory for studied pictures and words was tested in their study form or the alternate form. Form change cost was defined as the difference between recognition performance for same and different form items. Based on the results of Experiment 1 and previous studies, it was difficult to determine the relative cost for studied pictures and words due to a reversal of the mirror effect. We hypothesized that the reversed mirror effect results from subjects' basing their recognition decisions on their assumptions about the study form. Experiments 2 and 3 confirmed this hypothesis and generated a method for evaluating the relative cost for pictures and words despite the reversed mirror effect. More cost was observed for pictures than words, supporting the distinctiveness model of the picture superiority effect.     

Intellectual, mnemonic, and frontal functions in dementia with Lewy bodies: A comparison with early and advanced Parkinson's disease

Both Parkinson's disease (PD) and dementia with Lewy bodies (DLB) share a common neuropathological marker, the presence of Lewy bodies in brain stem and basal forebrain nuclei. DLB, in addition, is associated with Lewy bodies in the neocortex, and, in it's more common form, with Alzheimer-type pathological markers, particularly amyloid plaques. Published neuropsychological studies have focused on the differential profiles of DLB and Alzheimer's disease (AD). However, it is presently unclear whether DLB should be classified as a variant of AD or PD. In the present study we compare a healthy age-matched control group with three groups of patients, one with DLB, and two with PD. One of the PD groups was early in the course (PD-E) and the second, more advanced group (PD-A), was matched on severity of cognitive impairment with the DLB group. The results show that DLB was associated with a different pattern of neuropsychological impairment than the PD-A group, particularly in tests believed to be mediated by prefrontal cortical regions.     

Rapid Cycling

Rapid cycling is not a distinct disorder, but is a particularly severe form of bipolar disease. One in six patients with bipolar disease seen by psychiatrists either as an outpatient or as an inpatient suffers from four or more episodes per year. If at least four episodes occur within one year, this high-frequency phase is called ?rapid cycling“ (RC). Treatment for bipolar disorder with RC usually includes trialling mood stabilizers, such as lithium, anticonvulsants, and modern antipsychotics.In four out of five RC patients, treatment improves disease progression; however, some patients exhibit RC for many years.Specific studies have raised the suspicion that administering antidepressive therapy could facilitate an unfavorable course of bipolar affective disorder. The present case demonstrates disease progression and treatment attempts in a patient with distinct RC progression.     

Civic Friendship

This paper seeks to examine the plausibility of the concept of ‘Civic Friendship’ as a philosophical model for a conceptualisation of ‘belonging’. Such a concept, would hold enormous interest for educators in enabling the identification of particular virtues, attitudes and values that would need to be taught and nurtured to enable the civic relationship to be passed on from generation to generation. I consider both of the standard arguments for civic friendship: that it can be understood within the Aristotelian typology as either a form of utility friendship or as a form of virtue friendship. I argue that civic friendship may not be the most appropriate model and that attempts to resolve the problems through looking on it as a political metaphor leave it unable to fulfil the function for which it was originally designed in Ancient Greece. Finally, I emphasize the need to carefully consider which particular metaphors we choose for civic relationships and how we subsequently use them.     

Convolutional neural network based Alzheimer’s disease classification from magnetic resonance brain images

Alzheimer’s disease, the most common form of dementia is a neurodegenerative brain order that has currently no cure for it. Hence, early diagnosis of such disease using computer-aided systems is a subject of great importance and extensive research amongst researchers. Nowadays, deep learning or particularly convolutional neural network (CNN) is getting more attention due to its state-of-the-art performances in variety of computer vision tasks such as visual object classification, detection and segmentation. Several recent studies, that have used brain MRI scans and deep learning have shown promising results for diagnosis of Alzheimer’s disease. However, most common issue with deep learning architectures such as CNN is that they require large amount of data for training. In this paper, a mathematical model P_FS_EC_TL based on transfer learning is used in which a CNN architecture, VGG-16 trained on ImageNet dataset is used as a feature extractor for the classification task. Experimentation is performed on data collected from Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. The accuracy of the 3-way classification using the described method is 95.73% for the validation set.     

Preliminary results of imurek treatment of multiple sclerosis]

The authors, after presenting a survey of the literature on the treatment of multiple sclerosis with immunosuppressants, report their experience with Imurek. Of 53 patients with a chronic and progressive course of the disease, objective improvement could be observed in 17. In 20 patients the symptomatology remained unchanged, although 4 of them reported subjective improvement. In 16 patients, progression of the disease could not be stopped. Better results of treatment could be obtained for those forms of the disease where the course was, first, in the form of what may be referred to as outbursts and, later, in a chronic and progressive form. -Possible side effects are pointed out.     

Unifying diseases from a genetic point of view: the example of the genetic theory of infectious diseases

In the contemporary biomedical literature, every disease is considered genetic. This extension of the concept of genetic disease is usually interpreted either in a trivial or genocentrist sense, but it is never taken seriously as the expression of a genetic theory of disease. However, a group of French researchers defend the idea of a genetic theory of infectious diseases. By identifying four common genetic mechanisms (Mendelian predisposition to multiple infections, Mendelian predisposition to one infection, and major gene and polygenic predispositions), they attempt to unify infectious diseases from a genetic point of view. In this article, I analyze this explicit example of a genetic theory, which relies on mechanisms and is applied only to a specific category of diseases, what we call “a regional genetic theory.” I have three aims: to prove that a genetic theory of disease can be devoid of genocentrism, to consider the possibility of a genetic theory applied to every disease, and to introduce two hypotheses about the form that such a genetic theory could take by distinguishing between a genetic theory of diseases and a genetic theory of Disease. Finally, I suggest that network medicine could be an interesting framework for a genetic theory of Disease.