关键词： MeCP2   Rett syndrome   adenosine deaminase acting on RNA   ADAR   RNA editing  

摘要： Programmable RNA editing is gaining momentum as an approach to repair mutations, but its efficiency in repairing endogenous mutant RNA in complex tissue is unknown. Here we apply this approach to the brain and successfully repair a guanosine-to-adenosine mutation in methyl CpG binding protein 2 RNA that causes the neurodevelopmental disease Rett syndrome. Repair is mediated by hippocampal injections of juvenile Mecp2(317G>A) A mice with an adeno-associated virus expressing the hyperactive catalytic domain of adenosine deaminase acting on RNA 2 and Mecp2 guide. After 1 month, 50% of Mecp2 RNA is recoded in three different hippocampal neuronal populations. MeCP2 protein localization to heterochromatin is restored in neurons to 50% of wild-type levels. Whole-transcriptome RNA analysis of one neuronal population indicates that the majority of off-target editing sites exhibit rates of 30% or less. This study demonstrates that programmable RNA editing can be utilized to repair mutations in mouse models of neurological disease.

关键词： Oxygen   Carbon dioxide   Out-of-hospital cardiac arrest   Brain anoxia-ischemia   Cardio-pulmonary resuscitation   Critical care outcomes  

摘要： Background Exposure to extreme arterial partial pressures of oxygen (PaO2) and carbon dioxide (PaCO2) following the return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest (OHCA) is common and may affect neurological outcome but results of previous studies are conflicting. Methods Exploratory study of the International Cardiac Arrest Registry (INTCAR) 2.0 database, including 2162 OHCA patients with ROSC in 22 intensive care units in North America and Europe. We tested the hypothesis that exposure to extreme PaO(2)or PaCO(2)values within 24 h after OHCA is associated with poor neurological outcome at discharge. Our primary analyses investigated the association between extreme PaO(2)and PaCO(2)values, defined as hyperoxemia (PaO2 > 40 kPa), hypoxemia (PaO2 < 8.0 kPa), hypercapnemia (PaCO2 > 6.7 kPa) and hypocapnemia (PaCO2 < 4.0 kPa) and neurological outcome. The secondary analyses tested the association between the exposure combinations of PaO2 > 40 kPa with PaCO2 < 4.0 kPa and PaO(2)8.0-40 kPa with PaCO2 > 6.7 kPa and neurological outcome. To define a cut point for the onset of poor neurological outcome, we tested a model with increasing and decreasing PaO(2)levels and decreasing PaCO(2)levels. Cerebral Performance Category (CPC), dichotomized to good (CPC 1-2) and poor (CPC 3-5) was used as outcome measure. Results Of 2135 patients eligible for analysis, 700 were exposed to hyperoxemia or hypoxemia and 1128 to hypercapnemia or hypocapnemia. Our primary analyses did not reveal significant associations between exposure to extreme PaO(2)or PaCO(2)values and neurological outcome (P = 0.13-0.49). Our secondary analyses showed no significant associations between combinations of PaO(2)and PaCO(2)and neurological outcome (P = 0.11-0.86). There was no PaO(2)or PaCO(2)level significantly associated with poor neurological outcome. All analyses were adjusted for relevant co-variates. Conclusions Exposure to extreme PaO(2)or PaCO(2)values in the first 24 h

关键词： Neurological involvement   Kawasaki disease   Intravenous immunoglobulin resistance   Coronary artery lesions   Vasculitis  

摘要： Background Kawasaki disease (KD) is an acute, self-limiting systemic vasculitis that predominately affects children. Neurological involvement is a known complication of KD, however, its association with KD severity remains elusive. We aimed to systematically describe the general manifestations of neurological involvement in KD, determine whether neurological involvement is a marker of disease severity in patients with KD, and assess the relationship of such involvement with intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs). Methods We retrospectively reviewed data from 1582 patients with KD between January 2013 and December 2017. Profiles of patients with neurological symptoms (group A,n = 80) were compared to those of gender- and admission date-matched patients without neurological involvement (group B,n = 512). Multivariate logistic regression analyses were performed to determine whether neurological involvement was significantly associated with IVIG resistance. Results Neurological involvement was observed in 5.1% (80/1582) of patients with KD. The neurological manifestations were diffuse, presenting as headache (13/80, 16.3%), convulsions (14/80, 17.5%), somnolence (40/80, 50.1%), extreme irritability (21/80, 26.3%), signs of meningeal irritation (15/80, 18.8%), bulging fontanelles (7/80, 8.8%), and facial palsy (1/80, 1.3%). Neurological symptoms represented the initial and/or predominant manifestation in 47.5% (38/80) of patients with KD. The incidence of IVIG resistance and levels of inflammatory markers were higher in group A than in group B. However, neurological involvement was not an independent risk factor for IVIG resistance or CALs. Conclusion Rates of neurological involvement were relatively low in patients with KD. Neurological involvement was associated with an increased risk of IVIG resistance and severe inflammatory burden. Our results highlight the need for pediatricians to recognize KD with neurological involvement

关键词： blood brain barrier   cerebrovascular disease   inflammation   interleukins   interleukin-1 alpha   neuroprotective agents   stroke  

摘要： Supplemental Digital Content is available in the text.

摘要： The tendency to engage in addictive behaviors has long been tied to the actions of the dopamine system. Early theories were based on the fact that all addictive drugs and behaviors (such as gambling) increase dopamine levels in the striatum, and the evidence that dopamine signaled reward or reward prediction error. However, with a changing emphasis of addiction away from purely pharmacological models that emphasize tolerance and withdrawal, towards one of behavioral dyscontrol, is there still a place for abnormal dopamine signaling in addiction? Here we recast the dopamine theory of addiction based on the idea that tonic dopamine may index a continuous phenotype that goes from apathy to impulsivity and compulsivity. Higher tonic dopamine signaling would make individuals vulnerable to drug reinforcement and cue-induced craving. We relate this to computational models of dopamine signaling, and review clinical and neuroimaging evidence from Parkinson’s Disease, schizophrenia and bipolar disorder in support of this model.

关键词： Energy expenditure   Neurological diseases   Energy requirement   Alzheimer's disease   Parkinson's disease   Amyotrophic lateral sclerosis   Multiple sclerosis   Cerebral palsy  

摘要： Objectives:It has been reported that in most neurological patients, resting energy expenditure due to hypermetabolism is increased. Physical activity, which is another component of energy expenditure, varies depending on the course of the disease. Different mechanisms are used to explain changes in energy expenditure in this population. Pathological problems of centers that regulate energy balance in the brain, endocrine and metabolic dysfunction, mitochondrial damage, autonomic dysfunction and inflammatory anomalies are thought to be at the root of this situation. In this review study, studies about energy expenditure and energy requirement in neurological diseases have been examined and suggested practices in this field have been presented. Methods:We reviewed articles regarding selected from PubMed, Science Direct, EBSCO, and databases about energy expenditure and neurological diseases. Results:Based on the type of neurological diseases;factors such as stage of the disease, disease complications, metabolic status, mechanical ventilation, body composition, movement restrictions or hyperactivity change energy expenditure and, as a result, nutrition requirement. Determination of the energy requirement is the basic variable for adjusting medical nutrition therapy. Despite an increase in resting energy expenditure as a result of metabolic processes in most neurological disorders, the daily energy expenditure is reported to change based on the restriction of physical activity due to the disorder. Discussion:Determining patient's energy expenditure and energy requirements is regarded as the right approach in terms of improving the patient's quality of life, regulating appropriate medical nutrition treatment and increasing the effectiveness of other treatments.

关键词： 北京大学出版社   文献计量学   《中文核心期刊要目总览》   核心期刊   神经病学   精神病学   专家评审   中华神经医学杂志  

摘要： 《中华神经医学杂志》主编:我们谨此郑重通知:依据文献计量学的原理和方法,经研究人员对相关文献的检索、统计和分析,以及学科专家评审,贵刊《中华神经医学杂志》入编《中文核心期刊要目总览》2017年版(即第8版)之“神经病学与精神病学”类的核心期刊。该书由北京大学出版社出版。

关键词： difficulty   Diseases   Type  

摘要： Single-cell transcriptomic analysis has provided an unprecedented avenue for the identification of neuronal subtypes that are affected in neurological ***,this strategy is largely hindered by the difficulty of collecting fresh samples of adult human ***,postmortem brain tissue from both normal and diseased human subjects is more accessible.

关键词： 附属同济医院   同济医学院   开颅手术   柳叶刀   传统医学   神经内科   再出血率   神经病学  

摘要： 2019年,国际顶级杂志Lancet Neurol(《柳叶刀神经病学》)发表的最新流行病学调查表明,全球每年新发脑出血200万余例,我国发病率显著高于欧美国家,近60万例/年,致死、致残率高达50%。随着人口老龄化的加剧,脑出血这种以老年人罹患为主的疾病,正在严重地威胁着人们的健康,给我国家庭和社会造成沉重负担。为治疗脑出血,传统医学上主要采用开颅血肿清除术。虽然这一方法能有效清除血肿,但国际上多项研究证实:开颅手术损伤大、再出血率高、手术时间长、费用高、预后差。研发高效、精准的脑出血新诊疗技术和器械已迫在眉睫。华中科技大学同济医学院附属同济医院神经内科副主任、光谷院区常务副院长唐洲平教授致力于脑出血治疗和研究20余年,为了让更多患者重新拥抱幸福的生活,他一直在不懈地努力着……

关键词： 神经精神疾病   全国性学术会议   精神病学   临床荟萃   神经内科   精神科   神经病学   被引频次  

摘要： 由国家教育部主管、中山大学主办的《中国神经精神疾病杂志》创刊于1975年,是国内神经病学、精神病学领域内具有重要影响力的专业学术性核心期刊,被引频次及影响因子居临床医学期刊前列。我刊主要报道我国神经内科、神经外科、精神科临床和基础研究的新成果,介绍相关领域研究的新进展,推广先进的诊疗技术,组织专题学术讨论和召开全国性学术会议。辟有包括专家论坛、论著、短著述、研究简报、临床荟萃、讲座、综述、疑难病例讨论等诸多栏目,全面、实时地反映最新的学术思想和临床经验,其从基础到临床的广阔领域给致力于神经科学发展的研究者们提供了博大的舞台。