关键词： ubiquitin   viral oncogenesis   oncoproteins   tumor suppressors   Angelman syndrome   autism   small molecules   imprinting   E3 ligase   chromosome 15q  

摘要： The HECT (Homologous to the E6-AP Carboxyl Terminus)-family protein E6AP (E6-associated protein), encoded by theUBE3Agene, is a multifaceted ubiquitin ligase that controls diverse signaling pathways involved in cancer and neurological disorders. The oncogenic role of E6AP in papillomavirus-induced cancers is well known, with its action to trigger p53 degradation in complex with the E6 viral oncoprotein. However, the roles of E6AP in non-viral cancers remain poorly defined. It is well established that loss-of-function alterations of theUBE3Agene cause Angelman syndrome, a severe neurodevelopmental disorder with autosomal dominant inheritance modified by genomic imprinting on chromosome 15q. Moreover, excess dosage of theUBE3Agene markedly increases the penetrance of autism spectrum disorders, suggesting that the expression level of UBE3A must be regulated tightly within a physiologically tolerated range during brain development. In this review, current the knowledge about the substrates of E6AP-mediated ubiquitination and their functions in cancer and neurological disorders is discussed, alongside with the ongoing efforts to pharmacologically modulate this ubiquitin ligase as a promising therapeutic target.

关键词： Personality   Behavior   Lesion   Neurological event  

摘要： Research on changes in personality and behavior following brain damage has focused largely on negative outcomes, such as increased irritability, moodiness, and social inappropriateness. However, clinical observations suggest that some patients may actually show positive personality and behavioral changes following a neurological event. In the current work, we investigated neuroanatomical correlates of positive personality and behavioral changes following a discrete neurological event (e.g., stroke, benign tumor resection). Patients (N = 97) were rated by a well-known family member or friend on five domains of personality and behavior: social behavior, irascibility, hypo-emotionality, distress, and executive functioning. Ratings were acquired during the chronic epoch of recovery, when psychological status was stabilized. We identified patients who showed positive changes in personality and behavior in one or more domains of functioning. Lesion analyses indicated that positive changes in personality and behavior were most consistently related to damage to the bilateral frontal polar regions and the right anterior dorsolateral prefrontal region. These findings support the conclusion that improvements in personality and behavior can occur after a neurological event, and that such changes have systematic neuroanatomical correlates. Patients who showed positive changes in personality and behavior following a neurological event were rated as having more disturbed functioning prior to the event. Our study may be taken as preliminary evidence that improvements in personality and behavior following a neurological event may involve dampening of (premorbidly) more extreme expressions of emotion.

关键词： 神经系统疾病   诊疗  

ISBN: (纸本)9787547849897

摘要： 《病证结合神经病学》以现代神经病学疾病病名诊断为纲，以中国医药学辨证治疗为目，病证结合阐述临床常见神经疾病的辨识要点、临床决策、治疗推荐、常用药物、思路拓展。撰著思路新颖，内容独具一格，是一部临床价值较高的中西结合神经病学专著。病证结合临床诊疗模式是辨病与辨证相结合理论的突破与发展，将继续引领我国中医中西结合神经病学临床诊疗取得更加辉煌业绩。通过阅读本书可望提高中医、西医、中西结合临床医师的神经病诊疗水平。

关键词： Carrier testing   confidentiality   consent   diagnostic testing   genetic testing   genomics   MRCP   neurogenetics   neurology   next-generation sequencing   pre-symptomatic testing  

摘要： Genetic testing is now an integral part of most areas of medicine, including Neurology. This article aims to guide clinicians on the pathways for genetic testing, including ethical dilemmas that can arise in the care of families with a confirmed or suspected genetic condition. The new UK National Health Service Genomic Medicine Service will alter the way genomic services are offered across the country. As genetics becomes mainstream, it is increasingly important for non-geneticists to keep abreast of developments, and be aware of potential pitfalls and when to seek specialist advice. We explain patterns of inheritance, their complexities and the important distinctions between pre-symptomatic, diagnostic and carrier testing. We explore the ethical framework for testing, including confidentiality and consent, and testing in children and at-risk relatives. We outline the core technologies for genetic and genomic testing and the importance of liaison with clinical genetics services and medical genetics laboratories to remain up to date with the availability and appropriateness of any genetic test. © 2020

关键词： Genetic testing   Genetics research   Neurological disorders  

摘要： A high rate of consanguinity leads to a high prevalence of autosomal recessive disorders in inbred populations. One example of inbred populations is the Arab communities in Israel and the Palestinian Authority. In the Palestinian Authority in particular, due to limited access to specialized medical care, most patients do not receive a genetic diagnosis and can therefore neither receive genetic counseling nor possibly specific treatment. We used whole-exome sequencing as a first-line diagnostic tool in 83 Palestinian and Israeli Arab families with suspected neurogenetic disorders and were able to establish a probable genetic diagnosis in 51% of the families (42 families). Pathogenic, likely pathogenic or highly suggestive candidate variants were found in the following genes extending and refining the mutational and phenotypic spectrum of these rare disorders: ACO2, ADAT3, ALS2, AMPD2, APTX, B4GALNT1, CAPN1, CLCN1, CNTNAP1, DNAJC6, GAMT, GPT2, KCNQ2, KIF11, LCA5, MCOLN1, MECP2, MFN2, MTMR2, NT5C2, NTRK1, PEX1, POLR3A, PRICKLE1, PRKN, PRX, SCAPER, SEPSECS, SGCG, SLC25A15, SPG11, SYNJ1, TMCO1, and TSEN54. Further, this cohort has proven to be ideal for prioritization of new disease genes. Two separately published candidate genes (WWOX and PAX7) were identified in this study. Analyzing the runs of homozygosity (ROHs) derived from the Exome sequencing data as a marker for the rate of inbreeding, revealed significantly longer ROHs in the included families compared with a German control cohort. The total length of ROHs correlated with the detection rate of recessive disease-causing variants. Identification of the disease-causing gene led to new therapeutic options in four families.

关键词： gait analysis   machine learning   inertial measurement units   neurological disorders   falls  

摘要： Neurological patients can have severe gait impairments that contribute to fall risks. Predicting falls from gait abnormalities could aid clinicians and patients mitigate fall risk. The aim of this study was to predict fall status from spatial-temporal gait characteristics measured by a wearable device in a heterogeneous population of neurological patients. Participants (n= 384, age 49-80 s) were recruited from a neurology ward of a University hospital. They walked 20 m at a comfortable speed (single task: ST) and while performing a dual task with a motor component (DT1) and a dual task with a cognitive component (DT2). Twenty-seven spatial-temporal gait variables were measured with wearable sensors placed at the lower back and both ankles. Partial least square discriminant analysis (PLS-DA) was then applied to classify fallers and non-fallers. The PLS-DA classification model performed well for all three gait tasks (ST, DT1, and DT2) with an evaluation of classification performance Area under the receiver operating characteristic Curve (AUC) of 0.7, 0.6 and 0.7, respectively. Fallers differed from non-fallers in their specific gait patterns. Results from this study improve our understanding of how falls risk-related gait impairments in neurological patients could aid the design of tailored fall-prevention interventions.

关键词： Municipal solid waste   Landfill   Dumpsite   Combustion   Air pollution   Health effects   Symptoms  

摘要： Open municipal solid waste (MSW) combustion is a major emission source of particulate air pollution, polycyclic aromatic hydrocarbons, and more exotic hazardous organic pollutants including polychlorinated biphenyls and brominated flame retardants. However, the adverse impact of MSW combustion emission on health among the general population is unknown. Therefore, a cross-sectional study was conducted to explore the associations between potential exposure to MSW combustion-related air pollution and symptoms of adverse health effects among residents of a community adjacent to a large open landfill in Lagos, Nigeria. Using ordinal logistic regression and controlling for age, sex, and smoking, it was observed that residence for >= 11 years had increased odds (p < 0.05) of daily occurrence of tingling/numbness/whiteness of fingers (2.614), headaches (2.725), memory problems (2.869), tremor/cramps (2.748), and confusion (3.033) among other symptoms. These results indicate adverse health impacts of chronic exposure to MSW combustion emission.

关键词： Idiopathic CD4(+) lymphocytopenia   Progressive multifocal leukoencephalopathy   Sensorimotor neuropathy   Myasthenia gravis  

摘要： [...]repeat testing 2–3 months later, along with extensive immunological, haematological, rheumatological and infectious disease workup is required before labelling a patient as having ICL. [...]we sent for CD4+ levels, which were 123 cells/μL. Despite detailed evaluation, no other cause could be found for low CD4+ counts and they remained persistently low even after 6 weeks. Though HIV and ICL differ in etio-pathogenesis; the pattern of clinical presentation, in terms of opportunistic infections, immune disorders and malignancies seems to be similar. [...]ICL patients are afforded the prophylactic and therapeutic strategies as established for HIV-AIDS.