关键词： aminoacyl-tRNA synthetases   cytosolic and mitochondrial translation   Charcot-Marie-Tooth disease  

摘要： Aminoacyl-tRNA synthetases(ARSs) are ubiquitously expressed enzymes responsible for charging tRNAs with their cognate amino acids, therefore essential for the first step in protein synthesis. Although the majority of protein synthesis happens in the cytosol, an additional translation apparatus is required to translate the 13 mitochondrial DNA-encoded proteins important for oxidative phosphorylation. Most ARS genes in these cellular compartments are distinct, but two genes are common, encoding aminoacyl-tRNA synthetases of glycine (GARS) and lysine(KARS) in both mitochondria and the cytosol. Mutations in the majority of the 37 nuclear-encoded human ARS genes have been linked to a variety of recessive and dominant tissue-specific disorders. Current data indicate that impaired enzyme function could explain the pathogenicity, however not all pathogenic ARSs mutations result in deficient catalytic function;thus, the consequences of mutations may arise from other molecular mechanisms. The peripheral nerves are frequently affected, as illustrated by the high number of mutations in cytosolic and bifunctional tRNA synthetases causing Charcot-Marie-Tooth disease(CMT). Here we provide insights on the pathomechanisms of CMT-causing tRNA synthetases with specific focus on the two bifunctional tRNA synthetases(GARS, KARS).

关键词： IDH   ATRX   TERT   EGFR   BRAF   Histone   Mutation   Astrocytoma   Oligodendroglioma   Glioblastoma   Ependymoma   BRAF inhibitor   Tumour heterogeneity   MGMT   Temozolomide  

摘要： The emerging understanding of molecular changes in a wide range of brain tumours has led to a significant shift in how these tumours are diagnosed, managed and treated. This article will provide a hands-on overview of the relevant biomarkers and their association with newly defined biological tumour entities.

关键词： Acute otitis media   Chronic otitis media   Neurologic complications  

摘要： Purpose of Review The aim of this study is to discuss the symptoms, diagnosis, and management of the neurologic complications of acute and chronic otitis media. Recent Findings Antibiotic therapy has greatly reduced the frequency of complications of otitis media. However, it is of vital importance to remain aware of the possible development of neurologic complications. There is a trend toward less severe presenting symptoms including otorrhea, headache, nausea, and fever, with altered mental status and focal neurologic deficits presenting later. In order to reduce morbidity, early deployment of a multidisciplinary approach with prompt imaging and laboratory studies is imperative to guide appropriate management. Summary Complications of acute and chronic otitis media may present with neurologic signs and symptoms. It is important to recognize the possible otitic origin of such complications to ensure proper management and to decrease overall morbidity and mortality

关键词： glucose variability   outcome   subarachnoid hemorrhage   intensive care unit  

摘要： Purpose: In patients with aneurysmal subarachnoid hemorrhage (SAH), increased glucose variability (GV) is associated with increased mortality and cerebral infarction;however, there are no reports demonstrating an association between GV and neurological outcome. This study investigated whether GV had an independent effect on neurological outcomes in patients with SAH in the intensive care unit. Materials and Methods: Consecutive adult patients hospitalized with SAH between January 1, 2009, and May 31, 2015 (N = 122) were retrospectively reviewed. Univariate/multivariate analyses were performed to identify independent predictors of poor neurological outcome. Patients were divided according to the mean glucose level (80-139 vs 140-200 mg/dL) and further subdivided using quartiles (Q) of the standard deviation (SD, representing variability) of the glucose level (Q1, Q2 + 3, and Q4). Results: Unfavorable neurological outcomes occurred in 44.2% of the patients. On multiple regression analysis, age, Hunt and Kosnik grade, SD of glucose (odds ratio [OR], 1.09;95% confidence interval [CI], 1.02-1.17;P < .01), and minimum blood glucose level (OR, 0.95;95% CI, 0.91-0.99;P < .01) were significantly associated with unfavorable neurological outcomes. Both groups (mean glucose levels: 80-139 and 140-200 mg/dL groups) had increasing unfavorable neurological outcomes with increasing SD of glucose (Q1, 15.0%;Q2 + 3, 40.0%;Q4, 52.4% and Q1, 44.4%;Q2 + 3, 50%;Q4, 88.9% in the 80-139 and 140-200 mg/dL groups, respectively). Patients with minimum glucose of <90 mg/dL comprised >50% of unfavorable neurological outcome. Conclusion: Increased GV was an independent predictor of unfavorable neurological outcomes in patients with SAH.

摘要： Technological advances have changed the indications for and the way in which lumbar puncture is done. Suspected CNS infection remains the most common indication for lumbar puncture, but new molecular techniques have broadened CSF analysis indications, such as the determination of neuronal autoantibodies in autoimmune encephalitis. New screening techniques have increased sensitvity for pathogen detection and can be used to identify pathogens that were previously unknown to cause CNS infections. Evidence suggests that potential treatments for neurodegenerative diseases, such as Alzheimer's disease, will rely on early detection of the disease with the use of CSF biomarkers. In addition to being used as a diagnostic tool, lumbar puncture can also be used to administer intrathecal treatments as shown by studies of antisense oligonucleotides in patients with spinal muscular atrophy. Lumbar puncture is generally a safe procedure but complications can occur, ranging from minor (eg, back pain) to potentially devastating (eg, cerebral herniation). Evidence that an atraumatic needle tip design reduces complications of lumbar puncture is compelling, and reinforces the need to change clinical practice.

关键词： Silicon neuron   Hodgkin-Huxley   FPGA   Neurological diseases  

摘要： Neurological disorders affect millions of people which influence their cognitive and/or motor capabilities. The realization of a prosthesis must consider the biological activity of the cells and the connection between machine and biological cells. Biomimetic neural network is one solution in front of neurological diseases. The neuron replacement should be processed by reproducing the timing and the shape of the spike. Several mathematical equations which model neural activities exist. The most biologically plausible one is the Hodgkin-Huxley (HH) model. The connection between electrical devices and living cells require a tunable real-time system. The field programmable gate array (FPGA) is a nice component including flexibility, speed and stability. Here, we propose an implementation of HH neurons in FPGA serving as a presage for a modulating network opening a large scale of possibilities such as damage cells replacement and the study of the effect of the cells disease on the neural network.

关键词： M2 muscarinic acetylcholine receptor   Sarin   Long lasting neurological effects   Organophosphate compounds   Brain damage  

摘要： The effect of sarin on the binding parameters (KD & Bmax) of M2 muscarinic acetylcholine receptor (mAChR) was studied 24 h and 1 week post exposure. Male & female Sprague-Daweley rats were poisoned with 1XLD50 sarin (80 mu g/kg, im) followed by treatment of trimedoxime bromide and atropine (7.5:5 mg/kg, im) 1 min later. Brains were removed and analyzed for M2 mAChR binding, using [H-3] AFDX384, an M2 selective antagonist. A significant increase in KD of M2 mAChR was found in the cortex 24h post poisoning, displaying elevation from 4.65 +/- 1.16 to 8.45 +/- 1.06 nM and 5.24 +/- 0.93 to 9.29 +/- 1.56 nM in male and female rats, respectively. A rise in KD was also noted 1 week following exposure from 5.04 +/- 1.20 to 11.75+/-2.78 and from 5.37 +/- 1.02 to 11.66 +/- 1.73 nM, presenting an added increase of 51 and 40% (compared to 24 h) in males and females, respectively. Analysis of M2 receptor density (Bmax) revealed a significant reduction of 68% in males and insignificant reduction of 22% in females, 24 h after sarin exposure which was followed by 37% recovery in males and 100% recovery in females, 1 week later. These results indicate that sarin induces a long-term decreased affinity in M2 mAChR (elevated KDs) and a transient effect on the number of this receptor subtype (Bmax). We hypothesize that the reduced affinity of the M2 receptors (negative auto-regulatory receptors) may cause long-term brain deficits by impairing the normal regulation release of ACh into the synaptic cleft. (C) 2017 Elsevier B.V. All rights reserved.

关键词： mistranslation   elongation factor   ribosome stalling   tRNA modifications   neurodegeneration  

摘要： Errors during mRNA translation can lead to a reduction in the levels of functional proteins and an increase in deleterious molecules. Advances in next-generation sequencing have led to the discovery of rare genetic disorders, many caused by mutations in genes encoding the mRNA translation machinery, as well as to a better understanding of translational dynamics through ribosome profiling. We discuss here multiple neurological disorders that are linked to errors in tRNA aminoacylation and ribosome decoding. We draw on studies from genetic models, including yeast and mice, to enhance our understanding of the translational defects observed in these diseases. Finally, we emphasize the importance of tRNA, their associated enzymes, and the inextricable link between accuracy and efficiency in the maintenance of translational fidelity.

关键词： MEDICAL societies   NEUROLOGY  

摘要： Because of the changing autonomy of patients and their relationship with physicians, advocacy is likely to *** WFN engages in advocacy at several levels, particularly at the population level, which involves successful engagement in the ICD 11 (specifically in promoting stroke as a neurological disease), increasing awareness of non-communicable diseases in low-income countries, and participating in and making position statements in the WHO regional ***, educational sessions on advocacy at the World Congress of Neurology, the biennial conference organised by the WFN (in collaboration with the American Academy of Neurology), are not restricted to a scientific curriculum but also aim to create awareness on advocacy as an important aspect of the professional activity of any neurologist.

关键词： Mechanical ventilation  

摘要： Aims: Prior investigation has found that mechanical ventilation with lower tidal volumes (Vt) following out-of-hospital cardiac arrest is associated with better neurologic outcomes. The relationship between Vt and neurologic outcome following in-hospital cardiac arrest (IHCA) has not previously been explored. In the present study, we investigate the association between Vt and neurologic outcome following IHCA. Methods: This was an observational study using a prospectively collected database of IHCA patients at a tertiary care hospital in the United States. The relationship between time-weighted average Vt per predicted body weight (PBW) over the first 6- and 48 h after cardiac arrest and neurologic outcome were assessed using propensity-score adjusted logistic regression. Measurements and main results: Of 185 IHCA patients who received invasive mechanical ventilation within 6 h of return of spontaneous circulation (ROSC), the average Vt over the first 6 h was 7.7 +/- 2.0 ml/kg and 68 (36.8%) patients received an average Vt > 8.0 ml/kg. Of 121 patients who received mechanical ventilation for at least 48 h post-ROSC, the average Vt was 7.6 +/- 1.5 ml/kg and 46 (38.0%) patients received an average Vt > 8.0 ml/kg. There was no relationship between Vt/PBW over the first 6- or 48 h post-ROSC and neurologic outcome (OR 0.99;95% CI 0.84-1.16;p = 0.89;OR 1.03;95% CI 0.78-1.37;p = 0.83 respectively). Conclusions: This study did not identify a relationship between Vt and neurologic outcome following IHCA. This contrasts with results in OHCA, where higher Vt has been associated with worse neurologic outcome. Additional investigation is needed with respect to other potential benefits of low-Vt post IHCA. (C) 2018 Elsevier B.V. All rights reserved.