关键词： preterm   body composition   deficit fat free mass   hospitalization   neurologic outcome  

摘要： Preterm infants have a deficit of fat-free mass accretion during hospitalization. This study suggests that z score of fat-free mass at discharge is associated with neurologic outcome (P = .003) at 2 years of age, independent of sex, gestational age, and birth weight z score. Interventions to promote quality of growth should be considered.

关键词： Neuronal repair   Therapeutics   microRNA   Reprogramming   Neural stem cells   Neurons  

摘要： The loss of neurons due to injury and disease results in a wide spectrum of highly disabling neurological and neurodegenerative conditions, given the apparent limited capacity of endogenous repair of the adult central nervous system (CNS). Therefore, it is important to develop technologies that can promote de novo neural stem cell and neuron generation. Current insights in CNS development and cellular reprogramming have provided the knowledge to finely modulate lineage-restricted transcription factors and microRNAs (miRNA) to elicit correct neurogenesis. Here, we discuss the current knowledge on the direct reprogramming of somatic non-neuronal cells into neural stem cells or subtype specific neurons in vitro and in vivo focusing on miRNA driven reprogramming. miRNA can allow rapid and efficient direct phenotype conversion by modulating gene networks active during development, which promote global shifts in the epigenetic landscape pivoting cell fate decisions. Furthermore, we critically present state-of-the-art and recent advances on miRNA therapeutics that can be applied to the diseased CNS. Together, the advances in our understanding of miRNA role in CNS development and disease, recent progress in miRNA-based therapeutic strategies, and innovative drug delivery methods create novel perspectives for meaningful therapies for neurodegenerative disorders.

关键词： Stroke   relative neurological improvement   endovascular treatment   outcome  

摘要： Background and Purpose: Early judgment of long-term prognosis is the key to making medical decisions in acute anterior circulation large-vessel occlusion stroke (LVOS) after endovascular treatment (EVT). We aimed to investigate the relationship between the combination of 24-hour and 7-day relative neurological improvement (RNI) and 90-day functional outcome. Methods: We selected the target population from a multicenter ischemic stroke registry. The National Institutes of Health Stroke Scale (NIHSS) scores at baseline, 24 hours, and 7 days were collected. RNI was calculated by the following equation: (baseline NIHSS -24-hour/7-day NIHSS)/baseline NIHSS x 100%. A modified Rankin Scale score of 0-2 at 90 days was defined as a favorable outcome. Multivariable logistic regression analysis was used to evaluate the relationship between RNI and 90-day outcome. Receiver operator characteristic curve analysis was performed to identify the predictive power and cutoff point of RNI for functional outcome. Findings: A total of 568 patients were enrolled. Both 24-hour and 7-day RNI were independent predictors of 90-day outcome. The best cutoff points of 24-hour and 7-day RNI were 28% and 42%, respectively. Compared with those with 24-hour RNI of less than 28% and 7-day RNI of less than 42%, patients with 24-hour RNI of 28% or greater and 7-day RNI of 42% or greater had a 39.595-fold (95% confidence interval 22.388-70.026)increased probability of achieving 90-day favorable outcome. Conclusions: The combination of 24-hour and 7-day RNI very strongly predicts 90-day functional outcome in patients with acute anterior circulation LVOS who received EVT, and it can be used as an early accurate surrogate of long-term outcome. (c) 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

摘要： Click here to view the accompanying paper in this volume.

关键词： essential oils   terpenes   GABA receptor   sodium channel   transient receptor potential (TRP) channel   pain   epilepsy   analgesics   anticonvulsant   anxiolytic   antinociception   CNS   sensory neurons  

摘要： Essential oils and the constituents in them exhibit different pharmacological activities, such as antinociceptive, anxiolytic-like, and anticonvulsant effects. They are widely applied as a complementary therapy for people with anxiety, insomnia, convulsion, pain, and cognitive deficit symptoms through inhalation, oral administration, and aromatherapy. Recent studies show that essential oils are emerging as a promising source for modulation of the GABAergic system and sodium ion channels. This review summarizes the recent findings regarding the pharmacological properties of essential oils and compounds from the oils and the mechanisms underlying their effects. Specifically, the review focuses on the essential oils and their constituents targeting the GABAergic system and sodium channels, and their antinociceptive, anxiolytic, and anticonvulsant properties. Some constituents target transient receptor potential (TRP) channels to exert analgesic effects. Some components could interact with multiple therapeutic target proteins, for example, inhibit the function of sodium channels and, at the same time, activate GABA(A) receptors. The review concentrates on perspective compounds that could be better candidates for new drug development in the control of pain and anxiety syndromes.

关键词： Meningococcemia   Meningococcal meningitis   Cerebellitis   Serogroup W   Sequence type-11 complex  

摘要： Invasive meningococcal disease (IMD) caused by the serogroup W (MenW) sequence type-11 complex strain has recently emerged worldwide. Meningococcal infections due to this strain are associated with high case fatality and often atypical clinical manifestations. However, the annual IMD incidence was low, and MenW is rare in Japan. We described the first Japanese case of meningococcal meningitis and meningococcemia caused by this strain in a previously healthy 27-year-old woman. This case showed various neurological complications such as abducens palsy, cerebellitis, and cerebellar infarction, and reactive arthritis. This case provides useful information on the possibility of spreading IMD strains and the cause of various complications. (c) 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

关键词： Metoclopramide   Vigibase   Adverse drug reactions  

摘要： Despite FDA and EMA warnings of long-term use, little is known regarding the time to onset (TTO) of neurological adverse drug reactions (ADR) for metoclopramide. The aims of this study were, first, to evaluate whether neurological ADRs are more commonly reported for metoclopramide than for other medications, and second, to describe how time to onset of neurological ADRs differs by age and gender. All ADR reports with metoclopramide as the suspected/interacting drug were extracted from the WHOs Global ADR database VigibaseA (R) between 1967 and May 2016. Cox proportional hazards models were fit using TTO of neurological ADRs as the outcome and age, gender, and type of ADR as predictors. Proportional Reporting Ratios (PRRs) for neurological ADRs were compared across age and gender. Lawyer reports were excluded in the analysis. Over 47,000 ADR reports with metoclopramide were identified. Over one third (35.6%) of the reports came from lawyers. The majority of ADRs in general and neurological ADRs in specific occurred within the first 5 days of metoclopramide use (median 1 day). TTO increased with age. Neurological ADRs were reported two to four times as frequently for metoclopramide than for other drugs, with the highest PRRs observed in children (PRR = 4.24 for girls and 4.60 for boys). Most adverse drug reactions occur within the first 5 days of treatment with metoclopramide. Patients requiring use of metoclopramide should be carefully monitored for neurological ADRs during the first days of treatment.

关键词： Bilateral Arm Training   Intensive Care   Upper Limb Function   Early Mobility  

摘要： Upper limb paresis, common in many neurological conditions, is a major contributor of long-term disability and decreased quality of life. Evidence shows that repetitive, bilateral arm movement improves upper limb coordination after neurological injury. However, it is difficult to integrate upper limb interventions into very early rehabilitation of critically ill neurological patients because of patient arousal and medical acuity. This report describes the safety and feasibility of bilateral upper limb cycling in critically ill neurological patients with bilateral or unilateral paresis. Patients were included in this pilot observational series if they used upper limb cycle ergometry with occupational therapy while in the neurocritical care unit between May and August 2016. Patient demographics, neurological function, and hemodynamic status were recorded precycling and postcycling. Cycling parameters including duration and active and/or passive cycling were collected. No significant changes in hemodynamic or respiratory status were noted postintervention. No adverse effects or safety events were noted. In this series, upper limb cycle ergometry was a safe and feasible intervention for early rehabilitation in critically ill patients in the neurocritical care unit. Future studies will prospectively measure the impact of early upper limb cycle ergometry on neurological recovery and functional outcome in this population.

关键词： Diagnostic yield   Next-generation sequencing   Whole exome sequencing   Neurology  

摘要： To determine the diagnostic yield of different genetic test modalities in adult patients with neurological disorders, we evaluated all adult patients seen for genetic diagnostic evaluation in the outpatient neurology practice at the University of Pennsylvania between January 2016 and April 2017 as part of the newly created Penn Neurogenetics Program. Subjects were identified through our electronic medical system as those evaluated by the Program's single clinical genetic counselor in that period. A total of 377 patients were evaluated by the Penn Neurogenetics Program in different settings and genetic testing recommended. Of those, 182 (48%) were seen in subspecialty clinic setting and 195 (52%) in a General Neurogenetics Clinic. Genetic testing was completed in over 80% of patients in whom it was recommended. The diagnostic yield was 32% across disease groups. Stratified by testing modality, the yield was highest with directed testing (50%) and array comparative genomic hybridization (45%), followed by gene panels and exome testing (25% each). In conclusion, genetic testing can be successfully requested in clinic in a large majority of adult patients. Age is not a limiting factor for a genetic diagnostic evaluation and the yield of clinical testing across phenotypes (almost 30%) is consistent with previous phenotype-focused or research-based studies. These results should inform the development of specific guidelines for clinical testing and serve as evidence to improve reimbursement by insurance payers.

关键词： Drug discovery   Neurodegenerative diseases   Natural products   Myxobacteria  

摘要： Age-related disorders impose noticeable financial and emotional burdens on society. This impact is becoming more prevalent with the increasing incidence of neurodegenerative diseases and is causing critical concerns for treatment of patients worldwide. Parkinson's disease, Alzheimer's disease, multiple sclerosis and motor neuron disease are the most prevalent and the most expensive to treat neurodegenerative diseases globally. Therefore, exploring effective therapies to overcome these disorders is a necessity. Natural products and their derivatives have increasingly attracted attention in drug discovery programs that have identified microorganisms which produce a large range of metabolites with bioactive properties. Myxobacteria, a group of Gram-negative bacteria with large genome size, produce a wide range of secondary metabolites with significant chemical structures and a variety of biological effects. They are potent natural product producers. In this review paper, we attempt to overview some secondary metabolites synthesized by myxobacteria with neuroprotective activity through known mechanisms including production of polyunsaturated fatty acids, reduction of apoptosis, immunomodulation, stress reduction of endoplasmic reticulum, stabilization of microtubules, enzyme inhibition and serotonin receptor modulation. (C) 2018 Elsevier B.V. All rights reserved.