摘要： FIGURE: Expression and stability of wild-type (WT) or mutant CYFIP2 in HEK293T cells or cultured neurons. Second, we examined protein levels of wild-type or mutant CYFIP2 by transfecting the constructs into HEK293T cells or cultured rat cortical neurons (Fig). [Extracted from the article]

关键词： Mitochondria   Neurodegeneration   cholesterol   oxysterol  

摘要： The pharmacological targeting of cholesterol levels continues to generate interest due to the undoubted success of therapeutic agents, such as statins, in extending life expectancy by modifying the prognosis of diseases associated with the impairment of lipid metabolism. Advances in our understanding of mitochondrial dysfunction in chronic age-related diseases of the brain have disclosed an emerging role for mitochondrial cholesterol in their pathophysiology, thus delineating an opportunity to provide mechanistic insights and explore strategies of intervention. This review draws attention to novel signalling mechanisms in conditions linked with impaired metabolism associated with impaired handling of cholesterol and its oxidized forms (oxysterols) by mitochondria. By emphasizing the role of mitochondrial cholesterol in neurological diseases, we here call for novel approaches and new means of assessment. Linked Articles This article is part of a themed section on Mitochondrial Pharmacology: Featured Mechanisms and Approaches for Therapy Translation. To view the other articles in this section visit

关键词： Kinases   Neural stem cells   Cell therapy   Alzheimer's disease   Parkinson's disease   Endoplasmic reticulum  

摘要： Calcium is an ubiquitous second messenger used by any living cell. The fine-tuning of intracellular free calcium concentration ([Ca2+](i)) homeostasis and signalling pathways is crucial for the maintenance of the healthy organism. Many alterations in the homeostasis can be compensated by robust mechanisms;however, cells that already present some debility in those mechanisms, or that are over stimulated cannot compensate the stress and die. Many neurological diseases show [Ca2+] disbalance as trigger of apoptotic response resulting in massive neuronal loss and the neurodegeneration. In this review, we focus on presenting similarities and differences of neurological disorders like Huntington's, Parkinson's, Alzheimer's disease and schizophrenia and the current clinical trial status. Moreover, we describe the importance of Ca2+ signalling in neurogenesis, showing that interference of this signalling could go along with stem cell therapy in the central nervous system.

关键词： Nihilism   Neurological disease   Provider perspectives  

摘要： Objective: The notion of therapeutic nihilism may lead to early removal of care based upon perceived poor prognosis. The goal of this study was to examine if differences for nihilism perspectives exist between professions and within professions at the different levels of experience and exposure to neurological conditions. Method: Survey methods was used to assess perception of care futility and therapeutic nihilism using six case-based scenarios followed by five questions regarding practitioner care choices and perspective. Participants were student and professional occupational and physical therapists, nurses, and doctors (n = 110). Thematic analysis was completed to determine influences on patient care. Results: Six themes (quality of life, provider experience, prognosis/treatability, medical details, patient's age, and family/patient wishes) emerged that influenced treatment decisions across all participants. All provider groups reported prognosis and treatability as their number one factor for treatment decisions, then therapists mentioned QOL most, nurses cited age, and doctors said medical details. Differences between students and professionals were also apparent. Discussion: The perceived ability of the patient to recover (prognosis/treatability) with medical care was the most commonly cited reason for aggressive measures, with quality of life, medical details, and patient age also representing strong themes across disciplines and level of training. (C) 2019 Elsevier Ltd. All rights reserved.

关键词： headache education   neurology residency  

关键词： Dementia   Learning and memory   Neurodevelopmental disorders   Risk factors  

摘要： Neurological illnesses, including cognitive impairment, memory decline and dementia, affect over 50 million people worldwide, imposing a substantial burden on individuals and society. These disorders arise from a combination of genetic, environmental and experiential factors, with the latter two factors having the greatest impact during sensitive periods in development. In this Review, we focus on the contribution of adverse early-life experiences to aberrant brain maturation, which might underlie vulnerability to cognitive brain disorders. Specifically, we draw on recent robust discoveries from diverse disciplines, encompassing human studies and experimental models. These discoveries suggest that early-life adversity, especially in the perinatal period, influences the maturation of brain circuits involved in cognition. Importantly, new findings suggest that fragmented and unpredictable environmental and parental signals comprise a novel potent type of adversity, which contributes to subsequent vulnerabilities to cognitive illnesses via mechanisms involving disordered maturation of brain 'wiring'.

关键词： Cost   Mixed nursing staffing model   Nursing aids   Nursing outcomes   Registered nurses  

摘要： Background This study aimed to investigate the effect of nursing aids (NAs) and registered nurses (RNs) mixed nursing staffing model with different ratios on the nursing outcomes and cost in China. Methods Five thousand and ninety-one patients treated at Neurology and Neurosurgery Center were consecutively recruited in this study and divided into three groups according to the proportion of NAs and RNs: 100% RN group (N = 1756), 90% RN group (N = 1654), and 75% RN group (N = 1681). Nursing outcomes including medication error, unplanned endotracheal tube extubation, bloodstream infection, respiratory tract infection, urinary tract infection, pressure ulcer, ventilator weaning, morality, hospital stay, and nursing cost were recorded. Results No difference of patients' characteristics or RNs' characteristics among three groups was observed. Three-group comparison disclosed that medication error, urinary tract infection, ventilator weaning, and nursing cost were different among three groups, while no difference of unplanned endotracheal tube extubation, bloodstream infection, respiratory tract infection, pressure ulcer, mortality, or hospital stay was found. Two-group comparison revealed that medication error and nursing cost were reduced in 75% RN group compared with 90% RN group and 100% RN group, but urinary tract infection was increased while ventilator weaning was decreased in 75% RN group and 90% RN group compared with 100% RN group. Multivariate logistic regression also validated 75% RNs independently correlated with decreased medication error, ventilator weaning, and increased urinary tract infection. Conclusions NAs and RNs mixed nursing staffing model with 75% RNs reduces medication error and nursing cost, while increasing urinary tract infection and decreasing ventilator weaning.

摘要： Background: There have been few reports on the incidence and risk factors of the complications after spinal fixation surgery for osteoporotic vertebral collapse (OVC) with neurological deficits. This study aimed to identify the incidence and risk factors of the complications after OVC surgery. Methods: In this retrospective multicenter study, a total of 403 patients (314 women and 89 men;mean age 73.8 years) who underwent spinal fixation surgery for OVC with neurological deficits between 2005 and 2014 were enrolled. Data on patient demographics were collected, including age, sex, body mass index, smoking, steroid use, medical comorbidities, and surgical procedures. All postoperative complications that occurred within 6 weeks were recorded. Patients were classified into two groups, namely, complication group and no complication group, and risk factors for postoperative complications were investigated by univariate and multivariate analyses. Results: Postoperative complications occurred in 57 patients (14.1%), and the most common complication was delirium (5.7%). In the univariate analysis, the complication group was found to be older (p = 0.039) and predominantly male (p = 0.049), with higher occurrence rate of liver disease (p = 0.001) and Parkinson's disease (p = 0.039) compared with the no-complication group. In the multivariate analysis, the significant independent risk factors were age (p = 0.021;odds ratio [OR] 1.051, 95% confidence interval [CI] 1.007-1.097), liver disease (p < 0.001;OR 8.993, 95% CI 2.882-28.065), and Parkinson's disease (p = 0.009;OR 3.636, 95% CI 1.378-9.599). Conclusions: Complications after spinal fixation surgery for OVC with neurological deficits occurred in 14.1%. Age, liver disease, and Parkinson's disease were demonstrated to be independent risk factors for postoperative complications. (c) 2019 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

摘要： Xeroderma pigmentosum (XP) encompasses a group of rare diseases characterized in most cases by malfunction of nucleotide excision repair (NER), which results in an increased sensitivity to UV radiation in affected individuals. Approximately 25-30% of XP patients present with neurological symptoms, such as sensorineural deafness, mental deterioration and ataxia. Although it is known that dysfunctional DNA repair is the primary pathogenesis in XP, growing evidence suggests that mitochondrial pathophysiology may also occur. This appears to be secondary to dysfunctional NER but may contribute to the neurodegenerative process in these patients. The available pharmacological treatments in XP mostly target the dermal manifestations of the disease. In the present review, we outline how current understanding of the pathophysiology of XP could be used to develop novel therapies to counteract the neurological symptoms. Moreover, the coexistence of cancer and neurodegeneration present in XP led us to focus on possible new avenues targeting mitochondrial pathophysiology. Linked Articles This article is part of a themed section on Mitochondrial Pharmacology: Featured Mechanisms and Approaches for Therapy Translation. To view the other articles in this section visit