关键词： ABC transporters   Blood-brain barrier (BBB)   Neurodegenerative diseases   P-glycoprotein (P-gp)   Breast cancer resistance protein (BCRP)   Multidrug resistance-associated proteins (MRPs)  

摘要： ABC (ATP-binding cassette) transporters represent one of the largest and most diverse superfamily of proteins in living species, playing an important role in many biological processes such as cell homeostasis, cell signaling, drug metabolism and nutrient uptake. Moreover, using the energy generated from ATP hydrolysis, they mediate the efflux of endogenous and exogenous substrates from inside the cells, thereby reducing their intracellular accumulation. At present, 48 ABC transporters have been identified in humans, which were classified into 7 different subfamilies (A to G) according to their phylogenetic analysis. Nevertheless, the most studied members with importance in drug therapeutic efficacy and toxicity include P-glycoprotein (P-gp), a member of the ABCB subfamily, the multidrug-associated proteins (MPRs), members of the ABCC subfamily, and breast cancer resistance protein (BCRP), a member of the ABCG subfamily. They exhibit ubiquitous expression throughout the human body, with a special relevance in barrier tissues like the blood-brain barrier (BBB). At this level, they play a physiological function in tissue protection by reducing or limiting the brain accumulation of neurotoxins. Furthermore, dysfunction of ABC transporters, at expression and/or activity level, has been associated with many neurological diseases, including epilepsy, multiple sclerosis, Alzheimer's disease, and amyotrophic lateral sclerosis. Additionally, these transporters are strikingly associated with the pharmacoresistance to central nervous system (CNS) acting drugs, because they contribute to the decrease in drug bioavailability. This article reviews the signaling pathways that regulate the expression and activity of P-gp, BCRP andMRPs subfamilies of transporters, with particular attention at the BBB level, and their mis-regulation in neurological disorders. (C) 2020 Elsevier Inc. All rights reserved.

关键词： Breaking bad news   Diagnosis communication   Neurodegenerative conditions   Motor neurone disease   Multiple sclerosis   Parkinson's disease   Scoping review  

摘要： Objective: Delivering a life changing diagnosis can be a distressing experience for patients and a challenging task for professionals. Diagnosis delivery can be especially difficult for individuals with neurodegenerative diseases such as motor neurone disease (MND), multiple sclerosis (MS) and Parkinson's disease (PD). This review aims to scope the literature on doctors' and patients' perspectives on diagnosis delivery for these conditions in order to enhance our understanding in this area and identify potential research gaps. Methods: A scoping review methodology was used, and data were summarised using content analysis. Results: 47 studies fulfilled the inclusion criteria. Studies showed that although patients were generally satisfied with diagnosis delivery, a considerable proportion was still dissatisfied with aspects of the consultation, especially the information and time provided and the doctor's approach. Only six studies addressed doctors' perspectives, which focused more on doctors' practice. Conclusion: There was a significant research gap in professionals' perspectives. The review also found that although basic standards of good practice were being met, a significant proportion of patients were dissatisfied with diagnosis communication. Practice implications: Professionals delivering such diagnoses need to assess and respond to patients' information needs, provide time for questions and maintain an empathic attitude. (C) 2020 Elsevier B.V. All rights reserved.

关键词： Paediatric neurology   Training   Organization   Curriculum   EPNS European Paediatric Neurology syllabus   Specialty  

摘要： Background: Paediatric Neurology (PN) is a discipline focused on diagnosis, comprehensive management and research into diseases of the central and peripheral nervous system from fetal life to transition into adulthood. The European Paediatric Neurology Society first designed and published the European PN training programme in the European Paediatric Neurology Syllabus in 2002. This was important in gaining recognition for the sub-specialty from the European Academy of Paediatrics and the European Academy of Neurology and in 2003 PN was recognized as a sub-specialty of paediatrics and neurology by the Board of the European Union of Medical Specialties. In 2004, the EPNS founded the Committee of National Advisors (CNA) that comprised representatives from national Paediatric Neurology societies, in order to further enhance Europe wide standards in training and practice., The EPNS Training Advisory Board (TAB) offers nation specific advice/support to PN societies on developing training and care systems. In 2019, the 2nd revision of the Paediatric Neurology Syllabus was approved by the EPNS Board and CNA. We aim to give an overview of the training of Paediatric Neurology (PN) specialists (i.e. Paediatric Neurologists), the relevant professional bodies and the current practice of Paediatric Neurology in Europe, as defined geographically by the World Health Organization. Methods: A structured online data collection form was completed by CNA representatives from European countries. The data included training routes and structure of training, epidemiological data, nature of professional societies, organization of Paediatric Neurology care, research, academic life and recognition of the specialty. Results: Data was collected from 43 European countries of which 38 have a national PN Society. In 10 (6 European Union (EU) and 4 non-EU countries) PN is recognized as a core specialty. In 26 countries PN is recognized as a sub-specialty of Paediatrics, Neurology or both (15 EU-11 n

关键词： Insight   Neurological disease   Mood disorder   Cognitive profile  

摘要： Purpose: Many studies have evaluated the characteristics of insight, especially in psychiatric patient populations. However, this construct has been poorly examined within neurological disorders. We explored the relationship between altered insight, mood disorders and neurocognitive functioning in a sample of patients admitted to a neurological rehabilitation unit. Method: Each patient, at the time of hospitalization (T0), underwent an evaluation of the overall cognitive profile, of the frontal functions, and the compilation of scales aimed at investigating the 4 domains under examination of insight and anxiety-depressive symptomatology. After 3 months (T1), at the end of the rehabilitative and supportive treatment, the patients underwent the same evaluation performed at T0. Results: Our results showed significant differences between T0 and T1 in the variables examined related to insight. In particular, there was a correlation between the global cognitive profile, including executive functions, and all insight domains. This confirms how the degree of cognitive deficit, especially of executive type, affects all levels of awareness of the individual. We have also found correlations between mood disorders and insight. In particular, our results show that depression versus anxiety plays a fundamental role in a person's awareness. Conclusions: The study of insight is fundamental not only for the relapses it could have on the patient, but also on those to health care professionals. In fact, having an adequate insight could lead to a greater motivation of the patient to be more complimentary to pharmacological and rehabilitative therapies, also favoring social reintegration. (C) 2020 Elsevier Ltd. All rights reserved.

摘要： The article discusses a study which developed a novel and entertaining online educational method for introducing pre-clerkship students to common clinical presentations in neurology. Topics include learning objectives for the course called Transition to Clinical Practice in Neurology at McGill University, films reviewed by the students to help them achieve the goals online, and lessons learned from the online educational method used.

关键词： bile acid receptors   neuroprotective   tauroursodeoxycholic acid   ursodeoxycholic acid   alzheimer's disease   parkinson's disease   multiple sclerosis   hepatic encephalopathy  

摘要： Bile acids are commonly known as digestive agents for lipids. The mechanisms of bile acids in the gastrointestinal track during normal physiological conditions as well as hepatic and cholestatic diseases have been well studied. Bile acids additionally serve as ligands for signaling molecules such as nuclear receptor Farnesoid X receptor and membrane-bound receptors, Takeda G-protein-coupled bile acid receptor and sphingosine-1-phosphate receptor 2. Recent studies have shown that bile acid signaling may also have a prevalent role in the central nervous system. Some bile acids, such as tauroursodeoxycholic acid and ursodeoxycholic acid, have shown neuroprotective potential in experimental animal models and clinical studies of many neurological conditions. Alterations in bile acid metabolism have been discovered as potential biomarkers for prognosis tools as well as the expression of various bile acid receptors in multiple neurological ailments. This review explores the findings of recent studies highlighting bile acid-mediated therapies and bile acid-mediated signaling and the roles they play in neurodegenerative and neurological diseases.

关键词： Traumatic brain injury   Glucagon-like peptide-1   Exendin-4   Inflammation   Neurological outcomes   Animal models  

摘要： Traumatic brain injury (TBI) can be exacerbated and prolonged for months or even years by chronic inflammatory processes with long-term consequences on neurodegeneration and neurological impairment. However, there are no clear pharmacological therapies of benefit to manage neurological dysfunctions, which, relating to the molecular mechanisms underlying the behavioral deficits after TBI, have yet to be fully identified. Recently, a glucagon-like peptide 1 (GLP-1) agonist, Exendin-4, was approved not only for the treatment of type 2 diabetes mellitus, but it also played a neurotrophic role in various CNS neurological diseases. In this study, we evaluated the neuroprotective effects of Exendin-4 on neurological outcome, cerebral blood flow, neurodegeneration, and inflammatory responses by utilizing a cortical contusion impact injury (CCI) model in rats. We found that TBI rats displayed neurological impairments, neurodegeneration, reduction of cerebral blood flow, and inflammatory responses, while Exendin-4 promoted neurological, cognitive, and cerebral blood flow recovery and attenuated neural degeneration and inflammatory cytokines after TBI. Furthermore, Exendin-4 treatment significantly diminished the TBI-induced overexpression of TNF alpha and IL-1 beta, as well as phosphorylation of p38 and ERK1/2. These data suggest a strong beneficial action of the glucagon-like peptide-1 receptor agonist Exendin-4 in improving neurological outcomes by attenuating inflammatory responses induced by traumatic brain injury, which is of therapeutic potential for TBI.

摘要： The article describes the development of a digitised, contact-free iteration of the mock oral board examination for neurological surgery trainees and the assessment of its ability to deliver comparable utility to the programme from an education and training perspective. Topics include components of the American Board of Neurological Surgery (ABNS) licensing, educational goal of the digital examination, and benefits of such examination.

关键词： Out-of-hospital cardiac arrest   Post-cardiac arrest syndrome   Sequential Organ Failure Assessment score   Neurological outcome  

摘要： Background: Patients experiencing out-of-hospital cardiac arrest (OHCA) and subsequent post-cardiac arrest syndrome are often compromised by multi-organ failure. The Sequential Organ Failure Assessment (SOFA) score has been used to predict clinical outcome of patients requiring intensive care for multi-organ failure. Thus, the assessment of SOFA score is recommended as a criterion for sepsis. Although post-cardiac arrest patients frequently develop sepsis-like status in ICU, there are limited reports evaluating the SOFA score in post-cardiac arrest patients. We investigated the predictive value of the SOFA score in survival and neurological outcomes in patients with post-cardiac arrest syndrome. Methods: A total of 231 cardiovascular arrest patients achieving return of spontaneous circulation (ROSC) were finally extracted from the institutional consecutive database comprised of 1218 OHCA patients transferred to the institution between January 2015 and July 2018. The SOFA score was calculated on admission and after 48 h. Predictors of survival and neurological outcome defined as having cerebral-performance-category (CPC) 1 or 2 at 30 days were determined. Results: SOFA score was lower in survived patients (5.0 vs 10.0, p < 0.001) and those with favorable neurological outcome (5.0 vs 8.0, p < 0.001) as compared with the counterparts. The SOFA score on admission was an independent predictor of survival (OR 0.68, 95% confidence interval [CI] 0.59-0.78;p < 0.001) and favorable neurological performance (OR 0.79;95% CI 0.69-0.90;p < 0.001) at 30 days. Furthermore, a change in SOFA score (48-0 h) was predictive of favorable 30-day neurological outcome (OR 0.71, 95% CI 0.60-0.85;p < 0.001). Conclusions: Evaluation of the SOFA score in the ICU is useful to predict survival and neurological outcome in post-cardiac arrest patients. (C) 2020 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.