关键词： healthcare   health economics   research methods   telemedicine   teleneurology  

关键词： high concentration hydrogen   necroptosis   ischemia/reperfusion   mixed lineage kinase domain like protein   neurological function  

摘要： This study aimed to investigate the role of necroptosis in the neuroprotection of hydrogen in a mouse model of cerebral ischemia/reperfusion (I/R) injury. C57BL mice were randomly divided into sham group, I/R group, hydrogen/oxygen group (HO), nitrogen/oxygen group (NO). Middle cerebral artery occlusion (MCAO) for 1 hour followed by reperfusion was introduced to animals which were allowed to inhale 66.7% hydrogen/33.3% oxygen for 90 minutes since the beginning of reperfusion. Mice in NO group inhaled 66.7% nitrogen/33.3% oxygen. 24 hours after MCAO, brain infarction, brain water content and neurological function were evaluated. The protein expression of mixed lineage kinase domain like protein (MLKL) was detected at 3, 6, 12, 24 and 72 hours after reperfusion in HO group and the protein and mRNA expression of MLKL at 24 hours after MCAO in four groups. Hydrogen inhalation significantly reduced infarct volume, attenuated brain edema and improved neurobehavioral deficit in MCAO mice. The MLKL expression increased after MCAO and peaked at 6-24 hours after reperfusion. However, hydrogen inhalation had no significant effect on the MLKL expression at transcriptional and translational levels after MCAO. This study indicates high concentration hydrogen improves mouse neurological outcome after cerebral I/R injury independent of anti-necroptosis.

摘要： Neurological injury is the primary lethal mechanism of injury in children, and the primary etiology of long-term disability after trauma. Laboratories and clinical/translational teams have sought to develop stem/progenitor cell therapies to improve recovery in a clinical setting in which there is no significant reparative option. While none of these treatments are currently standard therapeutics, phase IIb clinical trials are underway in both adults and children in severe traumatic brain injury (TBI) and phase I/IIa trials in spinal cord injury. This review will characterize the cell therapy strategies: cell replacement and tissue integration vs. immunomodulation/enhanced endogenous tissue repair. TBI is somewhat different from other central nervous system injuries (spinal cord injury and stroke), in that TBI is a diffuse injury, whereas spinal cord injury and stroke are anatomically discrete. Importantly, this drives cell therapy approaches, as TBI is less apt to be treatable with a local cell replacement intervention. More localized injuries may be more amenable to local approaches and cell replacement to bridge focal gaps. This review focuses on a few reports in the field that highlight areas of progress, but is not intended to be a comprehensive survey of the state of regenerative medicine for neurological injuries.

关键词： DOHaD   Lead   MAPK   Sex differences   Transcriptomics   Zebrafish  

摘要： Developmental lead (Pb) exposure is linked to neurological health issues. Results from non-human primate and rodent studies suggest detrimental effects of an early life Pb exposure, showing transcriptional disturbances and pathological evidence of Alzheimer's disease in the adult animal brain. To elucidate the impacts of an embryonic Pb exposure on the adult brain, transcriptomic analysis was completed on the brain of zebrafish aged 12 months exposed to a control treatment or to an embryonic 100 mu g/L Pb exposure by sex. In the adult female zebrafish brain, significant changes in expression profiles occurred in a number of genes involved in neurological disease and nervous system development and function. On the other hand, in adult males, a number of genes with significant expression alterations were found to be associated with cancer and tumors. p38 mitogen-activated protein kinase (p38 MAPK) was also indicated as an upstream regulator of observed gene expression changes. Western blot analysis confirmed activation of p38 MAPK in the form of phosphorylated p38 MAPK in the male zebrafish brain. In addition, we compared transcriptomic changes observed in this study to a previous study with an embryonic exposure of 10 mu g/L Pb by sex, showing unique sets of genes dependent on Pb concentration. Overall, these results show sex-specific and concentration-dependent disturbances of global gene expression patterns in the brain of adult zebrafish exposed to Pb during embryogenesis.

摘要： Study objective: Use of magnetic resonance imaging (MRI) for cervical clearance after a negative cervical computed tomography (CT) scan result in alert patients with blunt trauma who are neurologically intact is not infrequent, despite poor evidence in regard to its utility. The objective of this study is to evaluate the utility and cost-effectiveness of using MRI versus no follow-up in this patient population. Methods: A modeling-based decision analysis was performed during the lifetime of a 40-year-old individual from a societal perspective. The 2 strategies compared were no follow-up and MRI. A Markov model with a 3% discount rate was used with parameters from the literature. Base cases and probabilistic and sensitivity analyses were performed to assess the cost-effectiveness of the strategies. Results: The cost of MRI follow-up was $11,477, with a health benefit of 24.03 quality-adjusted life-years;the cost of no follow-up was $6,432, with a health benefit of 24.08 quality-adjusted life-years. No follow-up was the dominant strategy, with a lower cost and a higher utility. Probabilistic sensitivity analysis showed no follow-up to be the better strategy in all 10,000 iterations. No follow-up was the better strategy irrespective of the negative predictive value of initial CT result, and it remained the better strategy when the incidence of missed unstable injury resulting in permanent neurologic deficits was less than 64.2% and the incidence of patients immobilized with a hard collar who still received cord injury was greater than 19.7%. Multiple 3-way sensitivity analyses were performed. Conclusion: MRI is not cost-effective for further evaluation of unstable injury in neurologically intact patients with blunt trauma after a negative cervical spine CT result.

关键词： Gait   Cerebellar disease   Parkinson's disease   Neurological exam  

摘要： Tandem gait testing is an integral part of the neurological exam. It is informative in a wide variety of disorders ranging from cerebellar disease to vestibular and peripheral neuropathies, parkinsonism, and other neurodegenerative conditions. We discuss the history and development of tandem gait testing as well as its technique, utility, and limitations in the assessment of neurological conditions. Tandem gait has emerged as a tool in the assessment of cerebellar disease, Huntington disease, idiopathic Parkinson's disease, atypical parkinsonism, peripheral neuropathies, and vestibulopathies. Its origin can be deduced from experimental observation and clinical experience as far back as the early nineteenth century. Despite the long history and ubiquitous performance of tandem gait testing, there is no standardized, guideline-based protocol to model for more homogenous research and clinical practices. Such a protocol should be developed using historical texts and manuscripts as well as the consensus of the medical research community. With standard protocols, further studies could define the sensitivity of abnormal tandem gait testing in cerebellar disorders, more diffuse neurodegeneration, and peripheral pathologies. Tandem gait can be a useful marker of dysfunction in neurologic conditions whose pathologies extend beyond the vermis or vestibulocerebellar module to include interconnected networks throughout the nervous system.

关键词： Chemical exposures   mold   pesticides   neural autoantibodies   antibody   tau proteins  

摘要： A number of studies have linked exposures to industrial and household chemicals and biological toxins to increased risk of autoimmunity in general and elevated levels of autoantibodies to neural antigens specifically. Elevated neural autoantibodies are biomarkers for many diseases such as multiple sclerosis and Parkinson's disease. Our study reports levels of six types of neural autoantibodies in a group of 24 toxicant-exposed patients. The patients were exposed to a variety of toxicants including contaminated drinking water (four patients), building water/mold damage (eight patients), pesticides (four patients), and other assorted toxic chemicals (eight patients). Levels of all six neural autoantibodies were significantly elevated in most patients and in the patient group at large, with mean antibody levels for the 24 chemically exposed patients (relative to a healthy control population), in descending order: 475% for tau proteins, 391% for microtubule associated proteins-2, 334% for neurofilament proteins (NFP), 302% for myelin basic protein, 299% for glial fibrillary acidic proteins, and 225% for tubulin. Tau protein autoantibodies were significantly elevated in the patient groups with peripheral neuropathy, muscle and joint pain, asthma, and chemical sensitivity. Autoantibodies to tubulin were significantly higher in the chemical sensitivity and asthma patients, autoantibodies to NFP were significantly higher in the patients with sleep apnea, whereas S-100B autoantibodies were significantly increased in patients with muscle/joint pain, asthma, and apnea/insomnia. In patients exposed to environmental toxicants, measurements of autoantibodies may be useful for prevention, diagnosis, and treatment. This study adds to the scientific literature the ability of a broad spectrum of environmental triggers adversely affecting the nervous system through the process of autoimmunity, which may explain the increasing incidence of neurodegenerative diseases.

关键词： resident-as-teacher   trainee-as-teacher   education   graduate medical education   residency   clinical teaching   child neurology   neurodevelopmental disabilities  

摘要： BACKGROUND: Clinical teaching skills programs for resident physicians are increasingly offered. Less attention has been devoted to the unique educational roles of specialty residents and subspecialty fellows, many of whom will become academic faculty physicians. These teaching roles, and therefore a trainee's learning needs and motivation, also change over the course of training. METHODS: We designed and implemented a two-year longitudinal teaching curriculum for child neurology and neurodevelopmental disabilities residents using adult learning theory principles: experiential learning and immediate applicability to specific roles. Core modules included teaching in clinical settings, adult learning, and giving feedback. Training-year-specific modules for second-year residents (n = 11) and final-year residents (n = 10) included teaching through consultation and promoting clinical reasoning in supervisory roles. Learners completed an 11-item self-assessment before and after intervention. RESULTS: The overall program significantly increased residents' self-assessed knowledge of how to assess the level of a learner (P = 0.02, Cohen d = 0.84) and comfort and skill in giving feedback (P = 0.04, d = 0.64;P = 0.04, d = 0.71). The final-year specific curriculum additionally increased self-assessed skill in teaching same-specialty residents (P = 0.05, d = 1.07) and in promoting clinical reasoning (P = 0.03, d = 1.14). The program was rated highly by trainees and faculty, and has been adopted as an ongoing part of our training program. CONCLUSIONS: Our experience offers a reproducible model and theoretical framework for child neurology, neurodevelopmental disabilities, and other specialty programs to develop customized trainee-as-teacher curricula with specialty- and training-year-specific content.

关键词： alcohol   development   epigenetics   gene   pregnancy   prenatal  

摘要： Several explanations for the diverse results in research on foetal alcohol spectrum disorders or alcohol-related neurodevelopmental disorder might be at hand: timing, amount and patterns of alcohol exposure, as well as complex epigenetic responses. The genetic background of the offspring and its interaction with other prenatal and post-natal environmental cues are likely also of importance. In the present report, key findings about the possible effects of low and moderate doses of maternal alcohol intake on the neuropsychological development of the offspring are reviewed and plausible mechanisms discussed. Special focus is put on the serotonergic system within developmental and gene-environment frameworks. The review also suggests guidelines for future studies and also summarizes some of to-be-answered questions of relevance to clinical practice. Contradictory findings and paucity of studies on the effects of exposure to low alcohol levels during foetal life for the offspring's neuropsychological development call for large prospective studies, as well as for studies including neuroimaging and multi-omics analyses to dissect the neurobiological underpinnings of alcohol exposure-related phenotypes and to identify biomarkers. Finally, it remains to be investigated whether any safe threshold of alcohol drinking during pregnancy can be identified.

关键词： Acute kidney injury   Stroke   Epidemiology   Risk factors   Outcomes  

摘要： Acute kidney injury (AKI) is proven to be an independent risk factor for adverse clinical outcomes in patients with stroke, but data about the epidemiology of AKI in these patients are not well characterized. Therefore, we investigated the incidence, risk factors, and the impact of AKI on the clinical outcomes in a group of Chinese patients with stroke. We retrospectively recruited 647 stroke patients from the neurology ICU between 2012 and 2013. AKI was identified according to the 2012 KDIGO criteria. Baseline estimated glomerular filtration rate (eGFR) was calculated using modified Chronic Kidney Disease Epidemiology Collaboration equation for Chinese patients. National Institutes of Health Stroke Scale (NIHSS) score was assessed for the stroke severity. A total of 135 (20.9%) patients developed AKI. Patients with AKI stages from 1 to 3 were 84 (62.2%), 26 (19.3%), and 25 (18.5%), respectively. Logistic regression analysis showed that independent risk factors for AKI were higher NIHSS score (OR, 1.027;95% CI 1.003-1.051), lower baseline eGFR (OR, 0.985;95% CI 0.977-0.993), the presence of hypertension (OR, 1.592;95% CI 1.003-2.529), and infectious complications (OR, 3.387;95% CI 1.997-5.803) (P < 0.05 for all). AKI patients were also significantly associated with all-cause mortality in the neurology ICU [OR and 95% CI of AKI-stage 1, AKI-stage 2, and AKI-stage 3 were 4.961 (2.191-11.232), 19.722 (6.354-61.217), and 48.625 (17.616-134.222), respectively (P < 0.001 for all)]. AKI is common among patients with stroke and is associated with worse clinical outcomes after stroke. Prevention of AKI seems to be very important among these patients, because they are exposed to many risk factors for developing AKI.