关键词： molecular diagnostics   stroke   multiple sclerosis   traumatic brain injury   Alzheimer's disease  

摘要： The identification of precision blood biomarkers which can accurately indicate damage to brain tissue could yield molecular diagnostics with the potential to improve how we detect and treat neurological pathologies. However, a majority of candidate blood biomarkers for neurological damage that are studied today are proteins which were arbitrarily proposed several decades before the advent of high-throughput omic techniques, and it is unclear whether they represent the best possible targets relative to the remainder of the human proteome. Here, we leveraged mRNA expression data generated from nearly 12,000 human specimens to algorithmically evaluate over 17,000 protein-coding genes in terms of their potential to produce blood biomarkers for neurological damage based on their expression profiles both across the body and within the brain. The circulating levels of proteins associated with the top-ranked genes were then measured in blood sampled from a diverse cohort of patients diagnosed with a variety of acute and chronic neurological disorders, including ischemic stroke, hemorrhagic stroke, traumatic brain injury, Alzheimer's disease, and multiple sclerosis, and evaluated for their diagnostic performance. Our analysis identifies several previously unexplored candidate blood biomarkers of neurological damage with possible clinical utility, many of which whose presence in blood is likely linked to specific cell-level pathologic processes. Furthermore, our findings also suggest that many frequently cited previously proposed blood biomarkers exhibit expression profiles which could limit their diagnostic efficacy.

关键词： Apicomplexa   behavioral disorder   mental health   personality changes   Toxoplasma gondii   toxoplasmosis   transcripts change  

摘要： Toxoplasmosis, a disease that disrupts fetal brain development and severely affects the host's brain, has been linked to many behavioral and neurological disorders. There is growing interest in how a single-celled neurotropic parasite, Toxoplasma gondii, can control or change the behavior of the host as well as how it dominates the host's neurons. Secrets beyond these could be answered by decoding the Toxoplasma gondii genome, unravelling the function of genomic sequences, and exploring epigenetics and mRNAs alterations, as well as the postulated mechanisms contributing to various neurological and psychiatric symptoms caused by this parasite. Substantial efforts have been made to elucidate the action of T. gondii on host immunity and the biology of its infection. However, the available studies on the molecular aspects of toxoplasmosis that affect central nervous system (CNS) circuits remain limited, and much research is still needed on this interesting topic. In my opinion, this parasite is a gift for studying the biology of the nervous system and related diseases. We should utilize the unique features of Toxoplasma, such as its abilities to modulate brain physiology, for neurological studies or as a possible tool or approach to cure neurological disease.

关键词： driving simulation   driving assessment   driving fitness evaluation   neurological deficit   brain injury   neurodegenerative disease  

摘要： Objective: To identify driving characteristics of fit-, unfit-, and conditionally fit-to-drive neurological patient populations using a driving simulator with three high-risk scenarios comprising rural, highway, and urban environments. Methods: The study included 91 neurological patients undergoing a multidisciplinary assessment for driver's license revalidation, consisting of a clinical, neuropsychological, functional, and on-road evaluation. The groups drove through three independent driving scenarios, during which a variety of measures describing reaction time, vehicular control, and traffic rule compliance were performed. One-way analysis of variance (ANOVA) with Bonferroni correction was used for group comparison, independently for each driving scenario, and Pearson correlations were calculated between simulator variables and neuropsychological test scores. Results: The fit- and unfit-to-drive population significantly differed (p < .05) in reaction times, regardless of the scenario. No significant differences in traffic rule compliance or vehicular control parameters were observed in the rural environment (p > .05). On the highway, the unfit group exhibited greater variability of steering wheel angle, higher steering reversal rate, and a higher rate of turn signal errors. In the urban environment, the unfit group oversped more, had more collisions, and exhibited greater lane position variability. The latter, along with reaction times in the rural and highway scenarios, was also shown to significantly differ between the conditional and unfit group (p < .05). No significant differences were observed between the fit and the conditional group (p > .05). Weak to moderate associations (range: -0.5 to 0.29) between neuropsychological tests and various simulator variables were also observed. Conclusions: Our results show that driving simulators are able to capture differences between (fit- and unfit-to-drive) neurological patient populations and therefore bear the pote

关键词： 临床见习   教学方法   神经病学   PBL教学   Language of Keywords: Chinese  

摘要： Objective: To report neurological manifestations seen in patients hospitalized with Coronavirus disease 2019 (COVID-19) from a large academic medical center in Chicago, Illinois. Methods: We retrospectively reviewed data records of 50 patients with COVID-19 who were evaluated by the neurology services from March 1, 2020 - April 30, 2020. Patients were categorized into 2 groups based on timing of developing neurological manifestations: the "Neuro first" group had neurological manifestations upon initial assessment, and the "COVID first" group developed neurological symptoms greater than 24 h after hospitalization. The demographics, comorbidities, disease severity and neurological symptoms and diagnoses of both groups were analyzed. Statistical analysis was performed to compare the two groups. Results: A total of 50 patients (48% African American and 24% Latino) were included in the analysis. Most common neurological manifestations observed were encephalopathy (n = 30), cerebrovascular disease (n = 20), cognitive impairment (n = 13), seizures (n = 13), hypoxic brain injury (n = 7), dysgeusia (n = 5), and extraocular movement abnormalities (n = 5). The "COVID-19 first" group had more evidence of physiologic disturbances on arrival with a more severe/critical disease course (83.3% vs 53.8%, p 0.025). Conclusion: Neurologic manifestations of COVID-19 are highly variable and can occur prior to the diagnosis of or as a complication of the viral infection. Despite similar baseline comorbidities and demographics, the COVID-19 patients who developed neurologic symptoms later in hospitalization had more severe disease courses. Differently from previous studies, we noted a high percentage of African American and Latino individuals in both groups.

关键词： GAD65   Autoimmune epilepsy   Limbic encephalitis   Cerebellar ataxia   Stiff-person syndrome   Immunotherapy  

摘要： We described the clinical and neuroimaging characteristics of seven Chinese patients with anti-GAD65 antibody-associated neurological disorders of whom epileptic seizures were the initial and main symptoms. All patients were given immunotherapy and followed up monthly. The outcome demonstrates that immunotherapy is helpful for non-seizure manifestations of anti-GAD65-associated neurological autoimmunity and is less effective in the treatment of seizures, yet partial responses can still occur in the early stage. Taken together we suggest a trial with immunotherapy in all patients in the early stage of the disease, and in patients with non-epilepsy symptoms in the later stage.

关键词： nanocarrier   FTY-720   particle size   neuritogenesis   integrin alpha 5  

摘要： Neurological disorders and diseases are on the rise in the world, while pharmacists are being encouraged to encapsulate drugs into the nanocarriers. The critical key question is which size of nanocarrier has a promising neurotherapeutic effect. In the present study, FTY-720, an FDA approved drug, was encapsulated into O/W nanocarriers. SEM and DLS data indicated in ultrasonication and stirring methods resulted in spherical nanocarriers with a particle size of 60 and 195 nm (nF60 and nF195), respectively. Further to investigate the effect of particle size on neuronal cells, MTT assay, PI flow-cytometry, LDH release, and NO production examinations were performed. Results showed that small nanocarriers increased cell viability along with the decline of dead cells, while both nanocarriers decreased LDH release and NO production as compared to the conventional drug. Notably, qRT-PCR and western blotting data related to apoptotic markers indicated in the increase of cell mortality in cells treated by nF190 was not due to the increase of apoptosis and Bax/Bcl2 ratio. It is worth mentioning that integrin alpha 5 as a cell surface receptor involves in neuritogenesis was over-expressed in neuronal cells treated by small nanocarriers. However, nF60 increased PTK2 over-expression along with neurite outgrowth, as well. In other words, nanocarriers at the size of 60 nm are preferred to 195 nm as a drug carrier in neurotherapy due to profound impacts on neural cells. Thanks to small nanocarrier broad positive action on neural viability and neurite outgrowth. The present study discloses a pharmaceutical strategy to design drugs based on their particle size efficiency.

关键词： neurology speciality   psychiatry specialty   philosophy   humanities   postgraduate education  

摘要： This Viewpoint reviews the historical convergence and then divergence of psychiatry and neurology as clinical disciplines and calls for a transformation of graduate and postgraduate education to integrate the two and span intersections of the humanities, philosophy, and science.

关键词： Stem cells   Stroke   Functional recovery  

摘要： Background The evidence on the efficacy of adipose derived stem cells (ADSCs) in the treatment of stroke is controversial. Therefore, the aim of present systematic review and meta-analysis is to evaluate the efficacy of ADSCs administration in the treatment of animal models of ischemic stroke. Methods An extensive search was performed on electronic databases of Medline, Embase, Scopus, CENTRAL and Web of Science until December 31, 2018. Animal studies that used ADSCs in treatment of ischemic stroke were included. The data were recorded as mean and standard deviation and then a pooled standardized mean difference (SMD) with 95% confidence interval (95% CI) was reported. Results Twenty articles were included in the present meta-analysis. It was observed that administration of ADSCs improves motor function (SMD = 2.52, 95% CI: 1.67 to 3.37,p < 0.0001) and neurological status (SMD = 2.05, 95% CI: 1.33 to 2.78,p < 0.0001) in animals following an ischemic stroke. Multivariate meta-regression showed the model of stroke induction (p = 0.017) and the number of transplanted cells (p = 0.007) affect the efficacy of ADSCs administration on motor function improvement following the stroke. Conclusion Moderate to high levels of evidence indicate a strong efficacy of ADSCs transplantation on motor function and neurological improvement following ischemic stroke in animal models. However, no reports regarding the dose-response effect of ADSCs administration on stroke exist in the literature. As a result, further pre-clinical studies are recommended to be conducted on the matter.

关键词： ACE2   Brain   COVID-19   Spike Protein  

摘要： Spike protein (S protein) is the virus "key" to infect cells and is able to strongly bind to the human angiotensin-converting enzyme2 (ACE2), as has been reported. In fact, Spike structure and function is known to be highly important for cell infection as well as for entering the brain. Growing evidence indicates that different types of coronaviruses not only affect the respiratory system, but they might also invade the central nervous system (CNS). However, very little evidence has been so far reported on the presence of COVID-19 in the brain, and the potential exploitation, by this virus, of the lung to brain axis to reach neurons has not been completely understood. In this Article, we assessed the SARS-CoV and SARS-CoV-2 Spike protein sequence, structure, and electrostatic potential using computational approaches. Our results showed that the S proteins of SARS-CoV-2 and SARS-CoV are highly similar, sharing a sequence identity of 77%. In addition, we found that the SARS-CoV-2 S protein is slightly more positively charged than that of SARS-CoV since it contains four more positively charged residues and five less negatively charged residues which may lead to an increased affinity to bind to negatively charged regions of other molecules through nonspecific and specific interactions. Analysis the S protein binding to the host ACE2 receptor showed a 30% higher binding energy for SARS-CoV-2 than for the SARS-CoV S protein. These results might be useful for understanding the mechanism of cell entry, blood-brain barrier crossing, and clinical features related to the CNS infection by SARS-CoV-2.