关键词： ATF2   KLF2   microRNA‐   125b   neurological function recovery   smurf1   spinal cord injury  

摘要： The purpose of this study is to investigate the role of microRNA-125b (miR-125b) and its mechanism in spinal cord injury (SCI) by targeting Smurf1. After loss- and gain-function approaches were conducted in SCI rat models and neural stem cells (NSCs) isolated from foetal rats, the Basso-Beattie-Bresnahan (BBB) score was calculated, and related protein expression was determined by Western blot analysis and cell apoptosis by TUNEL staining. NSC viability was detected by CCK-8, migration abilities by Transwell assay and apoptosis by flow cytometry. The relationship between miR-125b, Smurf1 and KLF2 was evaluated by dual-luciferase reporter gene experiments, Co-IP and in vivo ubiquitin modification assays. Inhibition of miR-125b and KLF2 and the up-regulation of Smurf1 and ATF2 were observed in SCI rats. BBB scores were elevated, the expression of Nestin, NeuN, GFAP, NF-200 and Bcl-2 protein was enhanced but that of Bax protein was reduced, and cell apoptosis was inhibited in SCI rats after up-regulating miR-125b or silencing ATF2. Smurf1 was a target gene of miR-125b, which promoted KLF2 degradation through its E3 ubiquitin ligase function, and KLF2 repressed the expression of ATF2 in NSCs. The results in vivo were replicated in vitro. miR-125b overexpression promotes neurological function recovery after SCI.

摘要： Objectives To review the clinical findings and outcome in dogs diagnosed with insulinoma, and to assess which factors are predictors of overall survival. Additionally, to describe the neurological manifestations of this population and their correlation with survival. Materials and Methods Retrospective multicentric study of canine insulinoma cases (2009 to 2020). Signalment, clinical history, neurological examination, diagnostic findings, treatment and outcome were obtained from clinical records. Univariate and multivariate analyses were used to compare the overall survival. Results One hundred and sixteen cases were included. Median duration of clinical signs before presentation was 1.5 months. The most common presenting clinical signs were weakness (59.5%), epileptic seizures (33.6%) and changes in consciousness or behaviour (27.6%). Three dogs were suspected to have paroxysmal dyskinesia. Thirty-two dogs had an abnormal neurological examination, most commonly showing obtundation (28.1%), decreased withdrawal reflexes (21.9%) and absent menace response (18.8%). Overall survival for dogs undergoing surgery (20 months) was significantly longer than in medically treated (8 months;adjusted hazard ratio: 0.33;95% confidence interval: 0.18, 0.59). Presence of metastases was the only other variable associated with prognosis (adjusted hazard ratio 1.72;95% confidence interval: 1.02, 2.91). Clinical Significance Clinical signs of canine insulinoma are vague and non-specific. Weakness, epileptic seizures and changes in mentation or behaviour were the most commonly reported. Obtunded mentation and forebrain neurolocalisation were the main neurological manifestations. Dogs undergoing surgery had a longer overall survival compared to medically treated cases, and dogs with metastasis had a shorter overall survival regardless of treatment modality. Abnormalities in the neurological examination did not correlate with prognosis.

关键词： Neurology   Pediatrics   Global health   Malaria  

关键词： COVID-19   Neuropathophysiology   Cytokine storm   Neurodegenerative disorders   Vaccine   Pandemic  

摘要： There are regular reports of extrapulmonary infections and manifestations related to the ongoing COVID-19 pandemic. Coronaviruses are potentially neurotropic, which renders neuronal tissue vulnerable to infection, especially in elderly individuals or in those with neuro-comorbid conditions. Complaints of ageusia, anosmia, myalgia, and headache;reports of diseases such as stroke, encephalopathy, seizure, and encephalitis;and loss of consciousness in patients with COVID-19 confirm the neuropathophysiological aspect of this disease. The brain is linked to pulmonary organs, physiologically through blood circulation, and functionally through the nervous system. The interdependence of these vital organs may further aggravate the pathophysiological aspects of COVID-19. The induction of a cytokine storm in systemic circulation can trigger a neuroinflammatory cascade, which can subsequently compromise the blood-brain barrier and activate microglia- and astrocyte-borne Toll-like receptors, thereby leading to neuronal tissue damage. Hence, a holistic approach should be adopted by healthcare professionals while treating COVID-19 patients with a history of neurodegenerative disorders, neuropsychological complications, or any other neuro-compromised conditions. Imperatively, vaccines are being developed at top priority to contain the spread of the severe acute respiratory syndrome coronavirus 2, and different vaccines are at different stages of development globally. This review discusses the concerns regarding the neuronal complications of COVID-19 and the possible mechanisms of amelioration.

关键词： Monoamine oxidase   Depression   Autism spectrum disorder   Schizophrenia   Neurodegenerative disease  

摘要： Monoamine oxidase enzymes are responsible for the degredation of serotonin, dopamine, and norepinephrine in the central neurvous system. Although it has been nearly 100 years since they were first described, we are still learning about their role in the healthy brain and how they are altered in various disease states. The present review provides a survey of our current understanding of monoamine oxidases, with a focus on their contributions to neuropsychiatric, neurodevelopmental, and neurodegenerative disease. Important species differences in monoamine oxidase function and development in the brain are highlighted. Sex-specific monoamine oxidase regulatory mechanisms and their implications for various neurological disorders are also discussed. While our understanding of these critical enzymes has expanded over the last century, gaps exist in our understanding of sex and species differences and the roles monoamine oxidases may play in conditions often comorbid with neurological disorders.

关键词： Neurolysin   endopeptidase 24   16   Modulator   Inhibitors   Allosteric  

摘要： Neurolysin, a member of the metallopeptidase M3 family, plays an important role in many biological processes by regulating bioactive oligopeptides in the central nervous system and periphery. Small molecule modulators of neurolysin have therapeutic potential in the treatment of schizophrenia, addiction, epilepsy, Huntington, Parkinson's, and Alzheimer's diseases, and tumors. In this article, the structure and function of neurolysin and its modulators are reviewed with the aim of providing researchers with perspective and insights toward exploring novel drug candidates.

关键词： isovaleric acidemia   isovaleric aciduria   long‐   term outcome   neonatal screening   newborn screening  

摘要： Isovaleric aciduria (IVA), a metabolic disease with severe (classic IVA) or attenuated phenotype (mild IVA), is included in newborn screening (NBS) programs worldwide. The long-term clinical benefit of screened individuals, however, is still rarely investigated. A national, prospective, observational, multi-center study of individuals with confirmed IVA identified by NBS between 1998 and 2018 was conducted. Long-term clinical outcomes of 94 individuals with IVA were evaluated, representing 73.4% (for classic IVA: 92.3%) of the German NBS cohort. In classic IVA (N = 24), NBS prevented untimely death except in one individual with lethal neonatal sepsis (3.8%) but did not completely prevent single (N = 10) or recurrent (N = 7) metabolic decompensations, 13 of them occurring already neonatally. IQ (mean +/- SD, 90.7 +/- 10.1) was mostly normal but below the reference population (P = .0022) and was even lower in individuals with severe neonatal decompensations (IQ 78.8 +/- 7.1) compared to those without crises (IQ 94.7 +/- 7.5;P = .01). Similar results were obtained for school placement. In contrast, individuals with mild IVA had excellent neurocognitive outcomes (IQ 105.5 +/- 15.8;normal school placement) and a benign disease course (no metabolic decompensation, normal hospitalization rate), which did not appear to be impacted by metabolic maintenance therapy. In conclusion, NBS reduces mortality in classic IVA, but does not reliably protect against severe neonatal metabolic decompensations, crucial for favorable neurocognitive outcome. In contrast, individuals with mild IVA had excellent clinical outcomes regardless of metabolic maintenance therapy, questioning their benefit from NBS. Harmonized stratified therapeutic concepts are urgently needed.

关键词： Out-of-hospital cardiac arrest   Ambient temperature   Bystander cardiopulmonary resuscitation  

摘要： Background: At lower ambient temperature, patients with out-of-hospital cardiac arrest (OHCA) easily experience hypothermia. Hypothermia has shown to improve the rate of successful return of spontaneous circulation (ROSC) in animal models. We hypothesized that lower temperature affects the impact of bystander cardiopulmonary resuscitation (CPR) on the increased odds of a favorable neurological outcome post-OHCA. Methods: This study used information collected by the prospective, nationwide, Utstein registry to examine data from 352,689 adult patients who experienced OHCA from 2012 to 2016 in Japan. The primary outcome was a 1-month favorable neurological outcomes. Multivariable logistic regression analyses were conducted to test the impact of bystander CPR according to the temperature on the favorable outcome. Results: A total of 201,111 patients with OHCA were included in the complete case analysis. The lower temperature group had lower proportions of receiving bystander CPR (46.5 vs. 47.9%) and having favorable outcome (2.1 vs 2.8%) than those in the higher group. Multivariable analysis revealed that bystander CPR at lower temperatures was significantly associated with favorable outcomes (adjusted odds ratio, 1.22;95% CI, 1.09-1.37), whereas bystander CPR at higher temperatures was not associated with favorable outcomes (1.02;0.92-1.13). The nonlinear relationship using a spline curve in the multivariable model revealed that odds ratio of favorable neurological outcomes associated with bystander CPR increased as the temperature decreased . Conclusion: Bystander CPR was associated with favorable neurological outcomes at lower temperatures. The odds of a favorable outcome associated with bystander CPR increased as the temperature decreased.

关键词： Spinal cord injury   Stabilization   Airway management   Ventilatory support  

摘要： Spinal cord injury (SCI) affects approximately 54 per 1 million people annually in the United States. Treatment strategies for this patient population focus on initial stabilization and early intervention. The cornerstones of early management are clinical assessment, characterization of the injury, medical optimization, and definitive surgical treatment, including surgical stabilization and/or decompression. This article discusses the important strategies in caring for patients with SCI that are supported with significant literature.