关键词： ATPase activity   immunofluorescence localization   neurological diseases   P4-ATPases   protein expression  

摘要： ATP8A2 is a P4-ATPase (adenosine triphosphate) that actively flips phosphatidylserine and phosphatidylethanolamine from the exoplasmic to the cytoplasmic leaflet of cell membranes to generate and maintain phospholipid asymmetry. Mutations in the ATP8A2 gene have been reported to cause severe autosomal recessive neurological diseases in humans characterized by intellectual disability, hypotonia, chorea, and hyperkinetic movement disorders with or without optic and cerebellar atrophy. To determine the effect of disease-associated missense mutations on ATP8A2, we expressed six variants with the accessory subunit CDC50A in HEK293T cells. The level of expression, cellular localization, and functional activity were analyzed by western blot analysis, immunofluorescence microscopy, and ATPase activity assays. Two variants (***376Met and ***429Met) expressed at normal ATP8A2 levels and preferentially localized to the Golgi-recycling endosomes, but were devoid of ATPase activity. Four variants (***429Asn, pAla544Pro, ***625Trp, and ***702Arg) expressed poorly, localized to the endoplasmic reticulum, and lacked ATPase activity. The expression of these variants was increased twofold by the addition of the proteasome inhibitor MG132. We conclude that the ***376Met and ***429Met variants fold in a native-like conformation, but lack key amino acid residues required for ATP-dependent lipid transport. In contrast, the ***429Asn, pAla544Pro, ***625Trp, and ***702Arg variants are highly misfolded and undergo rapid proteosomal degradation.

关键词： Biomarkers   Malnutrition   Risk factors  

摘要： Dehydration is common and frequently under-diagnosed in chronic malnourished children, leading to life-threatening conditions. In this pilot study we applied bioimpedance vector analysis (BIVA) to determine hydration status in 52 neurologically impaired (NI) paediatric patients (14.08 +/- 5.32). Clinical and biochemical data were used to define malnutrition and dehydration. Body composition analysis and hydration were also assessed by BIVA and we considered 143 normal-weight healthy subjects (15.0 +/- 1.7), as controls for hydration status assessment. BIVA revealed a pathological hydration status in NI children, showing higher resistance (p < 0.001) and reactance values (p = 0.001) compared to controls. No differences in reactance and resistance were detected between well-nourished and under-nourished subjects. Four patients out of 52 showed mild signs of dehydration;no severe dehydration was detected. Laboratory data, suggestive for dehydration, were similar in well-nourished and under-nourished NI subjects. In conclusion, in our sample of NI paediatrics, dehydration according to clinical signs and laboratory data was under-diagnosed. BIVA showed specific bioelectrical characteristics that could be compatible with impaired hydration status. Further studies are necessary to confirm that BIVA may an applicable tool for defining dehydration status and guiding rehydration in NI children.

关键词： Risk management   Indoor air   Microbiome   Diet   Chelation   Health policy  

摘要： The human environment and exposures arising therefrom are major contributors to neurological disorders ranging from stroke to neurodegenerative diseases. Reduction of exposure to environmental risk factors, with the goal of disease prevention or control, is addressed at the individual as well as the societal level and in recognition of differential subject vulnerability. We examine some practical solutions in high-income countries that may allow a better adaptation to environmental risks and reduce their adverse impact on the nervous system. We consider the citizen's role in reducing unhealthy exposures and explore new approaches to treatment. (C) 2019 Elsevier Masson SAS. All rights reserved.

关键词： Ischemic stroke   miR-494   HDAC3   neuron  

摘要： HDAC3 is an essential negative regulator of neuronal plasticity and memory formation. Although a chemical inhibitor has been invented, little is known about its endogenous modulators. We explored whether miR-494 affects HDAC3-mediated neuronal injury following acute ischemic stroke. A substantial increase in plasma miR-494 was detected in AIS patients and was positively associated with the mRS at one year after symptom onset. The miR-494 levels were transiently increased in the infarcted brain tissue of mice. In contrast, miR-494 levels were reduced in neurons but increased in the medium after OGD. Intracerebroventricular injection of miR-494 agomir reduced neuronal apoptosis and infarct volume at the acute stage of MCAO, promoted axonal plasticity and long-term outcomes at the recovery stage, suppressed neuronal ataxin-3 and HDAC3 expression and increased acetyl-H3K9 levels in the ipsilateral hemisphere. In vitro studies confirmed that miR-494 posttranslationally inhibited HDAC3 in neurons and prevented OGD-induced neuronal axonal injury. The HDAC3 inhibitor increased acetyl-H3K9 levels and reversed miR-494 antagomir-aggravated acute cerebral ischemic injury, as well as brain atrophy and long-term functional recovery. These results suggest that miR-494 may serve as a predictive biomarker of functional outcomes in AIS patients and a potential therapeutic target for the treatment of ischemic stroke.

关键词： addiction   controllable   enlightenment   gambling   reaching-grasping  

摘要： In this paper, I postulate that the processing of concepts which are deemed controllable is rooted in neurological machinery located in the posterior parietal cortex specialised for the processing of objects which are immediately actionable because they are within reach. This is demonstrated with reference to the near-miss effect in gambling behaviour, where it is argued that the configurative proximity of the near-miss outcome to the win outcome creates the impression that the win outcome is 'almost within reach' or controllable. The perceived realisability of the desired outcome increases subjective reward probability and the associated expected action value, which impacts decision-making and behaviour. When extended to substance addiction, this novel hypothesis adds fresh insight into understanding the motivational effects associated with cue exposure and opportunity for drug-taking. Moreover, by postulating that a perception of control can be generated to minimise unpleasant affective states, it can also reconcile contrasting models of decision-making and provide a neurological explanation for the efficacy of mindfulness-based techniques in treating addictions. With reference to the previously hypothesised link between the self and control, these ideas can provide an explanation for the increased subjective value of self-associated concepts in the 'endowment effect', as well as a neurological correlate for the concept of the 'narrative self'. This paper therefore provides an innovative and unifying perspective for the study and treatment of behavioural and substance addictions as well as contributing to our neurological understanding of philosophical approaches to the self.

关键词： Chordoma   Sacral tumor   Sacrectomy   En bloc resection   Piecemeal resection   Prognostic factor   Quality of life  

摘要： Background Surgical resection represents the main therapeutic method for sacral chordoma, but plans for resection mode must weigh neurological loss against complete tumor excision, a difficult balance to strike. The purpose of this study was to provide useful information contributing to surgical decision making in sacral chordoma. Methods A retrospective review was performed on 47 patients with large sacral chordoma. Prognostic factors affecting recurrence-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox proportional hazards model. Quality of life was assessed by the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire and compared using Student's t test. Results Resection mode was the independent prognostic factor affecting RFS, while independent prognostic factors affecting OS were resection mode and postoperative recurrence. As for quality of life, the en bloc resection group showed a higher score in emotional well-being, while the piecemeal resection group scored better in function well-being. No significant difference was identified in total the FACT-G score between two groups. Conclusions On the one hand, en bloc resection showed huge advantages in disease control for sacral chordoma. On the other hand, despite the unsatisfaction in functional well-being, en bloc resection did not sacrifice quality of life significantly in terms of the total FACT-G score.

关键词： Neurological soft signs   Healthy adults   Source-based morphometry   Cerebellum   Sensorimotor areas   Structural networks  

摘要： Neurological soft signs (NSS), as minor neurological deficits, have been identified in several psychiatric disorders, especially in schizophrenia. However, ifs unclear how the neuropathological processes of the disease affect NSS related brain morphological changes and whether it is confounded by the use of medication. As NSS also exist in healthy people, the potential confounding effects of psychopathology or medication will be excluded if NSS are investigated in healthy people. Therefore, we applied a novel multivariate approach, source-based morphometry (SBM), to study structural networks in relation to NSS in healthy adults based on structural magnetic resonance imaging (MRI) data. The Heidelberg Scale was applied to evaluate NSS. Using SBM, we constructed structural networks and investigated their associations with NSS in healthy adults. Six grey matter (GM) structural networks were identified. Sensory integration subscores were associated with the cerebellar component and the cortico-basal ganglia-thalamic component. Motor coordination subscores and total NSS scores were associated with the sensorimotor component. The present findings indicated that structural network abnormalities in cerebellar, subcortical and cortical sensorimotor areas contribute to NSS performance in healthy adults.

关键词： Bone cements   Iatrogenic disease   Adverse effects   Paresis   Pulmonary embolism  

摘要： Background The risk factors, incidence, and clinical management of pulmonary cement embolism and neurological deficit during percutaneous vertebroplasty (PVP) were evaluated. Methods Three thousand one hundred and seventy-five patients with symptomatic osteoporotic vertebral compression fractures (OVCFs) treated with PVP were retrospectively reviewed in a single institution. Clinical parameters such as age, gender, number of fractures, and time from fracture to vertebroplasty were recorded at the time of surgery. Image and surgical parameters including the amount of cement, the vertebral level, uni- or bipedicle surgical approach, and leakage pattern were recorded. Results Type-C leakage, including paraspinal (25%), intradiscal (26%), and posterior (0.7%) leakage, was more common than type-B (11.4%) and type-S leaks (4.9%). Cement leakage into the spinal canal (type-C posterior) occurred in 26 patients (0.7%), and four patients needed surgical decompression. Three in nine patients with leakage into thoracic spine needed decompressive surgery, but only one of 17 patients into lumbar spine needed surgery (p < 0.01). Age, gender, number of fractures, and time from fracture to vertebroplasty were not risk factors of pulmonary cement embolism or neurological deficit. The risk factor of pulmonary cement embolism was higher volume of PMMA injected (p < 0.001) and risk factor of neurological deficit was type-C posterior cement leakage into thoracic spine. The incidence of pulmonary cement embolism was significantly high in the volume of PMMA injected (PMMA injection < 3.5 cc: 0%;3.5-7.0 cc: 0.11%;> 7.0 cc: 0.9%;p < 0.01) which needed postoperative oxygen support. Conclusions Cement leakage is relatively common but mostly of no clinical significance. Percutaneous vertebroplasty in thoracic spine and high amount of PMMA injected should be treated with caution in clinical practice.

关键词： Cardiac arrest   Prognostication   Infrared pupillometry   Systematic review  

摘要： Background: Despite advances in resuscitation care, mortality rates following cardiac arrest (CA) remain high. Between one-quarter (in-hospital CA) and two-thirds (out of hospital CA) of patients admitted comatose to intensive care die of neurological injury. Neuroprognostication determines an informed and timely withdrawal of life sustaining treatment (WLST), sparing the patient unnecessary suffering, alleviating family distress and allowing a more utilitarian use of resources. The latest Resuscitation Council UK (2015) guidance on post-resuscitation care provides the current multi-modal neuroprognostication strategy to predict neurological outcome. Its modalities include neurological examination, neurophysiological tests, biomarkers and radiology. Despite each of the current strategy's predictive modalities exhibiting limitations, meta-analyses show that three, namely PLR (pupillary light reflex), CR (corneal reflex) and N20 SSEP (somatosensory-evoked potential), accurately predict poor neurological outcome with low false positive rates. However, the quality of evidence is low, reducing confidence in the strategy's results. While infrared pupillometry (IRP) is not currently used as a prognostication modality, it can provide a quantitative and objective measure of pupillary size and PLR, giving a definitive view of the second and third cranial nerve activity, a predictor of neurological outcome. Methods: The proposed study will test the hypothesis, "in those patients who remain comatose following return of spontaneous circulation (ROSC) after CA, IRP can be used early to help predict poor neurological outcome". A comprehensive review of the evidence using a PRISMA-P (2015) compliant methodology will be underpinned by systematic searching of electronic databases and the two authors selecting and screening eligible studies using the Cochrane data extraction and assessment template. Randomised controlled trials and retrospective and prospective studies will be include

关键词： Canine infectious hepatitis   Canine Adenovirus   Canine Adenovirus type 1   Neurological signs   Canine  

摘要： Background Infectious canine hepatitis is a rarely encountered disease, that is caused by Canine Adenovirus-1. Clinical signs can vary dramatically, and neurological signs are rarely seen. Neurological manifestation of this disease is rarely reported in the veterinary literature. Case presentation A 5-week-old, male entire Husky cross puppy presented for a one-day history of abnormal neurological behaviour (circling, ataxia, vocalization and obtund mentation). The puppy was euthanized shortly after presentation due to rapid deterioration. Histopathology raised concerns for Canine Adenovirus 1 (CAdV-1) based on vasculitis in the brain and intranuclear inclusion bodies in endothelial cell and hepatocytes;immunohistochemistry on brain tissue confirmed CAdV-1 infection. Conclusions This report discusses possible routes of infection and manifestations of adenovirus infections causing neurologic signs. It also provides a timely reminder that CAdV-1 should be considered a differential in unvaccinated dogs that present with neurological signs. Further studies are required to better understand the neurotrophic tendencies of this virus.