Prediction of Late Hospital Arrival in Patients with Mild and Rapidly Improving Acute Ischemic Stroke in a Rural Area of China.

Purpose: Among all ischemic stroke patients, more than half are mild and rapidly improving acute ischemic stroke (MaRAIS) patients. However, many MaRAIS patients do not recognize the disease early on, and thus they delay access to the treatment that would be most effective if provided earlier. This is especially true in rural areas. The aim of this study was to develop and validate a late hospital arrival risk nomogram in a rural Chinese population of patients with MaRAIS. Methods: We developed a prediction model based on a training dataset of 173 MaRAIS patients collected from September 9, 2019 to May 13, 2020. Data analyzed included demographics and disease characteristics. A least absolute shrinkage and selection operator (LASSO) regression model was used to optimize feature selection for the late hospital arrival risk model. Multivariable logistic regression analysis was applied to build a prediction model incorporating the features selected in the LASSO regression models. The discrimination, calibration, and clinical usefulness of the prediction model were assessed using the C-index, calibration plot, and decision curve analysis, respectively. Internal validation was then assessed using bootstrapping validation. Results: Variables contained in the prediction nomogram included transportation mode, history of diabetes, knowledge of stroke symptoms, and thrombolytic therapy. The model had moderate predictive power with a C-index of 0.709 (95% confidence interval: 0.636-0.783) and good calibration. In the internal validation, the C-index reached 0.692. The risk threshold was 30-97% according to the analysis of the decision curve, and the nomogram could be applied in clinical practice. Conclusion: This novel nomogram, which incorporates transportation mode, history of diabetes, knowledge of stroke symptoms, and thrombolytic therapy, was conveniently applied to facilitate individual late hospital arrival risk prediction among MaRAIS patients in a rural area of Shanghai, China.

Peptidyl arginine deiminase 4 and its potential role in Alzheimer's disease.

Alzheimer's disease (AD) is the main cause of dementia, and its pathogenesis is still not clear. Peptidyl arginine deiminases 4(PAD4) as one of the important members of PAD family, is the only protein with nuclear transfer function, it can regulate the expression of many proteins through citrullinating histone. PAD4 can also interact with many transcription factors, involved in regulating gene expression. PAD4 expression is closely related to the inflammatory factors secreted, cell autophagy, tumorigenesis and other neurodegenerative diseases. More importantly, PAD4 and its citrullinated protein were found in cortical and hippocampal neurons of AD patients. To study the expression and regulatory pathway of PAD4 in vivo and in vitro experiments on AD may be of helpful to elucidate the pathogenesis of AD. Meanwhile, detection of anti-citrullinated antibody will have potential value as novel biomarkers of AD.

FABP4 alleviates endoplasmic reticulum stress-mediated ischemia-reperfusion injury in PC12 cells via regulation of PPARγ.

Ischemic stroke is a life-threatening complication with a high rate of morbidity. Circulating fatty acid binding protein 4 (FABP4) has been reported to be associated with the outcome of acute ischemic stroke. The present study aimed to illustrate the function of FABP4 in ischemic stroke. PC12 cells exposed to oxygen glucose deprivation/reoxygenation (OGD/R) were used to mimic ischemia-reperfusion (I/R) injury in ischemic stroke. Cell viability was estimated using a Cell Counting Kit-8 assay. The expression of FABP4 in PC12 cells under OGD/R was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). PC12 cells were transfected with FABP4 small interfering RNA (siRNA), inflammatory cytokines and reactive oxygen species (ROS) were determined via RT-qPCR and ROS assay kit. Western blotting was performed to detect endoplasmic reticulum stress (ERS)-related proteins and peroxisome proliferator-activated receptor γ (PPARγ). Flow cytometry was used to evaluate the cell apoptotic rate. The expression of FABP4 increased gradually with the prolongation of reoxygenation within 8 h. FABP4-knockdown inhibited the transcription of inflammatory cytokines, the production of ROS and decreased cell apoptosis. Furthermore, decreased ERS-related proteins and increased PPARγ were estimated in PC12 cells transfected with FABP4 siRNA. PPARγ inhibitor GW9662 weakened the anti-apoptotic effect of FABP4-knockdown. Taken together, these results indicated that FABP4-knockdown suppressed cell apoptosis via relieving ERS; this effect was reversed by treatment of GW9662.

The Effects and Underlying Mechanisms of Cell Therapy on Blood-Brain Barrier Integrity After Ischemic Stroke.

Ischemic stroke is one of the main causes of mortality and disability worldwide. However, efficient therapeutic strategies are still lacking. Stem/progenitor cell-based therapy, with its vigorous advantages, has emerged as a promising tool for the treatment of ischemic stroke. The mechanisms involve new neural cells and neuronal circuitry formation, antioxidation, inflammation alleviation, angiogenesis, and neurogenesis promotion. In the past decades, in-depth studies have suggested that cell therapy could promote vascular stabilization and decrease blood-brain barrier (BBB) leakage after ischemic stroke. However, the effects and underlying mechanisms on BBB integrity induced by the engrafted cells in ischemic stroke have not been reviewed yet. Herein, we will update the progress in research on the effects of cell therapy on BBB integrity after ischemic stroke and review the underlying mechanisms. First, we will present an overview of BBB dysfunction under the ischemic condition and cells engraftment for ischemic treatment. Then, we will summarize and discuss the current knowledge about the effects and underlying mechanisms of cell therapy on BBB integrity after ischemic stroke. In particular, we will review the most recent studies in regard to the relationship between cell therapy and BBB in tissue plasminogen activator (t-PA)-mediated therapy and diabetic stroke.

Structural brain network measures are superior to vascular burden scores in predicting early cognitive impairment in post stroke patients with small vessel disease.

OBJECTIVES: In this cross-sectional study, we aimed to explore the mechanisms of early cognitive impairment in a post stroke non-dementia cerebral small vessel disease (SVD) cohort by comparing the SVD score with the structural brain network measures. METHOD: 127 SVD patients were recruited consecutively from a stroke clinic, comprising 76 individuals with mild cognitive impairment (MCI) and 51 with no cognitive impairment (NCI). Detailed neuropsychological assessments and multimodal MRI were performed. SVD scores were calculated on a standard scale, and structural brain network measures were analyzed by diffusion tensor imaging (DTI). Between-group differences were analyzed, and logistic regression was applied to determine the predictive value of SVD and network measures for cognitive status. Mediation analysis with structural equation modeling (SEM) was used to better understand the interactions of SVD burden, brain networks and cognitive deficits. RESULTS: Group difference was found on all global brain network measures. After adjustment for age, gender, education and depression, significant correlations were found between global brain network measures and diverse neuropsychological tests, including TMT-B (r = -0.209, p < .05), DSST (r = 0.206, p < .05), AVLT short term free recall (r = 0.233, p < .05), AVLT long term free recall (r = 0.264, p < .05) and Rey-O copy (r = 0.272, p < .05). SVD score showed no group difference and was not correlated with cognition tests. Network global efficiency (EGlobal) was significantly related to cognitive state (p < .01) but not the SVD score. Mediation analysis showed that the standardized total effect (p = .013) and the standardized indirect effect (p = .016) of SVD score on cognition was significant, but the direct effect was not. CONCLUSIONS: Brain network measures, but not the SVD score, are significantly correlated with cognition in post-stroke SVD patients. Mediation analysis showed that the cerebral vascular lesions produce cognitive dysfunction by interfering with the structural brain network in SVD patients. The brain network measures may be regarded as direct and independent surrogate markers of cognitive impairment in SVD.

Brief screening for mild cognitive impairment in subcortical ischemic vascular disease: a comparison study of the Montreal Cognitive Assessment with the Mini-Mental State Examination.

BACKGROUND AND PURPOSE: To assess the validity of the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE) in the detection of vascular mild cognitive impairment (VaMCI) in patients with subcortical ischemic vascular disease (SIVD). METHODS: Among 102 SIVD patients, both cutoff scores of the MMSE and MoCA for differentiating VaMCI from no cognitive impairment (NCI) or differentiating VaMCI from vascular dementia (VaD) were determined by the receiver operator characteristic (ROC) analysis. Optimal sensitivity with specificity of cutoff scores was obtained after the raw scores were adjusted for education. RESULTS: After adjusting for education, the MoCA cutoff score for differentiating VaMCI from NCI was at 24/25 and that for differentiating VaMCI from VaD was at 18/19. After applying the adjusted MoCA scores from 19 to 24 to identify VaMCI in all SIVD patients, sensitivity was at 76.7% and specificity was at 81.4% (κ = 0.579). The adjusted cutoff score of the MMSE for differentiating VaMCI from NCI was at 28/29 and that for differentiating VaMCI from VaD was at 25/26. The sensitivity and specificity of the adjusted MMSE was at 58.1 and 71.2%, respectively, when using the score from 26 to 28 to identify VaMCI in SIVD patients (κ = 0.294). CONCLUSIONS: The MoCA detected subcortical VaMCI better than the MMSE.

[A survey on the attitudes and confidence of general practitioners in handling dementia and its related problems].

OBJECTIVE: To investigate general practitioners (GPs)' attitudes and confidence in handling dementia and its related problems. METHOD: A questionnaire survey was conducted in GPs from Shanghai on 25th Sep, 2012. The questionnaire included the basic information of the GPs and their attitudes toward and confidence in handling dementia and its related problems. RESULTS: A total of 287 GPs from 73 hospitals participated in the survey.78.4% of them responded that they met fewer demented patients during their clinical practice and only 24.7% of them had attended some kinds of dementia-related knowledge training courses.Senior GPs were less enthusiastic than junior GPs in handling dementia and its related problems as they were more likely to think that dementia should be diagnosed by specialist (87.1% vs. 74.8%, OR = 2.28, 95%CI:1.14~4.57, P = 0.02), less likely to actively referral patients (22.0% vs. 10.1%, OR = 2.52, 95%CI:1.24~5.14, P = 0.01), and more likely to think about that GPs have very limited role in care of demented patients (9.7% vs. 0.7%, OR = 15.59, 95%CI:1.96~123.81, P = 0.00). CONCLUSION: The GPs in Shanghai are lack of trainings about the dementia and its' related knowledge and their attitudes toward the care of dementia are pessimistic. Thus, it is necessary to train the GPs more to enhance their confidence and enthusiasm in care of dementia.