The theory analysis and design for large parameter weak signal detector based on bistable stochastic resonance

Volume 3 Issue 11 (November 2015

Pathologically Activated Neuroprotection via Uncompetitive Blockade of \u3cem\u3eN\u3c/em\u3e-Methyl-d-aspartate Receptors with Fast Off-rate by Novel Multifunctional Dimer Bis(propyl)-cognitin

Uncompetitive N-methyl-d-aspartate (NMDA) receptor antagonists with fast off-rate (UFO) may represent promising drug candidates for various neurodegenerative disorders. In this study, we report that bis(propyl)-cognitin, a novel dimeric acetylcholinesterase inhibitor and γ-aminobutyric acid subtype A receptor antagonist, is such an antagonist of NMDA receptors. In cultured rat hippocampal neurons, we demonstrated that bis(propyl)-cognitin voltage-dependently, selectively, and moderately inhibited NMDA-activated currents. The inhibitory effects of bis(propyl)-cognitin increased with the rise in NMDA and glycine concentrations. Kinetics analysis showed that the inhibition was of fast onset and offset with an off-rate time constant of 1.9 s. Molecular docking simulations showed moderate hydrophobic interaction between bis(propyl)-cognitin and the MK-801 binding region in the ion channel pore of the NMDA receptor. Bis(propyl)-cognitin was further found to compete with [3H]MK-801 with a Ki value of 0.27 μm, and the mutation of NR1(N616R) significantly reduced its inhibitory potency. Under glutamate-mediated pathological conditions, bis(propyl)-cognitin, in contrast to bis(heptyl)-cognitin, prevented excitotoxicity with increasing effectiveness against escalating levels of glutamate and much more effectively protected against middle cerebral artery occlusion-induced brain damage than did memantine. More interestingly, under NMDA receptor-mediated physiological conditions, bis(propyl)-cognitin enhanced long-term potentiation in hippocampal slices, whereas MK-801 reduced and memantine did not alter this process. These results suggest that bis(propyl)-cognitin is a UFO antagonist of NMDA receptors with moderate affinity, which may provide a pathologically activated therapy for various neurodegenerative disorders associated with NMDA receptor dysregulation

The relationship between IGF1 and the expression spectrum of miRNA in the placenta of preeclampsia patients

Objectives: Pre-eclampsia (PE) affects many women worldwide and remains the leading cause of morbidity and mortality in neonatal and maternal settings. Abnormal expression of placental microRNAs (miRNAs) may be associated with PE. Material and methods: This study was conducted to the relationship between IGF1 and the expression spectrum of miRNA in the placenta of preeclampsia patient. The expression of miRNA in placental tissue was compared between pre-eclampsia (n = 6) and normal pregnant women (n = 5) miRNA targets were studied by computer simulation and functional assays. The role of miRNA was verified in trophoblast cell lines by apoptosis assay and invasion assay. Results: There was a significant increase in miRNAs in the placenta of women with pre-eclampsia compared with patients with normal pregnancy. Luciferase assay confirmed direct regulation of miRNA. Conclusions: The expression of IGF1 and miRNA was significantly increased in the placenta of patients with pre-eclampsia

Intensity of Left Atrial Spontaneous Echo Contrast as a Correlate for Stroke Risk Stratification in Patients with Nonvalvular Atrial Fibrillation.

The intensity of left atrial spontaneous echo contrast (LASEC) by transesophageal echocardiography (TEE) has been proposed as an important variable in the stratification of thromboembolic risk, particularly in patients with nonvalvular atrial fibrillation (NVAF). We hypothesized that the quantification of LASEC by ultrasound will improve its utility in predicting subsequent stroke events in patients with NVAF. Patients (n = 206) with definite NVAF receiving TEE were included for this prospective cohort study. Baseline clinical risk factors of stroke, CHADS2 score and CHA2DS2-Vasc, left atrial thrombus (LAT), the five-grades of LASEC and video intensity (VI) value of LASEC were measured. During 2 years follow-up, 20 patients (9.7%) developed stroke. VI value of LASEC in the patients with stroke was higher compared to patients without stroke (25.30 ± 3.61 vs. 8.65 ± 0.81, p \u3c 0.001). On logistic regression analysis, LAT, qualitative LASEC, graded LASEC, VI value of LASEC and CHADS2 and CHA2DS2-Vasc score were independent predictors of stroke. Among them, the highest area under the curve of receiver operating characteristic (ROC) in predicting stroke was VI value of LASEC (p \u3c 0.05). These results show that quantification of LASEC by VI value is the most favorable predictor of stroke in patients with NVAF, and calls for improving the utility of LASEC in predicting subsequent stroke events

Validation of a Disability Assessment Tool Based on the International Classification of Functioning, Disability, and Health in the Chinese Context

Background:The common standards of disability assessment for long-term care (LTC) insurance are currently absent. The International Classification of Functioning, Disability and Health (ICF) was designed for a better description of health and functioning, which could fill the demand gap for the standards of disability assessment and be a promising tool for the development of LTC insurance system.ObjectivesTo validate a disability assessment scale for disabled elderly individuals based on the ICF for LTC in the Chinese context.MethodsThe present study is a cross-sectional study. A disability assessment tool based on the ICF was developed by referring to other assessment tools and an expert consensus meeting in the initial phase of the study. The developed tool was used to evaluate 1,610 elderly individuals in the LTC institutions. The Cronbach's α coefficient and split-half reliability were applied to test the internal consistency of the tool, while the Interclass correlation coefficients (ICCs) were used to evaluate the interrater reliability (IRR). Factor analysis was performed to verify the construct validity of the tool. The scores from the Medical Outcomes Short Form-12 (SF-12) were correlated with that from the disability assessment tool, to assess the criterion-related validity.ResultsThe Cronbach's α coefficient and split-half reliability of the disability assessment tool were 0.969 and 0.877, respectively. The ICCs of the sum scale was 0.85, and the ICCs of each of the 20 items in the scale ranged from 0.78 to 0.94. The items were divided into three factors through analysis, which is consistent with the structure expectation. The scores of each item and the sum score of the disability assessment scale were negatively correlated with the scores of the physical and psychological fields in SF-12 (p < 0.001). Overall, the data indicated that the tool was characterized by good internal consistency, IRR, construct validity, and criterion-related validity.ConclusionsThe disability assessment tool based on the ICF is a reliable and valid tool for the collection of information on functioning across various LTC settings. The information of disability provided evidence for the distribution of LTC service and guided the development of LTC insurance standards

A genetic study and meta-analysis of the genetic predisposition of prostate cancer in a Chinese population.

Prostate cancer predisposition has been extensively investigated in European populations, but there have been few studies of other ethnic groups. To investigate prostate cancer susceptibility in the under-investigated Chinese population, we performed single-nucleotide polymorphism (SNP) array analysis on a cohort of Chinese cases and controls and then meta-analysis with data from the existing Chinese prostate cancer genome-wide association study (GWAS). Genotyping 211,155 SNPs in 495 cases and 640 controls of Chinese ancestry identified several new suggestive Chinese prostate cancer predisposition loci. However, none of them reached genome-wide significance level either by meta-analysis or replication study. The meta-analysis with the Chinese GWAS data revealed that four 8q24 loci are the main contributors to Chinese prostate cancer risk and the risk alleles from three of them exist at much higher frequencies in Chinese than European populations. We also found that several predisposition loci reported in Western populations have different effect on Chinese men. Therefore, this first extensive single-nucleotide polymorphism study of Chinese prostate cancer in comparison with European population indicates that four loci on 8q24 contribute to a great risk of prostate cancer in a considerable large proportion of Chinese men. Based on those four loci, the top 10% of the population have six- or two-fold prostate cancer risk compared with men of the bottom 10% or median risk respectively, which may facilitate the design of prostate cancer genetic risk screening and prevention in Chinese men. These findings also provide additional insights into the etiology and pathogenesis of prostate cancer.This work was conducted on behalf of the CHIPGECS and The PRACTICAL consortia (see Supplementary Consortia). We acknowledge the contribution of doctors, nurses and postgraduate research students at the CHIPGENCS sample collecting centers. We thank Orchid and Rosetrees for funding support. This work was also supported by National Natural Science foundation of China for funding support to H Zhang (Grant No: 30671793 and 81072377), N Feng (Grant No: 81272831), X Zhang (Grant No: 30572139, 30872924 and 81072095), S Zhao (Grant No: 81072092 and 81328017), Y Yu (Grant No: 81172448) and Program for New Century Excellent Talents in University from Department of Education of China (NCET-08-0223) and the National High Technology Research and Development Program of China (863 Program 2012AA021101) to X Zhang.This is the final version of the article. It first appeared from Impact Journals via http://dx.doi.org/10.18632/oncotarget.725