Plasma Exosomal MiRNAs Expression Profile in Mesial Temporal Lobe Epilepsy With Hippocampal Sclerosis: Case-Control Study and Analysis of Potential Functions.

BACKGROUND: To explore an expression profile in plasma exosomal miRNAs of mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE + HS) patients and investigate the associated clinical significance and putative pathways involved. METHODS: Plasma exosomal miRNAs were measured in six mTLE + HS patients who were confirmed with pre-surgical stereo-electroencephalography and six without hippocampal sclerosis (mTLE-HS) using Illumina HiSeq 2500. Then six dysregulated miRNAs were chosen for validation in an independent sample of 18 mTLE + HS patients and 18 mTLE-HS controls using RT-qPCR. Receiver operating characteristic curve was conducted to evaluate the diagnostic value of miRNAs in HS. Bioinformatic analyses were conducted to reveal in which pathways these miRNAs were involved. RESULTS: We revealed that a total of 42 exosomal miRNAs were differentially expressed in mTLE + HS. Among them, 25 were increased and 17 decreased. After validation, hsa-miR-129-5p, -214-3p, -219a-5p, and -34c-5p were confirmed as being upregulated, while hsa-miR-421 and -184 were significantly downregulated in mTLE + HS. Moreover, hsa-miR-184 had the best diagnostic value for discriminating mTLE + HS with 88.9% sensitivity and 83.3% specificity. These six miRNAs regulated several genes from neurotrophin-, hippo-, p53-, TGF- beta-, HIF- 1-, mTOR-related pathways. CONCLUSION: Six miRNAs were dysregulated in mTLE + HS patients and targeted several genes. This result might facilitate pathological mechanistic studies of miRNAs in HS and represent potential diagnostic biomarkers. These provided the rationale for further confirmation studies in larger cohorts of prospective patients.

Dynamic Network Connectivity Analysis to Identify Epileptogenic Zones Based on Stereo-Electroencephalography.

Objectives: Accurate localization of epileptogenic zones (EZs) is essential for successful surgical treatment of refractory focal epilepsy. The aim of the present study is to investigate whether a dynamic network connectivity analysis based on stereo-electroencephalography (SEEG) signals is effective in localizing EZs. Methods: SEEG data were recorded from seven patients who underwent presurgical evaluation for the treatment of refractory focal epilepsy and for whom the subsequent resective surgery gave a good outcome. A time-variant multivariate autoregressive model was constructed using a Kalman filter, and the time-variant partial directed coherence was computed. This was then used to construct a dynamic directed network model of the epileptic brain. Three graph measures (in-degree, out-degree, and betweenness centrality) were used to analyze the characteristics of the dynamic network and to find the important nodes in it. Results: In all seven patients, the indicative EZs localized by the in-degree and the betweenness centrality were highly consistent with the clinically diagnosed EZs. However, the out-degree did not indicate any significant differences between nodes in the network. Conclusions: In this work, a method based on ictal SEEG signals and effective connectivity analysis localized EZs accurately. The results suggest that the in-degree and betweenness centrality may be better network characteristics to localize EZs than the out-degree.

Localization of epileptogenic zone based on graph analysis of stereo-EEG.

Localization of the epileptogenic zone (EZ) is essential for the successful surgical treatment of medically intractable epilepsy. In the present study, stereo-EEG (SEEG) recordings were obtained from seven patients underwent presurgical evaluation for treatment of intractable epilepsy. Partial directed coherence (PDC) analysis was applied to construct peri-ictal effective connectivity networks. The graphic measures, in-degree, out-degree and betweenness centrality, were evaluated to localize the EZ. A receiver operating characteristic (ROC) analysis was used to quantify the localization accuracy. We found that the in-degree coincided well with the EZ identified by epileptologists' visual inspection in all seven patients who had a significant improvement in seizure outcomes, however, the other two measures were effective only in some cases. Furthermore, in all seven patients the electrode contact with the highest in-degree was always located within the EZ identified by epileptologists' visual inspection. These results indicate that the graph theory is an effective method to localize the EZ when suitable graphic measures were chosen. Furthermore, the in-degree was the most effective measure among the three graphic measures in localizing the EZ when the PDC method was used.

[Highly Efficient Bilayer-Structure Yellow-Green OLED with MADN Hole-Transport Layer and the Impedance Spectroscopy Analysis].

Abstract Highly efficient bilayer-structure yellow-green organic light-emitting device (OLED) has been demonstrated based on MADN as hole-transport layer (HTL) and host-guest coped system of [Alq3: 0.7 Wt% rubrene] as emitting and electron-trans- port layer. The device gives yellow-green emission through incomplete energy transfer from the host of Alq3 to the guest of ru- brene. An electroluminescent peak of 560 nm, 1931 CIE color coordinates of (0.46, 0.52) and a maximum current efficiency of 7.63 cd · A⁻¹ (which has been enhanced by 30% in comparison with the counterpart having conventional NPB HTL) are ob- served. The hole-transporting characteristics of MADN and NPB have been systematically investigated by constructing hole-only devices and employing impedance spectroscopy analysis. Our results indicate that MADN can be served as an effective hole-trans- port material and its hole-transporting ability is slightly inferior to NPB. This overcomes the shortcoming of hole transporting more quickly than electron in OLED and improves carrier balance in the emitting layer. Consequently, the device current efficien- cy is promoted. In addition, the current efficiency of bilayer-structure OLED with MADN as HTL is comparable to that of conv- entinol trilayer-structure device with MADN as HTL and Alq3 as electron-transport layer. This indicates that the simplified bi- layer-structure device can be achieved without sacrificing current efficiency. The emitting layer of [Alq: 0.7 Wt% rubrene possesses superior elecron-transporting ability.

Risk factors related to aneurysmal rebleeding.

OBJECTIVE: Rebleeding from ruptured intracranial aneurysms is a major cause of death and disability. The aim of this study was to investigate the incidence of rebleeding and the risk factors related to rebleeding before early aneurysm repair. METHODS: The incidence of rebleeding, demographic data, and clinical data from 326 patients with aneurysmal subarachnoid hemorrhage (SAH) were retrospectively collected. All clinical variables were examined by univariate analysis, and a binary logistic regression analysis was performed to identify the risk factors related to rebleeding. RESULTS: Rebleeding occurred in 70 (21.5%) of the 326 aneurysm patients during transfer or during the in-hospital stay (within 72 hours); 24 episodes (34.3%) occurred within 3 hours, and 44 episodes (62.9%) occurred within 6 hours after the initial SAH. Univariate analysis showed that there were significant differences between the rebleeding and nonrebleeding patients in terms of age, aneurysm size, systolic arterial blood pressure (SBP), Hunt-Hess grade and outcome at discharge. The binary logistic regression analysis revealed that age (odds ratio [OR] = 1.167), aneurysm size (OR = 1.624), SBP (OR = 3.338), and Hunt-Hess grade (OR = 2.512) were independent risk factors for aneurysmal rebleeding (for each P < 0.05). CONCLUSIONS: The incidence of early aneurysmal rebleeding within hours after the initial SAH is high during transfer or during the in-hospital stay. Advanced age, an aneurysm size larger than 10 mm, SBP higher than 160 mmHg, and poor Hunt-Hess grade were independent risk factors for aneurysmal rebleeding. The importance of early aneurysm repair should be emphasized because aneurysmal rebleeding contributes to a poor outcome.

Predictors of outcome in the surgical treatment for epilepsy.

BACKGROUND: Knowledge about factors influencing the prognosis of resective epilepsy surgery can be used to identify which patients are most suitable for surgical treatment. The aim of this study was to identify preoperative prognostic factors associated with the chance of achieving long-term seizure freedom. METHODS: We retrospectively reviewed seizure outcomes and clinical, electroencephalography (EEG), magnetic resonance imaging (MRI), histopathology, and surgical variables from 99 epilepsy surgery patients with at least one year of postoperative follow-up. Seizure outcomes were categorized based on the modified classification by the International League Against Epilepsy. RESULTS: We found that the seizure-free rate was 27.9% after one year, and that it stabilized at about 20.0% between two and six years after surgery. Univariate analysis showed that medial temporal lobe epilepsy with hippocampal sclerosis, MRI with visible focal lesions concordant with EEG, and regional ictal EEG and electrocorticography patterns were associated with a favorable surgical outcome. On the other hand, seizure recurrence within six months, incomplete focus resection, and surgical complications were associated with a poor outcome. Multivariate analysis showed that medial temporal lobe epilepsy with hippocampal sclerosis and MRI with visible focal lesions were independent presurgical predictors of a favorable outcome (P < 0.01). Seizure recurrence within six months was the only significant independent predictor associated with a poor outcome (P < 0.01). CONCLUSION: Hippocampal sclerosis and abnormal MRI findings are strongly associated with a favorable surgical outcome, whereas seizure recurrence within six months is associated with a poor outcome.

Pregnancy outcomes in women with heart disease.

BACKGROUND: As the Shanghai Obstetrical Cardiology Intensive Care Center, our hospital has accumulated a large number of clinical data of pregnant women with heart disease. This paper is a retrospective analysis of 1142 pregnancies in women with heart disease so as to evaluate the maternal and fetal outcomes of these patients. METHODS: A retrospective analysis was carried out for pregnancies in 1142 women with heart disease who delivered in Shanghai Obstetrical Cardiology Intensive Care Center between 1993 and 2007. RESULTS: In this study, main heart diseases in pregnancy were arrhythmia (n = 359, 31.4%), congenital heart disease (CHD; n = 291, 25.5%), and myocarditis and its sequelae (n = 284, 24.9%); based on the functional classification criteria of New York Heart Association (NYHA), more than half (n = 678, 59.4%) of patients were classified NYHA Class I; pregnant women in NHYA Class I-II (n = 951, 83.3%) commonly had arrhythmia, myocarditis and its sequelae, while those in NHYA Class III-IV (n = 191, 16.7%) mainly had CHD, rheumatic heart disease (RHD), cardiopathy induced by hypertensive disorders complicating pregnancy, and peripartum cardiomyopathy (PPCM). Cardiac failure occurred in 97 (8.5%) patients, and 8 (0.7%) maternal deaths and 12 (1.1%) perinatal deaths were reported in this study. Compared with those in NHYA Class I-II, women in NHYA Class III-IV had a significantly lower gestational age at birth (P < 0.05), lower birth weight (P < 0.01), and higher incidence of preterm delivery, small for gestational age and perinatal death (P < 0.01). The incidence of cardiac failure in pregnant women with cardiopathy induced by hypertensive disorders complicating pregnancy and PPCM was relatively high, with a rate of 80% and 52.2%, respectively. After cardiac operation, 131 (90.3%) women were in classified NHYA Class I-II and 14 (9.7%) in NHYA Class III-IV. CONCLUSIONS: Arrhythmia is the type of heart disease that has a highest incidence in patients with heart disease in pregnancy, while main types of heart disease that impair cardiac function are CHD and RHD; cardiac failure is more frequently caused by cardiopathy induced by hypertensive disorders complicating pregnancy and PPCM; impaired cardiac function increases perinatal morbidity; cardiac surgery before pregnancy could improve the cardiac function.