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Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive accumulation of Lewy body inclusions along with selective destruction of dopaminergic (DA) neurons in the nigrostriatal tract of the brain. Genetic studies have revealed much about the pathophysiology of PD, enabling the identification of both biomarkers for diagnosis and genetic targets for therapeutic treatment, which are evolved in tandem with the development of stem cell technologies. The discovery of induced pluripotent stem (iPS) cells facilitates the derivation of stem cells from adult somatic cells for personalized treatment and thus overcomes not only the limited availability of human embryonic stem cells but also ethical concerns surrounding their use. Non-viral, non-integration, or non-DNA-mediated reprogramming technologies are being developed. Protocols for generating midbrain DA neurons are undergoing constant refinement. The iPS cell-derived DA neurons provide cellular models for investigating disease progression in vitro and for screening molecules of novel therapeutic potential and have beneficial effects on improving the behavior of parkinsonian animals. Further progress in the development of safer non-viral/non-biased reprogramming strategies and the subsequent generation of homogenous midbrain DA neurons shall pave the way for clinical trials. A combined approach of drugs, cell replacement, and gene therapy to stop disease progression and to improve treatment may soon be within our reach. [ABSTRACT FROM AUTHOR]

Objectives: Endometriosis is a common gynecological disease affecting up to ~10% of women at reproductive age. Prior combined studies implied that MARVELD2 might be involved in the pathogenesis of certain malignancies. Here, 211 Han Chinese samples with ovarian endometriosis were analyzed for the presence of MARVELD2 mutations. Methods: We analyze the potential presence of MARVELD2 mutations by direct DNA sequencing. Results: A total of 7 variants, 5 missense and 2 synonymous variants, were identified in our 211 ovarian endometriosis samples with different frequencies. Among the 5 missense variant, a missense rare variant p.V198M (c.592G>A), was identified in 10 out of our 211 samples (4.74%). This rare variant was identified with extremely low frequency in 766 control samples from 766 Chinese women without endometriosis (0.13%, 1/766) and control samples in the public databases. The evolutionary conservation analysis results suggested that the MARVELD2 rare variant lead to highly conserved amino acid substitutions among 14 vertebrate species from Human to Snake. Furthermore, both the SIFT and Polyphen-2 programs predicted this rare variant to be 'disease causing'. However, we failed to observe any statistical significance between the MARVELD2 rare variant and the available clinical data. Conclusions: We identified a potential pathogenic rare variant in the MARVELD2 gene in Chinese samples with ovarian endometriosis, indicating the MARVELD2 rare variant might play an active role in the pathogenesis of endometriosis. [ABSTRACT FROM AUTHOR]

Background: Chronic subdural hematoma (CSDH) is a common disease that is more prevalent in older people. Surgical intervention is a safe treatment of choice. However, the recurrence rate is relatively high and the outcome is not always satisfactory among surgically treated patients. It is believed that aberrant angiogenesis and intracapsular inflammation contribute to the development of CSDH. Atorvastatin is reported to promote angiogenesis and suppress inflammation. We have recently shown that atorvastatin is effective to non-surgically reduce and eliminate CSDH with minimal side effects. Here, we report a clinical research trial protocol that is designed to evaluate the therapeutic effects of atorvastatin on CSDH.Methods/design: We have designed a multi-center, randomized, placebo-controlled, double blind clinical trial for evaluating the efficacy of oral atorvastatin in reducing CSDH. We have so far recruited 96 patients with CT-confirmed or MRI-confirmed CSDHs from 16 medical centers in China. These patients were originally recruited for the Oriental Neurosurgical Evidence-based Study Team (ONET) study. After informed consent is provided, patients are randomized to receive either atorvastatin (oral 20 mg/night for 8 weeks) or placebo (dextrin for 8 weeks); and followed for 16 weeks after the treatment. The primary outcome is the change in hematoma volume at the end of 8-week treatment. Secondary outcomes include: changes in 1) the hematoma volume at the 4(th), 12(th), and 24(th) weeks; 2) Markwalder's Grading Scale and Glasgow Coma Scale (MGS-GCS); 3) Glasgow Outcome Score (GOS) and 4) Activities of Daily Life-the Barthel Index scale (ADL-BI). Safety will be assessed during the study by monitoring adverse events, laboratory tests, electrocardiography (ECG), measurements of vital signs (temperature, pulse, and blood pressure) and body weight.Discussion: Results of this trial will provide critical information regarding whether atorvastatin is an effective and safe alternative to surgical treatment of CSDH.Trial Registration: ClinicalTrials.gov Identifier--NCT02024373 The date of trial registration: 7 August 2013. [ABSTRACT FROM AUTHOR]

The aim of the present study was to examine the relapse time and analyse the social, psychological and physical factors related to relapse among drugdependent patients who had undergone neurosurgery by ablating the nucleus accumbens (NAc surgical group) and those who had undergone detoxification with non-operative treatment in residential compulsory rehabilitation centres (control group). A total of 100 patients from the NAc surgical group and 92 patients from the control group were recruited in the study for 5 years. Information regarding their experiences of previous abstinence from drug use and the relapse time was obtained by interviews, while the relapse reasons were obtained through questionnaire. The study shows that there is a significant correlation in relapse reasons between the two groups. 'Relief from disturbance' (psychological factor) and 'peer influence' (social factor) were the two main factors associated with relapse. Factors like 'desire for last use' and 'boredom' (psychological factor) were more associated with relapse in the control group than the NAc surgical group. At 5 years post-operation, the number of patients in the employment and married status in non-relapse group was significantly higher than in the relapse group. There was also a statistical difference in the 5-year survival rate between them. The average relapse time was the first three years. Thus prevention of relapse to drug dependence after detoxification, especially for those with NAc surgery should be improved to focus on the main factors and time. [ABSTRACT FROM AUTHOR]

Objective: Dural arteriovenous fistula (DAVF) of the anterior cranial fossa is usually treated by surgical disconnection or endovascular embolization via the ophthalmic artery. The middle meningeal artery is a rarely used approach. This study investigated the safety and efficacy of embolization of DAVF of the anterior cranial fossa with Onyx through the middle meningeal artery. Methods: A retrospective review of a prospective cerebral vascular disease database was performed. Patients with DAVF of the anterior cranial fossa managed with embolization through the middle meningeal artery with Onyx were selected. Information on demography, symptoms and signs, angiographic examinations, interventional treatments, angiographic and clinical results, and follow-up was collected and analyzed. Results: Five patients were included in this study, four of whom had hemorrhage. All fistulas were fed by the bilateral ethmoidal arteries arising from the ophthalmic artery and by the anterior branch of the middle meningeal artery. The abnormal shunt unilaterally drained into the superior sagittal sinus with interposition of the cortical veins all five patients. All endovascular treatments were successful with evidence of an angiographic cure. No complications occurred, and all patients recovered uneventfully without neurologic deficits. There were nearly no symptoms among the patients during follow-up. Conclusion: Embolization of DAVF of the anterior cranial fossa via the middle meningeal artery with Onyx is safe, effective, and a good choice for management of DAVF. More cases are needed to verify these findings. [ABSTRACT FROM AUTHOR]

We demonstrate a simple low-cost approach as an alternative to conventional O2 plasma treatment to modify the surface of indium tin oxide (ITO) anodes for use in organic light-emitting diodes. ITO is functionalized with F- ions by electrochemical treatment in dilute hydrofluoric acid. An electrode with a work function of 5.2 eV is achieved following fluorination. Using this electrode, a maximum external quantum efficiency of 26.0% (91 cd/A, 102 lm/W) is obtained, which is 12% higher than that of a device using the O2 plasma-treated ITO. Fluorination also increases the transparency in the near-infrared region [ABSTRACT FROM AUTHOR]

Objective: This study evaluated the feasibility, safety, and efficacy of embolization of dural arteriovenous fistula via a very small, short feeding artery with the assistance of a balloon placed proximal to the tip of the microcatheter, such that the balloon serves as a plug. Methods: Eight patients who underwent treatment of DAVF by balloon-assisted transarterial embolization with Onyx were retrospectively reviewed. Gender, age, angiography findings, procedure details, clinical and angiographic outcomes, complications, and follow-up were recorded and analyzed. Results: Nine embolization procedures were performed in eight male patients via extracranial arteries. Balloon-assisted embolization was successful in all eight patients. A Hyperglide balloon was used in five patients, and a Hyperform balloon was used in three patients. Angiographic resolution of the fistula was achieved in all patients without complications. All patients recovered uneventfully. During the follow-up period of 7-19 months, all patients were asymptomatic except for one patient who experienced mild headaches. Conclusions: Treatment of DAVF by balloon-assisted embolization with Onyx achieved promising results, even in patients with very small and short feeding arteries. This technique allowed the treatment of DAVF cases where other techniques have failed. [ABSTRACT FROM AUTHOR]

Growing evidence has shown that proNGF-p75NTR-sortilin signaling might be a crucial factor in neurodegeneration, but it remains unclear if it may function in nigral neurons under aging and disease. The purpose of this study is to examine and quantify proNGF and sortilin expression in the substantia nigra and dynamic changes of aging in lactacystin and 6-hydroxydopamine (6-OHDA) rat models of Parkinson's disease using immunofluorescence, electronic microscopy, western blot and FLIVO staining methods. The expression of proNGF and sortilin was abundantly and selectively identified in tyrosine hydroxylase (TH)-containing dopamine neurons in the substantia nigra. These proNGF/TH, sortilin/TH-positive neurons were densely distributed in the ventral tier, while they were less distributed in the dorsal tier, where calbindin-D28K-containing neurons were numerously located. A correlated decrease of proNGF, sortilin and TH was also detected during animal aging process. While increase of proNGF, sortilin and cleaved (active) caspase-3 expression was found in the lactacystin model, dynamic proNGF and sortilin changes along with dopamine neuronal loss were demonstrated in the substantia nigra of both the lactacystin and 6-OHDA models. This study has thus revealed the presence of the proNGF-sortilin signaling complex in nigral dopamine neurons and its response to aging, lactacystin and 6-OHDA insults, suggesting that it might contribute to neuronal apoptosis or neurodegeneration during pathogenesis and disease progression of Parkinson's disease; the underlying mechanism and key signaling pathways involved warrant further investigation. [ABSTRACT FROM AUTHOR]

It is known that βig-h3 is involved in the invasive process of many types of tumors, but its mechanism in glioma cells has not been fully clarified. Using immunofluorescent double-staining and confocal imaging analysis, and co-immunoprecipitation assays, we found that βig-h3 co-localized with integrin α51β in U87 cells. We sought to elucidate the function of this interaction by performing cell invasion assays and gelatin zymography experiments. We found that siRNA knockdowns of βig-h3 and calpain-2 impaired cell invasion and MMP secretion. Moreover, βig-h3, integrins and calpain-2 are known to be regulated by Ca2+, and they are also involved in tumor cell invasion. Therefore, we further investigated if calpain-2 was relevant to βig-h3-integrin α5β1 interaction to affect U87 cell invasion. Our data showed that βig-h3 co-localized with integrin α5β1 to enhance the invasion of U87 cells, and that calpain-2, is involved in this process, acting as a downstream molecule. [ABSTRACT FROM AUTHOR]

Background and Purpose: Dural arteriovenous fistulas (DAVF) can affect a variety of cerebral venous structures and can present at various clinical stages. This study was designed to introduce the characteristic manifestation of DAVF detected with both carotid and transcranial color-coded duplex ultrasonography (CDUS) and to evaluate the diagnostic value of CDUS in DAVF. Methods: Nineteen patients with DAVF confirmed by cerebral angiography were studied with CDUS. The sonogram and spectrum of the affected area were observed. Hemodynamic parameters such as peak systolic velocity, end-diastolic velocity, mean velocity and resistance index (RI) were measured and recorded in the feeding artery, draining vein and extracranial artery. All results were compared with cerebral angiography. Fifty healthy volunteers were enrolled as a control group. Related hemodynamic changes were compared between the patients and normal controls. Results: The blood flow of fistulas presented as an irregular mosaic color bolus with a clear boundary detected with CDUS. Blood flow imaging of fistulas was abnormal in 12 cases and absent in 7 cases. The detection rate was 63% (12/19). Fifty-three main feeding arteries (73.6%) were detected by ultrasonography. All the venous drainages through the transverse sinus and superior ophthalmic vein were detected, while the ones through the superior sagittal sinus and cortical vein were not. There was a significant difference in average diameter, flow velocity and RI of the occipital artery and superficial temporal artery between the patients and normal controls (p < 0.05). Conclusions: CDUS could indicate DAVF by analyzing both imaging results of the diseased region and hemodynamic changes of the relative vasculature. It is a promising technique for the diagnosis and follow-up study of DAVF. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Repeat gamma knife radiosurgery (GKRS) is considered to be an effective treatment for refractory or recurrent trigeminal neuralgia (TN). Aims: The purpose of this report was to demonstrate the relationship between the outcome of repeat GKRS and prior operative procedures on patients with recurrent or refractory TN. Materials and Methods: A retrospective analysis was performed on 34 patients with refractory or recurrent TN who had undergone repeat GKRS; 21 patients had undergone other types of procedures, 11 of whom had undergone more than three such procedures prior to radiosurgery. The maximum dose of the repeat procedure was between 60 and 75 Gy. The mean follow-up time was 21.6 months. Statistical Analysis Used: The log-rank test and Fisher's exact test were used to analyze the data. Results: Excellent pain relief was achieved in 14 patients (41.2%) after repeat GKRS, while a successful outcome occurred in 29 of 34 patients (85.3%). Better pain relief occurred in the patients who did not have a prior procedure or who had undergone fewer than three prior procedures (P = 0.042). Twenty-four of 25 patients (96.0%) who had recurrent pain had a successful operation and five of nine patients (55.6%) who did not have significant relief of pain after the first procedure had a successful operation. The difference was statistically significant (P < 0.01). Only four patients had mild complications. Conclusion: It is more likely to relieve pain in patients with recurrent or refractory TN who did not have a prior procedure or who had fewer than three procedures before undergoing their first GKRS. Moreover, it seems that patients who had a good response following the initial GKRS had better results after a repeat procedure. [ABSTRACT FROM AUTHOR]