NEXMIF variants are associated with epilepsy with or without intellectual disability.

OBJECTIVES: Variants in NEXMIF had been reported associated with intellectual disability (ID) without epilepsy or developmental epileptic encephalopathy (DEE). It is unkown whether NEXMIF variants are associated with epilepsy without ID. This study aims to explore the phenotypic spectrum of NEXMIF and the genotype-phenotype correlations. MATERIALS AND METHODS: Trio-based whole-exome sequencing was performed in patients with epilepsy. Previously reported NEXMIF variants were systematically reviewed to analyze the genotype-phenotype correlations. RESULTS: Six variants were identified in seven unrelated cases with epilepsy, including two de novo null variants and four hemizygous missense variants. The two de novo variants were absent in all populations of gnomAD and four hemizygous missense variants were absent in male controls of gnomAD. The two patients with de novo null variants exhibited severe developmental epileptic encephalopathy. While, the patients with hemizygous missense variants had mild focal epilepsy with favorable outcome. Analysis of previously reported cases revealed that males with missense variants presented significantly higher percentage of normal intellectual development and later onset age of seizure than those with null variants, indicating a genotype-phenotype correlation. CONCLUSION: This study suggested that NEXMIF variants were potentially associated with pure epilepsy with or without intellectual disability. The spectrum of epileptic phenotypes ranged from the mild epilepsy to severe developmental epileptic encephalopathy, where the epileptic phenotypes variability are potentially associated with patients' gender and variant type.

LncRNA SNHG1 promotes α-synuclein aggregation and toxicity by targeting miR-15b-5p to activate SIAH1 in human neuroblastoma SH-SY5Y cells.

Numerous long non-coding RNAs (lncRNAs) have been identified as aberrantly expressed in Parkinson's disease (PD). However, limited knowledge is available concerning the roles of dysregulated lncRNAs and the underlying molecular regulatory mechanism in the pathological process of PD. In this study, we found that lncRNA small nucleolar RNA host gene 1 (SNHG1) and seven in absentia homolog 1 (SIAH1) were upregulated, but microRNA-15b-5p (miR-15b-5p) was downregulated in SH-SY5Y cells pretreated with MPP+, as well as in MPTP-induced mouse model of PD. Overexpression of SIAH1 enhanced cellular toxicity of α-synuclein in SH-SY5Y cells, as indicated by the reduction of cell viability and elevation of LDH release. The percentage of α-synuclein aggregate-positive cells and the number of α-synuclein aggregates per cell were increased in SH-SY5Y cells transfected with pcDNA-SIAH1, while decreased after transfection with short interfering RNA specific for SIAH1 (si-SIAH1). Bioinformatics and luciferase reporter assay revealed that SIAH1 was a direct target of miR-15b-5p. We also found that SNHG1 could directly bind to miR-15-5p and repress miR-15-5p expression. Upregulation of miR-15b-5p alleviated α-synuclein aggregation and apoptosis by targeting SIAH1 in SH-SY5Y cells overexpressing α-synuclein. Overexpression of SNHG1 enhanced, whereas SNHG1 knockdown inhibited α-synuclein aggregation and α-synuclein-induced apoptosis. Moreover, the neuroprotective effect of si-SNHG1 was abrogated by downregulation of miR-15b-5p. In summary, our data suggest that SNHG1, as a pathogenic factor, promotes α-synuclein aggregation and toxicity by targeting the miR-15b-5p/SIAH1 axis, contributing to a better understanding of the mechanisms of Lewy body formation and loss of dopaminergic neurons in PD.

Elevated Serum Levels of CXC Chemokine Ligand-12 Are Associated with Unfavorable Functional Outcome and Mortality at 6-Month Follow-up in Chinese Patients with Acute Ischemic Stroke.

The aim of this study was to examine whether the circulating CXC chemokine ligand-12 (CXCL12) level can predict a 6-month outcome in Chinese patients with acute ischemic stroke (AIS). In a prospective study, CXCL12 levels were measured on admission in the serum of 304 consecutive patients with AIS. The prognostic value of CXCL12 to predict the functional outcome and mortality within 1 year was compared with the National Institutes of Health Stroke Scale score and with other known outcome predictors. A receiver operating characteristic (ROC) curve was used to evaluate the accuracy of serum CXCL12 in predicting functional outcome and mortality. Patients with an unfavorable outcome and non-survivors had significantly increased CXCL12 levels on admission (P < 0.0001 and P < 0.0001). Multivariate logistic regression analysis adjusted for common risk factors showed that CXCL12 (≥12.4 ng/mL; third quartile) was an independent predictor of functional outcome (odds ratio [OR] = 8.81; 95 % confidence interval [CI] 4.92-24.79) and mortality (OR = 10.15; 95 %CI 2.44-27.98). The area under the receiver operating characteristic curve of CXCL12 was 0.84 (95 % CI 0.76-0.92) for functional outcome and 0.87 (95 % CI 0.80-0.93) for mortality. Circulating CXCL12 serum levels at admission is a useful and complementary biomarker to predict functional outcome and mortality 6 months after acute ischemic stroke.

Botulinum Toxin A for the Treatment of a Child with SUNCT Syndrome.

Background. Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) syndrome is an unusual cause of headache, mainly described in older adults, and is rare in children. Pain attacks may be severe, frequent, and prolonged. The therapeutic benefits of many drugs are disappointing. Patient and Methods. A 12-year-old boy suffered severe headache and toothache for 20 days. As treatment with nonsteroidal anti-inflammatory drugs, anticonvulsants, and steroids proved ineffective, he was treated with ipsilateral multisite subcutaneous injections of botulinum toxin A 70 U around the orbit, the temporal area, and the upper gum. Results. The pain had reduced in frequency and severity by the fourth day after treatment and had completely disappeared after 7 days. There were no side effects or recurrence during a subsequent 17-month follow-up period. Conclusion. Botulinum toxin A can be used to treat the first episode of SUNCT in children over the age of 12 years.

Botulinum toxin A in the treatment of trigeminal neuralgia.

AIMS: The aims of this study were to investigate the clinical effects and safety of botulinum toxin A (BTX-A) in treating trigeminal neuralgia and its influences on accompanied depression, anxiety, sleep disorders, and quality of life. METHODS AND MATERIAL: Eighty-seven patients with one-branch classical trigeminal neuralgia were injected with BTX-A in the pain area. The visual analogic scale score, sleep interference score, Hamilton Anxiety Scale score, Hamilton Depression Scale score, and side effects were assessed at 1 week prior to and 8 weeks after treatment, respectively. RESULTS: The effective rates after 1, 2, 4, and 8 weeks of treatment were 48.28%, 66.67%, 78.16%, and 80.46%, respectively. The effective rates of anxiety and depression were 90.32% and 96.77%, respectively. When compared to that before treatment, the quality of life was significantly better in terms of role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health (all P < 0.01), while physical function was not significantly improved (P = 0.317). CONCLUSION: BTX-A treatment can significantly relieve the pain in trigeminal neuralgia patients; improve anxiety, depression, and sleep; and increase the quality of life. BTX-A treatment is a safe and effective method to treat classical trigeminal neuralgia.

High Plasma Levels of D-Dimer Are Independently Associated with a Heightened Risk of Deep Vein Thrombosis in Patients with Intracerebral Hemorrhage.

Deep venous thrombosis (DVT) is a complication of stroke. Our aim was to determine whether D-dimer plasma levels at admission could be a risk factor for DVT in Chinese patients with acute intracerebral hemorrhage (ICH). From December 2012 to November 2014, all patients with first-ever acute ICH were included. At baseline, the demographical and clinical data were taken. These patients were assessed for DVT using color Doppler ultrasonography (CDUS) on 15 days after ICH and whenever clinically requested. Multivariate analyses were performed using logistic regression models. Receiver operating characteristic (ROC) curves were used to test the overall predictive accuracy of D-dimer and other markers. In our study, acute ICH was diagnosed in 265 patients and 210 completed a 15-day follow-up and were included in the analysis. Fifty-four (25.7 %) out of the 210 patients were diagnosed as DVT. Plasma D-dimer levels were significantly higher in ICH patients with DVT as compared to those without DVT (P < 0.0001). Multivariate logistic regression analysis adjusted for common risk factors showed that plasma D-dimer levels ≥1.20 mg/L were an independent predictor of DVT [odds ratio (OR) = 12.99, 95 % confidence interval (CI) = 3.17-32.98; P < 0.0001]. With an area under the curve (AUC) of 0.91 (95 % CI = 0.86-0.94), D-dimer showed a significantly greater discriminatory ability to predict DVT as compared with high-sensitivity C-reactive protein (Hs-CRP) (AUC = 0.77, 95 % CI = 0.70-0.82; P < 0.01), homocysteine (HCY) (AUC = 0.75, 95 % CI = 0.70-0.81; P < 0.01), and National Institutes of Health Stroke Scale (NIHSS) score (AUC = 0.80, 95 % CI = 0.72-0.85; P < 0.01). The present study suggested that elevated D-dimer plasma levels were independent predictors for DVT in Chinese patients with ICH.

Therapeutic effect of Botulinum toxin-A in 88 patients with trigeminal neuralgia with 14-month follow-up.

BACKGROUND: We investigated the long-term effects and safety of botulinum toxin-A (BTX-A) for treating trigeminal neuralgia (TN). We also studied long-term maintenance of this therapeutic effect. METHODS: A visual analog scale (VAS) score, pain attack frequency per day, patient's overall response to treatment and side effects during 14-month follow-up were evaluated in 88 patients with TN receiving BTX-A. The primary endpoints were pain severity (assessed by VAS) and pain attack frequency per day. The secondary endpoint was the patient's overall response to treatment, assessed using the Patient Global Impression of Change. The influence of different doses (≤50, 50-100 and ≥100 U) on the therapeutic effect was evaluated. RESULTS: Treatment was deemed "effective" within 1 month in 81 patients and at 2 months in 88 patients (100%). The shortest period of effective treatment was 3 months, and complete control of pain was observed in a maximum of 46 patients. The therapeutic effect decreased gradually after 3 months, and the prevalence of effective treatment at 14 months was 38.6%, with complete control of pain seen in 22 patients (25%). There was no significant difference in the prevalence of effective treatment between different dose groups at identical time points (p > 0.05). Three patients showed swelling at injection sites and 10 patients showed facial asymmetry, both of which disappeared spontaneously without special treatment. CONCLUSION: Local subcutaneous injection of BTX-A for TN treatment has considerable therapeutic effects lasting several months and is safe for this indication. At least one-quarter of patients maintained complete analgesia. The maintenance period of the therapeutic effect may be related to the reduction in the VAS score after the first injection of BTX-A.

[Local application of tranexamic acid reduces blood less in unilateral total knee arthroplasty: a retrospective comparison analysis].

OBJECTIVE: To investigate the efficacy and safety of tranexamic acid in patients who receiving unilateral total knee arthroplasty (TKA). METHODS: From March 2011 to March 2012, clinical data of 95 patients who received primary unilateral TKA were analyzed retrospectively, including 23 male and 72 female patients, age from 60 to 87 years, mean (71 ± 4) years. The patients in treatment group received 0.5 g of tranexamic acid inside knee joint after capsule closure, and patients in control group did not receive tranexamic acid. Two groups of patient's age, height, weight and disease diagnosis and other parameters of the differences were no statistical significance (P > 0.05). The amounts of intraoperative blood loss, postoperative visible blood loss, the hidden blood loss, and blood transfusion, the number of patients needing blood transfusion, symptoms of deep venous thrombosis and lower extremity ecchymosis were observed. The values of preoperative and 3 hours of postoperative D-dimer and related coagulation markers were recorded. Group t test was used to compare between the two groups. RESULTS: There were no significant differences in intraoperative blood loss (P > 0.05). The amounts of postoperative visible blood loss, the hidden blood loss was significant different (t = 17.51 and 64.18, P < 0.05). Transfusion of both groups were (470 ± 150) ml and (708 ± 245) ml. The value of postoperative hemoglobin and hematocrit was lower in control group as compared with those in treatment group (t = -18.88 and -13.05, P < 0.05). No deep venous thrombosis was observed through Doppler ultrasound examination. Postoperative 3 hours D-dimer in the two groups for (0.91 ± 0.44) and (1.21 ± 0.65) mg/L, were significantly higher than that of preoperative (0.36 ± 0.11) and (0.37 ± 0.14) mg/L, with a statistically significant difference (t = 5.40 and 44.68, P < 0.05), and the control group was higher than treatment group (t = 1.99, P < 0.05). There was not statistically significant difference between the coagulation indicators of the two groups. CONCLUSIONS: The local application of tranexamic acid intraoperatively in unilateral TKA patients could significantly reduce the amounts of postoperative blood loss and blood transfusion to avoid TKA patients' perioperative anemia-related complications. It is also safe, ecnomic and easy to use during surgery.

mTOR and tau phosphorylated proteins in the hippocampal tissue of rats with type 2 diabetes and Alzheimer's disease.

This study explored the effects of mammalian target of rapamycin (mTOR) on the increased risk of developing Alzheimer's disease (AD) in rats with type 2 diabetes mellitus (T2DM). Male Sprague-Dawley rats were randomly divided into four groups: control, T2DM, AD and T2DM+AD. Changes in the learning and memory abilities of the rats were observed using the Morris water maze. mTOR activity and tau protein hyperphosphorylation in the hippocampus were analyzed by immunohistochemical staining and RT-PCR. The learning and memory abilities of the experimental rats were weakened compared with those of the control group. The T2DM+AD group revealed significant changes over the T2DM and AD groups. Compared with the control, T2DM and AD groups, the mTOR protein and mRNA levels, hyperphosphorylation of tau protein and total tau protein mRNA levels were significantly increased in the T2DM+AD group. T2DM may excessively activate mTOR in the hippocampal tissue by impairing insulin signaling, thereby increasing the extent of tau hyperphosphorylation and promoting the occurrence of AD.