COVID-19 vaccination hesitancy and safety among adult people with epilepsy in eastern China.

OBJECTIVE: This study assesses the hesitancy and safety of vaccination administration for the novel 2019 Coronavirus Disease (COVID-19) among adult people with epilepsy (PWE). METHODS: We recruited adult PWE who visited the outpatient epilepsy clinic from August 2021 to February 2022. We administered a structured questionnaire and a face-to-face interview regarding demographic factors, epilepsy characteristics, and relevant vaccine issues to all patients. Factors related to receiving a vaccine and epilepsy-related events after vaccination were then analyzed. RESULTS: A total of 501 PWE were surveyed; 288 were unvaccinated and 213 were vaccinated. Patients without jobs (OR: 0.59; 95% CI: 0.37-0.95, p = 0.03) were less likely to receive the vaccine compared to students or those with jobs. Other factors associated with vaccination were a higher number of anti-seizure medications (OR: 0.72; 95% CI: 0.55-0.95, p = 0.02) and a lower pre-vaccine seizure frequency (OR: 2.21; 95% CI: 1.06-4.59, p = 0.03). Of the 213 vaccinated patients, 10 (4.70%) reported at least one local and/or systemic side effect. Most patients (92.50%) did not report worse seizures within one month of vaccination. Poor ASM adherence (OR: 15.06; 95% CI: 1.75-129.87, p = 0.01) and fatigue/stimulant drinks such as caffeine (OR: 50.59; 95% CI: 7.57-337.94, p < 0.01) were significantly associated with seizure worsening within one month of receiving the COVID-19 vaccination. CONCLUSION: Almost two-fifths of patients with adult PWE have received a COVID-19 vaccine. Attention should be paid to educating epilepsy patients without jobs on the significance and safety of the vaccine. There was a low risk of seizure worsening in the short term after vaccination in PWE.

KCOSS: an ultra-fast k-mer counter for assembled genome analysis.

MOTIVATION: The k-mer frequency in whole genome sequences provides researchers with an insightful perspective on genomic complexity, comparative genomics, metagenomics and phylogeny. The current k-mer counting tools are typically slow, and they require large memory and hard disk for assembled genome analysis. RESULTS: We propose a novel and ultra-fast k-mer counting algorithm, KCOSS, to fulfill k-mer counting mainly for assembled genomes with segmented Bloom filter, lock-free queue, lock-free thread pool and cuckoo hash table. We optimize running time and memory consumption by recycling memory blocks, merging multiple consecutive first-occurrence k-mers into C-read, and writing a set of C-reads to disk asynchronously. KCOSS was comparatively tested with Jellyfish2, CHTKC and KMC3 on seven assembled genomes and three sequencing datasets in running time, memory consumption, and hard disk occupation. The experimental results show that KCOSS counts k-mer with less memory and disk while having a shorter running time on assembled genomes. KCOSS can be used to calculate the k-mer frequency not only for assembled genomes but also for sequencing data. AVAILABILITYAND IMPLEMENTATION: The KCOSS software is implemented in C++. It is freely available on GitHub: https://github.com/kcoss-2021/KCOSS. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Dystrophia canthorum in Waardenburg syndrome with a novel MITF mutation.

AIM: To reveal a novel MITF gene mutation in Waardenburg syndrome (WS), which is an autosomal dominant inherited neurogenic disorder that consists of various degrees of sensorineural deafness and pigmentary abnormalities in the eyes, hair and skin. METHODS: The genetic analysis of the Chinese family was conducted by whole-exome sequencing, then the results were confirmed by Sanger sequencing. RESULTS: WS is classified into type I to IV, which are identified by the W index, clinical characteristics and additional features. The MITF gene mostly accounts for WS type II. In this study, a de novo heterozygous mutation in the MITF gene, c.638A>G in exon 7, was identified in the patient diagnosed with WS type I features, as the W index was 2.17 (over 2.10), with dystrophia canthorum, congenital bilateral profound hearing loss, bilateral heterochromia irides, premature greying of the hair, and excessive freckling on the face at birth. She also underwent refractive errors and esotropia, reduced pigmentation of the choroid and visible choroid vessels. The mutation was not found in previous studies or mutation databases. CONCLUSION: The novel mutation in the MITF gene, which altered the protein in amino acids 213 from the glutamic acid to glycine, is the genetic pathological cause for WS features in the patient. Those characteristics of this family revealed a novel genetic heterogeneity of MITF in WS, which expanded the database of MITF mutations and offered a possible in correcting the W index value of WS in distinct ethnicities. Moreover, ocular symptoms should be emphasized in all types of WS patients.

Cytoprotective role of humanin in lens epithelial cell oxidative stress­induced injury.

Oxidative stress-induced injury and apoptosis of human lens epithelial cells (HLECs) are early events in the development of age­related cataracts (ARCs). Humanin (HN) is a mitochondrial­related peptide that serves a cytoprotective role in various cell types and animal models. Following HN knockdown or overexpression, the level of reactive oxygen species (ROS), mitochondrial membrane potential and mitochondrial DNA copy number, cell viability, LDH activity and apoptosis of HLECs under oxidative stress were detected, and apoptosis and autophagy were detected via transmission electron microscopy. The results suggested that HN may be involved in the response of HLECs to oxidative stress, and that HN expression was significantly upregulated under oxidative stress conditions. Furthermore, exogenous HN reduced intracellular ROS content and mitochondrial damage, and enhanced mitochondrial biosynthesis; however, this protection was lost in an endogenous HN knockdown cell model. In addition, to the best of our knowledge, the present study was the first to identify that HN increased mitochondrial autophagy, which was involved in reducing ROS production under oxidative stress. The present study indicated a potential mechanism underlying the anti­oxidative damage and apoptotic effects of HN under oxidative stress. In conclusion, HN may be a potential therapeutic target for ARCs as it has a significant cellular protective effect on HLECs under oxidative stress; therefore, further study is required to investigate its role in the occurrence and development of ARCs.

Development of mucoadhesive cationic polypeptide micelles for sustained cabozantinib release and inhibition of corneal neovascularization.

Corneal neovascularization (CNV) is one of the leading risk factors for vision loss. Anti-angiogenic drugs can theoretically be extended to the treatment of CNV. However, the application of these drugs is often hindered by traditional administration methods, e.g., eye drops, which is ascribed to the unique structure of the cornea and tear film. In this study, cationic polypeptide nanoparticles with mucoadhesive ability that carry lipophilic cabozantinib (a tyrosine kinase inhibitor), called Cabo-NPs, were developed for sustained cabozantinib release and inhibition of CNV. The polypeptides were synthesized via N-carboxyanhydride ring-opening polymerization and could self-assemble into micelles with cabozantinib in aqueous solution. The Cabo-NPs possessed good biocompatibility both in corneal epithelial cells and mouse corneas. More importantly, in vitro angiogenesis assays demonstrated the strong inhibitory effect of Cabo-NPs on cell migration and tube formation. Furthermore, the Cabo-NPs exerted superior anti-angiogenic effects with remarkable reductions in the neovascular area, which were as effective as the clinical dexamethasone but without apparent side effects. The therapeutic mechanism of the Cabo-NPs is closely related to the significant decrease in proangiogenic and proinflammatory factors, suppressing neovascularization and inflammation. Overall, cationic Cabo-NPs offer a new prospect for safe and effective CNV treatment via enhancing the bioavailability of lipophilic cabozantinib.

Regional differences in the global burden of age-related macular degeneration.

BACKGROUND: Age-related Macular Degeneration (AMD) is the leading cause of blindness. This study aims to analyze regional differences on the global burden of AMD and help direct related policy making. METHODS: Disability-adjusted life years (DALY) data were collected from the Global Burden of Disease Study (GBD) 2017 to estimate the AMD burden. Mean education years, human development index (HDI) and Public Health Expenditure were extracted from the Human Development Report 2018, and latitude data were obtained from the Google Earth. These four factors were analyzed to see their importance in regional differences of AMD burden, using Kruskal-Wallis test, Dunn's multiple comparisons test as well as regression analysis. RESULTS: Global age-standardized DALY rates have decreased since 2011. Based on the WHO region system, age-standardized DALY rates in African and Eastern Mediterranean region were significantly lower than those of other four regions. Linear regression analysis indicated that age-standardized DALY rates were inversely related to HDI and mean education years. CONCLUSIONS: The age-standardized AMD burden had a decreasing tendency recently. Lower socioeconomic status and fewer education years were associated with higher AMD burden. The finding of this study may highlight the importance of national development and education on relieving AMD burden.

Association of IGF1R polymorphisms (rs1546713) with susceptibility to age-related cataract in a Han Chinese population.

AIM: To explore the susceptible association between the insulin-like growth factor-1 receptor (IGF1R) single nucleotide polymorphism (SNP) and age-related cataract (ARC), and investigate the underlying mechanisms in human lens epithelium (HLE) cells. METHODS: Totally 1190 unrelated participants, comprising 690 ARC patients and 500 healthy individuals in Han Chinese population were recruited and genotyped for target SNP. The χ 2-test was used to detect genotypic distribution between the patient and control groups and the logistic regression was performed to adjust the age and gender. Meanwhile, different biological experimental methods, such as cell counting kit 8 (CCK-8) assay, flow cytometry, quantitative real time polymerase chain reaction (Q-PCR) and Western blot, were used to detect cell viability, cell cycle progression and apoptosis in HLE cells or IGF1R knockdown HLE cells. RESULTS: The rs1546713 in IGF1R gene was identified (P=0.046, OR: 1.606, 95%CI: 1.245-2.071), which shown a significant relevance with ARC risk under the dominant model. The results demonstrated that IGF1R knockdown inhibited cell proliferation by inducing cell cycle arrested at S phase and promoting apoptosis. Mechanistically, the cell cycle blocked at S phase was linked with the alterations of cyclin A, cyclin B, cyclin E and P21. The pro-apoptosis function of IGF1R may related with stimulating the activation of Caspase-3 and altering the expression levels of apoptotic proteins, including Bcl-2, Bax and Caspase-3. CONCLUSION: This study first report that IGF1R polymorphisms may affect susceptibility to ARCs in Han Chinese population and provide new clues to understand the pathogenic mechanism of ARCs. Notably, IGF1R is likely a potential target for ARC prevention and treatment.

The impact of GJA3 SNPs on susceptibility to age-related cataract.

AIM: To determine the association of gap junction protein alpha 3 (GJA3) gene tag single-nucleotide polymorphisms (SNPs) with susceptibility to age-related cataract (ARC). METHODS: In total, 486 ARC patients were matched with 500 healthy controls. All the participants underwent complete ophthalmic examinations. Haplotype-tagging SNPs of GJA3 gene were selected from the HapMap Beijing Han Chinese population. Genomic DNA was extracted from the peripheral blood leukocytes of all the subjects. Under three different genetic models: dominant, recessive, and additive, the association between SNPs and ARC was examined. After adjusting for age and sex, the genetic effects of the GJA3 SNPs were evaluated with logistic regression analysis. RESULTS: Four tag GJA3 SNPs (rs6490519, rs9506430, rs9509053, and rs9552089) were included in the present study. None of the SNPs showed a significant relationship with an altered risk of total ARC under the dominant, recessive, or additive models. In the subgroup analysis, rs9506430 had a significant effect on the formation of a posterior subcapsular cataract (P=0.002, OR: 0.227, 95%CI: 0.088-0.590) under the recessive model. CONCLUSION: Our study indicates that GJA3 variants may influence the development of posterior subcapsular cataracts. Further studies need to be designed to confirm this possibility.

Abnormal dynamics of functional connectivity density in children with benign epilepsy with centrotemporal spikes.

Converging evidence has shown the link between benign epilepsy with centrotemporal spikes (BECTS) and abnormal functional connectivity among distant brain regions. However, prior research in BECTS has not examined the dynamic changes in functional connectivity as networks form. We combined functional connectivity density (FCD) mapping and sliding windows correlation analyses, to fully capture the functional dynamics in patients with respect to the presence of interictal epileptic discharges (IEDs). Resting-state fMRI was performed in 43 BECTS patients and 28 healthy controls (HC). Patients were further classified into two subgroups, namely, IED (n = 20) and non-IED (n = 23) depending on the simultaneous EEG-fMRI recordings. The global dynamic FCD (dFCD) was measured using sliding window correlation. Then we quantified dFCD variability using their standard deviation. Compared with HC, patients with and without IEDs both showed invariable dFCD (decreased) among the orbital fontal cortex, anterior cingulate cortex and striatum, as well as variable dFCD (increased) in the posterior default mode network (P < 0.05, AlphaSim corrected). Correlation analysis indicated that the variable dFCD in precuneus was related to seizure onset age (P < 0.05, uncorrected). BECTS with IEDs showed variable dFCD in regions related to the typical seizure semiology. The abnormal patterns of fluctuating FCD in BECTS suggest that both active and chronic epileptic state may contribute to altered dynamics of functional connectivity associated with cognitive disturbances and developmental alterations. These findings highlight the importance of considering fluctuating dynamic neural communication among brain systems to deepen our understanding of epilepsy diseases.

The impact of GJA8 SNPs on susceptibility to age-related cataract.

The gap junction protein alpha 8 (GJA8) gene has been widely studied in human congenital cataracts. However, little is known about its relationship with age-related cataract (ARC). In this study, three GJA8-tagged single nucleotide polymorphisms related to an increased ARC risk were identified: rs2132397 for general ARC under both dominant and additive models; rs7541950 for general ARC under both recessive and additive models; and rs6657114 for cortical cataract under the recessive model. To uncover the underlying mechanisms, this study also sought to explore whether GJA8 is involved in the autophagy process in human lens epithelial cells. The results showed that GJA8 may participate in autophagy to maintain the intracellular environment, which may be a novel mechanism for cataract formation induced by GJA8. In conclusion, this study identified the genetic susceptibility of GJA8 polymorphisms on ARC and provides new clues for fully understanding the pathological mechanism of GJA8 variants in affecting lens opacity.

Intronic pentanucleotide TTTCA repeat insertion in the SAMD12 gene causes familial cortical myoclonic tremor with epilepsy type 1.

Familial cortical myoclonic tremor with epilepsy is an autosomal dominant neurodegenerative disease, characterized by cortical tremor and epileptic seizures. Although four subtypes (types 1-4) mapped on different chromosomes (8q24, 2p11.1-q12.2, 5p15.31-p15.1 and 3q26.32-3q28) have been reported, the causative gene has not yet been identified. Here, we report the genetic study in a cohort of 20 Chinese pedigrees with familial cortical myoclonic tremor with epilepsy. Linkage and haplotype analysis in 11 pedigrees revealed maximum two-point logarithm of the odds (LOD) scores from 1.64 to 3.77 (LOD scores in five pedigrees were >3.0) in chromosomal region 8q24 and narrowed the candidate region to an interval of 4.9 Mb. Using whole-genome sequencing, long-range polymerase chain reaction and repeat-primed polymerase chain reaction, we identified an intronic pentanucleotide (TTTCA)n insertion in the SAMD12 gene as the cause, which co-segregated with the disease among the 11 pedigrees mapped on 8q24 and additional seven unmapped pedigrees. Only two pedigrees did not contain the (TTTCA)n insertion. Repeat-primed polymerase chain reaction revealed that the sizes of (TTTCA)n insertion in all affected members were larger than 105 repeats. The same pentanucleotide insertion (ATTTCATTTC)58 has been reported to form RNA foci resulting in neurotoxicity in spinocerebellar ataxia type 37, which suggests the similar pathogenic process in familial cortical myoclonic tremor with epilepsy type 1.

Hydrogen peroxide-induced apoptosis of human lens epithelial cells is inhibited by parthenolide.

AIM: To explore the effect of parthenolide on hydrogen peroxide (H2O2)-induced apoptosis in human lens epithelial (HLE) cells. METHODS: The morphology and number of apoptotic HLE cells were assessed using light microscopy and flow cytometry. Cell viability was tested by MTS assay. In addition, the expression of related proteins was measured by Western blot assay. RESULTS: Apoptosis of HLE cells was induced by 200 µmol/L H2O2, and the viability of these cells was similar to the half maximal inhibitory concentration (IC50), as examined by MTS assay. In addition, cells were treated with either different concentrations (6.25, 12.5, 25 and 50 µmol/L) of parthenolide along with 200 µmol/L H2O2 or only 50 µmol/L parthenolide or 200 µmol/L H2O2 for 24h. Following treatment with higher concentrations of parthenolide (50 µmol/L), fewer HLE cells underwent H2O2-induced apoptosis, and cell viability was increased. Further, Western blot assay showed that the parthenolide treatment reduced the expression of caspase-3 and caspase-9, which are considered core apoptotic proteins, and decreased the levels of phosphorylated nuclear factor-κB (NF-κB), ERK1/2 [a member of the mitogen-activated protein kinase (MAPK) family], and Akt proteins in HLE cells. CONCLUSION: Parthenolide may suppress H2O2-induced apoptosis in HLE cells by interfering with NF-κB, MAPKs, and Akt signaling.

Differential patterns of dynamic functional connectivity variability of striato-cortical circuitry in children with benign epilepsy with centrotemporal spikes.

Benign epilepsy with centrotemporal spikes (BECTS) is characterized by abnormal (static) functional interactions among cortical and subcortical regions, regardless of the active or chronic epileptic state. However, human brain connectivity is dynamic and associated with ongoing rhythmic activity. The dynamic functional connectivity (dFC) of the distinct striato-cortical circuitry associated with or without interictal epileptiform discharges (IEDs) are poorly understood in BECTS. Herein, we captured the pattern of dFC using sliding window correlation of putamen subregions in the BECTS (without IEDs, n = 23; with IEDs, n = 20) and sex- and age-matched healthy controls (HCs, n = 28) during rest. Furthermore, we quantified dFC variability using their standard deviation. Compared with HCs and patients without IEDs, patients with IEDs exhibited excessive variability in the dorsal striatal-sensorimotor circuitry related to typical seizure semiology. By contrast, excessive stability (decreased dFC variability) was found in the ventral striatal-cognitive circuitry (p < .05, GRF corrected). In addition, correlation analysis revealed that the excessive variability in the dorsal striatal-sensorimotor circuitry was related to highly frequent IEDs (p < .05, uncorrected). Our finding of excessive variability in the dorsal striatal-sensorimotor circuitry could be an indication of increased sensitivity to regional fluctuations in the epileptogenic zone, while excessive stability in the ventral striatal-cognitive circuitry could represent compensatory mechanisms that prevent or postpone cognitive impairments in BECTS. Overall, the differentiated dynamics of the striato-cortical circuitry extend our understanding of interactions among epileptic activity, striato-cortical functional architecture, and neurocognitive processes in BECTS.

Effects of ABCB1, ABCC2, UGT2B7 and HNF4α genetic polymorphisms on oxcarbazepine concentrations and therapeutic efficacy in patients with epilepsy.

PURPOSE: The aim of the study is to investigate the effects of ABCB1, ABCC2, UGT2B7 and HNF4α genetic polymorphisms on plasma oxcarbazepine (OXC) concentrations and therapeutic efficacy in Han Chinese patients with epilepsy. METHODS: We recruited 116 Han Chinese patients with epilepsy who were receiving OXC monotherapy. Blood samples were taken and OXC levels were measured. The polymorphisms of ABCB1 rs1045642, ABCC2 rs2273697, UGT2B7 rs7439366, and HNF4α rs2071197 were determined. The therapeutic efficacy of OXC at the 1-year time-point was assessed. Data analysis was performed using IBM SPSS Statistics 22.0. RESULTS: The genetic polymorphism of ABCB1 rs1045642 was found to be associated with normalized OXC concentration and therapeutic efficacy in patients with epilepsy (P<0.05). As for UGT2B7 rs7439366, the allele polymorphism exhibited a correlation with treatment outcome, but not OXC concentration. The polymorphisms of ABCC2 rs2273697 and HNF4α rs2071197 was not associated with OXC concentrations and therapeutic efficacy. CONCLUSION: These results suggested that ABCB1 rs1045642 and UGT2B7 rs7439366 may affect OXC pharmacokinetics and therapeutic efficacy in Han Chinese patients with epilepsy. However, further studies in larger populations and other ethnic groups are required.

Clinical value and predictors of subclinical seizures in patients with temporal lobe epilepsy undergoing scalp video-EEG monitoring.

The aim of this study was to determine the clinical importance and predictors of SCSs in a large population of patients with temporal epilepsy (TLE) undergoing video electroencephalographic (VEEG) monitoring. We reviewed the VEEG data of 327 consecutive patients with TLE admitted to our epilepsy center between August 2012 and January 2017. Demographic, electro-clinical, and neuroimaging data were recorded and re-analyzed. To our knowledge, this is the first study assessing SCSs recorded by long-term VEEG monitoring in patients with TLE. Twenty-seven of 327 (8.3%) patients exhibited SCSs during VEEG monitoring. Of these patients, 24 had both SCSs and clinical seizures. The mean duration of the SCSs was 23.18s (range: 5-1307s). Of the 27 patients with SCSs, 24 (88.9%) showed localizing value during the diagnostic process. Seventeen patients exhibited colocalization with clinical seizures, 4 showed useless localization related to clinical seizures, and 3 did not have clinical seizures. Sixteen patients (59.3%) experienced their first SCSs within the first 24h of monitoring and one had the first SCSs within 20min. Multivariate logistic regression analysis showed that age <18years at VEEG monitoring (OR=3.272, 95% CI=1.283-8.343, p=0.013) and bilateral IEDs (OR=4.558, 95% CI=1.982-10.477, p<0.001) were independently associated with the presence of SCSs. Thus, SCSs are not uncommon in patients with TLE, particularly those with age <18years or bilateral IEDs, and should be considered of significant clinical relevance during the diagnostic process.

Epileptic Discharge Related Functional Connectivity Within and Between Networks in Benign Epilepsy with Centrotemporal Spikes.

Benign epilepsy with centrotemporal spikes (BECTS) is a common childhood epilepsy syndrome associated with abnormalities in neurocognitive domains, particularly during interictal epileptiform discharges (IEDs). Here, we investigated the effects of IEDs on brain's intrinsic connectivity networks in 43 BECTS patients and 28 matched healthy controls (HCs). Patients were further divided into IED and non-IED subgroups based on simultaneous EEG-fMRI recordings. Functional connectivity within and between five networks, corresponding to seizure origination and cognitive processes, were analyzed to measure IED effects. We found that patients exhibited increased connectivity within the auditory network (AN) and the somato-motor network (SMN), and decreased connectivity within the basal ganglia network and the dorsal attention network, suggesting that both transient and chronic seizure activity may disturb normal network organization. The IED group showed decreased functional connectivity within the default mode network (DMN) compared with the non-IED group and HCs, implying that the DMN was selectively impaired during epileptiform discharges associated with altered self-referential cognitive functions. Moreover, the IED group exhibited increased positive correlations between the AN and the SMN, which suggests a possible excessive influence of centrotemporal spiking on information processing in the auditory system. The association between epileptic activity and network dysfunctions highlights their importance in investigating the pathological mechanism underlying BECTS.

BRAF V600E mutation in epilepsy-associated glioneuronal tumors: Prevalence and correlation with clinical features in a Chinese population.

PURPOSE: Glioneuronal tumors (GNTs) are the most common histological type of brain tumors in patients who received epilepsy surgery, and part of them presented with BRAF V600E mutation. We aimed to verify the presence of the BRAF V600E mutation in epilepsy-associated GNTs from Chinese population and evaluate the association with clinical features. METHODS: Data from 35 patients diagnosed with GNTs, including 24 gangliogliomas and 11 dysembryoplastic neuroepithelial tumors, were retrospectively collected. DNA was extracted from GNTs tissues and BRAF V600E mutation was examined by DNA sequencing. The correlations between BRAF V600E mutation and clinical features were analyzed. RESULTS: Totally, BRAF V600E mutations were detected in 11 patients with GNTs, the rate of mutation were 33.3% and 27.3% in GGs (8/24) and DNTs (3/11), respectively. The probability of BRAF V600E mutation in females (7/12, 58.3%) was significantly higher than that in males (4/23, 17.4%) (P=0.022). Moreover, patients with BRAF-mutated GNTs had a significantly wider variety of seizure types compared to GNTs with BRAF wild-type status (P=0.027). However, no significant correlation between the BRAF status and certain clinical features, such as age of seizure onset, duration of epilepsy, age at surgery, location of the tumor and postoperative seizure free, were observed. CONCLUSION: We demonstrated the presence of BRAF V600E mutation in Chinese epileptic patients with GNTs, which was significantly correlated with gender and multiple seizure types. Large sample studies and long-term follow-up are required for further confirmation.

Decreased Network Efficiency in Benign Epilepsy with Centrotemporal Spikes.

Purpose To investigate the functional connectome alterations in benign epilepsy with centrotemporal spikes with respect to the occurrence of interictal epileptic discharges (IEDs) during functional magnetic resonance (MR) imaging. Materials and Methods This prospective study was approved by the local institutional review board and was HIPAA compliant. All participants were consecutively enrolled with written informed consent. Forty-three right-handed patients were classified into IED (n = 20, 13 girls and seven boys; mean age ± standard deviation, 9.00 years ± 1.95) and non-IED (n = 23, 11 girls and 12 boys; mean age, 10.22 years ± 2.13) groups on the basis of electroencephalographic data simultaneously recorded during resting-state functional MR imaging at 3.0 T. The functional connectome features (estimated with graph theoretical analysis) in patient groups and control subjects who were matched for sex, age, and education level (n = 28, all right-handed, 13 girls and 15 boys; mean age, 10.00 years ± 2.31) were compared by using one-way analysis of variance. Results Patients with IEDs and those without IEDs showed consistently abnormal global topology in their functional networks (ie, decreased global efficiency; P < .05) relative to that of control subjects, with no differences between the two patient groups (P > .05). Decreased regional efficiency and connectivity strength were observed in the patients with IEDs and those without (mainly in the perirolandic and frontal areas) relative to control subjects (P < .05). Moreover, the altered functional features significantly correlated with clinical characteristics (ie, disease duration and age at symptom onset, P < .05). Conclusion These findings suggest that decreased global and regional efficiency are prominent functional deficits in children with benign epilepsy with centrotemporal spikes and can be readily identified with resting-state functional MR imaging, irrespective of IEDs. © RSNA, 2016 Online supplemental material is available for this article.

Specific OCT1 and ABCG2 polymorphisms are associated with Lamotrigine concentrations in Chinese patients with epilepsy.

PURPOSE: The pharmacokinetics of Lamotrigine (LTG) varies widely among patients with epilepsy. In this study, we are aiming to investigate the effects of OCT1, ABCG2, ABCC2 and HNF4α genetic polymorphisms on plasma LTG concentrations and therapeutic efficacy in Chinese patients with epilepsy. METHODS: The study cohort comprised 112 Han Chinese patients with epilepsy who were receiving LTG monotherapy. Blood samples were taken and LTG levels were measured. The polymorphisms of OCT1 rs2282143, rs628031, ABCG2 rs2231142, rs2231137, ABCC2 rs2273697 and HNF4α rs2071197, rs3212183 were determined. The therapeutic efficacy of LTG at the 1-year time-point was assessed. Data analysis was performed using IBM SPSS Statistics 22.0. RESULTS: There were significant associations between OCT1 rs628031, ABCG2 rs2231142 polymorphisms and normalized LTG concentrations in patients with epilepsy (P<0.05). On the other hand, polymorphisms of OCT1 rs2282143, ABCG2 rs2231137, ABCC2 rs2273697 and HNF4α rs2071197, rs3212183 exhibited no correlation with LTG concentrations. Additionally, no significant association existed between all the studied genotypes and LTG treatment response. CONCLUSIONS: These results suggested that the polymorphisms of OCT1 rs628031 and ABCG2 rs2231142 may affect LTG metabolism in Chinese patients with epilepsy. However, future studies are necessary to be investigated in a larger cohort of epileptic patients.

Metabolic syndrome risk factors and dry eye syndrome: a Meta-analysis.

AIM: To explore the relationship between metabolic risk factors and dry eye syndrome (DES). METHODS: Retrieved studies on the association of metabolic syndrome risk factors (hypertension, hyperglycemia, obesity, and hyperlipidemia) and DES were collected from PubMed, Web of Science, and the Cochrane Library in December 2015. Odds ratio (OR) with 95% confidence interval (CI) were pooled to evaluate the final relationship. Subgroup analyses were conducted according to diagnostic criteria of DES. RESULTS: Nine cross-sectional studies and three case-control studies were included in this Meta-analysis. The pooled results showed that people with hypertension, hyperglycemia, and hyperlipidemia had a higher risk of suffering from DES (P<0.05), especially the typical DES symptoms. On the other hand, obesity did not increase the risk of DES. CONCLUSION: The present Meta-analysis suggests that all metabolic risk factors except obesity were risk factors for DES.