SUMMARYPurpose: Schizophrenia and epilepsy may share a mutual susceptibility. This study examined the bidirectional relation between the two disorders. Methods: We used claims data obtained from the Taiwan National Health Insurance database to conduct retrospective cohort analyses. Analysis 1 compared 5,195 patients with incident schizophrenia diagnosed in 1999-2008 with 20,776 controls without the disease randomly selected during the same period, frequency matched with sex and age. Analysis 2 comprised a similar method to compare 11,527 patients with newly diagnosed epilepsy with 46,032 randomly selected sex-and age-matched controls. At the end of 2008, analysis 1 measured the incidence and risk of developing epilepsy and analysis 2 measured the incidence and risk of developing schizophrenia. Key Findings: In analysis 1, the incidence of epilepsy was higher in the schizophrenia cohort than in the nonschizophrenia cohort (6.99 vs. 1.19 per 1,000 person-years) with an adjusted hazard ratio (aHR) of 5.88 [95% confidence interval (CI) 4.71-7.36] for schizophrenia patients. In analysis 2, the incidence of schizophrenia was higher in the epilepsy cohort than in the nonepilepsy comparison cohort (3.53 vs. 0.46 per 1,000 person-years) with an aHR of 7.65 (95% CI 6.04-9.69) for epilepsy patients. The effect of schizophrenia on subsequent epilepsy was greater for women, but the association between epilepsy and elevated incidence of schizophrenia was more pronounced in men. Significance: We found a strong bidirectional relation between schizophrenia and epilepsy. These two conditions may share common causes. Further studies on the mechanism are required.

Background High levels circulating saturated fatty acids are associated with diabetes, obesity and hyperlipidemia. In heart, the accumulation of saturated fatty acids has been determined to play a role in the development of heart failure and diabetic cardiomyopathy. High-density lipoprotein (HDL) has been reported to possess key atheroprotective biological properties, including cellular cholesterol efflux capacity, anti-oxidative and anti-inflammatory activities. However, the underlying mechanisms are still largely unknown. Therefore, the aim of the present study is to test whether HDL could protect palmitic acid (PA)-induced cardiomyocyte injury and explore the possible mechanisms. Results H9c2 cells were pretreated with HDL (50–100 μg/ml) for 2 h followed by PA (0.5 mM) for indicated time period. Our results showed that HDL inhibited PA-induced cell death in a dose-dependent manner. Moreover, HDL rescued PA-induced ROS generation and the phosphorylation of JNK which in turn activated NF-κB-mediated inflammatory proteins expressions. We also found that PA impaired the balance of BCL 2 family proteins, destabilized mitochondrial membrane potential, and triggered subsequent cytochrome c release into the cytosol and activation of caspase 3. These detrimental effects were ameliorated by HDL treatment. Conclusion PA-induced ROS accumulation and results in cardiomyocyte apoptosis and inflammation. However, HDL attenuated PA-induced lipotoxicity and oxidative dysfunction via ROS suppression. These results may provide insight into a possible molecular mechanism underlying HDL suppression of the free fatty acid-induced cardiomyocyte apoptosis.

The FUT2 genes encoding for the phenotypes Le(a+b+) and Le(a+b-) are the same. The function and character of the mutant enzyme may play an important role in the phenotype. The methods used in this study are clinically applicable in population studies of the FUT2 gene polymorphism to explore relationships among different ethnic groups and correlations between phenotype and genotype.

BackgroundIdiopathic membranous nephropathy (IMN) is one of the most common forms of autoimmune nephritic syndrome in adults. The purpose of this study is to evaluate whether polymorphisms of PLA2R1 affect the development of IMN.MethodsTaiwanese-Chinese individuals (129 patients with IMN and 106 healthy controls) were enrolled in this study. The selected single nucleotide polymorphisms (SNPs) in PLA2R1 were genotyped by real-time polymerase chain reaction using TaqMan fluorescent probes, and were further confirmed by polymerase chain reaction-restriction fragment length polymorphism. The roles of the SNPs in disease progression were analyzed.ResultsGenotype distribution was significantly different between patients with IMN and controls for PLA2R1 SNP rs35771982 (p = 0.015). The frequency of G allele at rs35771982 was significantly higher in patients with IMN as compared with controls (p = 0.005). In addition, haplotypes of PLA2R1 may be used to predict the risk of IMN (p = 0.004). Haplotype H1 plays a role in an increased risk of IMN while haplotype H3 plays a protective role against this disease. None of these polymorphisms showed a significant and independent influence on the progression of IMN and the risk of end-stage renal failure and death (ESRF/death). High disease progression in patients having C/T genotype at rs6757188 and C/G genotype at rs35771982 were associated with a low rate of remission.ConclusionsOur results provide new evidence that genetic polymorphisms of PLA2R1 may be the underlying cause of IMN, and the polymorphisms revealed by this study warrant further investigation.

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Aim-To compare the eYcacy and safety of an indomethacin treatment strategy based on serial echocardiographic measurement of patent ductus arteriosus (PDA) flow pattern with a standard protocol. Methods-Neonates weighing less than 1500 g at birth, who required respiratory support, and who had developed symptomatic PDA, were studied. PDA was confirmed in all infants using colour Doppler echocardiography, and serial observations of the ductal flow pattern were made. Infants randomly assigned to receive conventional indomethacin treatment (protocol group) were given an initial dose of 0.2 mg/kg, followed by 0.1 or 0.2 mg/kg, depending on age, 12 hourly for two further doses, and were eligible for a second course. Those randomly assigned to the ductal flow pattern assessment (ECHO group) received further doses of indomethacin after 24 hours, only if their flow pattern was "pulsatile" or "growing." Results-There was no significant diVerence in the primary outcome measures between the two groups. The closure rate was 89.1% and 87.2%, respectively, in the protocol and ECHO groups. The mean (SD) doses of indomethacin were significantly higher in the protocol group: 3.2 (1.4) doses compared with 1.6 (0.9) doses. There was a significantly higher incidence of hypoglycaemia, impaired urine output, and gastrointestinal bleeding in the protocol group. Conclusions-An indomethacin treatment strategy for PDA based on measurement of the ductal flow pattern is associated with a reduction in the total doses of indomethacin administered, and a reduced rate of complications, compared with a conventional protocol. There is no diVerence in closure rate.

The recruitment of bone marrow-derived endothelial progenitor cells (EPCs) facilitates physiological and pathological processes involved in new blood vessel synthesis. Glucocerebroside, an extract of Cordyceps militaris, inhibits inflammatory cytokine production and monocyte migration, although its anti-angiogenic properties in human EPCs has remained largely unknown up until now. We describe how glucocerebroside reduces migration as well as tube formation induced by vascular endothelial growth factor (VEGF) stimulation in human EPCs, without affecting cell viability. This inhibitory effect was achieved through the focal adhesion kinase (FAK)/c-Src pathways. We also found that glucocerebroside reduced VEGFpromoted upregulation of the transcription factor Runx2 in the EPCs. The in vivo chick embryo chorioallantoic membrane model demonstrated that glucocerebroside reduces new vessel formation. Our investigation is the first to show that glucocerebroside reduces angiogenesis in human EPCs and to describe the underlying mechanisms. Further investigations are needed to examine the effects of glucocerebroside in other angiogenesis-related disorders. ARTICLE HISTORY

BackgroundThis study presents an evaluation of the bidirectional correlation between attention deficit hyperactivity disorder (ADHD) and epilepsy using 2 cohorts from the same population database.MethodsWe used data from the Taiwan National Health Insurance Research Database to establish 2 separate cohort studies with participants <19 years old. We subdivided Cohort 1 in 2 groups: (1) 2468 patients initially diagnosed with epilepsy during the period 1999–2008, and (2) 9810 randomly selected sex- and age-matched non-epileptic controls. We subdivided Cohort 2 into 2 groups: (1) 3664 patients with newly diagnosed ADHD and (2) 14 522 sex- and age-matched non-ADHD patients. We evaluated the risk of subsequent ADHD in relationship to epilepsy and vice versa in the 2 cohorts at the end of 2008.ResultsThe ADHD incidence in Cohort 1 was 7.76 in patients with epilepsy and 3.22 in those without epilepsy (per 1000 person-years) after a median follow-up of 7–7.5 years. The adjusted hazard ratio (HR) for ADHD was 2.54 (95% CI 2.02–3.18) in the epilepsy group compared to the non-epilepsy group. In Cohort 2, the incidence of epilepsy was 3.24 in patients with ADHD and 0.78 in those without ADHD (per 1000 person-years) after a median follow-up of 3–3.5 years and an HR of 3.94 (95% CI 2.58–6.03).ConclusionThis study shows a bidirectional association between ADHD and epilepsy in the 2 cohort studies. Causative factors may be common between these 2 disorders, leading to a cascade of transcriptional changes in the brain that alter behavior or cognition prior to seizures.