Distinctive genomic signature of neural and intestinal organoids from familial Parkinson's disease patient-derived induced pluripotent stem cells.

AIMS: The leucine-rich repeat kinase 2 (LRRK2) G2019S mutation is the most common genetic cause of Parkinson's disease (PD). There is compelling evidence that PD is not only a brain disease but also a gastrointestinal disorder; nonetheless, its pathogenesis remains unclear. We aimed to develop human neural and intestinal tissue models of PD patients harbouring an LRRK2 mutation to understand the link between LRRK2 and PD pathology by investigating the gene expression signature. METHODS: We generated PD patient-specific induced pluripotent stem cells (iPSCs) carrying an LRRK2 G2019S mutation (LK2GS) and then differentiated into three-dimensional (3D) human neuroectodermal spheres (hNESs) and human intestinal organoids (hIOs). To unravel the gene and signalling networks associated with LK2GS, we analysed differentially expressed genes in the microarray data by functional clustering, gene ontology (GO) and pathway analyses. RESULTS: The expression profiles of LK2GS were distinct from those of wild-type controls in hNESs and hIOs. The most represented GO biological process in hNESs and hIOs was synaptic transmission, specifically synaptic vesicle trafficking, some defects of which are known to be related to PD. The results were further validated in four independent PD-specific hNESs and hIOs by microarray and qRT-PCR analysis. CONCLUSION: We provide the first evidence that LK2GS also causes significant changes in gene expression in the intestinal cells. These hNES and hIO models from the same genetic background of PD patients could be invaluable resources for understanding PD pathophysiology and for advancing the complexity of in vitro models with 3D expandable organoids.

Development and validation of reverberation-chamber type whole-body exposure system for mobile-phone frequency.

We developed whole-body exposure systems for in-vivo study at cellular (848.5 MHz) and Personal Communication System (PCS, 1,762.5 MHz) frequency, utilizing reverberation chamber. The field uniformities in the test area of the designed chambers were verified by simulation and measurement. In the whole-body exposure environment, Specific Absorption Rate (SAR) distributions inside of mice were calculated using Finite Difference Time Domain (FDTD) simulation. Key results are presented in this article.

Increased macrosomia and perinatal morbidity independent of maternal obesity and advanced age in Korean women with GDM.

OBJECTIVE: To examine the impact of gestational diabetes mellitus(GDM) on perinatal outcome in a setting where influences of maternal age and obesity would be minimal. RESEARCH DESIGN AND METHODS: A case-control study was done to compare the outcome of pregnancy in 65 women with GDM and 153 women with normal carbohydrate metabolism matched for age, height, and prepregnancy weight. RESULTS: The frequencies of preeclampsia and primary cesarean sections were higher and delivery was earlier in pregnancies complicated by GDM. Birth weight, symmetry index, and chest circumference were greater, and macrosomia and need for phototherapy were more common in offspring of mothers with GDM. Cord-serum C-peptide and insulin concentrations were higher in the infants of mothers with GDM and were strongly correlated with birth weight and symmetry index. However, maternal age, prepregnancy weight, and prepregnancy BMI were not correlated with birth weight. Postprandial glucose levels during the first 2 weeks after diagnosis of GDM had associations with the infants' birth weight, symmetry index, and cord insulin concentration in the diet-treated patients with GDM. CONCLUSIONS: Antepartum maternal glucose metabolism was significantly associated with fetal hyperinsulinemia and excessive fetal growth in relatively nonobese Korean women. These findings support a direct role for metabolic factors in the adverse outcomes in pregnancies complicated by GDM.

Screening for gestational diabetes mellitus in Korea.

OBJECTIVES: To examine the effect of clinical characteristics on the prevalence of gestational diabetes mellitus (GDM) and to find the most effective screening program for GDM in Korea. METHODS: Universal screening with a 50-g glucose load at 24-28 weeks' gestation, as recommended by the Third International Workshop-Conference on Gestational Diabetes Mellitus, was carried out among 3581 consecutive Korean women. Women with a 1-h plasma glucose > or = 130 mg/dl underwent a 3-h 100-g oral glucose tolerance test. The women's clinical characteristics and risk factors for GDM were recorded at the time of the screening test. RESULTS: The overall prevalence of GDM in Korean women was 2.2 cases/100. Although only 1.3% of this population was obese, the prevalence of GDM was found to be significantly increased with increasing body mass index. When 135 mg/dl is used as a threshold, the number of women requiring a diagnostic test decreases to 19.5%, enabling identification of 98.8% of women with GDM. CONCLUSION: Universal screening using 135 mg/dl as a threshold and early screening of those with two or more risk factors represent the most effective paradigm for Korea.