Neuronal modeling of alternating hemiplegia of childhood reveals transcriptional compensation and replicates a trigger-induced phenotype.

Alternating hemiplegia of childhood (AHC) is a rare neurodevelopmental disease caused by heterozygous de novo missense mutations in the ATP1A3 gene that encodes the neuronal specific α3 subunit of the Na,K-ATPase (NKA) pump. Mechanisms underlying patient episodes including environmental triggers remain poorly understood, and there are no empirically proven treatments for AHC. In this study, we generated patient-specific induced pluripotent stem cells (iPSCs) and isogenic controls for the E815K ATP1A3 mutation that causes the most phenotypically severe form of AHC. Using an in vitro iPSC-derived cortical neuron disease model, we found elevated levels of ATP1A3 mRNA in AHC lines compared to controls, without significant perturbations in protein expression. Microelectrode array analyses demonstrated that in cortical neuronal cultures, ATP1A3+/E815K iPSC-derived neurons displayed less overall activity than neurons differentiated from isogenic mutation-corrected and unrelated control cell lines. However, induction of cellular stress by elevated temperature revealed a hyperactivity phenotype following heat stress in ATP1A3+/E815K neurons compared to control lines. Treatment with flunarizine, a drug commonly used to prevent AHC episodes, did not impact this stress-triggered phenotype. These findings support the use of iPSC-derived neuronal cultures for studying complex neurodevelopmental conditions such as AHC and provide a platform for mechanistic discovery in a human disease model.

Existence of glioma stroma mesenchymal stemlike cells in Korean glioma specimens.

PURPOSE: It was presented that mesenchymal stem cells (MSCs) can be isolated from western glioma specimens. However, whether MSCs exist in glioma specimens of different ethnicities is unknown. To verify the existence of MSCs in an independent cohort, we undertook studies to isolate MSCs from a group of Korean patients. We hypothesized that cells resembling MSCs that were deemed mesenchymal stemlike cells (MSLCs) exist in an independent cohort of Korean gliomas. METHODS: We cultured fresh glioma specimens using the protocols used for culturing MSCs. The cultured cells were analyzed with fluorescence-activated cell sorting (FACS) for surface markers associated with MSCs. Cultured cells were exposed to mesenchymal differentiation conditions. To presume possible locations of MSLCs in the glioma, sections of glioma were analyzed by immunofluorescent labeling for CD105, CD31, and NG2. RESULTS: From nine of 31 glioma specimens, we isolated cells resembling MSCs, which were deemed Korean glioma stroma MSLCs (KGS-MSLCs). KGS-MSLCs were spindle shaped and adherent to plastic. KGS-MSLCs had similar surface markers to MSCs (CD105(+), CD90(+), CD73(+), and CD45(-)). KGS-MSLCs were capable of mesenchymal differentiation and might be located around endothelial cells, pericytes, and in a disorganized perivascular area inside glioma stroma. CONCLUSIONS: We found that cells resembling MSCs indeed exist in an independent cohort of glioma patients, as presented in western populations. We could presume that the possible location of KGS-MSLCs was in perivascular area or in glioma stroma that was a disorganized vascular niche. It might be possible that KGS-MSLCs could be one of constituent of stroma of glioma microenvironment.

α-Glucosidase inhibiton and antiglycation activity of laccase-catalyzed catechin polymers.

Catechin polymers were produced by laccase (12 U/mL) in a mixture of sodium acetate buffer (1% (+)-catechin, 100 mM, pH 5) and methanol (buffer:methanol = 95:5, v/v). The freeze-dried catechin polymers were recovered from the precipitate after dialysis followed by centrifugation. Catechin polymers extracted with 20% ethanol had potent inhibitory activity against α-glucosidase with an IC50 value of 4 µg/mL, and they were present as a mixture of dimers, trimers, and tetramers. The antihyperglycemic effect of the catechin polymers was confirmed by an oral maltose tolerance test. The catechin polymers also had significantly improved antiglycation and superoxide dismutase-like activities compared to those of (+)-catechin. Since formation of advanced glycation end products and oxidative stress are accelerated in hyperglycemic conditions, we suggest that enzymatic production of catechin polymers could have a potential protective effect in type 2 diabetes, diabetic complications, and other free radical related diseases.

Factors affecting diabetic screening behavior of Korean adults: a multilevel analysis.

PURPOSE: We investigated the role of individual and community level factors on diabetes screening test behavior. METHODS: We used individual-level data from 170,193 adults aged 30 years or older who were not diagnosed with diabetes and participated in the 2009 community health survey. Community-level data includes 253 communities and were collected from various national statistics. Multilevel logistic regression analysis was conducted. RESULTS: The rate of diabetes screening within the year prior to this study was 53.2%. Community variance of Model I, Model II and Model III was 0.236, 0.252 and 0.238, respectively. The proportional change in variance of Model II and Model III was -6.8% and -1.2%. The odds ratio for participation of diabetic screening of areas with bottom financial independence compared to areas with top was 0.84 (95% confidence interval, 0.74-0.96); the odds ratio of areas with top internist compared to areas with bottom was 1.15 (95% confidence interval, 1.01-1.31). CONCLUSION: This study identified a contextual effect influencing the participation of Korean adults in diabetes screening. It is necessary to develop specific policies that consider not only individual factors, but also community factors relating to individual behaviors to increase the likelihood of diabetes screening.

[The knowledge, attitude and practice of blood pressure management from the patient's viewpoint: a qualitative study].

OBJECTIVES: This study adopted a qualitative method to explore the layman's beliefs and experience concerning high blood pressure and its management in order to develop a strategy to increase adherence to proper medical treatment. METHODS: Semi-structured interviews that focused on personal experiences with hypertension and its management were conducted with 26 hypertensive patients. The participants were selected according to a BP above 140/90 mmHg (hypertension stage 1), based on the seventh report of the Joint National Committee on prevention, detection, evaluation and treatment of high blood pressure (JNC-VII). The interviews lasted for approximately 30 minutes (range: 20-60 minutes). The resulting questions were formulated into open-ended questions. The interview questionnaire was composed 17 items to examine non-adherence to treatment and 19 items to examine adherence to treatment. RESULTS: Most participants recognized that the direct cause of high blood pressure was unhealthy behavior rather than inheritance. Thus, the hypertensive patient believed they could recover their blood pressure to a normal level through removing the direct cause of hypertension (weight reduction, diet, exercise) instead of taking drugs. The reasons for these statements were that the drugs for controlling hypertension are not natural or they are artificial, and they may have side effects, and drugs are not treatment for the root cause of hypertension. Most of the hypertensive patients chose to manage their behaviors as soon as they knew their blood pressure was high. Therefore, we should not divide the subjects into two groups according to their taking drugs or not, but they should be divided into two groups according to their willingness or not to manage their condition. CONCLUSIONS: For developing a strategy for an individual approach to hypertension management, we need to develop a client-centered attitude and strategy. That is, we need to tailor our approach to individual cases to avoid generalizations and stereotyping when developing an adherence increasing strategy.

[The relations of socioeconomic status to health status, health behaviors in the elderly].

OBJECTIVES: To analyze the relationships of socioeconomic status(SES) to health status and health behaviors in the elderly. METHODS: Data were obtained from self-administered questionnaire of 4,587 persons, older than 65 years, living in a community. We measured the sociodemographic characteristics, socioeconomic status, health status (subjective health status, acute disease, admission experience, dental state, chronic disease etc.), activities of daily living (ADL), instrumental activities of daily living (IADL), and mini-mental state examination-Korean (MMSE-K). Binary and multinominal logistic regression analyses were employed to analyze factors affecting on the socioeconomic status of the elderly. RESULTS: With regard to the SES and health status, those with a low SES had poorer subjective health states and lower satisfaction about their physical health. Also, acute disease experiences, admission rates and tooth deciduation rates were higher in those of low SES. In the view of physical and cognitive functions, the ADL, IADL and MMSE-K scores were also lower in those of low SES. However, with regard to health behaviors, lower smoking and alcohol drinking rates were found in the low SES group, and a similar trend was shown with regular physical exercise, eating breakfast, and regular physical health check-up. From these findings, we surmise that those with low SES have a poorer health condition and less money to spend on health, therefore, they can not smoke or drink alcohol, exercise and or have a physical health check-up. CONCLUSION: This study suggests that socioeconomic status plays an important role in health behaviors and status of the elderly. Low socioeconomic status bring about unhealthy behavior and poor health status in the elderly. Therefore, more specific target oriented(esp. low SES persons) health promotion activities for the elderly are very important to improve not only their health status, but their health inequity also.