Development and application of rTMS device to murine model.

Repetitive transcranial magnetic stimulation (rTMS) is attracting attention as a new treatment technique for brain lesions, and many animal studies showing its effects have been reported. However, the findings of animal application researches cannot directly represent the effects of rTMS in human, mainly due to size difference and mechanistic characteristics of rTMS. Therefore, the authors purposed to develop a mouse rTMS to simulate clinical application and to confirm. Firstly, a virtual head model was created according to magnetic resonance images of murine head. Then, simulations of rTMS stimulation with different coils were performed on the murine head phantom, and an rTMS device for mice was fabricated based on the optimal voltage conditions. Lastly, strengths of magnetic fields generated by the two rTMS devices, for human (conventional clinical use) and mouse (newly fabricated), were measured in air and on mouse head and compared. Resultantly, the magnetic field intensity generated by coil of mouse was lower than human's (p < 0.01), and no differences were found between the predicted simulation values and the measured intensity in vivo (p > 0.05). Further in vivo researches using miniaturized rTMS devices for murine head should be followed to be more meaningful for human.

Therapeutic efficacy of repetitive transcranial magnetic stimulation in an animal model of Alzheimer's disease.

Previous studies on repetitive transcranial magnetic stimulation (rTMS) suggested potential neurorestorative properties in Alzheimer's disease (AD). This study aimed to investigate therapeutic effects of rTMS on an AD mouse model at high and low frequencies. The subject mice were allocated into the AD model group (AD induced by intracerebroventricular amyloid beta 42 oligomer [Aß42] injection) and the saline-injected control group. Each group was subdivided according to rTMS treatment: high frequency (20 Hz), low frequency (1 Hz), and not rTMS-treated. Behavioural assessments with Y-maze test and novel object recognition task were performed; the results indicated cognition recovery by both the frequencies of rTMS after treatment in the AD model (Ps < 0.01). Tendency of further effects by high frequency compared to low frequency rTMS was also shown in Y-maze test. Neurotransmitter assay showed increment in dopamine concentration and upregulation of dopamine-receptor 4 (DR4) by rTMS in AD mice with higher response by high frequency stimulation (Ps < 0.05). Only high-frequency rTMS induced an elevation of brain-derived neurotrophic factor (BDNF) levels and enhanced the expression of Nestin and NeuN in the brain tissue (Ps < 0.05). Under in vitro conditions, Aß42 incubated mouse hippocampal cell showed an increase in dopamine levels and BDNF by application of high-frequency rTMS treatment. In conclusion, rTMS might have a potential therapeutic effect on AD, and it seems to be related with dopaminergic activation. High frequency of stimulation seems to induce higher efficacy than that induced by low frequency, with elevated expressions of DR4 gene and neurogenic proteins.

Inflammation in the Prediction of Type 2 Diabetes and Hypertension in Healthy Adults.

BACKGROUND: While inflammation is associated with obesity and insulin resistance, their inter-relationships in the development of type 2 diabetes or hypertension are not clear. AIM OF THE STUDY: To evaluate inflammatory markers in prediction of type 2 diabetes and hypertension. METHODS: The study population of this retrospective cohort study consisted of individuals who participated in a comprehensive health screening program with measurement of white blood cell count and C-reactive protein from 2002-2010 (N = 96,606) in nondiabetic and normotensive Koreans. Median follow up time were 3.7 years for incident type 2 diabetes and 3.3 years for hypertension. Multivariate Cox proportional hazards models were performed to assess risk for type 2 diabetes or hypertension by white blood cell or C-reactive protein quartiles with adjustment of various possible confounding factors including insulin resistance. RESULTS: During the follow-up period, 1448 (1.5%) developed type 2 diabetes and 10,405 (10.8%) developed hypertension. Among men, comparison of adjusted hazard ratios (HR) for incident type 2 diabetes in the highest versus lowest white blood cell or C-reactive protein quartiles were 1.48 [95% confidence interval (CI), 1.20-1.83] and 1.30 (95% CI, 1.07-1.57), respectively. Among women, white blood cell but not C-reactive protein was significantly associated with type 2 diabetes [HR 1.79 (95% CI 1.24-2.57)]. White blood cell and C-reactive protein quartiles were also modestly associated with incident hypertension in both sexes. CONCLUSIONS: Although white blood cell and C-reactive protein are associated with adiposity and insulin resistance, these inflammatory markers also independently predict type 2 diabetes and/or hypertension.

The association between dietary cholesterol intake and subclinical atherosclerosis in Korean adults: The Kangbuk Samsung Health Study.

BACKGROUND: The Scientific Report of the Dietary Guidelines Advisory Committee (2015) concluded that restriction of dietary cholesterol is unnecessary in most adults for the prevention of cardiovascular disease. OBJECTIVE: We aimed to assess the risk for subclinical atherosclerosis according to coronary artery calcium score (CACS), based on dietary cholesterol intake in apparently healthy Korean adults. METHODS: This was a cross-sectional study performed in 30,068 participants (mean age 40.8 years; 84.5% men) in a health screening program in Korea. The data were collected from 2001 to 2013 and analyzed in 2015. Total energy intake and dietary cholesterol intake were assessed with a food frequency questionnaire. The participants were stratified according to quartile of dietary cholesterol intake. CACS was measured by multi-detector computed tomography. Lipid profiles were measured, and the participants were divided into 6 groups according to low-density lipoprotein cholesterol (LDL-C) level: <70, 70 to 99, 100 to 129, 130 to 159, 160 to 189, and ≥190 mg/dL. RESULTS: The presence of coronary artery calcification was defined as CACS>0. Dietary cholesterol intake did not correlate with mean value of serum LDL-C level. For both genders, the odds ratio for coronary artery calcification was not significantly greater with greater amounts of dietary cholesterol (as assessed by quartile). The risk for coronary artery calcification was not higher in subjects with LDL-C 70-129 mg/dL compared with those with LDL-C < 70 mg/dL; however, the risk was significantly greater in subjects with LDL-C ≥ 130 mg/dL compared with those with LDL-C < 70 mg/dL. CONCLUSIONS: Dietary cholesterol intake did not have an association with LDL-C level or with risk for coronary artery calcification in apparently healthy Korean adults. The results have to be translated with consideration of limitation of population-based studies.

Association between serum uric acid and cardiovascular mortality and all-cause mortality: a cohort study.

OBJECTIVE: Previous studies have reported the association among serum uric acid (SUA) levels and cardiovascular and all-cause mortality; however, the results have been inconsistent. The aim of this study was to investigate whether SUA is independently associated with cardiovascular and all-cause mortality in relatively healthy Korean adults. METHODS: A total of 396 951 individuals were enrolled for the study between 2002 and 2012. About 39 991 participants were excluded for various reasons. All-cause and cardiovascular mortality data were collected. Cox proportional hazards models were used to estimate adjusted hazard ratios and 95% confidence intervals for all-cause and cardiovascular mortality according to baseline uric acid quintiles, and the third, middle SUA quintile was the reference group. RESULTS: A total of 356 960 participants were considered to be eligible for the analysis, and median follow-up duration was 5.88 years. The lowest and highest quintiles of SUA were less than 5.2 and more than 7.1 mg/dl in men, and less than 3.5 and more than 5.0 mg/dl in women, respectively. A total of 2082 deaths (312 from cardiovascular disease and 1770 from other causes) occurred during follow-up. In the highest SUA group, adjusted hazard ratios for all-cause mortality were 1.24 (1.01, 1.51) in men and 1.04 (0.76, 1.42) in women, and for cardiovascular mortality were 1.15 (0.72, 1.83) in men and 1.69 (0.70, 4.04) in women after adjustment for various possible confounding factors. CONCLUSION: In the current large relatively healthy population-based observational study, SUA showed no significant association with all-cause and cardiovascular mortality.

Application of new guidelines for the primary prevention of atherosclerotic cardiovascular disease in a Korean population.

AIM: We investigated the proportion of people who would qualify for statin treatment with an atherosclerotic cardiovascular disease (ASCVD) 10-year risk of ≥7.5% and who exhibit an LDL cholesterol (LDL-C) of 70 to 189 mg/dL according to the new ACC/AHA guidelines for the treatment of increased cardiovascular risk. METHODS: The study population (8,742 subjects) included individuals who underwent health examinations at Kangbuk Samsung Hospital in South Korea in 2010. We also evaluated the data obtained from the 2008-2010 Korea National Health and Nutrition Examination Survey (KNHANES) of 16,892 adults. RESULTS: Approximately 90% of men ≥60 years of age and women ≥70 years of age had an ASCVD 10-year risk of ≥7.5% and LDL-C level of ≥70 mg/dL. The proportions of subjects with a Framingham 10-year risk of ≥10%, coronary artery calcium score of >20 and >100 and fatty liver each increased in association with an increasing ASCVD 10-year risk quartile in both sexes. Furthermore, age was significantly associated with the ASCVD 10-year risk in both sexes (all p-value <0.001). The KNHANES data also showed that over 85.0% of men ≥60 years of age and 95.0% of women ≥70 years of age had an ASCVD 10-year risk of ≥7.5% and an LDL-C level of ≥70 mg/dL. CONCLUSIONS: Adopting the new ASCVD prevention guidelines would result in the treatment of almost all Korean men and women (≥60 years and ≥70 years of age, respectively) without evidence of cardiovascular disease. Therefore, Asian-specific guidelines are needed to avoid unnecessary over treatment in an aging global population.

Estimation of plasma apolipoprotein B concentration using routinely measured lipid biochemical tests in apparently healthy Asian adults.

BACKGROUND: Increased low-density lipoprotein cholesterol (LDL) concentration is associated with increased risk of coronary heart disease (CHD) but a substantial risk of cardiovascular disease often remains after LDL concentrations have been treated to target. Apolipoprotein B (apo B) is the major apolipoprotein contained within atherogenic lipoproteins such as LDL, and apo B is a more reliable indicator of cardiovascular risk than LDL concentration. AIM AND METHODS: Our aim was to develop a formula for calculating apo B using lipid biochemistry measurements that are commonly available in clinical practice. We examined the clinical and laboratory data from 73,047 Koreans who underwent a medical health check that included apolipoprotein B concentration. The study sample was randomly divided into a training set for prediction model building and a validation set of equal size. Multivariable linear regression analysis was used to develop a prediction model equation for estimating apo B and to validate the developed model. RESULTS: The best results for estimating apo B were derived from an equation utilising LDL and triglyceride (TG) concentrations [ApoB = -33.12 + 0.675*LDL + 11.95*ln(tg)]. This equation predicted the apo B result with a concordance correlation coefficient (CCC and 95%CIs) = 0.936 (0.935,0.937)). CONCLUSION: Our equation for predicting apo B concentrations from routine analytical lipid biochemistry provides a simple method for obtaining precise information about an important cardiovascular risk marker.