Improving mass accuracy in matrix-assisted laser desorption ionization time-of-flight mass spectrometry analysis of pathogenic proteins using 6xHIS-tagged internal calibration.

RATIONALE: Linear mode of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOFMS) has been routinely used for bacterial identification in the clinic, depending on the pattern analysis of spectral libraries rather than accurate mass measurement of ribosomal proteins (10-15 kDa). However, a demand for more accurate mass analysis of pathogens (e.g. KPC-2 carbapenemase) has been recently increasing for diagnostic purposes. METHODS: We introduced a 6xHIS-tagged KPC-2 (i.e. hKPC-2) and used it as an internal mass calibrator for the mass calibration of target proteins. After internal mass calibration (In-Cal), we evaluated the observed mass of KPC-2 against the theoretical mass of hKPC-2, which has 823 Da mass difference from the target protein. We further assessed the accuracy and precision of our calibration method regarding the identification of KPC-2 and other pathogens in clinical isolates (n = 42). RESULTS: Among several candidates for internal mass calibrators, the In-Cal using a 6xHIS-tagged protein on the target showed the highest mass accuracy and precision in the detection of target proteins (e.g. KPC-2). The application of hKPC-2 as an internal calibrator showed substantial improvement of mass accuracy, mass precision and also quantification of KPC in linearity and repeatability for KPC detection in the clinical isolates. CONCLUSIONS: Our In-Cal method using 6xHIS-tagged protein in MALDI-TOFMS allows successful mass calibration (<3.5 Da) of pathogenic proteins (>20 kDa) and provides high mass accuracy as much as that of medium- and high-resolution mass spectrometry.

A modified quick, easy, cheap, effective, rugged, and safe method for determination of by-products originating from ozonation of chlorpyrifos and diazinon spiked in cherry tomato and perilla leaf.

In this study, sample pretreatment methods have been developed for the determination of chlorpyrifos, diazinon, and their by-products present in cherry tomato and perilla leaf using liquid chromatography-tandem mass spectrometry. To optimize a quick, easy, cheap, effective, rugged, and safe method, the recoveries at each step were evaluated. The steps improved the recoveries of chlorpyrifos, chlorpyrifos oxon, diazinon, diazoxon, and 2-isopropyl-6-methyl-4-pyrimidinol up to 80% or more by removing interferents, but diethyl phosphate was almost lost during the partition procedure, and the 3,5,6-trichloro-2-pyridinol recovery was below 65%. Therefore, the compounds were evaluated using different solvent compositions based on a quick polar pesticides method; note that 100% methanol showed acceptable extraction results. The optimized method provided method detection limits ranging from 0.03 to 1.22 ng/g and good linearities (R2  > 0.996). The recovery values were between 82.1 and 113.3%. The intra- and interday reproducibility was evaluated to be within 8.6 and 9.9%, respectively. The method was applied to determine the degradation efficiency of chlorpyrifos and diazinon and their by-products formed during plasma treatment.

Subclinical left ventricular diastolic dysfunction and incident type 2 diabetes risk: the Korean Genome and Epidemiology Study.

BACKGROUND: Subclinical left ventricular (LV) diastolic dysfunction in type 2 diabetes (T2D) is a common finding and represents an early sign of diabetic cardiomyopathy. However, the relationship between LV diastolic dysfunction and the incident T2D has not been previously studied. METHODS: A total of 1817 non-diabetic participants (mean age, 54 years; 48% men) from the Korean Genome and Epidemiology Study who were free of cardiovascular disease were studied. LV structure and function were assessed by conventional echocardiography and tissue Doppler imaging. Subclinical LV diastolic dysfunction was defined using age-specific cutoff limits for early diastolic (Em) velocity, mitral E/Em ratio, and left atrial volume index. RESULTS: During the 6-year follow-up period, 273 participants (15%) developed T2D. Participants with incident T2D had greater LV mass index (86.7 ± 16.4 vs. 91.2 ± 17.0 g/m2), worse diastolic function, reflected by lower Em velocity (7.67 ± 1.80 vs. 7.47 ± 1.70) and higher E/Em ratio (9.19 ± 2.55 vs. 10.23 ± 3.00), and higher prevalence of LV diastolic dysfunction (34.6 vs. 54.2%), compared with those who did not develop T2D (all P < 0.001). In a multivariate logistic regression model, lower Em velocity (odd ratio [OR], 0.867; 95% confidence interval [CI] 0.786-0.957) and the presence of LV diastolic dysfunction (OR, 1.617; 95% CI 1.191-2.196) were associated with the development of T2D, after adjusting for potential confounding factors. CONCLUSIONS: In a community-based cohort, the presence of subclinical LV diastolic dysfunction was a predictor of the progression to T2D. These data suggest that the echocardiographic assessment of LV diastolic function may be helpful in identifying non-diabetic subjects at risk of incident T2D.

Efficacy and safety of evogliptin monotherapy in patients with type 2 diabetes and moderately elevated glycated haemoglobin levels after diet and exercise.

AIMS: To evaluate the efficacy and safety of evogliptin, a newly developed dipeptidyl peptidase-4 inhibitor, in patients with type 2 diabetes (T2D) inadequately controlled by diet and exercise. MATERIALS AND METHODS: In this randomized, double-blind, placebo-controlled, parallel-group, multicentre, phase III study, 160 patients with T2D were assigned to either evogliptin 5 mg or placebo for 24 weeks. The primary endpoint was the mean change in glycated haemoglobin (HbA1c) from baseline to week 24. RESULTS: The mean baseline HbA1c levels were similar in the evogliptin and the placebo groups (7.20% ± 0.56% vs 7.20% ± 0.63%, respectively). At week 24, evogliptin significantly reduced HbA1c levels from baseline compared with placebo (-0.23% vs 0.05%, respectively, P < .0001). Additionally, the proportion of patients achieving HbA1c <6.5% was significantly higher in the evogliptin group than in the placebo group (33.3% vs 15.2%; P = .008). The overall incidence of adverse events, including hypoglycaemia, was similar in the 2 groups. CONCLUSIONS: In this 24-week study, once-daily evogliptin monotherapy significantly improved glycaemic control and was well tolerated in patients with T2D.

Peroxisome proliferator-activated receptor γ upregulates galectin-9 and predicts prognosis in intestinal-type gastric cancer.

The importance of PPARγ (peroxisome proliferator-activated receptor γ) in gastric cancer (GC) is unclear. We investigated the role of PPARγ in GC cell lines and an animal model, and its prognostic significance of PPARγ in GC patients. We controlled PPARγ and galectin-9 expression by using siRNAs and lentiviral constructs. Interaction between PPARγ and galectin-9 was evaluated using luciferase and chromatin immunoprecipitation assays. PPARγ expression in GCs was determined by immunohistochemical staining of tissue microarrays and survival analysis was done. Overexpression of PPARγ was accompanied by increased galectin-9. Enhanced PPARγ or galectin-9 expression increased E-cadherin expression; decreased expression of N-cadherin, fibronectin, snail, twist and slug and reduced cell invasion and migration. PPARγ bound to the galectin-9 promoter region. Galectin-9 activity increased in PPARγ-overexpressing cells but decreased in PPARγ siRNA-treated cells. In a zebrafish xenograft model, the number of migrated cancer cells and number of fish with AGS cells in the tail vein were reduced in PPARγ-overexpressing GC cells. PPARγ was expressed in 462 of the 688 patients (69.2%) with GC. In 306 patients with intestinal-type GC, those with PPARγ-positive tumors had lower overall and cancer-specific mortalities than those with PPARγ-negative tumors. PPARγ expression was an independent prognostic factor for overall and GC-specific mortality in patients with intestinal-type GC (adjusted hazard ratio, 0.42; 95% CI, 0.22-0.81). PPARγ inhibits cell invasion, migration and epithelial-mesenchymal transition through upregulation of galectin-9 in vitro and in vivo.

Unprotected daily sun exposure is differently associated with central adiposity and ß-cell dysfunction by gender: the Korean National Health and Nutrition Examination Survey (KNHANES) V.

BACKGROUND: Ultraviolet irradiation by sun exposure has been associated with both harms and benefits to metabolic health. OBJECTIVE: The objective of this study was to determine whether unprotected daily sun exposure is associated with the prevalence of diabetes and explore the underlying mechanism. METHODS: We analyzed the Korean National Health and Nutrition Survey V from 2010 to 2011. Participants 19-60 years of age were asked about the average amount of time they had been exposed to direct sunlight per day since the age of 19. We categorized participants into three groups with different levels of lifetime daily sun exposure and explored the association of sun exposure with the prevalence of diabetes. RESULTS: The risk of diabetes was higher in subjects with more than 5h of unprotected sun exposure per day, with an odds ratio of 2.39 (95% CI 1.75-3.25), compared to those with less than 2h of sun exposure, and the association remained significant after adjusting for diabetes risk factors. Long-term sun exposure was associated with increased central obesity and the possibility of an increase in visceral adiposity, especially among women, and with decrease in beta cell function and peripheral adiposity or percent body fat in men. CONCLUSIONS: Our study provides a cutoff for upper limit of sun exposure and suggests unprotected daily sun exposure for more than 5h should be avoided to prevent diabetes. Increased central adiposity and decreased beta cell function were observed in women and men, respectively, who had long-term unprotected daily sun exposure.

Resistant starch and type 2 diabetes mellitus: Clinical perspective.

The immediate and well-documented benefits of carbohydrate restriction include improved glycemic control in individuals with diabetes mellitus. Starch, a significant source of carbohydrates, is categorized as rapidly digestible, slowly digestible, or resistant starch (RS). RS, which is a non-viscous fermentable fiber, has shown promise in animal studies for antidiabetic effects by improving glucose metabolism. Although the exact mechanism by which RS affects glucose metabolism remains unclear, it is expected to positively impact glucose tolerance and insulin sensitivity. The fermentation of RS by colonic microbiota in the large bowel produces short-chain fatty acids, which exert multiple metabolic effects on glucose regulation and homeostasis. Moreover, RS may influence glucose metabolism via bile acid modulation, independent of its fermentation. Diets rich in RS could aid in blood glucose homeostasis. However, it is uncertain whether they can alter the metabolic pathology associated with glucose regulation. In essence, RS has the potential to lower postprandial glucose levels similarly to a low-glycemic index diet. Yet, its efficacy as a medical nutrition therapy for type 2 diabetes needs further investigation. To confirm the role of RS in glycemic control and to possibly recommend it as an additional dietary approach for people with type 2 diabetes mellitus, a well-designed, large-scale intervention is required.

The cutoff values of visceral fat area and waist circumference for identifying subjects at risk for metabolic syndrome in elderly Korean: Ansan Geriatric (AGE) cohort study.

BACKGROUND: In Korea, the cutoff values of waist circumference (WC) for the identification of metabolic syndrome (MetS) were suggested to be 90 cm for men and 85 cm for women based on the analysis mainly in middle-aged adults. As aging is associated with increased fat, especially abdominal visceral fat, the cutoff value of WC may differ according to age. In addition, the usefulness of visceral abdominal fat area (VFA) to predict MetS in the elderly has not been studied yet. We aimed to suggest WC and VFA criteria and to compare the predictability of WC and VFA to identify people at risk for MetS. METHODS: A total of 689 elderly subjects aged>or=63 years (308 men, 381 women) were chosen in this cross-sectional study from an ongoing, prospective, population-based study, the Ansan Geriatric (AGE) cohort study. VFA was measured by single slice abdominal computed tomography scanning. The metabolic risk factors except WC (plasma glucose, blood pressure, serum triglycerides and HDL cholesterol levels) were defined using modified NCEP-ATP III criteria. We estimated the accuracy of VFA and WC for identifying at least two of these factors by receiver operating characteristic (ROC) curve analysis. RESULTS: Two hundred three of 308 men and 280 of 381 women had >or=2 metabolic risk factors. The area under the ROC curve (AUC) value for VFA to predict the presence of >or=2 metabolic risk factors was not significantly different from that for WC (men, 0.735 and 0.750; women, 0.715 and 0.682; AUC values for VFA and WC, respectively). The optimal cutoff points for VFA and WC for predicting the presence of >or=2 metabolic risk factors were 92.6 cm2 and 86.5 cm for men and 88.9 cm2 and 86.5 cm for women. CONCLUSION: WC had comparable power with VFA to identify elderly people who are at risk for MetS. Elderly Korean men and women had very similar cutoff points for both VFA and WC measurements for estimating the risk of MetS. Age-specific cutoff point for WC might be considered to identify subjects at risk for MetS.

Adolescents' Attitudes and Intentions toward Help-Seeking and Computer-Based Treatment for Depression.

OBJECTIVE: Many depressed adolescents do not seek professional help despite there being evidence-based treatments for depression, such as cognitive behavioral therapy or computer-based therapy. To increase professional help-seeking behavior in depressed adolescents, it is necessary to positively change help-seeking attitudes. This study aimed to explore the effect of sub-groups of help-seeking attitudes, gender, and depression level on adolescents' help-seeking intentions and their perceptions of computer-based psychotherapy. METHODS: Participants were 246 adolescents aged 13-18 years recruited from six middle and high schools in South Korea. Measures were self-administered questionnaires, and included the Patient Health Questionnaire-9, the Attitudes Toward Seeking Professional Psychological Help Scale, the Intention to Seek Counseling Inventory, Preferences for Depression Treatment, and the Perceptions of Computerized Therapy Questionnaire. RESULTS: Help-seeking intentions were positively related with female gender and the recognition of the need for help. A higher level of confidence in therapists was related to high preference for computer-based therapy and face-to-face therapy. Adolescents with more severe depression were more likely to prefer pharmacotherapy. The perceptions of computer-based therapy were more positive in male adolescents, and in adolescents with a higher level of confidence in therapists yet a lower level of interpersonal openness. CONCLUSION: To promote adolescents' help-seeking behavior, improvement of the recognition of the need for help is required, especially among male adolescents. Computer-based therapy provides an alternative for male adolescents with high confidence in therapists yet low interpersonal openness. Consideration of the help-seeking attitudes and gender is needed when providing therapeutic intervention to depressed adolescents.

Longitudinal changes in left ventricular structure and function in patients with type 2 diabetes: Normal weight versus overweight/obesity.

OBJECTIVE: Although reported to be independent of obesity, the longitudinal changes of left ventricular structure and function have not been well characterized in normal-weight individuals with type 2 diabetes compared with overweight/obese individuals with type 2 diabetes. METHODS: A total of 558 participants in the Korean Genome and Epidemiology Study who underwent tissue Doppler echocardiography at baseline (cycle 4) and after 8 years (cycle 8) were classified into three groups based on body mass index and diabetes status: (1) normal-weight individuals without type 2 diabetes, (2) normal-weight individuals with type 2 diabetes and (3) overweight/obese individuals with type 2 diabetes. RESULTS: Only overweight/obese individuals with type 2 diabetes group had higher adjusted left ventricular mass index and lower tissue Doppler imaging early diastolic velocity and E/Em ratio compared with the normal-weight individuals without type 2 diabetes group at baseline and after 8 years. Participants in overweight/obese individuals with type 2 diabetes group also showed the higher prevalence and odds of left ventricular hypertrophy (16.0%; adjusted odds ratio: 2.24; 95% confidence interval: 1.22-5.06) and left ventricular diastolic dysfunction (49.1%; 3.45; 1.01-4.32). Among participants with normal left ventricular structure and function at baseline, only overweight/obese individuals with type 2 diabetes group was associated with greater incidence of left ventricular hypertrophy (relative risk: 2.28; 1.04-4.98) over 8 years but not diastolic dysfunction. CONCLUSION: Cross-sectional and longitudinal observations suggest that increasing body mass index category and its associated metabolic abnormalities at baseline are associated with an increased risk for left ventricular hypertrophy and greater impairment in left ventricular diastolic parameters.

Polyaniline-grafted nanodiamonds for efficient photothermal tumor therapy.

Polyaniline-grafted nanodiamond (PAN-ND) nanoparticles were fabricated by polymerizing aniline at the surface of amine-modified NDs for efficient photothermal therapy (PTT). A series of PAN from different aniline concentrations were also prepared to compare the properties and the efficiency of PTT. The polymerization rate of aniline was faster in the presence of NDs than that of aniline alone. Compared to PAN nanoparticles, PAN-ND has a spherical shape, smaller size, and ultimately higher cellular uptake efficiency. The temperature of aqueous PAN-ND dispersion increased to 44.4 °C after laser irradiation for 5 min. In addition, the UV absorbance intensity of PAN-ND increased at the lower pH at the near infrared (NIR) region, resulting in an enhanced photothermal effect at a tumor site. Notably, the viability of HeLa cells treated with PAN-ND decreased by less than 20%, suggesting the high efficiency of PTT. The PAN-ND can be a potential candidate for efficient photothermal tumor therapy.

Trends in socioeconomic inequalities in five major risk factors for cardiovascular disease in the Korean population: a cross-sectional study using data from the Korea National Health and Nutrition Examination Survey, 2001-2014.

OBJECTIVES: To examine trends in socioeconomic inequalities in major cardiovascular disease (CVD) risk factors among the Korean population. DESIGN: Cross-sectional study. SETTING: A nationally representative population survey database. PARTICIPANTS: A total of 42 725 Koreans, aged 25-64 years, who participated in the Korean National Health and Nutrition Examination Survey (KNHANES) II (2001) to VI (2013-2014). MAIN OUTCOME MEASURES: Trends in socioeconomic inequalities in five major CVD risk factors (smoking, obesity, diabetes, hypertension and hypercholesterolaemia). RESULTS: Gender differences were noted in the time trends in socioeconomic inequalities in smoking, obesity, diabetes and hypertension. Among men, low socioeconomic status (SES) was associated with higher prevalence of smoking, but not with obesity, diabetes or hypertension. The magnitudes of socioeconomic inequalities in smoking, obesity and diabetes remained unchanged, and the magnitude of the inequality in hypertension decreased over time. However, among women, low SES was associated with higher prevalence of smoking, obesity, diabetes and hypertension. Time trends towards increasing socioeconomic inequalities, measured by income, in smoking, obesity and diabetes were found in women. Unlike the other CVD risk factors, hypercholesterolaemia was not associated with socioeconomic inequality. CONCLUSIONS: SES had a stronger impact on major CVD risk factors among Korean women than men. Moreover, socioeconomic inequalities in smoking, obesity and diabetes worsened among Korean women over time. Public policies to prevent smoking, obesity and diabetes in women with lower SES are needed to address inequalities.

Ninjurin1 Is Up-regulated in Circulating Prostate Tumor Cells and Plays a Critical Role in Prostate Cancer Cell Motility.

BACKGROUND/AIM: Ninjurin1 is a 17-kDa membrane protein that is highly expressed in circulating tumor cells (CTCs) obtained from locally-advanced prostate cancer patients. As CTCs are implicated in the initiation of distant metastasis, we examined the potential contribution of Ninjurin1 to the motility of prostate cancer cells. MATERIALS AND METHODS: Ninjurin1 expression was evaluated in CTCs harvested from seven locally advanced patients with no metastatic hallmarks using real-time polymerase chain reaction (PCR). The role of Ninjurin1 in cell motility was investigated using small interfering RNA (siRNA), neutralizing antibodies against Ninjurin1 and Ninjurin1-overexpressing adenoviruses. RESULTS: Ninjurin1 was ranked as the most significantly up-regulated adhesion protein identified by RNA-Seq analysis. Both Ninjurin1 down-regulation by siRNA and neutralizing antibodies blocking Ninjurin1 homophilic interactions effectively inhibited cell motility. In contrast, cell motility was enhanced in prostate cancer cells infected with adenovirus enabling Ninjurin1 overexpression. CONCLUSION: Ninjurin1-neutralizing antibodies or Ninjurin1-targeting siRNA merit further development for patients with metastatic potential.

Clinical Guidelines for the Management of Adrenal Incidentaloma.

An adrenal incidentaloma is an adrenal mass found in an imaging study performed for other reasons unrelated to adrenal disease and often accompanied by obesity, diabetes, or hypertension. The prevalence and incidence of adrenal incidentaloma increase with age and are also expected to rise due to the rapid development of imaging technology and frequent imaging studies. The Korean Endocrine Society is promoting an appropriate practice guideline to meet the rising incidence of adrenal incidentaloma, in cooperation with the Korean Adrenal Gland and Endocrine Hypertension Study Group. In this paper, we discuss important core issues in managing the patients with adrenal incidentaloma. After evaluating core proposition, we propose the most critical 20 recommendations from the initially organized 47 recommendations by Delphi technique.

Target-organ damage and incident hypertension: the Korean genome and epidemiology study.

OBJECTIVE: Hypertension is associated with cardiovascular organ damage. However, data are scanty on whether individual forms or combinations of subclinical target organ damage (TOD) increase the risk of incident hypertension in nonhypertensive study participants. METHODS: A total of 1785 nonhypertensive participants from the fourth biennial examination (2007-2008) of the Korean Genome and Epidemiology Study were followed-up for four years. Echocardiographic left ventricular (LV) hypertrophy, LV diastolic dysfunction, increased carotid intima-media thickness (cIMT), and brachial-ankle pulse wave velocity (baPWV) were defined according to the current guidelines. RESULTS: During 4-year follow-up, 19.9% of participants developed hypertension. In multivariate Cox proportional hazards models, the adjusted hazard ratios for developing hypertension were 1.39, 1.66, 1.48, and 0.78 for higher values of the LV mass index, cIMT, baPWV, and tissue Doppler e' velocity, respectively (all P < 0.01). The hazard ratios for LV hypertrophy, LV diastolic dysfunction, cIMT >75th percentile, and baPWV ≥ 1400 cm/s were 1.61, 1.30, 1.86, and 2.07, respectively (all P < 0.05). Compared with participants without any TOD, those with combinations of TOD types had significantly greater risk for developing hypertension (hazard ratio = 2.12 and 3.98 for 1-2 and 3-4 TOD sites, respectively, all P < 0.001). CONCLUSION: In the nonhypertensive population, each subclinical form of TOD independently predicts incident hypertension. In addition, the combinations of various forms of TOD are associated with stepwise increases in the risk for developing hypertension. The results suggest that asymptomatic TOD does not always exist in an intermediate stage in the cardiovascular continuum.

Sodium Excretion and Cardiovascular Structure and Function in the Nonhypertensive Population: The Korean Genome and Epidemiology Study.

BACKGROUND: The effect of sodium intake on the cardiovascular system remains controversial. The purpose of this study is to investigate the relation between sodium intake and cardiovascular structure and function in the nonhypertensive population. METHODS: We performed a cross-sectional analysis in 1,586 nonhypertensive subjects who participated in the Korean Genome Epidemiology Study (2007-2008). Sodium intake was assessed by estimating the 24-hour urinary sodium excretion from a spot urine sample. Changes in cardiovascular structure and function were assessed by using tissue Doppler echocardiography, the carotid intima-media thickness (CIMT), and the brachial-ankle pulse wave velocity (baPWV). RESULTS: Systolic and diastolic blood pressures increased with increasing tertiles of estimated 24-hour urinary sodium excretion. In multivariate analyses adjusting for covariates, there were stepwise decreases in the baPWV (P = 0.003) and CIMT (P = 0.001) values as the estimated 24-hour urinary sodium excretion increased, whereas no significant differences in left ventricular (LV) structural and functional parameters were observed across the tertiles of estimated 24-hour urinary sodium excretion. Multiple linear regression analyses revealed that the estimated 24-hour urinary sodium excretion was independently and inversely associated with baPWV (P < 0.001) and CIMT (P = 0.001), but not with LV parameters. CONCLUSIONS: In the nonhypertensive population, urinary sodium excretion was inversely related to baPWV and CIMT. However, there were no associations between urinary sodium excretion and LV structure or function.

Adult multisystem langerhans cell histiocytosis presenting with central diabetes insipidus successfully treated with chemotherapy.

We report the rare case of an adult who was diagnosed with recurrent multisystem Langerhans cell histiocytosis (LCH) involving the pituitary stalk and lung who present with central diabetes insipidus and was successfully treated with systemic steroids and chemotherapy. A 49-year-old man visited our hospital due to symptoms of polydipsia and polyuria that started 1 month prior. Two years prior to presentation, he underwent excision of right 6th and 7th rib lesions for the osteolytic lesion and chest pain, which were later confirmed to be LCH on pathology. After admission, the water deprivation test was done and the result indicated that he had central diabetes insipidus. Sella magnetic resonance imaging showed a mass on the pituitary stalk with loss of normal bright spot at the posterior lobe of the pituitary. Multiple patchy infiltrations were detected in both lung fields by computed tomography (CT). He was diagnosed with recurrent LCH and was subsequently treated with inhaled desmopressin, systemic steroids, vinblastine, and mercaptopurine. The pituitary mass disappeared after two months and both lungs were clear on chest CT after 11 months. Although clinical remission in multisystem LCH in adults is reportedly rare, our case of adult-onset multisystem LCH was treated successfully with systemic chemotherapy using prednisolone, vinblastine, and 6-mercaptopurine, which was well tolerated.

Visceral adiposity and skeletal muscle mass are independently and synergistically associated with left ventricular structure and function: the Korean Genome and Epidemiology Study.

BACKGROUND: Obesity and low muscle mass may coexist as age-related changes in body composition. We aimed to investigate the effect of visceral adiposity and skeletal muscle mass on left ventricular (LV) structure and function in the general population. METHODS: A total of 1941 participants without known cardiovascular disease were enrolled from the Korean Genome and Epidemiology Study. Visceral fat area (VFA) was assessed by computed tomography. Appendicular skeletal muscle mass (ASM) was estimated by dual-energy X-ray absorptiometry and was used as a percentage of body weight (ASM/Wt). LV structure and function were assessed by tissue Doppler imaging (TDI) echocardiography. RESULTS: Across VFA tertiles, ASM increased, but ASM/Wt decreased (all P<0.001). In multivariate models adjusted for conventional cardiovascular risk factors, LV mass index and LV diastolic parameters, such as left atrial dimension, TDI Ea velocity, and E/Ea ratio, were significantly impaired as VFA increased. On the other hand, an increase in ASM/Wt was associated with a decrease in LV mass index and improvement of LV diastolic parameters. With regard to LV mass index and TDI Ea velocity, VFA and ASM/Wt showed synergistic effects (all P interaction<0.05). When both VFA and ASM/Wt were simultaneously included in the same model, both remained independent predictors of LV mass index and TDI Ea velocity. CONCLUSIONS: More visceral fat and less muscle mass are independently and synergistically associated with an increase in LV mass index and impairment of LV diastolic parameters. Further research is needed to explore the complex mechanisms underlying these associations.

Non-alcoholic fatty liver disease, metabolic syndrome and subclinical cardiovascular changes in the general population.

OBJECTIVE: The effect of non-alcoholic fatty liver disease (NAFLD) on cardiovascular system remains controversial. We investigated the independent contribution of NAFLD to cardiovascular structure and function in the general population. METHODS: A total of 1886 participants without known cardiovascular disease were enrolled from the Korean Genome Epidemiology Study. The participants were divided into four groups, based on the presence of NAFLD, metabolic syndrome (MetS), neither or both. NAFLD was diagnosed by CT. Changes in cardiovascular structure and function were assessed by tissue Doppler imaging (TDI) echocardiography, carotid ultrasound and brachial-ankle pulse wave velocity (baPWV). RESULTS: In multivariate analyses, subjects with both NAFLD and MetS had a higher E/Ea ratio and baPWV, as well as a lower TDI Ea velocity (all p<0.001) than those with neither NAFLD nor MetS. Subjects with either NAFLD or MetS also showed significant differences in TDI Ea velocity and baPWV (all p<0.05). However, no significant differences of carotid intima-media thickness (CIMT) values were seen among the four groups. Multivariate linear regression revealed that both NAFLD and MetS were independent predictors of TDI Ea velocity and baPWV (all p<0.001). Both MetS and NAFLD were not a determinant of CIMT. CONCLUSIONS: NAFLD was associated with early alterations of cardiovascular system, independent of established cardiovascular risk factors and MetS.

Early abnormalities of cardiovascular structure and function in middle-aged Korean adults with prehypertension: The Korean Genome Epidemiology study.

BACKGROUND: Prehypertension is associated with increased cardiovascular morbidity and mortality. However, there are few population-based studies on the changes of cardiovascular structure and function that characterize prehypertension. The aim of this study was to assess whether prehypertension is associated with abnormalities of cardiovascular structure and function in the general Korean population. METHODS: We analyzed the cross-sectional relationships between prehypertension and cardiovascular structure and function in a sample from the Korean Genome Epidemiology Study. A total of 1,671 individuals (54.5% women; mean age: 53 ± 6 years) without hypertension and diabetes mellitus were enrolled. Cardiovascular structure and function were assessed by conventional echocardiography, tissue Doppler imaging (TDI), carotid ultrasonography, and pulse wave velocity (PWV). RESULTS: The left ventricular (LV) mass index was significantly higher in subjects with prehypertension than in those with normotension (41 ± 8 g/m²·7 vs. 38 ± 7 g/m²·7, P < 0.001). LV diastolic parameters, such as the E/A ratio, TDI E(a) velocity, and E/E(a) ratio, were also impaired in subjects with prehypertension (all P < 0.001). Compared with normotension, prehypertension was characterized by a significantly higher common carotid artery intima-media thickness and a higher brachial-ankle PWV (all P < 0.001). These abnormalities of cardiovascular structure and function remained significant after adjustment for covariates. CONCLUSIONS: In this population-based cohort, we found that subtle alterations in cardiovascular structure and function were already present at the prehypertensive stage. Whether such subtle alterations convey an increased risk of cardiovascular events and whether the changes are reversible with treatment warrant further study.