BACKGROUND: The aim of this study was to investigate the association between obesity and prehypertension (preHT) after adjustment for socioeconomic position and health behavior factors. METHODS: The study sample included 1973 Korean men and women, 45-64 years of age. Subjects were classified into three groups based on their baseline blood pressure: prehypertensive, hypertensive and normotensive. Men with a waist circumference ≥90 cm or women ≥80 cm were considered abdominally obese. Body mass index (BMI) obesity was defined as having a BMI ≥25. The prevalence of abdominal obesity and BMI obesity was calculated with age adjustment using a direct method. Multinomial logistic regression analysis was applied. RESULTS: The prevalence of preHT in our study was 52.8%. We found that subjects with abdominal obesity were 2.06 times as likely to be prehypertensive as those without it and people with BMI obesity were 1.89 times as likely to be prehypertensive as those without it. Interestingly, men with BMI obesity had a higher preHT risk, while women with abdominal obesity had a higher preHT risk. CONCLUSIONS: Statistical analyses of a community-based random sample of the Korean population indicate that obesity is associated with preHT in Korean middle-aged subjects.

BACKGROUND No selection criteria for helical tomotherapy (HT) based stereotactic ablative radiotherapy (SABR) to treat early stage non-small cell lung cancer (NSCLC) or solitary lung metastases has been established. In this study, we investigate the dosimetric selection criteria for HT based SABR delivering 70 Gy in 10 fractions to avoid severe toxicity in the treatment of centrally located lesions when adequate target dose coverage is desired. MATERIALS AND METHODS 78 HT-SABR plans for solitary lung lesions were created to prescribe 70 Gy in 10 fractions to the planning target volume (PTV). The PTV was set to have ≥95% PTV receiving 70 Gy in each case. The cases for which dose constraints for ≥1 OAR could not be met without compromising the target dose coverage were compared with cases for which all target and OAR dose constraints were met. RESULTS There were 23 central lesions for which OAR dose constraints could not be met without compromising PTV dose coverage. Comparing to cases for which optimal HT-based SABR plans were generated, they were associated with larger tumor size (5.72±1.96 cm vs. 3.74±1.49 cm, p<0.0001), higher lung dose, increased number of immediately adjacent OARs ( 3.45±1.34 vs. 1.66±0.81, p<0.0001), and shorter distance to the closest OARs (GTV: 0.26±0.22 cm vs. 0.88±0.54 cm, p<0.0001; PTV 0.19±0.18 cm vs. 0.48±0.36 cm, p = 0.0001). CONCLUSION Delivery of 70 Gy in 10 fractions with HT to meet all the given OAR and PTV dose constraints are most likely when the following parameters are met: lung lesions ≤3.78 cm (11.98 cc), ≤2 immediately adjacent OARs which are ≥0.45 cm from the gross lesion and ≥0.21 cm from the PTV.

Active autophagy coupled with rapid mitochondrial fusion and fission constitutes an important mitochondrial quality control mechanism and is critical to cellular health. In our previous studies, we found that exposure of cells to nicotinamide (NAM) causes a decrease in mitochondrial content and an increase in mitochondrial membrane potential (MMP) by activating autophagy and inducing mitochondrial fragmentation. Here, we present evidence to show that the effect of NAM is mediated through an increase of the [NAD+]/[NADH] ratio and the activation of SIRT1, an NAD+-dependent deacetylase that plays a role in autophagy flux. The [NAD+]/[NADH] ratio was inversely correlated with the mitochondrial content, and an increase in the ratio by the mobilization of Malate-aspartate shuttle resulted in autophagy activation and mitochondrial transformation from lengthy filaments to short dots. Further, treatment of cells with SIRT1 activators, fisetin or SRT1720, induced similar changes in the mitochondrial content. Importantly, the activators induced mitochondrial fragmentation only when SIRT1 expression was intact. Meanwhile, MMP did not increase when the cells were treated with the activators, suggesting that the change in MMP is not induced by the mitochondrial turnover per se and that elevation of the [NAD+]/[NADH] ratio may activate additional mechanisms that cause MMP augmentation. Put together, our results indicate that a metabolic state resulting in elevated [NAD+]/[NADH] ratio can modulate mitochondrial quantity and quality via pathways that may include SIRT1-mediated mitochondrial autophagy.

BACKGROUND Despite the importance of olfactory function, no effective medications have been identified to treat olfactory disorders. This study was performed to evaluate the functional recovery of olfaction damaged by 3-methylindole (3MI) in a mouse model with hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins). METHODS In a randomized placebo-controlled trial, 24 healthy female BALB/c mice (aged 9-10 weeks and weighing 18-20 g each) were randomly allocated to statin-treated or control groups. Olfactory loss was induced by i.p. injections of 3MI. Atorvastatin (10 mg/kg) or normal saline was then administered per os with a gastric tube for 3 weeks. The effects of treatment were evaluated by food-finding tests and Western blot analysis. RESULTS Both groups showed complete losses of olfactory function 1 week after 3MI injection. Three weeks after 3MI injection, 9 of the 12 mice in the statin-treated group (75%) passed a food-finding test, in which they were able to find the food within 3 minutes, at least two times out of three trials. However, only two mice in the control group (16.6%) passed the food-finding test, and this difference was statistically significant (p = 0.004; chi-square test). The expression level of the olfactory marker protein was also elevated in the statin-treated group (p = 0.030; Wilcoxon rank sum test). CONCLUSION Statins are associated with recovery of olfaction after 3MI injection in a mouse model.

Purpose: Hereditary thrombophilia (HT) is a major risk factor for idiopathic pulmonary embolism (iPE) and shows different prevalence among ethnic groups. The prevalence and clinical characteristics of HT in Korean patients with iPE were investigated. Materials and Methods: Patients with PE on computed tomography (CT) scan were recruited, and those with malignancy were excluded. Patients were divided into iPE and provoked PE (pPE) groups. The presence of HT in the iPE group was assessed by DNA sequencing of the corresponding gene in patients who had low levels of natural anticoagulants. The clinical characteristics of iPE with HT (iPE/HT+) were compared with those of iPE without HT (iPE/HT-) and pPE. Results: Out of 161 patients, 84 patients had iPE and 77 patients had pPE. Among 54 patients in the iPE group whose coagulation profiles were tested, 28 patients were diagnosed with HT (51.9%; 28/54). Compared with the iPE/HT- and pPE groups, the iPE/HT+ group showed the highest proportion of male patients (71.4%; p<0.001); the youngest mean age (44±14 years; p<0.001); and the highest frequencies for history of venous thromboembolism (64.3%; p<0.001), concurrent deep vein thrombosis (75.0%; p=0.021), and adverse clinical outcomes (42.9%, p<0.001). Protein C deficiency was the most common HT. On molecular genetic tests, causative mutation was identified in 13 patients. Conclusion: In this study of Korean patients, about half of the patients with iPE had HT. Patients with iPE and HT were mostly young males with deep venous thrombosis (DVT), previous venous thromboembolism (VTE), and frequent adverse clinical outcomes. Therefore, Korean patients with iPE should be tested for HT.

We report our experience of very late stent thrombosis (VLST) in a young male patient who underwent implantation of two paclitaxel-eluting stents (PES) six years ago. The patient was compliant with standard dual antiplatelet therapy, but he presented with acute myocardial infarction which was associated with VLST. Intravascular ultrasound showed neointimal rupture with thrombus within the PES implanted in the right coronary artery. The lesion was successfully treated with balloon angioplasty without complications, however he was found to be hyporesponsive to clopidogrel when tested for adenosine diphosphate-induced platelet aggregation. The patient was discharged after uneventful recovery with triple anti-platelet therapy using aspirin, clopidogrel and cilostazol. To the best of our knowledge, a time interval of 2,223 days is the longest reported time interval between PES deployment and VLST occurrence. VLST may indeed occur in clinically stable patients, as multiple factors can influence the pathological mechanisms of VLST.

Recently, a revised Ghent nosology has been established for the diagnosis of Marfan syndrome (MFS) that puts more weight on the aortic root aneurysm and ectopia lentis. We compared the application of the Ghent and revised Ghent nosologies in adult Korean patients for whom there is suspicion of MFS. From January 1995 to June 2010, we enrolled 106 patients older than 20 years for whom there was suspicion of MFS, and who had undergone genetic analysis of the fibrillin-1 gene (FBN1). Of 106 patients, 86 patients (81%) fulfilled the criteria of the Ghent nosology, and 84 patients (79%) met the criteria of the revised Ghent nosology. The two patients who met the Ghent nosology criteria, but not the criteria of the revised Ghent nosology were diagnosed with Loeys-Dietz syndrome and MASS phenotype. The level of agreement between both nosologies was very high (κ = 0.94, 95% confidence interval: 0.86 to 1.0). Marfan-like syndromes were diagnosed in 30%(6/20 patients) with negative Ghent and revised Ghent criteria and no FBN1 mutations. These results suggest that adult Korean patients who fulfill the old Ghent criteria almost all fulfill the new criteria for the diagnosis of MFS. © 2011 Wiley Periodicals, Inc.

Among the cardiovascular manifestations in the Marfan syndrome (MFS), aortic dissection stands out as a major cause of early mortality. The aim of this study was to test the hypothesis that patients with the MFS who experience aortic dissection differ in clinical features and outcomes from those with aortic dissection not related to the MFS. Data from patients diagnosed with aortic dissection from December 1994 to March 2009 at 1 of the major medical centers in Korea were reviewed. The clinical presentations, dissection characteristics, and outcomes of patients with and those without the MFS in a Korean population were compared. Of 445 patients with aortic dissection, 46 (10%) had the MFS. Compared to non-MFS patients, those with the MFS developed aortic dissection at younger ages (33 ± 10 vs 57 ± 13 years, p <0.001) and were less frequently hypertensive (11% vs 73%, p <0.001). During the follow-up period, patients with the MFS more often developed aortic dilatation and expansion of the dissection (39% vs 18%, p = 0.003) and showed a higher rate of reoperation (30% vs 9%, p <0.001). In conclusion, in Korean patients, aortic dissection with the MFS had different characteristics and poorer outcomes than aortic dissection without the MFS. These findings underscore the importance of accurate diagnosis and surveillance of this condition in the MFS.

Loeys-Dietz syndrome (LDS) is an inherited disorder that is characterized by the triad of arterial tortuosity and aneurysms, hypertelorism and a bifid uvula or cleft palate. The disease is caused by heterozygous mutations in the genes encoding transforming growth factor β receptors 1 and 2 (TGFBR1 and TGFBR2, respectively). However, studies of patients with LDS are limited in Korea. From June 2000 to December 2010, 13 patients (10 probands) diagnosed with LDS were enrolled. The multidisciplinary data of the patients were reviewed retrospectively. The frequency of each clinical manifestation in Korean patients with LDS was compared with Western populations as described in the report by Loeys et al. Twelve (92%) of the 13 LDS patients had arterial tortuosity, 9 (69%) patients had hypertelorism and 11 (85%) patients had bifid uvula or cleft palate. Mutations in either TGFBR1 or TGFBR2 were detected in nine probands (90%). Of the mutations, five novel mutations were detected; three in TGFBR2 and two in TGFBR1. Blue sclera and atrial septal defect were not observed in the Korean patients, and the frequency of blue sclera was significantly lower in our Korean population than previously-described Western population (0 vs 40%; P=0.005). Despite the restricted number of patients in our study, we identified five novel mutations in the TGFBR1 and TGFBR2 genes and, except for blue sclera, no differences in phenotype are apparent between Korean patients and Western patients.Journal of Human Genetics advance online publication, 24 November 2011; doi:10.1038/jhg.2011.130.

ADP-ribosylation factor 4 (ARF4) is a member of the Ras superfamily of small guanine nucleotide-binding proteins. ARF4 is known to interact with the epidermal growth factor receptor (EGFR) and mediates the EGF-dependent signal pathway, and has an anti-apoptotic function in human glioblastoma-derived U373MG cells. Although ARF4 plays a role in cancer cells, the molecular mechanism underlying regulation of its expression and its exact functions in breast cancer are unknown. In this study, we investigated the regulatory mechanism of ARF4 expression and its involvement in breast cancer cell migration. Our results show that phorbol 12-myristate 13-acetate (PMA) treatment increases ARF4 expression at both the transcriptional and translational levels. We found that the novel transcription factor small leucine zipper protein (sLZIP) binds directly to the CRE motif of the -43 to -35 region in the ARF4 promoter and regulates PMA-induced ARF4 expression. We also found that PMA-stimulated ARF4 expression increases AP-1 promoter activity, leading to induction of breast cancer cell migration. These results indicate that sLZIP-regulated ARF4 expression in response to PMA is involved in breast cancer cell migration, and sLZIP and ARF4 are potential therapeutic target molecules for treating breast cancer invasion and metastasis.