Bacillus Calmette-Guerin (BCG) vaccine is the only licensed vaccine for tuberculosis (TB) prevention. Previously, our group demonstrated the vaccine potential of Rv0351 and Rv3628 against Mycobacterium tuberculosis (Mtb) infection by directing Th1-biased CD4 + T cells coexpressing IFN-γ, TNF-α, and IL-2 in the lungs. Here, we assessed immunogenicity and vaccine potential of the combined Ags (Rv0351/Rv3628) formulated in different adjuvants as subunit booster in BCG-primed mice against hypervirulent clinical Mtb strain K (Mtb K). Compared to BCG-only or subunit-only vaccine, BCG prime and subunit boost regimen exhibited significantly enhanced Th1 response. Next, we evaluated the immunogenicity to the combined Ags when formulated with four different types of monophosphoryl lipid A (MPL)-based adjuvants: 1) dimethyldioctadecylammonium bromide (DDA), MPL, and trehalose dicorynomycolate (TDM) in liposome form (DMT), 2) MPL and Poly I:C in liposome form (MP), 3) MPL, Poly I:C, and QS21 in liposome form (MPQ), and 4) MPL and Poly I:C in squalene emulsion form (MPS). MPQ and MPS displayed greater adjuvancity in Th1 induction than DMT or MP did. Especially, BCG prime and subunit-MPS boost regimen significantly reduced the bacterial loads and pulmonary inflammation against Mtb K infection when compared to BCG-only vaccine at a chronic stage of TB disease. Collectively, our findings highlighted the importance of adjuvant components and formulation to induce the enhanced protection with an optimal Th1 response.

BACKGROUND: Bone marrow-derived mesenchymal stem cells (BMSCs) and bone morphogenetic protein-2 (BMP-2) have been studied for bone repair because they have regenerative potential to differentiate into osteoblasts. The development of injectable and in situ three-dimensional (3D) scaffolds to proliferate and differentiate BMSCs and deliver BMP-2 is a crucial technology in BMSC-based tissue engineering. METHODS: The proliferation of mouse BMSCs (mBMSCs) in collagen/poly-γ-glutamic acid (Col/γ-PGA) hydrogel was evaluated using LIVE/DEAD and acridine orange and propidium iodide assays. In vitro osteogenic differentiation and the gene expression level of Col/γ-PGA(mBMSC/BMP-2) were assessed by alizarin red S staining and quantitative reversetranscription polymerase chain reaction. The bone regeneration effect of Col/γ-PGA(mBMSC/BMP-2) was evaluated in a mouse calvarial bone defect model. The cranial bones of the mice were monitored by micro-computed tomography and histological analysis. RESULTS: The developed Col/γ-PGA hydrogel showed low viscosity below ambient temperature, while it provided a high elastic modulus and viscous modulus at body temperature. After gelation, the Col/γ-PGA hydrogel showed a 3D and interconnected porous structure, which helped the effective proliferation of BMSCs with BMP-2. The Col/γ-PGA (mBMSC/BMP-2) expressed more osteogenic genes and showed effective orthotopic bone formation in a mouse model with a critical-sized bone defect in only 3–4 weeks. CONCLUSION The Col/γ-PGA(mBMSC/BMP-2) hydrogel was suggested to be a promising platform by combining collagen as a major component of the extracellular matrix and γ-PGA as a viscosity reducer for easy handling at room temperature in BMSC-based bone tissue engineering scaffolds.

PURPOSE: To investigate trends in blood pressure (BP) and hypertension prevalence in Korea. MATERIALS AND METHODS: Based on the Korean National Health and Nutrition Examination Survey (KNHANES) I (1998), II (2001), III (2005), IV (2007–2009), V (2010–2012), and VI (2013–2014), 56077 participants (23974 men and 32103 women) were included. RESULTS: Mean systolic BP (SBP) and diastolic BP (DBP) decreased in both sexes (male SBP: 128.1 to 120.2 mm Hg, male DBP: 82.0 to 78.5 mm Hg; female SBP: 125.7 to 116.0 mm Hg and female DBP: 77.4 to 73.2 mm Hg from the KNHANES I–VI). The age-standardized prevalence of hypertension was significantly decreased in both sexes (male; 33.3% to 30.3%, female; 28.7% to 22.7%, all p for trend < 0.001). Regardless of taking anti-hypertensive medication or not, SBP and DBP declined universally in both sexes. Compared to the KNHANES I, the odds ratios (95% confidence intervals) of the KNHANES II to VI for less-than-normotensive and less-than-hypertensive BP increased in both sexes. CONCLUSION: Mean BP levels in both sexes and hypertension prevalence showed downward trends during the 16-year period.
Adult* ; Blood Pressure* ; Epidemiology ; Female ; Humans ; Hypertension* ; Korea ; Male ; Nutrition Surveys ; Odds Ratio ; Prevalence*

BACKGROUND: Increasing evidence supports interplay between aldosterone and parathyroid hormone (PTH), which may aggravate cardiovascular complications in various heart diseases. Negative structural cardiovascular remodeling by primary aldosteronism (PA) is also suspected to be associated with changes in calcium levels. However, to date, few clinical studies have examined how changes in calcium and PTH levels influence cardiovascular outcomes in PA patients. Therefore, we investigated the impact of altered calcium homeostasis caused by excessive aldosterone on cardiovascular parameters in patients with PA. METHODS: Forty-two patients (mean age 48.8±10.9 years; 1:1, male:female) whose plasma aldosterone concentration/plasma renin activity ratio was more than 30 were selected among those who had visited Severance Hospital from 2010 to 2014. All patients underwent adrenal venous sampling with complete access to both adrenal veins. RESULTS: The prevalence of unilateral adrenal adenoma (54.8%) was similar to that of bilateral adrenal hyperplasia. Mean serum corrected calcium level was 8.9±0.3 mg/dL (range, 8.3 to 9.9). The corrected calcium level had a negative linear correlation with left ventricular end-diastolic diameter (LVEDD, ρ=−0.424, P=0.031). Moreover, multivariable regression analysis showed that the corrected calcium level was marginally associated with the LVEDD and corrected QT (QTc) interval (β=−0.366, P=0.068 and β=−0.252, P=0.070, respectively). CONCLUSION: Aldosterone-mediated hypercalciuria and subsequent hypocalcemia may be partly involved in the development of cardiac remodeling as well as a prolonged QTc interval, in subjects with PA, thereby triggering deleterious effects on target organs additively.
Adenoma ; Aldosterone ; Calcium* ; Heart Diseases ; Homeostasis ; Humans ; Hyperaldosteronism* ; Hypercalciuria ; Hyperplasia ; Hypocalcemia ; Metabolism* ; Parathyroid Hormone ; Plasma ; Prevalence ; Renin ; Veins

BACKGROUND: The aim of this study was to investigate the relationship between serum ferritin and diabetes mellitus (DM) in the Korean population. METHODS: This cross-sectional study included 9,576 subjects (4,264 men, 2,394 pre-menopausal women, and 2,918 post-menopausal women) older than 19 years using data from the 2010-2012 Korean National Health and Nutrition Examination Survey. DM was defined as fasting plasma glucose ≥126 mg/dL, glycosylated hemoglobin ≥6.5%, or use of any glucose-lower medication including insulin therapy. RESULTS: The overall prevalence of DM was 12.0, 3.6, and 17.3% in men, pre-menopausal women, and post-menopausal women, respectively. DM prevalence was greater with ferritin levels from Q1 to Q4: 10.3, 10.2, 12.7, and 14.8% in men; 2.0, 2.8, 2.8, and 6.4% in pre-menopausal women; and 13.9, 14.4, 18.1, and 22.9% in post-menopausal women, respectively. Compared with participants in Q1, the odds ratios (95% confidence intervals) for DM among participants in Q4 were 1.67 (1.20-2.32) in men, 2.06 (0.91-4.66) in pre-menopausal women, and 1.60 (1.09-2.35) in post-menopausal women after adjusting for age and other covariates. CONCLUSION: Serum ferritin concentration was positively associated with a higher risk of DM in adult men and post-menopausal women.
Adult ; Blood Glucose ; Cross-Sectional Studies ; Diabetes Mellitus* ; Fasting ; Female ; Ferritins* ; Hemoglobin A, Glycosylated ; Humans ; Insulin ; Insulin Resistance ; Male ; Nutrition Surveys ; Odds Ratio ; Prevalence

BACKGROUND: It has not been determined which obesity index might be most appropriate to predict nonalcoholic fatty liver disease in Asian populations. This study aimed to evaluate the usefulness of the waist-to-height ratio in assessing patients with nonalcoholic fatty liver disease and to identify the optimal cut-off values useful for predicting nonalcoholic fatty liver disease. METHODS: Receiver operating characteristic curve analyses were conducted in order to assess the accuracy of the waist circumference, body mass index, and waist-to-height ratio for detecting nonalcoholic fatty liver disease among 616 women aged 20 years or older. To evaluate the optimal value of anthropometric indices, the Youden J-index (sensitivity+specificity-1) was used. RESULTS: The area under the ROC curve of waist-to-height ratio was highest among anthropometric obesity indices as follows: 0.776 (0.731-0.822) for waist circumference, 0.775 (0.728-0.822) for body mass index, and 0.792 (0.748-0.836) for waist-to-height ratio, respectively. Using a waist-to-height ration cut-off value of 0.49, the sensitivity and specificity for detecting nonalcoholic fatty liver disease were 72.3 % and 74.7%, respectively. CONCLUSION: These results demonstrated that the waist-to-height ratio may be a better obesity index for identifying individuals at risk for nonalcoholic fatty liver disease in Korean women.
Anthropometry ; Asian Continental Ancestry Group ; Body Mass Index ; Fatty Liver ; Female ; Humans ; Obesity ; ROC Curve ; Sensitivity and Specificity ; Waist Circumference

Adjuvants can be defined as pharmacological and immunological components that are able to modify and/or enhance antigen-specific immune responses. Based on the interdisciplinary research between immunology and material science/engineering, various vaccine adjuvant materials have been developed. By rational design and engineering of antigen or adjuvant materials, immune-modulatory vaccine systems generated to activate immune system. Here, we review the current progress of bioengineered prophylactic and/or therapeutic vaccine adjuvant for cancer and/or infectious disease, and discuss the prospect of future vaccine adjuvant materials.
Adjuvants, Immunologic ; Allergy and Immunology ; Communicable Diseases* ; Immune System ; Immunomodulation ; Immunotherapy*

BACKGROUND: In management of osteoporosis, several concerns here have been raised. The current issue included the utilization of dual energy X-ray absorptiometry (DXA) and fracture-risk assessment (FRAX), screening of vitamin D deficiency and secondary osteoporosis, and long-term use of bisphosphonate and calcium supplements. There was no study on physicians' attitude on these current issues in Korea. Therefore, we investigated the physicians' attitude on these issues by survey. METHODS: We administered a 30-item questionnaire to all members of Korean Society for Bone and Mineral Research by email survey form. One hundred participants answered the questionnaire. The questionnaire included the questions about the physicians' attitude to current issues and the barriers to osteoporosis treatment in Korea. RESULTS: Most physicians used bone densitometry devices (99%) and, central DXA was the most accessible device (95%). Eighty-eight percent were aware of FRAX(R), but among them, only 19.3% used it. The main reason for not using FRAX(R) was the lack of time in their proactive (76%). Screening for vitamin D status and secondary osteoporosis was performed by 59% and 52% of the respondents, respectively. The lack of awareness among patients and high costs of medication were perceived as the most important barriers to osteoporosis management in Korea. CONCLUSIONS: This study provides physicians' perspective to the current issue for diagnostic and treatment of osteoporosis in Korea. To further improve osteoporosis management, educational programs for patients and doctors, and the improvement of reimbursement system should be considered in Korea.
Absorptiometry, Photon ; Calcium ; Surveys and Questionnaires ; Densitometry ; Electronic Mail ; Humans ; Korea ; Mass Screening ; Osteoporosis* ; Vitamin D ; Vitamin D Deficiency

Pancreatic neuroendocrine tumors (pNETs) are rare neoplasms, which most commonly metastasize to the liver. However, intrathoracic metastases from pNETs are encountered infrequently. This report describes a case of nonfunctioning pNET with multiple cardiac metastases. A 56-year-old male presented with a palpable abdominal mass that showed progressive enlargement. Findings on computed tomography (CT) of the abdomen revealed two relatively well-marginated inhomogeneous low-attenuation masses, one in the head of the pancreas and the other in the tail. Multiple enhancing masses in the left pericardium with myocardial involvement were observed on chest CT and transthoracic echocardiography. Needle biopsies were performed on the mass in the tail of the pancreas and the left ventricular apical pericardium; histologic examination by hematoxylin and eosin morphology and immunohistochemical staining showed pNET in both. This is the first report of pNET with multiple cardiac metastases to previously undescribed metastatic sites.
Abdomen ; Biopsy, Needle ; Echocardiography ; Eosine Yellowish-(YS) ; Head ; Heart Neoplasms ; Hematoxylin ; Humans ; Liver ; Male ; Neoplasm Metastasis ; Neuroectodermal Tumors, Primitive ; Neuroendocrine Tumors ; Pancreas ; Pericardium ; Thorax

BACKGROUND: This study was to determine the impact on the national healthcare expenditure for the treatment of osteoporosis and fractures if the coverage period for osteoporosis medication was extended from maximum a year to continuous period as required. METHODS: Preserving the current reimbursement guidelines, maximum one year's coverage for osteoporosis medication was set as scenario A. Continuous coverage for patients who require medication was set as scenario B. As costs of medical service utilization are paid by the Korean National Health Insurance Program, all items were investigated and analyzed from the payer's perspective. The combined treatment costs for osteoporosis and osteoporotic fractures were assessed for each scenario. RESULTS: Over five years the cost of osteoporosis medication in scenario A will increase from 184.3 billion KRW to 204.6 billion KRW. The cost of osteoporotic fracture treatment will increase from 1,037.3 billion KRW to 1,822.7 billion KRW. In scenario B, the cost of osteoporosis medication will increase from 209.5 billion KRW to 388.1 KRW. The cost of osteoporotic fracture treatment will increase from 600.0 billion KRW to 1,054.3 billion KRW. The result showed savings of 2.50 trillion KRW cumulatively for five years when reimbursement coverage for osteoporosis treatments is extended from one year to as long as it's clinically required. CONCLUSIONS: This study demonstrates that effective osteoporosis management through appropriate insurance coverage for osteoporosis medication should be considered not only for the patient's viewpoint, but in terms of national insurance budget as well.
Budgets ; Delivery of Health Care ; Health Care Costs ; Health Expenditures ; Humans ; Income ; Insurance ; Insurance Coverage ; Korea ; National Health Programs ; Osteoporosis ; Osteoporotic Fractures ; Republic of Korea