ABSTRACT
In this study, we aimed to identify a toxic mechanism and the potential health effects of ambient dusts in an underground subway station. At 24 h exposure to human bronchial epithelial (BEAS-2B) cells (0, 2.5, 10, and 40 µg/mL), dusts located within autophagosome-like vacuoles, whereas a series of autophagic processes appeared to be blocked. The volume, potential and activity of mitochondria decreased in consistent with a condensed configuration, and the percentage of late apoptotic cells increased accompanying S phase arrest. While production of reactive oxygen species, expression of ferritin (heavy chain) protein, secretion of IL-6, IL-8 and matrix metalloproteinases, and the released LDH level notably increased in dust-treated cells (40 µg/mL), intracellular calcium level decreased. At day 14 after a single instillation to mice (0, 12.5, 50, and 200 µg/head), the total number of cells increased in the lungs of dust-treated mice with no significant change in cell composition. The pulmonary levels of TGF-ß, GM-CSF, IL-12 and IL-13 clearly increased following exposure to dusts, whereas that of CXCL-1 was dose-dependently inhibited. Additionally, the population of cytotoxic T cells in T lymphocytes in the spleen increased relative to that of helper T cells, and the levels of IgA and IgM in the bloodstream were significantly reduced in the dust-treated mice. Subsequently, to improve the possibility of extrapolating our findings to humans, we repeatedly instilled dusts (1 time/week, 4 weeks, 0.25 and 1.0 mg/head) to monkeys. The total number of cells, the relative portion of neutrophils, the level of TNF-α significantly increased in the lungs of dust-treated monkeys, and the expression of cytochrome C was enhanced in the lung tissues. Meanwhile, the pulmonary level of MIP-α was clearly reduced, and the expression of caveolin-1 was inhibited in the lung tissues. More importantly, inflammatory lesions, such as granuloma, were seen in both mice and monkeys instilled with dusts. Taken together, we conclude that dusts may impair the host's immune function against foreign bodies by inhibiting the capacity for production of antibodies. In addition, iron metabolism may be closely associated with dust-induced cell death and inflammatory response.
Subject(s)
Dust , Railroads , Animals , Cell Death , Dust/analysis , Lung/chemistry , Mice , Reactive Oxygen SpeciesABSTRACT
The physical properties of DNA have been suggested to play a central role in spatio-temporal organization of eukaryotic chromosomes. Experimental correlations have been established between the local nucleotide content of DNA and the frequency of inter- and intra-chromosomal contacts but the underlying physical mechanism remains unknown. Here, we combine fluorescence resonance energy transfer (FRET) measurements, precipitation assays, and molecular dynamics simulations to characterize the effect of DNA nucleotide content, sequence, and methylation on inter-DNA association and its correlation with DNA looping. First, we show that the strength of DNA condensation mediated by poly-lysine peptides as a reduced model of histone tails depends on the DNA's global nucleotide content but also on the local nucleotide sequence, which turns out to be qualitatively same as the condensation by spermine. Next, we show that the presence and spatial arrangement of C5 methyl groups determines the strength of inter-DNA attraction, partially explaining why RNA resists condensation. Interestingly, multi-color single molecule FRET measurements reveal strong anti-correlation between DNA looping and DNA-DNA association, suggesting that a common biophysical mechanism underlies them. We propose that the differential affinity between DNA regions of varying sequence pattern may drive the phase separation of chromatin into chromosomal subdomains.
Subject(s)
Base Sequence/physiology , Chromatin/chemistry , DNA Packaging/genetics , DNA/chemistry , Nucleic Acid Conformation , Chemical Fractionation/methods , Chemical Precipitation , Chromatin/metabolism , Chromatin Assembly and Disassembly/genetics , DNA/metabolism , Fluorescence Resonance Energy Transfer , Histones/metabolism , Molecular Dynamics SimulationABSTRACT
High-dose radiation-induced tissue damage is a major limiting factor in the medical application of nuclear technology. Herein, we tested 28-day repeated-dose toxicity of KMRC011, an agonist of toll-like receptor (TLR) 5, which is being developed as a medical countermeasure for radiation, using cynomolgus monkeys. KMRC011 (0.01, 0.02 or 0.04 mg/kg/day) was intramuscularly injected once daily for 4 weeks, and each two monkeys in both control and 0.04 mg/kg/day group were observed for an additional 2-week recovery period. There were no dose-related toxicological changes in mortality, clinical observations, body weight, food consumption, ophthalmological findings, electrocardiographs, coagulation, serum chemistry, organ weights, or urinalysis and urine chemistry. Although treatment-related changes, such as increased white blood cells, increased absolute and relative neutrophils, decreased relative lymphocytes and inflammatory lesions, were noted in the maximum dose group, these findings were not observed after the 2-week recovery period. Further, we considered that the kidneys and heart may be target organs of TLR5 agonists, as well as the spleen, and that autophagic signals can be triggered in tissue damage and the repair process. Importantly, accumulation of p62 protein, an indicator of autophagy, and a decrease of caveolin-1 protein, a regulator of TLR5 protein half-life, were found in both tissues from the highest dose group. Therefore, we conclude that the no-observed-adverse-effect level for KMRC011 may be greater than 0.04 mg/kg/day in male and female monkeys. Additionally, we propose that further studies are needed to identify the molecular signals, which are related to KMRC011-induced adverse effects.
Subject(s)
Peptide Fragments/toxicity , Radiation-Protective Agents/toxicity , Toll-Like Receptor 5/agonists , Animals , Autophagy/drug effects , Dose-Response Relationship, Drug , Female , Heart/drug effects , Injections, Intramuscular , Kidney/drug effects , Macaca fascicularis , Male , Peptide Fragments/blood , Radiation-Protective Agents/pharmacokinetics , Random Allocation , Spleen/drug effects , ToxicokineticsABSTRACT
AIM: The main purposes of the study were (i) to evaluate serum vitamin D concentration in the forms of 25(OH)D2 , 25(OH)D3 and total 25(OH)D in Korean postmenopausal women using the LC-MS/MS method, which offers increased sensitivity and selectivity; (ii) to determine the relationship between the bone turnover marker, parathyroid hormone (PTH) and 25(OH)D3 , total 25(OH)D separately; and (iii) to determine the factors that may be associated with vitamin D deficiency using body composition analysis and laboratory blood tests. METHOD: A total of 200 postmenopausal women were recruited from November 2012 to March 2014. To control for seasonal ultraviolet exposure time differences in serum 25(OH)D, laboratory tests were performed only from November to March when vitamin D is not synthesized. Independent relationships between 25(OH)D3 , total 25(OH)D and other variables were assessed by multiple regression analysis. RESULTS: The mean serum 25(OH)D2 , 25(OH)D3 and total 25(OH)D levels were 0.51 (±0.44) ng/mL, 14.23 (±7.05) ng/mL and 14.69 (±7.13) ng/mL, respectively. Both 25(OH)D3 and total 25(OH)D were positively correlated with erythrocyte sedimentation rate (ESR), Apo A-I and C-terminal cross-linked telopeptides of type I collagen in Korean postmenopausal women. Both serum 25(OH)D3 and total 25(OH)D were negatively correlated with alkaline phosphatase , PTH and percent body fat. However, osteocalcin showed a negative correlation (r = -0.451; P = 0.041) with only 25(OH)D3 and not with total 25(OH)D (r = -0.417; P = 0.064). CONCLUSION: Both 25(OH)D3 and total 25(OH)D were negatively correlated with PTH, a bone formation marker (alkaline phosphatase) and percent body fat. Both 25(OH)D3 and total 25(OH)D were positively correlated with a bone resorption marker (C-terminal cross-linked telopeptides of type I collagen), ESR and Apo A-I after multiple regression analysis.
Subject(s)
Alkaline Phosphatase/blood , Apolipoprotein A-I/blood , Biomarkers/blood , Calcifediol/blood , Collagen Type I/blood , Parathyroid Hormone/blood , Peptides/blood , Postmenopause/blood , Vitamin D/analogs & derivatives , 25-Hydroxyvitamin D 2/blood , Aged , Blood Sedimentation , Female , Humans , Middle Aged , Republic of Korea , Vitamin D/bloodABSTRACT
PURPOSE: The purpose of this study was to evaluate the association between ascending aortic diameter (AAD) as measured with low-dose chest computed tomography (LDCT) and hypertension in Korean men. METHODS: Korean men (n=1,050) who were screened for lung cancer using LDCT imaging at a health promotion center in Seoul, Korea between January 1 and December 31were recruited for the study. AAD is the longest length of ascending aorta measured from approximately 15 mm above left main coronary ostium to the mid-slice level of the right pulmonary artery. RESULTS: AAD were divided into quartiles, and the degree of hypertension was determined based on the quartiles of the AAD using logistic regression. Odds ratios (OR) for the proportion of hypertension in Q2 (1.70, 95% CI: 1.11-2.59), Q3 (2.72, 95% CI: 1.81-4.09) and Q4 (3.94, 95% CI: 2.63-5.89) were significantly greater than that of Q1 (P for trend < 0.001). Even after controlling for confounding covariates of age, BMI, total cholesterol, HDL-cholesterol, fasting glucose, GGT, ALT, eGFR, smoking status and alcohol intake, there was significant correlation. CONCLUSION: AAD was significantly associated with the degree of hypertension.
Subject(s)
Aorta/diagnostic imaging , Aorta/pathology , Hypertension/diagnostic imaging , Hypertension/pathology , Adult , Aged , Analysis of Variance , Humans , Logistic Models , Male , Middle Aged , Odds Ratio , Retrospective Studies , Tomography, X-Ray ComputedABSTRACT
A strategy to produce sufficient anticoagulant properties with reduced risk of bleeding may be possible through inhibition of factor XI (FXI), a component of the intrinsic coagulation cascade. The objective of this work was to determine the safety profile of ISIS 416858, a 2'-methoxyethoxy (2'-MOE) antisense oligonucleotide inhibitor of FXI, with focus on assessment of bleeding risk. Cynomolgus monkeys administered ISIS 416858 (4, 8, 12, and 40 mg/kg/wk, subcutaneous) for up to 13 weeks produced a dose-dependent reduction in FXI (mRNA in liver and plasma activity) and a concomitant increase in activated partial thromboplastin time (APTT). ISIS 416858 (20 or 40 mg/kg/wk) reduced plasma FXI activity by 80% at 4 weeks of treatment that resulted in a 33% increase in APTT by 13 weeks with no effects on PT, platelets, or increased bleeding following partial tail amputation or gum and skin laceration. The dose-dependent presence of basophilic granules in multiple tissues in ISIS 416858-treated animals was an expected histologic change for a 2'-MOE antisense oligonucleotide, and no toxicity was attributed to hepatic FXI reduction. Basophilic granules reflect cellular drug uptake and subsequent visualization on hematoxylin staining. These results suggest that ISIS 416858 has an acceptable preclinical safety profile and is a promising clinical candidate to treat thrombotic disease.
Subject(s)
Factor XI/antagonists & inhibitors , Hemorrhage/prevention & control , Oligonucleotides, Antisense/pharmacology , Partial Thromboplastin Time , Animals , Blood Coagulation/drug effects , Dose-Response Relationship, Drug , Drug Administration Schedule , Factor XI/genetics , Factor XI/metabolism , Female , Gene Expression Regulation/drug effects , Hemorrhage/blood , Infusions, Intravenous , Injections, Subcutaneous , Macaca fascicularis , Male , Oligonucleotides/administration & dosage , Oligonucleotides/genetics , Oligonucleotides, Antisense/administration & dosage , Oligonucleotides, Antisense/genetics , Reverse Transcriptase Polymerase Chain Reaction , Risk Factors , Treatment OutcomeABSTRACT
The goal of this study was to evaluate the association between gallbladder (GB) polyps and metabolic syndrome. A total of 5,685 healthy subjects were included, and 485 of these subjects had GB polyps and 744 had metabolic syndrome. In this study, metabolic syndrome was diagnosed according to standards suggested by the AHA/NHLBI ATP III 2005, and abdominal obesity (≥ 90 cm in men and ≥ 85 cm in women for Korean) was diagnosed according to standards set forth by the Korean Society for Study of Obesity. Biphasic logistic regression adjusted for age and gender was used to evaluate the association between metabolic syndrome and GB polyps. Subjects who were male (OR, 1.493; 95% CI, 1.11-2.00) and hepatitis B suface Ag (HBsAg) positive (OR, 1.591; 95% CI, 1.06-2.38) were significantly more likely to have GB polyps. The metabolic syndrome group had a higher risk of GB polyps (OR, 1.315; 95% CI, 1.01-1.69) than the group without metabolic syndrome. In conclusion, subjects who were HBsAg positive and male appear to be associated with the risk of GB polyps. The presence of metabolic syndrome also appears to be associated with the risk of GB polyps in Koreans.
Subject(s)
Gallbladder Diseases/diagnosis , Metabolic Syndrome/diagnosis , Adult , Age Factors , Asian People , Female , Gallbladder Diseases/etiology , Hepatitis B Surface Antigens/blood , Humans , Logistic Models , Male , Metabolic Syndrome/complications , Middle Aged , Odds Ratio , Republic of Korea , Risk Factors , Severity of Illness Index , Sex FactorsABSTRACT
BACKGROUND: Nonhuman primates (NHPs) are superior model for ocular research due to its morphological and physiological similarities with humans. Thus, the effect of four different anesthetic combinations [ketamine (10 mg/kg), ketamine + xylazine (7 + 0.6 mg/kg), zoletil (4 mg/kg), and zoletil + xylazine (4 + 0.2 mg/kg)] on intraocular pressure (IOP) was determined in cynomolgus monkeys. RESULTS: The administration of ketamine + xylazine or zoletil + xylazine resulted in lower IOP compared to ketamine or zoletil alone. Moreover, the IOP in male monkeys was higher than in females. The difference between the right and left eye was not found. CONCLUSIONS: Anesthetics affected the IOP, and gender differences should be considered when measuring the IOP of nonhuman primates (NHPs).
ABSTRACT
Recently, some researchers have demonstrated that inhaled zinc oxide nanoparticles (ZnONPs) induce an acute systemic inflammatory response in workers. Considering nonhuman primates are preferably considered an animal model for translational research due to their proven similarity with humans in terms of genetics and physiology, we intratracheally instilled ZnONPs to cynomolgus monkey for 14 days and identified the toxic mechanism and bioaccumulation. ZnONPs were rapidly ionized or aggregated in a simulated pulmonary fluid, and they attracted neutrophils to the lungs and increased the pulmonary level of inflammatory mediators. Additionally, thickened alveolar walls, fibrin clots, and hemorrhages were observed in the lungs of the monkeys instilled with the higher dose accompanied by cell debris in the alveolar ducts and alveoli. Dark-field microscopy images revealed translocation of ZnONPs into other tissues accompanied by an increase in the relative weight of livers to body weight. In addition, when instilled at the higher dose, the albumin/globulin ratio notably decreased compared to the control, whereas the C-reactive protein (CRP) level was significantly elevated. ZnONPs also clearly induced apoptotic cell death in a 24 h exposure to alveolar macrophages. Taken together, part of inhaled ZnONPs may be ionized in the lung, resulting in acute toxic effects, including cell death and tissue damage, and the rest may move to other tissues in the form of particles, causing a systemic inflammatory response. Based on the proven evidence among workers, we also suggest that the CRP level can be recommended as a biomarker for ZnONPs-induced adverse health effects.
Subject(s)
Lung , Nanoparticles , Systemic Inflammatory Response Syndrome , Zinc Oxide , Animals , Lung/drug effects , Macaca fascicularis , Nanoparticles/toxicity , Zinc Oxide/toxicityABSTRACT
BACKGROUND: Several reports have raised the possibility that newly addressed lipid measures might be superior to the traditional ones for cardiovascular risk prediction. However, data on the associations between these lipid measures with metabolic syndrome (MetS) is limited. METHODS AND RESULTS: A cross-sectional study of participants in routine health examinations was performed. The associations between lipid measure variables (total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), TC/HDL-C, LDL-C/HDL-C, TG/HDL-C ratio and non-HDL-C) and MetS, insulin resistance (IR) by homeostatic model assessment (HOMA) and adiponectin were analyzed in 6,546 participants (3,820 men; mean age 46.0+/-9.2 years in men, 44.6+/-9.5 years in women). In multivariable adjusted regression analysis, the 3 lipid ratios of TC/HDL-C, LDL-C/HDL-C and TG/HDL-C showed significant association with the number of MetS components, HOMA and log adiponectin level in both men and women without MetS (P<0.001, respectively), though these relations were weaker in participants with MetS. The mean levels of the lipid ratios also associated with increasing numbers of the MetS components, quartiles of HOMA and adiponectin. CONCLUSIONS: Lipid ratios of TC/HDL-C, LDL-C/HDL-C and TG/HDL-C, as well as TG and HDL, were consistently associated with MetS and IR in participants without MetS. Lipid ratios might be used as integrated and simple lipid measures.
Subject(s)
Adiponectin/blood , Insulin Resistance , Lipids/blood , Metabolic Syndrome/blood , Models, Biological , Adult , Asian People , Female , Humans , Male , Metabolic Syndrome/epidemiology , Middle Aged , Republic of Korea/epidemiologyABSTRACT
In the study here, the potential applicability of KMRC011 - an agonist of toll-like receptor-5 - as a countermeasure for radiation toxicities was evaluated. Following a single 5.5 Gy total body irradiation (TBI, surface absorbed dose = 7 Gy) of Co60 γ-rays, mortality rates and degrees of pathological lesions that developed over 80 days were compared in monkeys that received TBI only and a group that was injected once with KMRC011 (10 µg/kg) after TBI. Compared to the TBI-only hosts (80%), the death rate was significantly improved by the use of KMRC011 (40%), all deaths in both groups occurred in the period from Days 19-24 post-TBI. Further analysis of monkeys that survived until the end of the experiment showed that AST and ALT levels were elevated only in the TBI group, and that radiation-induced tissue damage was alleviated by the KMRC011 injection. Additionally, expression of cell death-related proteins was lower in tissues from the KMRC011-treated hosts than in those in the TBI-only group. Other measured parameters, including body weight, food uptake, and hematological values did not significantly differ between the two groups over the entire period. The results of this study, thus demonstrate that KMRC011 could potentially be used as a medical countermeasure for the treatment of acute radiation exposure.
Subject(s)
Peptide Fragments/pharmacology , Radiation Injuries, Experimental/prevention & control , Radiation-Protective Agents/pharmacology , Toll-Like Receptor 5/agonists , Animals , Drug Evaluation, Preclinical , Humans , Immunity, Innate/drug effects , Immunity, Innate/radiation effects , Injections, Intramuscular , Macaca fascicularis , Male , Peptide Fragments/therapeutic use , Radiation Injuries, Experimental/immunology , Radiation-Protective Agents/therapeutic use , Signal Transduction/drug effects , Signal Transduction/immunology , Signal Transduction/radiation effects , Toll-Like Receptor 5/metabolism , Whole-Body IrradiationABSTRACT
A B-cell activating factor of the tumor necrosis factor (TNF) family (BAFF) is an essential B-cell survival factor. Myasthenia gravis (MG) is one of the most typical antibody-mediated autoimmune disorders. To test whether serum BAFF levels are increased in MG patients, we compared the serum BAFF levels of 40 MG patients with those of 30 healthy controls. Serum BAFF levels of MG group were significantly higher than those of healthy group. These results suggested that the BAFF might play a role in the immunopathogenesis of MG and further study on B-cell and T-cell activation may be needed.
Subject(s)
B-Cell Activating Factor/blood , Myasthenia Gravis/blood , Adult , Autoantibodies/blood , Autoantibodies/immunology , Autoantigens/immunology , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Middle Aged , Receptors, Cholinergic/immunologyABSTRACT
As indicators of obesity, waist circumference (WC), body mass index (BMI), and adiponectin are well-known risk factors for diabetes mellitus. The objectives of this study were to measure the independent association between these obesity indicators and diabetes and to examine the combined effect of these indicators on diabetes in a Korean population. The WC, BMI, and serum adiponectin were measured in 4459 healthy Koreans and were classified into tertile groups for men and women. The independent and combined associations of the obesity indicators with diabetes were measured using logistic regression analyses. Diabetes was defined as fasting serum glucose greater than 126 mg/dL or taking medication. Levels of adiponectin were inversely associated with BMI and WC and directly associated with age and high-density lipoprotein (HDL) cholesterol (P < .001). After adjusting for age, BMI, WC, and other lifestyle factors, low levels of adiponectin were associated with an increased prevalence of diabetes. Further adjustment for HDL cholesterol and triglyceride attenuated this association in women but not men. The combined effects of WC and adiponectin on diabetes progressively increased; however, the interaction of these 2 variables was not statistically significant. The combined effect of BMI and adiponectin on diabetes showed similar results. These results suggest that adiponectin was associated with diabetes. The association was independent of BMI and WC and was partly modified by HDL and triglyceride. There were no effect modifications of adiponectin with WC and BMI on diabetes.
Subject(s)
Adiponectin/blood , Diabetes Mellitus/blood , Adult , Aged , Aged, 80 and over , Body Mass Index , Cholesterol, HDL/blood , Cross-Sectional Studies , Diabetes Mellitus/etiology , Female , Humans , Logistic Models , Male , Middle Aged , Sex Characteristics , Triglycerides/bloodABSTRACT
BACKGROUND: The aim of this study was to examine the correlation between the number of remaining natural teeth (NRT) and the appendicular skeletal muscle mass index (SMI) in older adults. METHODS: This study was based on data from the 2008-2010 Korea National Health and Nutritional Examination Surveys. The participants were 2,378 older participants (984 men and 1,394 women) aged over 65 years. Survey dentists conducted oral health examinations, and ASM was measured using dual-energy X-ray absorptiometry. RESULTS: The participants with NRT≥20 had more ASM and SMI than those with NRT<20 in both sexes. SMI was correlated with NRT in men (r=0.018, p<0.001) and in women (r=-0.007, p<0.001). The positive correlation between the NRT and SMI remained significant in men even after adjusting for age, marital status, income, smoking, drinking, physical activity, protein intake, energy intake, calcium intake, body mass index, fasting blood glucose level, medications, and prostheses (ß=0.011, p=0.001). In women, the correlation disappeared after adjustment for smoking, alcohol, physical activity, protein intake, energy intake, calcium intake, marital status, income, fasting basal glucose, medication administration, and prostheses. CONCLUSION: This study showed a correlation between NRT and SMI in those ≥65 years of age in Korea. The relationship persisted in men, but not in women, even after adjusting for confounders.
ABSTRACT
Considering that cigarette smoke condensate (CSC) is primarily absorbed through the alveoli in the lungs, herein, we used a mouse alveolar macrophage cell line (MH-S cells). After 24â¯h exposure, CSC decreased dose-dependently cell viability accompanying an increase in intracellular ROS and NO level. CSC structurally or functionally damaged organelles including mitochondria, ER and lysosome and enhanced the expression of proteins related to apoptosis, ER stress and DNA damage accompanying an elevated proportion of annexin V-bound cells. Meanwhile, the expression of certain proteins related to mitochondrial dynamics (OPA1 and DRP1) and autophagy (ATG5) did not overall show significant dose-dependent change in cells exposed to CSC. More importantly, conversion of LC3-I to LC3B-II, a representative marker for autophagy, was also unclear. Considering that intracellular organelles work together in harmony to perform defense mechanism against foreign bodies, we investigated changes in immune response following CSC exposure. The level of IFN-γ and MIP-1α was elevated in CSC-exposed cells, whereas the MCP-1α level decreased. The expression of chemokine receptors (CD195 and CXCR2) and an adhesion molecule (CD54) increased by CSC treatment, the expression of certain antigen presentation-related proteins (MHC class II, CD40, and CD80) were also enhanced. Meanwhile, the expression of CD86, a co-stimulatory molecule for antigen presentation, dose-dependently decreased. In conclusion, we suggest that CSC may induce apoptotic cell death and disturbance in host defense mechanisms by impairing function of cellular components.
Subject(s)
Macrophages, Alveolar/drug effects , Organelles/drug effects , Smoke/adverse effects , Tobacco Products , Animals , Apoptosis/drug effects , Apoptosis Regulatory Proteins/metabolism , Cell Line , Cytokines/metabolism , DNA Damage , Macrophages, Alveolar/immunology , Macrophages, Alveolar/metabolism , Macrophages, Alveolar/ultrastructure , Mice , Microscopy, Electron, Transmission , Nitric Oxide/metabolism , Organelles/ultrastructure , Reactive Oxygen Species/metabolism , Receptors, CCR5/metabolism , Receptors, Interleukin-8B/metabolismABSTRACT
To assess the relevance of previous epidemiologic studies on bisphosphonate-related osteonecrosis of the jaw (BRONJ), we first conducted a systematic review of large population-based observational studies and evaluated the validity of claims-based algorithms for the identification of BRONJ. Studies containing primary observational epidemiologic data regarding bisphosphonate (BP) exposure and outcomes of osteonecrosis of the jaw were systematically reviewed. Using surrogates for identifying potential BRONJ cases from a population-based hospital registry, validation was performed through medical chart review. Positive predictive value (PPV) was estimated for each diagnostic code and for the overall algorithm utilized. Various strategies to increase PPV were also performed. Seventeen studies were systematically reviewed and presented with variations in study quality as well as inconsistent findings. Moreover, there was a high level of methodological heterogeneity. A total of 1920 patients were identified through the ICD-10 algorithm with potential BRONJ, although only 109 cases were confirmed, corresponding to an overall PPV of 5.68% (95% confidence interval [CI] 4.68-6.81). Only K10.2 (inflammatory conditions of the jaw) exhibited a relatively high PPV of 26.18%, which increased to 74.47% after confinement to BP users. Other strategies to increase PPV value were not effective. Our findings showed that the overall PPV for BRONJ identification was very low, indicating low validity of the current algorithm and possible overestimation of ONJ occurrence. There is an urgent need to develop more reliable and specific operational definitions for the identification of BRONJ cases in large population databases. © 2016 American Society for Bone and Mineral Research.
Subject(s)
Algorithms , Bisphosphonate-Associated Osteonecrosis of the Jaw/epidemiology , Uncertainty , Aged , Female , Humans , Male , Risk FactorsABSTRACT
BACKGROUND: The sodium intake of Koreans was higher than that recommended by the World Health Organization. Urinary sodium, which is correlated with sodium intake, can be easily calculated by the Tanaka's equation. This study aimed to evaluate the association between urinary sodium and metabolic syndrome in Korean adults using the 2010-2011 Korean National Health and Nutrition Examination Survey (KNHANES). METHODS: A total of 5,870 participants from the 2010-2011 KNHANES were included in this study. Twenty-four hour urinary sodium was calculated by the Tanaka's equation using spot urine. Participants were divided into tertiles based on urinary sodium levels. The association between urinary sodium and metabolic syndrome was analyzed using multivariate logistic regression analysis. RESULTS: The odds ratios (ORs) and 95% confidence intervals (CIs) of metabolic syndrome for the 2nd and 3rd tertile of urinary sodium levels was 1.51 (1.16-1.97) and 1.56 (1.23-1.97) compared to the lowest tertile of urinary sodium in men. The ORs and 95% CIs of metabolic syndrome in women were 1.20 (0.95-1.51) for the 2nd tertile and 2.16 (1.68-2.78) for the 3rd tertile. These associations remained statistically significant, even after adjusting for multiple covariates such as age, education, regular exercise, smoking, and alcohol consumption. CONCLUSION: These findings indicate that urinary sodium is significantly associated with metabolic syndrome in Korean adults.
ABSTRACT
Mounting evidence suggests that not all obese subjects are at increased cardiovascular risk. However, the relationship between the metabolically healthy obese (MHO) phenotype and cardiovascular diseases (CVDs) or stroke remains unclear. Therefore, we retrospectively investigated the prevalence of CVDs or stroke according to metabolic health with obese.We studied 3695 subjects (40-85 years) from the Fifth Korean National Health and Nutrition Examination Survey. Participants were divided into 2 groups and 6 subgroups based on the body mass index (BMI) and metabolic syndrome (MetS) components: healthy (exhibiting none of the 5 MetS components) with the followings: healthy-normal weight (BMI < 23âkg/m), healthy-overweight (BMI = 23-24.9âkg/m), and healthy-obese (BMI ≥ 25âkg/m); and unhealthy (exhibiting 2 or more MetS components) with the followings: unhealthy-normal weight, unhealthy-overweight, and unhealthy-obese.In the healthy group (n = 1726), there were 76 CVDs or stroke patients (4.4%), whereas in the unhealthy group (n = 1969), there were 170 (8.6%). The prevalence was significantly different between the 2 groups (Pâ<â0.001). However, the prevalence was not significantly different among healthy subgroups (P = 0.4072). The prevalence in unhealthy subgroups also demonstrated no statistically significant difference (P = 0.3798).We suggest that the prevalence of CVDs or stroke is different between metabolically healthy and unhealthy phenotype. Furthermore, MHO did not reveal higher CVDs or stroke prevalence rather than metabolically healthy other groups. Additional cohort studies are needed to explain causality between CVDs or stroke incidence and subjects exhibiting the MHO phenotype.
Subject(s)
Cardiovascular Diseases/epidemiology , Health Status , Life Style , Metabolic Diseases/epidemiology , Nutrition Surveys , Obesity/epidemiology , Stroke/epidemiology , Adult , Aged , Aged, 80 and over , Cardiovascular Diseases/etiology , Cross-Sectional Studies , Female , Humans , Incidence , Male , Middle Aged , Obesity/complications , Population Surveillance/methods , Prevalence , Republic of Korea/epidemiology , Risk Factors , Stroke/etiologyABSTRACT
BACKGROUND: There is little research regarding whether working as a physician affects cancer risk. Moreover, there is no research on cancer prevalence among physicians in Korea. This study utilized the Korea National Cancer Incidence Database to determine whether the prevalence of cancer among physicians differs from the prevalence of cancer within the general population. METHODS: We analyzed the medical records of a representative sample of 382 doctors who underwent a health examination between 2010 and 2013 at a health examination center in a Ewha Womans University Medical Center.Cancer incidence was measured as cases that were eventually diagnosed as cancer according to a biopsy. RESULTS: We collected medical records from 382 physicians (mean age, 51.9±8.1 years) and calculated the standardized prevalence ratios compared to the general population. Thirty physicians (9 male and 21 female) were identified as having cancer. Physicians had a significantly higher prevalence of cancer compared to the general population.Cancer prevalence in male physicians was found to be 2.47 times higher than the prevalence expected within the general population (P=0.006). Among female physicians, cancer prevalence was 3.94 times higher than that in the general population (P<0.001). CONCLUSION: This study revealed that physicians had a higher prevalence of cancer compared to the general population in Korea, which suggests that there may be a problem present in the health care of physicians. Changes to the working environment of physicians will be needed to reduce the high prevalence of cancer among physicians.
ABSTRACT
BACKGROUND: Insulin resistance (IR) reduces reactivity of the target organ to blood insulin. Researchers have attempted to evaluate IR using various serum lipid concentration ratios. We aimed to determine the most strongly IR-predictive lipid profile ratios for each sex by studying associations between lipid concentration ratios and IR using data from the fifth Korea National Health and Nutrition Examination Survey (KNHANES V-1) 2010. METHODS: Overall, 8958 individuals participated in health interview and examination surveys. Among them, 1910 individuals who completed physical examinations and 8-h fasting blood tests and were older than 20 years of age were enrolled (929 men and 981 women). The lipid-ratio-related study outcomes were the low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL-C/HDL-C), triglyceride (TG)/HDL-C, and non-HDL-C (LDL-C + TG/5)/HDL-C ratios. We divided subjects into 4 groups according to lipid profile ratio quartiles for a comparison of homeostasis model assessment (HOMA)-IR values. Regression analyses were performed after adjusting for the confounding factors of age, body mass index, and diabetes mellitus history. RESULTS: HOMA-IR values tended to increase significantly along with LDL-C/HDL-C, TG/HDL-C, and non-HDL-C/HDL-C ratios in both sexes. In men, multiple linear regression analyses showed that after adjusting for confounding factors, a significant positive association remained only with the LDL-C/HDL-C ratio (p = 0.0238, R(2) = 0.3605, root mean squared error [MSE] =0.3512). In women, multiple linear regression analyses showed that after adjusting for confounding factors, significant positive associations remained with the LDL-C/HDL-C (p < 0.0001, R-square = 0.2329, root MSE = 0.3776), TG/HDL-C (p = 0.0001, R(2) = 0.2373, root MSE = 0.3766), and non-HDL-C/HDL-C ratios (p < 0.0001, R(2) = 0.2456, root MSE = 0.3745). CONCLUSION: The LDL-C/HDL-C ratio in men and LDL-C/HDL-C, TG/HDL-C, and non-HDL-C/HDL-C ratios in women might be clinically significant predictors of IR in healthy Korean adults. However, additional large-scale studies are required to confirm these findings.