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The pandemic has highlighted the importance of sanitary, affordable, and secure housing. This publication shares lessons from Asian Development Bank (ADB) assistance in the housing sector between 2000 and 2020. It notes the need to balance supporting the poor and vulnerable with making markets work better. The authors identify two essential components of an effective housing ecosystem: (i) well-targeted subsidies for low-income households, and (ii) housing finance and supply for middle-income households that enables them to pay their own way.

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).

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.

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.

In this chapter, the authors propose urban development strategies for Pyongyang, North Korea. First, the authors highlight the concept of “city to city,” rather than “country to country,” to be introduced to facilitate closer exchange and potential cooperation between the cities in South and North Korea. Second, the authors suggest including the improvement of living conditions in the housing sector in development plans. Third, the authors highlight the importance of South Korea in terms of sharing its experiences and know-how. Lastly, the authors explore that the concept of land swapping, which has been proceeded between Singapore and Malaysia, should be introduced as one of possible urban development strategies to initiate urban development in North Korea.

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.

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.

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.

Background: Vitamin D is effective in prevention of osteoporosis. Lower than recommended intake of vitamin D leads to an increased risk of cancer, hypertension, cardiovascular disease, diabetes mellitus, and autoimmune disease. We aimed to evaluate the relationship between serum vitamin D levels and metabolic syndrome in Korean elderly people. Methods: In this cross-sectional study, we assessed 1,515 participants aged ≥65 years from Korean National Health and Nutritional Examination Survey 2012. We excluded patients with chronic renal and hepatic failure along with those who were bed-ridden for more than 15 days. In total, 1,264 individuals were enrolled. Results: We observed that higher levels of vitamin D were associated with lower prevalence of metabolic syndrome (odds ratio [OR], 0.33; 95% confidence interval [CI], 0.154–0.709; P=0.004). The adjusted OR for triglyceride concentration in individuals with optimum vitamin D intake was 0.41 (95% CI, 0.18–0.92; P=0.029). Conclusion: These findings indicate that levels of vitamin D are significantly associated with the prevalence of metabolic syndrome and triglyceride concentration in the Korean elderly people.

Background: This study aimed to evaluate the association between smoking and bone mineral density in Korean men. Methods: We assessed the data for 2,821 participants aged ≥19 years, obtained from the Korean National Health and Nutritional Examination Survey 2010. We compared the bone mineral density values taking into account life style-related factors and examined the relationship between smoking and bone mineral density. To investigate the impact of smoking on bone mineral density, a logistic regression analysis was conducted. Results: Bone mineral density values for the femur neck in former smokers were significantly lower than that in never smokers (P

prevalence of chronic kidney disease was analyzed based on the quartiles. Results: The results showed a positive correlation between an increasing tendency of the odds ratio (OR) for the prevalence rate of chronic kidney disease (95% confidence interval) and an increase in the TG/HDL-C ratio in an unadjusted model for Korean adults (P for trend

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

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-β, 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.

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.

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.

Despite the previous studies showing the relationship between microalbuminuria and insulin resistance, longitudinal effect of insulin resistance on development of microalbuminuria is not clearly identified in non-diabetic population.One thousand six hundred three non-diabetic Korean men without microalbuminuria in 2005 had been followed up for the development of microalbuminuria until 2010. Microalbuminuria was evaluated by urine-albumin creatinine ration, and insulin resistance was evaluated by homeostasis model assessment of insulin resistance (HOMA-IR). Cox proportional hazards model was used to estimate the risk for microalbuminuria according to the tertile of HOMA-IR.During 5465.8 person-y of average follow-up, microalbuminuria developed in 76 (4.7%) participants. Incidence of microalbuminuria increased in proportion to the level of HOMA-IR (tertile 1: 3.0%, tertile 2: 4.1%, tertile 3: 7.1%, P0.001). When the 1st tertile of HOMA-IR was set as reference, hazard ratios and 95% confidence interval were 1.15 (0.56-2.35) and 2.07 (1.05-4.09) for those in the 2nd and 3rd tertiles of HOMA-IR, even after adjusting multiple covariates, respectively (P for linear trend=0.054).Increased insulin resistance was a predictor of microalbuminuria in Korean men.

Aims There have been several studies on the association between metabolic syndrome (MetS) and microalbuminuria. However, none has examined whether MetS is associated with the prospective development of microalbuminuria. Accordingly, we performed a prospective study to evaluate the longitudinal effects of baseline number of MetS traits on the development of microalbuminuria in Korean men. Methods 1649 Korean men without microalbuminuria in 2005 were included and followed prospectively until 2010 with the endpoint being the development of microalbuminuria. MetS was defined according to the joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention. Microalbuminuria was evaluated by urine albumin creatinine ratio (UACR). Risk estimations for development of microalbuminuria were analyzed according to the number of MetS traits using multivariate adjusted Cox proportional hazards model. Results During 5611.8 person-years of follow-up (median 3.40 ± 1.46 years), microalbuminuria developed in 91 (5.5%) participants between 2006 and 2010. After adjusting for multiple covariates, the hazard ratios (95% confidence interval) for development of microalbuminuria comparing 1, 2 and 3–5 MetS traits vs 0 were 2.57 (0.97–6.82), 2.94 (1.09–7.98) and 3.85 (1.37–10.86), respectively. Conclusions The number of MetS traits independently associated with the future development of microalbuminuria during the 5-year follow-up period, and MetS per se was an independent risk factor for microalbuminuria.

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 24 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.

The main purposes of the study were (i) to evaluate serum vitamin D concentration in the forms of 25(OH)DA 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)DThe mean serum 25(OH)DBoth 25(OH)D

BACKGROUND Although measuring would size using digital photography is a quick and simple method to evaluate the skin wound, the possible compatibility of it has not been fully validated. PURPOSE To investigate the error rate of our newly developed wound surface area calculation using digital photography. METHODS Using a smartphone and a digital single lens reflex (DSLR) camera, four photographs of various sized wounds (diameter: 0.5-3.5 cm) were taken from the facial skin model in company with color patches. The quantitative values of wound areas were automatically calculated. The relative error (RE) of this method with regard to wound sizes and types of camera was analyzed. RESULTS RE of individual calculated area was from 0.0329% (DSLR, diameter 1.0 cm) to 23.7166% (smartphone, diameter 2.0 cm). In spite of the correction of lens curvature, smartphone has significantly higher error rate than DSLR camera (3.9431±2.9772 vs 8.1303±4.8236). However, in cases of wound diameter below than 3 cm, REs of average values of four photographs were below than 5%. In addition, there was no difference in the average value of wound area taken by smartphone and DSLR camera in those cases. CONCLUSION For the follow-up of small skin defect (diameter

Graduate School of Education, Seoul National University,Seoul, KoreaOBJECTIVES: This study investigated the associationbetween bone mineral density (BMD) and periodontitisin a representative sample of Korean adults.MATERIAL AND METHODS: Of 36 188 individuals whoparticipated in the Korea National Health and NutritionExamination Survey in 2008, 2009, and 2010, 9977participants aged ≥40 years were included in this cross-sectional study. The associations of BMD of lumbarspine, total femur, and femoral neck with periodontitiswere investigated using logistic regression analysis.Additionally, dose–response relationships with BMDdivided into quintiles and the association between oste-oporosis and periodontitis were investigated.RESULTS: With the set of Community PeriodontalIndex (CPI) ≥ 3 as a dependent variable, logistic regres-sion analysis revealed that a decrease of BMD was sig-nificantly associated with higher odds of periodontitis[range of adjusted odds ratios (AORs); 1.15–1.20,P < 0.001 for all BMD sites]. Similarly, these associa-tions were also found in the CPI 4 model. With regardto dose–response relations, the lower the BMD quintile,the higher the AORs appeared with statistical signifi-cance in the CPI ≥ 3 model. (P for trend < 0.001) Partic-ipants with osteoporosis had 2.26 and 1.91 times higherodds for CPI ≥ 3 and CPI 4, respectively, than thosewith normal BMD, indicating a significant associationbetween the two diseases.CONCLUSIONS: Our results suggest that BMD issignificantly associated with periodontitis.Oral Diseases (2014) 20, 609–615Keywords: osteoporosis; periodontitis; bone mineral density;osteopenia; National Health and Nutrition Examination Survey;Community Periodontal Index

Background Studies on factors which may predict the risk of diabetes are scarce. This prospective cohort study was conducted to determine the association between adiponectin and type 2 diabetes among Korean men and women. Methods A total of 42,845 participants who visited one of seven health examination centers located in Seoul and Gyeonggi province, Republic of Korea between 2004 and 2008 were included in this study. The incidence rates of diabetes were determined through December 2011. To evaluate the effects of adiponectin on type 2 diabetes, the Cox proportional hazard model was used. Results Of the 40,005 participants, 959 developed type 2 diabetes during a 6-year follow-up. After the adjustment for age, body mass index (BMI), and waist circumference, the risks for type 2 diabetes in participants with normoglycemia had a 1.70-fold (95% confidence interval [CI], 1.21 to 2.38) increase in men and a 1.83-fold (95% CI, 1.17 to 2.86) increase in women with the lowest tertile of adiponectin when compared to the highest tertile of adiponectin. For participants with impaired fasting glucose (IFG), the risk for type 2 diabetes had a 1.46-fold (95% CI, 1.17 to 1.83) increase in men and a 2.52-fold (95% CI, 1.57 to 4.06) increase in women with the lowest tertile of adiponectin. Except for female participants with normoglycemia, all the risks remained significant after the adjustment for fasting glucose and other confounding variables. Surprisingly, BMI and waist circumference were not predictors of type 2 diabetes in men or women with IFG after adjustment for fasting glucose and other confounders. Conclusion A strong association between adiponectin and diabetes was observed. The use of adiponectin as a predictor of type 2 diabetes is considered to be useful.

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.

Objective Cardiovascular disease risk increases after menopause, which may be related to insulin resistance, and arterial stiffness is a significant predictor of atherosclerosis. We investigated the relationships among insulin resistance, adiponectin, and arterial stiffness in normoglycemic normotensive postmenopausal women. Methods From 9,555 participants who had routine health checkups, 455 normoglycemic normotensive postmenopausal women were enrolled. Serum concentrations of glucose, total cholesterol, triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) and adiponectin were measured. Insulin resistance was estimated by the insulin resistance index of homeostasis model assessment (HOMA-IR). Pulse wave velocity (PWV) was evaluated to assess arterial stiffness. Results The women were stratified into three groups according to their HOMA-IR values, and comparisons were made among the three groups. There were significant differences in metabolic parameters between the groups. The mean age, body mass index, waist circumference, fasting plasma glucose, TG, systolic blood pressure (SBP), diastolic blood pressure (DBP), aortic PWV, and peripheral PWV increased sequentially with the degree of insulin resistance. Meanwhile, HDL-C and adiponectin levels decreased with the worsening of insulin resistance. Age, body mass index, fasting plasma glucose, TG, insulin, SBP, HOMA-IR, aortic PWV, and peripheral PWV were significantly higher in women with central obesity, and HDL-C and adiponectin were significantly lower in women with central obesity. Aortic PWV and peripheral PWV were significantly correlated with age, waist circumference, total cholesterol, SBP, DBP, insulin, and HOMA-IR, but adiponectin was not associated with PWV. The results of multiple regression analysis indicated that SBP, DBP, and insulin resistance were independently correlated with PWV. Conclusions Insulin resistance was independently associated with PWV in normoglycemic normotensive postmenopausal women.

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

The aims of this study were to determine (1) whether the urinary mid pregnancy and placental delivery oxidative stress levels are related to the intrauterine condition and (2) whether long-lasting adverse oxidative stress is related to the birth size. We investigated pregnant women when they were at 24-28 weeks of pregnancy from October 2001 to May 2003 and at their delivery. Samples were obtained at each investigation time. Other information of mothers and their birth records were tracked from medical charts at Ewha Womans University Hospital in Seoul, South Korea. We quantified mid pregnancy oxidative stress by measuring urinary levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) in 272 subjects. Intrauterine oxidative stress at delivery was measured by placental levels of 8-OHdG and MDA in 54 and 38 subjects, respectively. To identify the correlated intrauterine oxidative stress conditions, we evaluated kappa statistics and Pearson's correlations between maternal and placental oxidative stress. The relationships between intrauterine oxidative stress and birth sizes were examined by a general linear model. The levels of oxidative stress were divided to two groups based on their 75th percentile values. There was no correlation between urinary mid pregnancy and placental delivery oxidative stress levels for both MDA (kappa index=0.32, r=0.21) and 8-OHdG (kappa index=-0.13, r=-0.11). Both the urinary mid pregnancy and delivery 8-OHdG levels were significantly related to birth size. The birth size was largest in the 8-OHdG group. In addition, birth size was worse in the group with both high urinary mid pregnancy and placental oxidative stress than in any other combinations of low and high groups of urinary mid pregnancy and placental delivery oxidative stress. This evidence for a weak correlation between urinary mid pregnancy and placental delivery oxidative stress levels and its interactive effects on birth size suggest that the period from the middle to the end of pregnancy is critical window to intrauterine growth and also represents a modifiable period of the intrauterine condition. Therefore, applying interventions to pregnant women with high oxidative stress levels at midterm could contribute to increasing birth sizes.

We aimed to assess how metabolic profiles, surrogate markers of insulin resistance, and subclinical atherosclerosis are interrelated in subjects with impaired fasting glucose (IFG) and investigate whether the diagnosis of metabolic syndrome (MetS) further increases the risk of cardiovascular disease among subjects already at risk. We analyzed 1739 Korean subjects with IFG. The parameters of MetS, plasma adiponectin level, and pulse wave velocity (PWV) were assessed. Subjects with MetS had unfavorable metabolic parameters, lower adiponectin level, and higher peripheral PWV compared to those without MetS. Adiponectin correlated with fasting glucose, waist circumference, triglyceride, HDL-cholesterol, BMI, HOMA-IR, and the number of MetS components. In addition to blood pressure, peripheral PWV was associated with triglyceride, waist circumference, and the number of MetS components while aortic PWV correlated positively with fasting plasma glucose. Multiple linear regression analysis revealed that adiponectin correlated with HDL-cholesterol, HOMA-IR, fasting glucose, waist circumference, and triglyceride, peripheral PWV with blood pressure, body mass index, waist circumference, and the number of MetS components, and aortic PWV with fasting plasma glucose. In subjects with IFG, concurrent MetS increases PWV and has an unfavorable effect on cardiovascular risks, and these risks were further increased by additional MetS components.

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.

Pregnancy is associated with increased susceptibility to oxidative stress. Deficiencies in antioxidants during pregnancy and placental oxidant-antioxidant imbalance may impair the development of the fetoplacental unit or the eventual offspring. In order to elucidate the association of prenatal status of vitamin C with the oxidative stress and apoptotic activity in normal full-term placentas, we evaluated the content of placental lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and the trophoblast apoptotic index in normal-term human pregnancies. Tissue samples of placentas obtained from 80 normal-term pregnancies were categorized into 40 cases with a lower level of prenatal vitamin C (8.997 microg/ml) and 40 cases with a higher level of prenatal vitamin C (or =11.734 microg/ml). We evaluated the placental LOX-1 content and the trophoblast apoptotic index with Western blot analysis and immunohistochemistry, and then determined their correlation with the prenatal status of vitamin C. We confirmed that the trophoblast expression for the endothelial scavenger receptor LOX-1 and the apoptotic activity were significantly lower in the group with a higher prenatal level of vitamin C, indicating that placental oxidative stress and the apoptotic index were associated with the maternal status of vitamin C. We therefore postulate that the maternal status of antioxidant vitamins during pregnancy can affect fetal development.