Changes in proteinuria and the associated risks of ischemic heart disease, acute myocardial infarction, and angina pectoris in Korean population.

OBJECTIVES: Proteinuria is widely used to predict cardiovascular risk. However, there is insufficient evidence to predict how changes in proteinuria may affect the incidence of cardiovascular disease. METHODS: The study included 265,236 Korean adults who underwent health checkups in 2003-2004 and 2007-2008. They were categorized into 4 groups based on changes in proteinuria (negative: negative → negative; resolved: proteinuria ≥1+ → negative; incident: negative → proteinuria ≥1+; persistent: proteinuria ≥1+ → proteinuria ≥1+). We conducted 6 years of follow-up to identify the risks of developing ischemic heart disease (IHD), acute myocardial infarction (AMI), and angina pectoris according to changes in proteinuria. A multivariate Cox proportional-hazards model was used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident IHD, AMI, and angina pectoris. RESULTS: The IHD risk (expressed as HR [95% CI]) was the highest for persistent proteinuria, followed in descending order by incident and resolved proteinuria, compared with negative proteinuria (negative: reference, resolved: 1.211 [95% CI, 1.104 to 1.329], incident: 1.288 [95% CI, 1.184 to 1.400], and persistent: 1.578 [95% CI, 1.324 to 1.881]). The same pattern was associated with AMI (negative: reference, resolved: 1.401 [95% CI, 1.048 to 1.872], incident: 1.606 [95% CI, 1.268 to 2.035], and persistent: 2.069 [95% CI, 1.281 to 3.342]) and angina pectoris (negative: reference, resolved: 1.184 [95% CI, 1.065 to 1.316], incident: 1.275 [95% CI, 1.160 to 1.401], and persistent: 1.554 [95% CI, 1.272 to 1.899]). CONCLUSIONS: Experiencing proteinuria increased the risks of IHD, AMI, and angina pectoris even after proteinuria resolved.

Changes in smoking status, amount of smoking and their relation to the risk of microvascular complications in men with diabetes mellitus.

BACKGROUND: Smoking is a definite risk factor for macrovascular complications in diabetes mellitus (DM). However, the effect of smoking on microvascular complications is inconclusive. METHOD: Study participants were 26,673 diabetic men who received health check-up both in 2003-2004 and 2009, excluding women. Assessing smoking status (never, quitting and current) at 2003-2004 and 2009, changes in smoking status were categorised into 7 groups (never - never, never - quitting, never - current, quitting-quitting, quitting-current, current-quitting and current-current). Smoking amount was categorised into never, light (0-10 pack years), moderate (10-20 pack years), and heavy smoking (>20 pack years) based on 2009 data. They were followed-up until 2013 to identify incident microvascular complications. We calculated the adjusted hazard ratios (HR) and 95% confidence interval (CI) (adjusted HR [95% CI]) for incident microvascular complications according to changes in smoking status and smoking amount. RESULTS: Current-quitting (1.271 [1.050-1.538]), current-current (1.243 [1.070-1.444]) and heavy smoking (1.238 [1.078-1.422]) were associated with an increased risk of overall microvascular complications. The risk of nephropathy increased in current-current smoking (1.429 [1.098-1.860]) and heavy smoking (1.357 [1.061-1.734]). An increased risk of neuropathy was observed in current-quitting smoking (1.360 [1.076-1.719]), current-current smoking (1.237 [1.025-1.492]) and heavy smoking (1.246 [1.048-1.481]). However, we couldn't see the interpretable findings for the association between smoking and retinopathy. CONCLUSIONS: Lasting and heavy smoking increases the risk of microvascular complications, including nephropathy and neuropathy. Quitting smoking and reducing smoking amount are imperative in preventing microvascular complications in DM patients.

Correlation of commute time with the risk of subjective mental health problems: 6th Korean Working Conditions Survey (KWCS).

Background: Studies conducted so far on the link between commute time and mental health among Koreans remain insufficient. In this study, we attempted to identify the relationship between commute time and subjective mental health using the 6th Korean Working Conditions Survey (KWCS). Methods: Self-reported commute time was divided into four groups: ≤ 30 (group 1), 30-60 (group 2), 60-120 (group 3), and > 120 minutes (group 4). Subjective depression was defined as a score of 50 points or less on the WHO-5 well-being index. Subjective anxiety and fatigue were defined as answering 'yes' to the questionnaire on whether they had experienced it over the past year. The analysis of variance, t-test, and χ2 test was used to analyze the differences among the characteristics of the study participants according to commute time, depression, anxiety, and fatigue. Odds ratios (ORs) and 95% confidence intervals (CIs) for depression, anxiety, and fatigue according to commute time were calculated using multivariate logistic regression models adjusted for sex, age, monthly income, occupation, company size, weekly working hours, and shift work status. Results: Long commute times showed increased ORs and graded increasing trends for depression, anxiety, and fatigue. The ORs for depression increased significantly in group 2 (1.06 [1.01-1.11]), group 3 (1.23 [1.13-1.33]), and group 4 (1.31 [1.09-1.57]) compared to group 1 (reference). The ORs for anxiety increased significantly in group 2 (1.17 [1.06-1.29]), group 3 (1.43 [1.23-1.65]) and group 4 (1.89 [1.42-2.53]). The ORs for fatigue increased significantly in group 2 (1.09 [1.04-1.15]), group 3 (1.32 [1.21-1.43]), and group 4 (1.51 [1.25-1.82]). Conclusions: This study highlights that the risk of depression, anxiety, and fatigue increases with commute time.

Effect of gonadotropin-releasing hormone agonist treatment on near final height in girls with central precocious puberty and early puberty.

PURPOSE: The aim of this study was to examine whether gonadotropin-releasing hormone (GnRH) agonist treatment is effective in preserving final height in patients with central precocious puberty (CPP) or early puberty (EP). METHODS: The medical records of 40 patients with CPP and 206 patients with EP who completed GnRH agonist treatment following diagnosis were analyzed retrospectively. Height and height standard deviation (height SDS) scores based on bone age (BA) were measured and calculated at baseline, after treatment completion, and at final follow-up to compare changes within and between groups. Predicted adult height (PAH) was estimated by the height corresponding to height SDS for BA in girls at 18 years 11 months of age based on the growth chart. RESULTS: PAH at baseline did not differ significantly between the CPP group (153.67±4.95) and the EP group (154.77±3.72). In the CPP group, PAH significantly increased at treatment completion (156.01±4.61) and at final follow-up (158.52±6.04) compared to baseline. In the EP group, PAH significantly increased at treatment completion (157.7±3.60) and at final follow-up (159.31±4.26) compared to baseline. The increase in PAH at all timepoints compared to baseline did not significantly differ between the CPP and EP groups. CONCLUSION: Both CPP and EP groups had significantly greater PAH after treatment, with no difference in the amount of increase between groups. These results show that GnRH agonist treatment can help increase final height even in patients diagnosed with EP after the age of 8 years.

The relationship between visual display terminal usage at work and symptoms related to computer vision syndrome.

Background: Although it is well known that the usage of visual display terminal (VDT) at the workplace causes computer vision syndrome (CVS), previous studies mainly focused on computer use and the health of white-collar workers. In this study, we explored the relationship between the usage of VDT including various devices, and symptoms related to CVS in a large population including pink-collar workers and blue-collar workers. Methods: 21,304 wage workers over the age of 20 years were analyzed from the 6th Korean Working Conditions Survey. To investigate the association between VDT use at work and symptoms related to CVS among wage workers, odds ratios (ORs) and 95% confidence interval (CI) were calculated by multivariate logistic regression models. Results: In the group with the highest VDT usage at work, the OR of headache/eyestrain was 2.16 (95% CI: 1.86-2.52). The OR of suspected CVS patients was significantly increased in the highest group of usage of VDT at work (OR: 1.69; 95% CI, 1.39-2.06). Compare with the reference group, the OR for headache/eyestrain in the highest group of VDT usage was 2.81 (95% CI: 2.13-3.70) in white-collar workers, 1.78 (95% CI: 1.32-2.40) in pink-collar workers, and 1.59 (95% CI: 1.18-2.15) in blue-collar workers. Conclusions: We observed a relationship in which the use of VDT in the workplace increases the risk of headache/eyestrain regardless of occupational classification. Our findings emphasize the importance of paying attention to the health of VDT workers and making plans to improve their working conditions.

Incidence of congenital hypothyroidism by gestational age: a retrospective observational study.

BACKGRUOUND: Congenital hypothyroidism (CH) is the leading cause of preventable physical and intellectual disabilities. This study aimed to assess the incidence and clinical characteristics of CH in newborns. METHODS: We retrospectively reviewed the medical records of all newborns delivered at the Pusan National University Hospital between January 2011 and March 2021. The incidence of CH was compared according to gestational age, birth weight, and small for gestational age (SGA). The patients aged ≥3 years who could not maintain normal thyroid function and required levothyroxine treatment were diagnosed with permanent CH. Logistic regression analysis was performed to compare CH risks. RESULTS: Of 3,722 newborns, 40 were diagnosed with CH (1.07%). Gestational age and birth weight were significantly associated with CH incidence. The odds ratios (ORs) of CH in infants delivered at 32-37, 28-31, and <28 weeks were 2.568 (95% confidence interval [CI], 1.141-5.778), 5.917 (95% CI, 2.264-15.464), and 7.441 (95% CI, 2.617-21.159) times higher, respectively, than those delivered at term. The ORs of CH in infants weighing 1,500-2,499 g, 1,000-1,499 g, and <1,000 g were 4.664 (95% CI, 1.928-11.279), 11.076 (95% CI, 4.089-29.999), and 12.544 (95% CI, 4.350-36.176) times greater, respectively, than those in infants weighing ≥2,500 g. The OR of CH was 6.795 (95% CI, 3.553-13.692) times greater in SGA than in non-SGA infants. CONCLUSION: The CH incidence in South Korea has increased significantly compared with that in the past. Gestational age, birth weight, and SGA were significantly associated with CH incidence.

No difference in follow-up estimated glomerular filtration rate between hypertensive and matched nonhypertensive kidney donors.

BACKGROUND: According to current guidelines, kidney donor candidates with controlled hypertension using 1 or 2 antihypertensive drugs may be considered as donor. However, this recommendation is based on the study that antihypertensive drug was initiated in mainly "after donor registration" and this may be white-coat hypertension because of donation-related anxiety. We compared the follow-up eGFR between kidney donors with preexisting hypertension and matched nonhypertensive donors. METHODS: This single-center retrospective study classified 97 living hypertensive donors previously receiving antihypertensive drugs into two groups: 1 drug group (61 donors) and 2 drugs group (36 donors). We compared the follow-up eGFR between each donor previously receiving antihypertensive drugs and three matched nonhypertensive donors in terms of age, sex, and follow-up duration. RESULTS: At a mean (range) of 51 months (12-214) in the 1 drug group, and 54 months (12-175) in the 2 drugs group after donation, there was no significant difference in follow-up eGFR between hypertensive donors previously receiving antihypertensive drugs and matched controls in each group and in total donors. There was no difference in the incidence of the patients with follow-up eGFR<45mL/min/m2 in each group and their matched controls. Multiple linear regression analysis showed that baseline eGFR was the only independent predictor for the final follow-up eGFR in the total donors. CONCLUSION: Our results support the current guidelines that donor candidates with controlled hypertension using 1 or 2 antihypertensive drugs may be considered as donors, and may increase the strength of this recommendation.

The risk of gastric cancer according to changes in smoking status among Korean men.

OBJECTIVES: Smoking is a risk factor for gastric cancer. Studies have shown that the risk of gastric cancer can vary by smoking status and smoking amount at a single point in time. However, few data have been reported about the effect of changes in smoking status over time on the risk of gastric cancer. METHODS: This study collected data from the National Health Insurance Corporation in Korea on 97,700 Korean men without gastric cancer who underwent health check-ups from 2002 to 2013. The smoking status (never smoked, quit smoking, and currently smoking) of study participants was assessed in 2003-2004 and 2009, and the results were categorized into 7 groups: never-never, never-quit, never-current, quit-quit, quit-current, current-quit, and current-current. Participants were followed until 2013 to identify incident gastric cancer. A multivariate Cox proportional hazard model was used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident gastric cancer according to changes in smoking status and smoking amount (pack-years). RESULTS: Compared with group 1 (never-never), participants currently smoking in 2009 (never-current, quit-current, and current-current) had higher HRs for gastric cancer (never-quit: 1.077; 95% CI, 0.887 to 1.306, never-current: 1.347; 95% CI, 0.983 to1.846, quit-quit: 1.086; 95% CI, 0.863 to 1.366, quit-current: 1.538; 95% CI, 1.042 to 2.269, current-quit: 1.339; 95% CI, 1.077 to 1.666, and current-current: 1.589; 95% CI, 1.355 to 1.864, respectively). The risk for gastric cancer was highest in heavy smokers, followed by moderate smokers. CONCLUSIONS: In all categories of smoking status, current smoking was associated with the highest risk of gastric cancer. Heavy smoking was associated with an increased risk of gastric cancer, even in former smokers.

Association of metabolites of benzene and toluene with lipid profiles in Korean adults: Korean National Environmental Health Survey (2015-2017).

BACKGROUND: Environmental exposure to benzene and toluene is a suspected risk factor for metabolic disorders among the general adult population. However, the effects of benzene and toluene on blood lipid profiles remain unclear. In this study, we investigated the association between urinary blood lipid profiles and metabolites of benzene and toluene in Korean adults. METHODS: We analyzed the data of 3,423 adults from the Korean National Environmental Health Survey Cycle 3 (2015-2017). We used urinary trans,trans-muconic acid (ttMA) as a biomarker of benzene exposure, and urinary benzylmercapturic acid (BMA) as an indicator of toluene exposure. Multivariate logistic regression analyses were performed to explore the association between blood lipid profiles and urinary metabolites of benzene and toluene. Additionally, we examined the linear relationship and urinary metabolites of benzene and toluene between lipoprotein ratios using multivariate regression analyses. RESULTS: After adjusting for covariates, the fourth quartile (Q4) of ttMA [odds ratio (OR) (95% confidence interval, CI = 1.599 (1.231, 2.077)] and Q3 of BMA [OR (95% CI) = 1.579 (1.129, 2.208)] were associated with an increased risk of hypertriglyceridemia. However, the Q4 of urinary ttMA [OR (95% CI) = 0.654 (0.446, 0.961)] and Q3 of urinary BMA [OR (95% CI) = 0.619 (0.430, 0.889)] decreased the risk of a high level of low-density lipoprotein cholesterol (LDL-C). Higher urinary ttMA levels were positively associated with the ratio of triglycerides to high-density lipoproteins [Q4 compared to Q1: ß = 0.11, 95% CI: (0.02, 0.20)]. Higher urinary metabolite levels were negatively associated with the ratio of low-density lipoprotein to high-density lipoprotein [Q4 of ttMA compared to reference: ß = -0.06, 95% CI: (-0.11, -0.01); Q4 of BMA compared to reference: ß = -0.13, 95% CI: (-0.19, -0.08)]. CONCLUSION: Benzene and toluene metabolites were significantly and positively associated with hypertriglyceridemia. However, urinary ttMA and BMA levels were negatively associated with high LDL-C levels. These findings suggest that environmental exposure to benzene and toluene disrupts lipid metabolism in humans.

Percutaneous pericardial catheter drainage for symptomatic uremic pericardial effusions with narrow safety margins.

BACKGROUND: Percutaneous pericardial catheter drainage (PCD) for pericardial effusion is generally known to be limited by the high risk associated with effusions that are less than 10 mm thick. The objective was to report cases who underwent percutaneous PCD for symptomatic uremic pericardial effusions, which were less than 10 mm thick after cardiologist declined to perform the PCDs because of the narrow safety margins. MATERIALS AND METHODS: Thirteen consecutive cases (11 patients) (median age, 56 years, range, 31-83) with symptomatic uremic pericardial effusion (thickness <10 mm) affecting the pericardial space anterior to the right ventricle underwent ultrasound- and fluoroscopy-guided percutaneous PCD between September 2015 and April 2022. Information regarding the clinical criteria, echocardiographic features, PCD details, nature of effusion, and outcomes, including success and complications were retrospectively evaluated. RESULTS: Pigtail catheter (8.5-Fr) insertion was successful for all patients, with a median procedure time of 7 minutes (range 4~12) without procedure-related complications. The median amount of drainage on the day of PCD was 700 mL (range, 250-1100). The median duration of catheter indwelling was 5 days (range, 1~32). In one case, the catheter was removed after 1 day due to chest pain. For all patients, pericardial effusion evacuation was achieved with relief of associated symptoms, representing 100% clinical success. CONCLUSION: Percutaneous PCD may be safely performed for patients with symptomatic uremic pericardial effusions and narrow safety margins of less than 10 mm.

Fasting blood glucose and risk of incident pancreatic cancer.

BACKGROUND: The number of patients with diabetes and impaired fasting blood glucose in Korea is rapidly increasing compared to the past, and other metabolic indicators of population are also changed in recent years. To clarify the mechanism more clearly, we investigated the association between fasting blood glucose and incidence of pancreatic cancer in this retrospective cohort study. METHODS: In Korea National Health Information Database, 19,050 participants without pancreatic cancer in 2009 were enrolled, and followed up until 2013. We assessed the risk of incident pancreatic cancer according to the quartile groups of fasting blood glucose level (quartile 1: <88 mg/dL, quartile 2: 88-97 mg/dL, quartile 3: 97-109 mg/dL and quartile 4: ≥109 mg/dL). Multivariate Cox-proportional hazard model was used in calculating hazard ratios (HRs) and 95% confidence interval (CI) for incident pancreatic cancer. RESULTS: Compared with quartile1 (reference), unadjusted HRs and 95% CI for incident pancreatic cancer significantly increased in order of quartile2 (1.39 [1.01-1.92]), quartile3 (1.50 [1.09-2.07]) and quartile4 (2.18 [1.62-2.95]), and fully adjusted HRs and 95% CI significantly increased from quartile2 (1.47 [1.05-2.04]), quartile3 (1.61 [1.05-2.04]) to quartile4 (2.31 [1.68-3.17]). CONCLUSION: Fasting blood glucose even with pre-diabetic range was significantly associated with the incident pancreatic cancer in Korean.

Change in smoking status and its relation to the risk of gastroduodenal ulcer in Korean men.

BACKGROUND AND AIM: Smoking is associated with the increased risk of gastroduodenal ulcer. However, although smoking status can vary over time, most of studies have analyzed this association with smoking status at a single point of time. We analyzed the risk of gastroduodenal ulcer according to change in smoking status for more than 5 years. METHODS: Study participants were 43 380 Korean adults free of gastroduodenal ulcer who received health check-up between 2002 and 2013. Through evaluating their smoking status (never, quitter, and current) at 2003-2004 and 2009, they were categorized them into seven groups (never-never, never-quitter, never-current, quitter-quitter, quitter-current, current-quitter, and current-current) and monitored until 2013 to identify incident gastroduodenal ulcer. Cox-proportional hazard model was used to calculate the adjusted hazard ratios (HRs) and 95% confidence interval (CI) for incident gastroduodenal ulcer according to changes in smoking status and smoking amount. RESULTS: Compared with never-never group (reference), other groups had the significantly increased adjusted HRs and 95% CI for gastroduodenal ulcer. In particular, participants with current smoking (never-current, quitter-current, and current-current) had the relatively higher HRs than other groups (never-quitter: 1.200 [1.070-1.346], never-current: 1.375 [1.156-1.636], quitter-quitter: 1.149 [1.010-1.306], quitter-current: 1.325 [1.058-1.660], current-quitter: 1.344 [1.188-1.519], and current-current: 1.379 [1.256-1.513]). Heavy smoker had the highest risk for gastroduodenal ulcer, followed by moderate and light smoker. CONCLUSION: People who ever experienced smoking had increased risk of gastroduodenal ulcer. Out of smoking status, current smoking is more associated with the increased risk of gastroduodenal ulcer than past smoking.

The association of pancreatic cancer incidence with smoking status and smoking amount in Korean men.

OBJECTIVES: Our study examined the dose-response relationship between smoking amounts (pack-years) and the risk of developing pancreatic cancer in Korean men. METHODS: Of 125,743 participants who underwent medical health checkups in 2009, 121,408 were included in the final analysis and observed for the development of pancreatic cancer. We evaluated the associations between smoking amounts and incident pancreatic cancer in 4 groups classified by pack-year amounts. Cox proportional hazards models were used to estimate the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of incident pancreatic cancer by comparing groups 2 (<20 pack-year smokers), 3 (20-≤40 pack-year smokers), and 4 (>40 pack-year smokers) with group 1 (never smokers). RESULTS: During 527,974.5 person-years of follow-up, 245 incident cases of pancreatic cancer developed between 2009 and 2013. The multivariate-adjusted HRs (95% CIs) for incident pancreatic cancer in groups 2, 3, and 4 were 1.05 (0.76 to 1.45), 1.28 (0.91 to 1.80), and 1.57 (1.00 to 2.46), respectively (p for trend=0.025). The HR (95% CI) of former smokers showed a dose-response relationship in the unadjusted model, but did not show a statistically significant association in the multivariate-adjusted model. The HR (95% CI) of current smokers showed a dose-response relationship in both the unadjusted (p for trend=0.020) and multivariate-adjusted models (p for trend=0.050). CONCLUSIONS: The risk of developing pancreatic cancer was higher in current smokers status than in former smokers among Korean men, indicating that smoking cessation may have a protective effect.

Chromosomal Microarray in Children With Developmental Delay: The Experience of a Tertiary Center in Korea.

Background and Objectives: Chromosomal microarray (CMA) is a first-tier genetic test for children with developmental delay (DD), intellectual disability (ID), autism spectrum disorders (ASDs), and multiple congenital anomalies (MCA). In this study, we report our experiences with the use of CMA in Korean children with unexplained DD/ID. Methods: We performed CMA in a cohort of 308 children with DD/ID between January 2010 and September 2020. We also retrospectively reviewed their medical records. The Affymetrix CytoScan 750 K array with an average resolution of 100 kb was used to perform CMA. Results: Comorbid neurodevelopmental disorders were ASD (37 patients; 12.0%), epilepsy (34 patients; 11.0%), and attention deficit hyperactivity disorders (12 patients; 3.9%). The diagnostic yield was 18.5%. Among the 221 copy number variants (CNVs) identified, 70 CNVs (57 patients; 18.5%) were pathogenic. Deletion CNVs were more common among pathogenic CNVs (PCNVs) than in non-PCNVs (P < 0.001). The size difference between PCNVs and non-PCNVs was not significant (P = 0.023). The number of included genes within CNV intervals was significantly higher in PCNVs (average 8.6; 0-347) than in non-PCNVs (average 47.5; 1-386) (P < 0.001). Short stature and hearing difficulty were also more common in the PCNV group than in the non-PCNV group (P = 0.010 and 0.070, respectively). Conclusion: This study provides additional evidence for the usefulness of CMA in genetic testing of children with DD/ID in Korea. The pathogenicity of CNVs correlated with the number of included genes within the CNV interval and deletion type of the CNVs, but not with CNV size.

Association between urinary trans,trans-muconic acid and diabetes: a cross-sectional analysis of data from Korean National Environmental Health Survey (KoNEHS) cycle 3 (2015-2017).

BACKGROUND: Benzene is a ubiquitous air pollutant that is well known to cause hematopoietic effects in humans including leukemia. Recently, several studies have discussed its non-carcinogenic effects such as diabetes. This study aimed to investigate the association between diabetes and urinary trans,trans-muconic acid (t,t-MA), one of benzene metabolite, using adult data from Korean National Environmental Health Survey (KoNEHS) cycle 3 (2015-2017). METHODS: This study analyzed 3,777 adults (1,645 men and 2,132 women) from the KoNEHS cycle 3 (2015-2017). The distribution and fraction of each independent variable were presented separately according to the urinary benzene metabolite levels (t,t-MA quartiles) and diabetes to determine the general characteristics of the subjects. Odds ratios (ORs) were calculated using logistic regression after stratification by gender and smoking status to identify the association between urinary t,t-MA and diabetes. RESULTS: Compared with the first quartile (reference), the risk of diabetes significantly increased above the 4th (1.834 [1.107-3.039]) quartile in men and above the 3rd (1.826 [1.095-3.044]) and 4th (2.243 [1.332-3.776]) quartiles in women after adjustment. Stratified analysis based on smoking revealed that the ORs for the 3rd (1.847 [1.146-2.976]) and 4th (1.862 [1.136-3.052]) quartiles in non-smokers and those for the 2nd (1.721 [1.046-2.832]), 3rd (1.797 [1.059-3.050]), and 4th (2.546 [1.509-4.293]) quartiles in smokers were significantly higher. CONCLUSIONS: We confirmed that urinary t,t-MA is significantly associated with diabetes regardless of gender and smoking status. And further studies are necessary to access the clinical impacts of this findings.

Relationship between urinary phthalate metabolites and diabetes: Korean National Environmental Health Survey (KoNEHS) cycle 3 (2015-2017).

BACKGROUND: We aimed to determine relationship diabetes according to urinary phthalate metabolites using adult data from Korean National Environmental Health Survey cycle 3 (2015-2017). METHOD: This study was conducted on 3,781 adults aged 19 years and older (1,648 men and 2,133 women) based on KoNEHS cycle 3. Participants' data were analyzed by gender; Relationship between phthalate metabolites in the urine and diabetes was analyzed by dividing the sociodemographic variables, health behavior-related variables, and urinary phthalate metabolite concentrations into quartiles. To determine the relationship between urinary phthalate metabolites and the prevalence of diabetes, the odds ratio (OR) was calculated using logistic regression analysis. RESULTS: Based on the 1st quartile of each metabolite, the ORs for di-2-ethylhexyl phthalate (DEHP) (4th quartile), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) (2nd quartile, 3rd quartile and 4th quartile), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) (4th quartile), mono-(2-ethyl-5-carboxypentyl) phthalate (MECCP) (4th quartile), mono-n-butyl phthalate (MnBP) (3rd quartile and 4th quartile), mono-benzyl phthalate (MBzP) (2nd quartile) and 4th quartile), and mono (3-carboxypropyl) phthalate (MCPP) (3rd quartile and 4th quartile) were significantly higher after the adjustment in men. The ORs for DEHP (2nd quartile, 3rd quartile and 4th quartile), MEHHP (2nd quartile, 3rd quartile and 4th quartile), MEOHP (4th quartile), MECCP (4th quartile), MBzP (4th quartile), and MCPP (4th quartile) were significantly higher after the adjustment in women. CONCLUSION: This study investigated relationship between urinary phthalate metabolites and diabetes. The higher urinary phthalate metabolites, the higher the prevalence of diabetes. Further regulation of phthalate may be needed, and further studies are warranted to confirm the association between phthalate concentration and other chronic diseases (such as hypertension, hyperlipidemia, and cardiovascular disease).

Relationship between seafood consumption and bisphenol A exposure: the Second Korean National Environmental Health Survey (KoNEHS 2012-2014).

BACKGROUND: This study aimed to identify the relationship between exposure to bisphenol A (BPA) and seafood consumption using a nationally representative data of the general Korean population. METHODS: This study was conducted on 5,402 adults aged 19 years and older (2,488 men, 2,914 women) based on the second Korean National Environmental Health Survey (2012-2014). We stratified the data according to gender and analyzed urinary BPA concentrations in terms of sociodemographic characteristics, health behavior, dietary factor, and seafood consumption. In the high and low BPA exposure groups, the odds ratios (ORs) were calculated using logistic regression analysis according to the top 75th percentile concentration. RESULTS: In men, large fish and tuna and other seafood categories had significantly higher ORs before and after adjustment in the group who consumed seafood more than once a week than in the group who rarely consumed seafood, with an adjusted value of 1.97 (95% confidence interval [CI]: 1.12-3.48) and 1.74 (95% CI: 1.10-2.75), respectively. In the shellfish category, the unadjusted OR was 1.61 (95% CI: 1.00-2.59), which was significantly higher in the group who consumed seafood more than once a week than in the group who rarely consumed seafood. However, the OR after adjusting for the variables was not statistically significant. In women, the frequency of seafood consumption and the concentration of urinary BPA were not significantly associated. CONCLUSIONS: BPA concentration was higher in men who frequently consumed large fish and tuna, shellfish and other seafood in this study.

ALK inhibitors of bis-ortho-alkoxy-para-piperazinesubstituted-pyrimidines and -triazines for cancer treatment.

Syntheses of various bis-ortho-alkoxy-para-piperazineanilino-pyrimidines and -triazines of KRCA-0008 analogs are described and their structure-activity-relationship to anaplastic lymphoma kinase (ALK) is discussed. 5-trifluoromethyl-2,4-pyrimidine analog (2) seems to be most potent in both biochemical and cellular assay in this study, however it shows inferior mice xenograft activity to Crizotinib presumably due to its sub-optimal PK parameters. 4,6-disubstituted pyrimidine and 2,4-disubstituted triazine derivatives of KRCA-0008 are less potent or inactive to ALK wt., and this observation is explained with their molecular modeling compared to KRCA-0008.

Novel 2,4-dianilino-5-fluoropyrimidine derivatives possessing ALK inhibitory activities.

A new series of 2,4-dianilino-5-fluoropyrimidine derivatives were designed and synthesized and their anaplastic lymphoma kinase (ALK) inhibitory activities were evaluated by biochemical and cell-based assays in order to discover a new ALK inhibitor. Most compounds synthesized showed good inhibitory activities against ALK and good cytotoxic activities in H3122 cell line. The best compound 6f showed good activity against wild-type ALK along with crizotinib-resistant mutant ALK, and it showed 6 times better activity in cell-based assay than crizotinib. Some SAR studies were performed by the comparisons of the activities between 6 and the designed-synthesized compounds.

Novel bis-ortho-alkoxy-para-piperazinesubstituted-2,4-dianilinopyrimidines (KRCA-0008) as potent and selective ALK inhibitors for anticancer treatment.

The synthesis of bis-ortho-alkoxy-para-piperazinesubstituted-2,4-dianilinopyrimidines is described and their structure-activity-relationship to anaplastic lymphoma kinase (ALK) is presented. KRCA-0008 is selective and potent to ALK and Ack1, and displays drug-like properties without hERG liability. KRCA-0008 demonstrates in vivo efficacy comparable to Crizotinib in xenograft mice model.