Intracellular and in vivo activities of oxazolidinone drugs against Mycobacterium avium complex infection.

The prevalence of Mycobacterium avium complex-pulmonary disease (MAC-PD) has become a growing concern worldwide, and current treatments involving macrolides (clarithromycin [CLR] or azithromycin), ethambutol, and rifampicin have limited success, highlighting the need for better therapeutic strategies. Recently, oxazolidinone drugs have been identified as novel anti-tuberculosis drugs effective against drug-resistant M. tuberculosis. However, the effects of these drugs against MAC are still controversial due to limited data. Here, we first evaluated the intracellular anti-MAC activities of two oxazolidinone drugs, linezolid (LZD) and delpazolid (DZD), against 10 macrolide-susceptible MAC strains and one macrolide-resistant M. avium strain in murine bone marrow-derived macrophages (BMDMs) and found that both drugs demonstrated similar potential. The synergistic efficacies with CLR were then determined in a chronic progressive MAC-PD murine model by initiating a 4-week treatment at 8 weeks post-infection. Upon assessment of bacterial burdens and inflamed lesions, oxazolidinone drugs exhibited no anti-MAC effect, and there was no significant difference in the synergistic effect of CLR between LZD and DZD. These findings suggest that oxazolidinone drugs inhibit intracellular bacterial growth, even against macrolide-resistant MAC, but their clinical application requires further consideration.

In vitro and intracellular activities of novel thiopeptide derivatives against macrolide-susceptible and macrolide-resistant Mycobacterium avium complex.

Unsatisfactory outcomes following long-term multidrug treatment in patients with Mycobacterium avium complex (MAC) pulmonary disease have urged us to develop novel antibiotics. Thiopeptides, a class of peptide antibiotics derived from natural products, have potential as drug candidates that target bacterial ribosomes, but drug development has been hampered due to their extremely poor solubility. Here, we evaluated three new compounds (AJ-037, AJ-039, and AJ-206) derived from the thiopeptide micrococcin P2 with enhanced aqueous solubility; the derivatives were generated based on structure-activity relationship analysis. We conducted in vitro drug susceptibility and intracellular antimycobacterial activity testing of the three thiopeptide derivatives against various MAC strains, including macrolide-resistant MAC clinical isolates. These compounds showed low MICs against MAC, similar to that of clarithromycin (CLR). In particular, two compounds, AJ-037 and AJ-206, had intracellular antimycobacterial activities, along with synergistic effects with CLR, and inhibited the growth of MAC inside macrophages. Moreover, these two compounds showed in vitro and intracellular anti-MAC activities against macrolide-resistant MAC strains without showing cross-resistance with CLR. Taken together, the results of the current study suggest that AJ-037 and AJ-206 can be promising anti-MAC agents for the treatment of MAC infection, including for macrolide-resistant MAC strains. IMPORTANCE Novel antibiotics for the treatment of MAC infection are urgently needed because the treatment outcomes using the standard regimen for Mycobacterium avium complex (MAC) pulmonary disease remain unsatisfactory. Here, we evaluated three novel thiopeptide derivatives (AJ-037, AJ-039, and AJ-206) derived from the thiopeptide micrococcin P2, and they were confirmed to be effective against macrolide-susceptible and macrolide-resistant MAC. Our thiopeptide derivatives have enhanced aqueous solubility through structural modifications of poorly soluble thiopeptides. The thiopeptide derivatives showed minimal inhibitory concentrations against MAC that were comparable to clarithromycin (CLR). Notably, two compounds, AJ-037 and AJ-206, exhibited intracellular antimycobacterial activities and acted synergistically with CLR to hinder the growth of MAC within macrophages. Additionally, these compounds demonstrated in vitro and intracellular anti-MAC activities against macrolide-resistant MAC strains without showing any cross-resistance with CLR. We believe that AJ-037 and AJ-206 can be promising anti-MAC agents for the treatment of MAC infections, including macrolide-resistant MAC strains.

Increased suicide risk of psychiatric patients following the recent utilization of health care services: results from a nationwide cohort study in South Korea.

Purpose: This study aimed to examine whether and to what degree the suicide risk of psychiatric patients is associated with psychiatric and non-psychiatric health service utilization. Methods: We selected incident psychiatric patients, including schizophrenia, bipolar disorders, borderline personality disorder, depressive disorders, other affective disorders, and post-traumatic stress disorder patients, in 2007-2010 and followed them up until 2017 based on the data linkage between the Korean National Health Insurance and National Death Registry. We analyzed the time-dependent association between suicide and four types of health service (psychiatric vs. non-psychiatric and outpatient vs. inpatient) utilization using a time-dependent Cox regression. Results: The suicide risk of psychiatric patients was significantly increased with recent psychiatric and non-psychiatric admission and psychiatric outpatient visits. The adjusted suicide hazard ratios for recent outpatient visits were similar to or even higher than those for recent psychiatric admission. The adjusted suicide hazard ratios of schizophrenia patients for psychiatric admission, psychiatric outpatient visits, and non-psychiatric admission within the recent 6 months were 2.34 (95% confidence interval [CI]: 2.12-2.58, p < 0.001), 2.96 (95% CI: 2.65-3.30, p < 0.001), and 1.55 (95% CI: 1.39-1.74, p < 0.001), respectively. Suicide risk was not associated with recent non-psychiatric outpatient visits in patients, except for the depressive disorders group showing a negative association. Conclusion: Our results highlight the priority of suicide prevention for psychiatric patients in the clinical setting. Additionally, our results warrant the precaution against increased suicide risk of psychiatric patients after psychiatric and non-psychiatric discharge.

Blood Pressure Trajectories for 16 Years and the Development of Left Ventricular Hypertrophy and Increased Left Atrial Size: The Korean Genome and Epidemiology Study.

Background: Elevated single blood pressure (BP) measurement can be associated with the development of hypertension-mediated target organ damage including left ventricular hypertrophy (LVH) and left atrial (LA) enlargement (LAE). However, long-term patterns of BP and their effects on LVH and LAE are poorly understood. We evaluated the association between the BP trajectories and the presence of LVH and LAE. Methods: We analyzed a total of 2,565 participants (1,267 males, 47.8 ± 6.7 years old) from the first biennial examination (2001-2002) of the Korean Genome and Epidemiology Study. The presence of LVH and LAE was identified by echocardiography performed at the 8th biennial examination (2015-2016). Latent mixture modeling was used to identify trajectories in mid-BP ((systolic BP + diastolic BP)/2) over time. Linear logistic regression was used for assessing BP trajectories with the outcomes. Results: We identified 4 distinct mid-BP trajectories: group 1 (lowest, 20.9%, n = 536), group 2 (36.2%, n = 928), group 3 (32.3%, n = 828), and group 4 (highest, 10.6%, n = 273). Compared with the lowest group, trajectories with elevated mid-BP had greater odds ratios having LVH and LAE by multivariable-adjusted regression models. Adjusted odd ratios for LVH were 2.033 (95% CI = 1.462-2.827, P < 0.001) for group 2, 3.446 (95% CI = 2.475-4.797, P < 0.001) for group 3, and 4.940 (95% CI = 3.318-7.356, P < 0.001) for group 4. Adjusted odd ratios for LAE were 1.200 (95% CI = 0.814-1.769, P = 0.358) for group 2, 1.599 (95% CI = 1.084-2.360, P = 0.018) for group 3, and 1.944 (95% CI = 1.212-3.118, P = 0.006) for group 4. Conclusions: Higher long-term mid-BP was an independent risk factor of cardiac structural changes such as LVH and LAE among middle-aged population.

Vaccination inducing durable and robust antigen-specific Th1/Th17 immune responses contributes to prophylactic protection against Mycobacterium avium infection but is ineffective as an adjunct to antibiotic treatment in chronic disease.

Mycobacterium avium complex (MAC) causing pulmonary disease in humanshas emerged worldwide. Thus, effective strategies simultaneously aiming to prevent MAC infection and accelerate therapeutic efficacy are required. To this end, subunit vaccine-induced protection against a well-defined virulent Mycobacterium avium (Mav) isolate was assessed as a preventative and therapeutic modality in murine models. Mav-derived culture filtrate antigen (CFA) was used as a vaccine antigen with glucopyranosyl lipid A stable emulsion (GLA-SE) or GLA-SE plus cyclic-di-GMP (GLA-SE/CDG), and we compared the immunogenicities, protective efficacies and immune correlates. Interestingly, CFA+GLA-SE/CDG immunization induced greater CFA-specific Th1/Th17 responses in both the lung and spleen than among the tested groups. Consequently, protective efficacy was optimally achieved with CFA+GLA-SE/CDG by significantly reducing bacterial loads along with long-lasting maintenance of antigen-specific Th1/Th17 cytokine-producing multifunctional T cell responses and relevant cytokine productions. Thus, we employed this subunit vaccine as an adjunct to antibiotic treatment. However, this vaccine was ineffective in further reducing bacterial loads. Collectively, our study demonstrates that strong Mav CFA-specific Th1/Th17 responses are critical for preventative protection against Mav infection but may be ineffective or even detrimental in an established and progressive chronic disease, indicating that different approaches to combating Mav infection are necessary according to vaccination purposes.

Host-directed anti-mycobacterial activity of colchicine, an anti-gout drug, via strengthened host innate resistance reinforced by the IL-1ß/PGE2 axis.

BACKGROUND AND PURPOSE: To diversify and expand possible tuberculosis (TB) drug candidates and maximize limited global resources, we investigated the effect of colchicine, an FDA-approved anti-gout drug, against Mycobacterium tuberculosis (Mtb) infection because of its immune-modulating effects. EXPERIMENTAL APPROACH: We evaluated the intracellular anti-Mtb activity of different concentrations of colchicine in murine bone marrow-derived macrophages (BMDMs). To elucidate the underlying mechanism, RNA sequencing, biological and chemical inhibition assays, and Western blot, quantitative real-time PCR, enzyme-linked immunosorbent assay (ELISA), and immunohistochemical analyses were employed. Finally, type I interferon-dependent highly TB-susceptible A/J mice were challenged with virulent Mtb H37Rv, and the host-directed therapeutic effect of oral colchicine administration on bacterial burdens and lung inflammation was assessed 30 days post-infection (2.5 mg·kg-1 every 2 days). KEY RESULTS: Colchicine reinforced the anti-Mtb activity of BMDMs without affecting cell viability, indicating that colchicine facilitated macrophage immune activation upon Mtb infection. The results from RNA sequencing, NLRP3 knockout BMDM, IL-1 receptor blockade, and immunohistochemistry analyses revealed that this unexpected intracellular anti-Mtb activity of colchicine was mediated through NLRP3-dependent IL-1ß signalling and Cox-2-regulated PGE2 production in macrophages. Consequently, the TB-susceptible A/J mouse model showed remarkable protection, with decreased bacterial loads in both the lungs and spleens of oral colchicine-treated mice, with significantly elevated Cox-2 expression at infection sites. CONCLUSIONS AND IMPLICATIONS: The repurposing of colchicine against Mtb infection in this study highlights its unique function in macrophages upon Mtb infection and its novel potential use in treating TB as host-directed or adjunctive therapy.

The Association between Serum Uric Acid Levels and 10-Year Cardiovascular Disease Risk in Non-Alcoholic Fatty Liver Disease Patients.

Non-alcoholic fatty liver disease (NAFLD) and serum uric acid (SUA) levels are risk factors for developing cardiovascular disease (CVD). Additionally, previous studies have suggested that high SUA levels increase the risk of having NAFLD. However, no study has investigated the relationship between SUA and CVD risk in NAFLD. This study analyzed the relationship between SUA and CVD in NAFLD. Data for this study used the 2016-2018 Korean National Health and Nutrition Examination Survey, which represents the Korean population. A total of 11,160 NAFLD patients were included. Participants with hepatic steatosis index ≥ 30 were considered to have NAFLD. Ten-year CVD risk was estimated using an integer-based Framingham risk score. Estimated 10-year CVD risk ≥ 20% was considered high risk. Multiple logistic regression was conducted to calculate the odds ratios (ORs) associated with SUA level and CVD risk. High CVD risk OR increases by 1.31 (95% CI 1.26-1.37) times per 1 mg/dL of SUA. After adjustment, SUA still had an increased risk (OR 1.44; 95% CI 1.38-1.51) of CVD. Compared with the lowest SUA quartile group, the highest quartile group showed a significantly higher risk of having CVD before (OR 2.76; 95% CI 2.34-3.25) and after (OR 4.01; 95% CI 3.37-4.78) adjustment. SUA is independently associated with CVS risk in NAFLD.

Control of a nosocomial measles outbreak among previously vaccinated adults in a population with high vaccine coverage: Korea, 2019.

We describe a measles outbreak among previously vaccinated healthcare workers (HCWs) and inpatients and the control measures implemented at a tertiary care hospital in 2019. Case-patients were laboratory-confirmed measles with throat swabs tested by quantitative polymerase chain reactions (PCR), during April-May 2019. Medical histories and documented immunization records were obtained. We compared attack rates (ARs) among HCWs by occupational subgroup and age and examined the outbreak-associated costs. The index case was not ascertained. Among 26 measles case-patients (22 HCWs, four inpatients) aged 18-28 years, 25 had previously received measles-mumps-rubella (MMR) vaccine (12/26, 46% (two doses); 13/26, 50% (one dose)), and 16 (62%) had positive results of measles IgG prior to measles diagnosis. ARs were higher among HCWs aged < 30 years (1.88%), especially in the subgroup under 25 years of age (2.22%). Control measures included work restrictions for seronegative HCWs (218/2320, 9.4%) in immunity verification, administration of the MMR vaccine (207 HCWs) or intravenous immunoglobulin (2 HCWs and 11 inpatients), enhanced health surveillance of HCWs, and mandatory assessment of patients with measles-like symptoms at the infectious diseases screening units. The hospital spent 90,417,132 Korean won (US $79,733) in response to the outbreak. Measles outbreaks can occur in healthcare settings despite high population immunity, highlighting the importance of stronger vaccination policies, particularly among young HCWs. Moreover, an effective outbreak response comprising immunization activities and enhanced surveillance of HCWs and patients to rapidly detect measles-like symptoms at a prodromal phase is essential to control nosocomial measles outbreaks.

Antinociceptive effect of N-(9,13b-dihydro-1H-dibenzo[c, f]imidazo[1,5-a]azepin-3-yl)-2-hydroxybenzamide on different pain models in mice

Abstract N-(9,13b-dihydro-1H-dibenzo[c,f]imidazo[1,5-a]azepin-3-yl)-2-hydroxybenzamide (DDIAHB) is a new drug developed through molecular modelling and rational drug design by the molecular association of epinastine and salicylic acid. The present study was designed to assess the possible antinociceptive effects of DDIAHB on different pain models in male ICR mice. DDIAHB exerted the reductions of writhing numbers and pain behavior observed during the second phase in the formalin test in a dose-dependent manner. Moreover, DDIAHB increased the latency in the hot-plate test in a dose-dependent manner. Furthermore, intragastric administration DDIAHB caused reversals of decreased pain threshold observed in both streptozotocin-induced diabetic neuropathy and vincristine-induced peripheral neuropathy models. Additionally, intragastric pretreatment with DDIAHB also caused reversal of decreased pain threshold observed in monosodium urate-induced pain model. We also characterized the possible signaling molecular mechanism of the antinociceptive effect-induced by DDIAHB in the formalin model. DDIAHB caused reductions of spinal iNOS, p-STAT3, p-ERK and p-P38 levels induced by formalin injection. Our results suggest that DDIAHB shows an antinociceptive property in various pain models. Moreover, the antinociceptive effect of DDIAHB appear to be mediated by the reductions of the expression of iNOS, p-STAT3, p-ERK and p-P38 levels in the spinal cord in the formalin-induced pain model.

Incidence Hypertension and Fasting Blood Glucose from Real-World Data: Retrospective Cohort for 7-Years Follow-Up.

This retrospective cohort study was done to investigate the incidence of hypertension and its relation to the fasting blood glucose level in Korea. The eligible non-hypertensive subjects (n = 3,396,187) among the National Health Insurance Service-National Health Screening (NHIS-HEALS) examinees (n = 10,644,911) in 2009 were followed up until 2015. A Cox proportional hazards regression was used to estimate the risk of the high blood glucose level for the incident hypertension while controlling for covariates' confounding effect. The cumulative incidence rate was 10.6% for seven years (11.6% in men and 8.3% in women). The incidence density was 1474.8 per 100,000 person-years. High fasting blood glucose (adjusted Hazard Ratio (aHR), 1.836; 95% confidence interval (CI), 1.810 to 1.862), prediabetes (aHR, 1.249; 95% CI, 1.237 to 1.260), a history of diabetes mellitus (aHR, 1.635; 95% CI, 1.605 to 1.666), high triglyceride (aHR, 1.292; 95% CI, 1.280 to 1.303), a history of dyslipidemia (aHR, 1.279; 95% CI, 1.253 to 1.305) and prehypertension group (aHR, 1.964; 95% CI, 1.948 to 1.979) were significantly related to the incident hypertension after adjusting for covariates. Among real-world data in Korea, high blood glucose level was the independent risk factor for developing hypertension.

Risk Factors Influencing the Occurrence and Severity of Symptomatic Dry Eye Syndrome: A Cross-sectional Study.

Propose: We aimed to investigate the prevalence and risk factors of dry eye syndrome (DES) among a population-based cohort study.Methods: This cross-sectional study was conducted on 475 subjects (184 men and 291 women) enrolled in the Study Group for Environmental Eye Disease at July 2013. Using the ocular surface disease index (OSDI), we measured the DES severity and defined DES as OSDI score ≥13. Current symptoms of DES and possible risk factors such as body mass index, occupations, comorbidities, exercise, smoking and drinking status were assessed by multivariate logistic regression.Results: Prevalence of DES was significantly higher in women (52.6%) than in men (41.9%) (p < .001). Compared to white-collar workers, blue-collar workers and unemployed persons showed significantly higher DES prevalence and severity. Compared to those with low BMI (<23.0 kg/m2), people with extremely high BMI (≥30.0 kg/m2) had significantly higher odds ratio (OR) of having DES after fully adjusted for sex, age, hypertension, diabetes, menopausal status, hormone replacement therapy, occupation, and lifestyle factors (OR: 2.83, 95% confidence interval: 1.04-7.71).Conclusions: We found some novel factors which have been unknown to the relationship with DES through the five years observation of the cohort. The positive associations of unemployment status, blue-collar work, alcohol habit, and obesity with DES suggests a person's comprehensive condition, not individual factors, contribute significantly in developing DES. Further studies will be helpful to understand the underlying mechanisms.

The association of cortisol curve features with incident diabetes among whites and African Americans: The CARDIA study.

INTRODUCTION: A flatter diurnal cortisol curve has been associated with incident diabetes among older white adults. However, this relationship has not been examined among middle-aged individuals or African Americans [AA]. We analyzed the longitudinal association of baseline diurnal cortisol curve features with incident diabetes over a 10 year period in a cohort of AA and white participants who were, on average, 40 years old. METHODS: Salivary cortisol was collected immediately post-awakening, then subsequently 45 min, 2.5 h, 8 h, and 12 h later, as well as at bedtime. Cortisol curve features included wake-up cortisol; cortisol awakening response (CAR); early, late, and overall decline slopes; bedtime cortisol; and 16 -h area under the curve (AUC). Salivary cortisol (nmol/L) was log-transformed due to positively skewed distributions. Diabetes was defined as fasting plasma glucose ≥ 126 mg/dL or taking diabetes medication. Logistic regression models were used to investigate the association of log-transformed cortisol curve features with incident diabetes. The analysis was stratified by race and adjusted for age, sex, education, depressive symptoms, smoking status, beta-blocker and steroid medication use and BMI. RESULTS: Among 376 AA and 333 white participants (mean age 40 years), 67 incident diabetes cases occurred over 10 years. After full adjustment for additional covariates, a 1-unit log increase in CAR was associated with a 53 % lower odds of incident diabetes among whites (Odds Ratio [OR] 0.47, 95 % CI: 0.24, 0.90). A 1-SD increase in late decline slope was associated with a 416 % higher odds of incident diabetes among whites (OR 5.16, 95 % CI: 1.32, 20.20). There were no significant associations in AAs. CONCLUSION: A robust CAR and flatter late decline slope are associated with lower and higher odds of incident diabetes, respectively, among younger to middle-aged whites and may provide a future target for diabetes prevention in this population.

Metabolic biomarkers and long-term blood pressure variability in military young male adults.

BACKGROUND: Metabolic syndrome is a cluster of cardiovascular risk factors, including central obesity, high blood pressure, elevated plasma glucose, reduced high-density lipoprotein and elevated triglyceride levels. AIM: To investigate the relationship between metabolic biomarkers and long-term blood pressure variability (BPV) in young males. METHODS: A cohort of 1112 healthy military males aged 18-40 years from the cardiorespiratory fitness and hospitalization events in armed forces study in eastern Taiwan was prospectively included. The following metabolic biomarkers were used: Waist circumference, serum uric acid (SUA), triglycerides, high density lipoprotein, triglycerides, and fasting glycose. BPV was assessed by average real variability (ARV) and standard deviation (SD) across 4 clinic visits during the study period (2012-14, 2014-15, 2015-16, and 2016-18). Multivariable linear regression analysis was used to determine the association after adjusting for age, body mass index, systolic and diastolic blood pressure (SBP and DBP), lipid profiles, physical activity, alcohol intake and tobacco smoking status. RESULTS: In the unadjusted model, waist circumference was significantly and positively correlated with ARVDBP and SDDBP [ß (standard errors) = 0.16 (0.049) and 0.22 (0.065), respectively], as was SUA [ß = 0.022 (0.009) and 0.038 (0.012), respectively]. High-density lipoprotein was negatively correlated with ARVSBP [ß = -0.13 (0.063)]. There were no associations with the other metabolic biomarkers. In contrast, only SUA was significantly correlated with SDSBP and SDDBP [ß = 0.019 (0.011) and 0.027 (0.010), respectively] in the adjusted model. CONCLUSION: Our findings showed that of traditional metabolic biomarkers, SUA had the strongest positive correlation with long-term systolic and diastolic BPV in young male adults, and the clinical relevance needs further investigation.

A Clofazimine-Containing Regimen Confers Improved Treatment Outcomes in Macrophages and in a Murine Model of Chronic Progressive Pulmonary Infection Caused by the Mycobacterium avium Complex.

Treatment outcomes using the standard regimen (a macrolide, ethambutol, and rifampicin) for Mycobacterium avium complex-pulmonary disease (MAC-PD) remain unsatisfactory. Thus, improved treatment regimens for MAC-PD are required. Clofazimine has recently been revisited as an effective drug against mycobacterial infection. We performed a comparison between the standard regimen and an alternative regimen (replacing the rifampicin of the standard regimen with clofazimine) based on the intracellular anti-MAC activities of the individual drugs in a murine model of chronic progressive MAC-pulmonary infection (MAC-PI). The intracellular anti-MAC activities of the individual drugs and their combinations in murine bone marrow-derived macrophages (BMDMs) were determined. The treatment efficacies of the standard and clofazimine-containing regimens were evaluated in mice chronically infected with M. avium by initiating 2- and 4-week treatment at 8 weeks post-infection. Bacterial loads in the lung, spleen, and liver were assessed along with lung inflammation. Insufficient intracellular anti-MAC activity of rifampicin in BMDMs was recorded despite its low in vitro minimum inhibitory concentrations (MICs), whereas optimal intracellular killing activity against all tested MAC strains was achieved with clofazimine. Compared to the standard regimen, the clofazimine-containing regimen significantly reduced CFUs in all organs and achieved marked reductions in lung inflammation. The replacement of rifampicin with clofazimine in the treatment regimen resulted in more favorable outcomes in an animal model of chronic progressive MAC-PI. Intriguingly, 2 weeks of treatment with the clofazimine-containing regimen reduced bacterial loads more effectively than 4 weeks of treatment with the standard regimen in M. avium-infected mice. Thus, the clofazimine-containing regimen also had a treatment-shortening effect.

Triglyceride to high density lipoprotein cholesterol ratio among adolescents is associated with adult hypertension: the Kangwha study.

BACKGROUND: The triglyceride to high density lipoprotein cholesterol (TG/HDL-C) ratio associated with hypertension in adults. However, whether the TG/HDL-C ratio in adolescents predicts future hypertension remains unclear. Here, we evaluated the prospective association between the TG/HDL-C ratio in adolescents and hypertension in early adulthood. METHODS: The Kangwha Study is an ongoing prospective cohort study that has tracked the blood pressure of first grade elementary school students since 1986. We followed up 272 participants who completed health examinations at the age of 16 and 35 years. We excluded 27 participants with adolescent hypertension, defined as those whose blood pressures were above the age- and sex-specific 95th percentiles of the Korean population, and finally analysed 245 participants. We defined high and low TG/HDL-C ratio groups according to the age- and sex-specific 75th percentile of the TG/HDL-C ratio (1.04 for boys and 0.81 for girls) of the Korean population. Adult hypertension was defined by a systolic/diastolic blood pressure ≥ 140/90 mmHg or by taking antihypertensive medication at the age of 35 years. Logistic regression analysis was performed to evaluate the association between adolescent TG/HDL-C ratio and adult hypertension after adjusting for age at follow-up, sex, baseline systolic blood pressure, waist circumference, and total cholesterol and fasting glucose levels. RESULTS: During the 20-year follow-up, 11 (18.3%) individuals developed hypertension in the high TG/HDL-C ratio group and 10 (5.4%) individuals developed hypertension in the low TG/HDL-C ratio group. The adjusted odds ratio for incident hypertension in the high TG/HDL-C ratio group, compared with the low TG/HDL-C ratio group, was 3.40 (95% confidence interval 1.24-9.31). CONCLUSIONS: High TG/HDL-C ratio in adolescence is associated with hypertension in early adulthood.

Aminotransferase levels, body mass index, and the risk of diabetes: a prospective cohort study.

PURPOSE: To investigate whether the relationship between body mass index (BMI) and incident diabetes is modified by different alanine or aspartate aminotransferases (ALT or AST) levels. METHODS: We carried out an analysis of 6484 participants aged 40 years or older using data from the Korean Genome Epidemiology Study. The serum aminotransferase levels were stratified into low and high groups according to the median values and classified into three groups: both low, either high, and both high. To assess the association between BMI and incident diabetes according to the serum aminotransferase levels, multiple logistic regression models were used. RESULTS: In participants with high levels of both ALT and AST, compared with the first BMI quartile, the adjusted odds ratios for incident diabetes of the second, third, and fourth BMI quartiles were 1.72 (95% confidence interval, 0.84-3.55), 2.19 (1.11-4.33), and 3.08 (1.60-5.90), respectively (P trend < .001). In participants with either high ALT or AST, the adjusted odds ratios were 3.58 (1.23-10.41), 2.65 (0.90-7.76), and 5.28 (1.86-15.02), respectively (P trend = .005). However, in participants with both low ALT and AST levels, high BMI was not independently associated with the risk of incident diabetes. CONCLUSIONS: There was a strong association between BMI and incident diabetes among individuals with high aminotransferase levels, whereas no association was observed among those with low aminotransferase levels.

Serum high-density lipoprotein cholesterol concentration and functional state: The Korean Urban Rural Elderly (KURE) Study.

BACKGROUND: Functional state and cholesterol metabolism are important for older adults; however, this association has not been fully investigated among community-dwelling older adults. Thus, we investigated the association of HDL cholesterol with multiple functional state measures in an elderly Korean population. METHODS: This cross-sectional analysis included 3514 participants, aged 65 years or older, who participated in baseline health assessment for the Korean Urban Rural Elderly cohort study from 2012 to 2015. HDL cholesterol concentration was analyzed using both continuous and categorical variables. Functional state was assessed by the mini-mental state examination (MMSE), activities of daily living (ADL) scale, instrumental activities of daily living (IADL) scale, timed up-and go (TUG) test, and chair-rise test (CRT). Multiple logistic regression models were used to investigate independent association between HDL cholesterol and functional state, after adjusting for sex, age, body mass index, systolic blood pressure, fasting glucose, lipid-lowering drug, history of cancer and cardiovascular disease, and health behaviors. RESULTS: HDL cholesterol concentration was significantly associated with MMSE, ADL, IADL, TUG, and CRT in the unadjusted model. After adjustment for covariates, the association remained significant for MMSE (standardized ß=0.059, p=0.001), ADL (standardized ß=-0.053, p=0.004), and CRT (standardized ß=-0.037, p=0.037). In fully-adjusted model, Participants who had a lower HDL concentration (<40mg/dL) showed significantly increased odds for having MMSE decline (OR 1.451, 95% CI 1.119-1.883) and ADL dependency (OR 2.251, 95% CI 1.119-4.526), compared reference group (≥60mg/dL). CONCLUSIONS: Higher HDL cholesterol concentration was associated with better functional state among Korean older adults.

Association between Mean Corpuscular Hemoglobin Concentration and Future Depressive Symptoms in Women.

Insufficient hemoglobin and depression share several symptoms and often occur in the same patients. Here, we sought to clarify their relationship by investigating two indices of oxygenation at the tissue level: mean corpuscular hemoglobin concentration (MCHC) and hemoglobin level. We hypothesized that MCHC would be more informative than hemoglobin levels. This prospective, longitudinal, community-based study included 337 participants (108 men and 229 women; age range, 38-87 years) who received evaluations of MCHC, hemoglobin levels and depressive symptom scores (DSS) during baseline and follow-up examinations, which were performed in 2008-2011 and 2010-2012, respectively. MCHC and hemoglobin levels were measured as part of complete blood counts, while DSS was evaluated using the Beck Depression Inventory. Associations were analyzed using linear regression. We found a statistically significant association between baseline MCHC and follow-up DSS (ß = -0.69, p = 0.026), which remained statistically significant after controlling for potential confounders (ß = -0.71, p = 0.011). Further, when we analyzed the relationship separately for men and women, we observed that it remained stable for women before (ß = -1.00, p = 0.014) and after (ß = -1.09, p = 0.003) adjusting for confounders. The stable association indicates that MCHC may be superior to hemoglobin level as a prognostic factor for future depressive symptoms in women. MCHC is easy to measure and low MCHC is usually treatable. Therefore, screening and intervention efforts could be targeted at women with low MCHC, who appear to have elevated risks of developing depressive symptoms.

Association between changes in systolic blood pressure and incident diabetes in a community-based cohort study in Korea.

An association between hypertension and diabetes has been reported; however, the temporal relationship of blood pressure changes and incident diabetes has not been fully investigated in the general population. We examined whether increasing blood pressure is associated with the risk of developing diabetes among community-dwelling Korean adults. This study included 2225 participants (859 men and 1366 women) aged 27-87 years from the Korean Genome Epidemiology Study. The participants were free of diabetes and cardiovascular disease at baseline. Incident diabetes was defined as fasting blood glucose⩾126 mg dl-1 or hemoglobin a1c ⩾6.5% (48 mmol mol-1) at follow-up examination and/or a physician's diagnosis of diabetes during the follow-up period. The effects of the baseline level and change in blood pressure on the risk of incident diabetes were assessed by multivariate logistic regression analysis. During the mean follow-up of 2.6 years, new-onset diabetes was observed in 5.0% (43/859) of the men and 3.4% (47/1366) of the women. In the multivariate model, the baseline systolic blood pressure was not significantly associated with incident diabetes (adjusted odds ratio 0.93 per 10 mmHg, P=0.747). However, an increase in systolic blood pressure during the follow-up period was independently associated with incident diabetes (adjusted odds ratio 5.53 per 5 mmHg per year, P=0.002) after adjusting for the baseline blood pressure and other potential confounders. Increasing blood pressure, but not a high baseline blood pressure, was independently associated with the risk of diabetes in Korean adults.