Comparison of Office Blood Pressure, Automated Unattended Office Blood Pressure, Home Blood Pressure, and 24-Hour Ambulatory Blood Pressure Measurements.

BACKGROUND: Although previous studies have reported differences of blood pressure (BP) according to BP measurement methods, studies in Korean population were scarce. This study aimed to compare BP differences according to different BP measurement methods and assess hypertension phenotype. METHODS: This prospective study recruited 183 individuals (mean 55.9 years; 51.4% males). The BP measurements included office BP (auscultatory attended office BP [ausAOBP], automated attended office BP [aAOBP], and automated unattended office BP [aUAOBP]) and out-of-office BP (home BP [HBP] and ambulatory BP [ABP]) measurements taken within one week of each other. RESULTS: The mean systolic/diastolic BP differences between ausAOBP and other BPs according to different BP measurement methods were 3.5/2.3 mmHg for aAOBP; 6.1/2.9 mmHg for aUAOBP; 15.0/7.3 mmHg for daytime ABP; and 10.6/3.4 mmHg for average HBP. The increasing disparity between ausAOBP and other BPs in multivariable regression analysis was significantly associated with increasing BP. The prevalence of white-coat hypertension and masked hypertension in 107 individuals not taking antihypertensive medication was 25.4-26.8% and 30.6-33.3% based on ausAOBP, daytime ABP, and average HBP, respectively. The prevalence of white-coat uncontrolled hypertension and masked uncontrolled hypertension in 76 of those taking antihypertensive medication was 31.7-34.1% and 17.1-37.1%, respectively. CONCLUSION: This study showed a large disparity between office BP and out-of-office BP which became more pronounced when office BP by auscultation increased, suggesting that various BP measurement methods should be used to more accurately assess BP status.

Association of environmental tobacco smoke exposure with metabolic syndrome: A longitudinal Cohort Study of 71,055 never smokers.

BACKGROUND AND AIMS: Effects of environmental tobacco smoke (ETS) exposure and a change in ETS exposure status on metabolic syndrome (MetS) remain unknown. Thus, the aim of this study was to evaluate the effect of ETS exposure on MetS in self-reported and cotinine-validated never smokers. METHODS AND RESULTS: From a large longitudinal cohort study, 71,055 cotinine-validated never smokers without MetS at baseline were included. These participants were divided into four groups (no, new, former, and continuous ETS exposure groups) based on their ETS exposure status at baseline and follow-up. The association between ETS exposure and MetS was assessed using multivariable Cox hazard regression analyses. During a median follow-up of 33 months, 15.0 cases/10,000 person-years (PY) developed MetS. Incidence rates per 10,000 PY of MetS in no, new, former, and continuous ETS exposure groups were 14.0, 18.5, 16.5, and 19.0, respectively. In multivariable Cox hazard regression analyses, the new and continuous ETS exposure groups showed increased risk of MetS compared to the no ETS exposure group (hazard ratio [95% confidence interval]: 1.35 [1.16, 1.56], p-value < 0.001 for the new ETS exposure group and 1.19 [1.06, 1.34], p-value = 0.004 for the continuous ETS exposure group). However, the former ETS exposure group did not show an increased risk of MetS (0.96 [0.88, 1.05], p-value = 0.36). CONCLUSION: This study showed that ETS exposure and changes in ETS exposure status over approximately three years could modify the risk of MetS, suggesting that avoidance of ETS may not increase the risk of incidence of MetS.

Effect of physical activity on the development and the resolution of nonalcoholic fatty liver in relation to body mass index.

BACKGROUND: Data on whether physical activity (PA) levels are related to nonalcoholic fatty liver disease (NAFLD) when considering body mass index (BMI) are scarce. We assessed whether PA affects the development or resolution of NAFLD in conjunction with BMI changes. METHODS: Overall, 130,144 participants who underwent health screening during 2011-2016 were enrolled. According to the PA level in the Korean version of the validated International PA Questionnaire Short Form, participants were classified into the inactive, active, and health-enhancing PA (HEPA) groups. RESULTS: In participants with increased BMI, the hazard ratio (HR) and 95% confidence interval after multivariable Cox hazard model for incident NAFLD was 0.97 (0.94-1.01) in the active group and 0.94 (0.89-0.99) in the HEPA group, whereas that for NAFLD resolution was 1.03 (0.92-1.16) and 1.04 (0.88-1.23) (reference: inactive group). With increased BMI, high PA affected only new incident NAFLD. PA enhancement or maintenance of sufficient PA prevented new incident NAFLD. In participants with decreased BMI, the HRs were 0.98 (0.90-1.07) and 0.88 (0.78-0.99) for incident NAFLD and 1.07 (0.98-1.17) and 1.33 (1.18-1.49) for NAFLD resolution in the active and HEPA groups, respectively. With decreased BMI, high PA reduced incident NAFLD and increased NAFLD resolution. Maintenance of sufficient PA led to a considerable resolution of NAFLD. CONCLUSION: In this large longitudinal study, PA prevented incident NAFLD regardless of BMI changes. For NAFLD resolution, sufficient PA was essential along with BMI decrease. Maintaining sufficient PA or increasing the PA level is crucial for NAFLD prevention or resolution.

Effects of Age, Sex, and Obesity on N-Terminal Pro B-Type Natriuretic Peptide Concentrations in the General Population.

BACKGROUND: Data regarding complex relationships between age, sex, obesity and N-terminal pro B-type natriuretic peptide (NT-proBNP) remain scarce. Thus, we investigated sex-specific associations of obesity and NT-proBNP levels among adults in the general healthy population in Korea.Methods and Results:The associations of age, sex and obesity-associated parameters (waist circumference [WC], body mass index [BMI] and body weight) with NT-proBNP were analyzed in 39,937 healthy adult participants. Multivariable regression models adjusted for factors known to affect NT-proBNP were used to identify associations between NT-proBNP and obesity-related parameters. NT-proBNP levels were higher in females than males. Older age was also associated with higher NT-proBNP levels in the overall population (P<0.001). When accounting for age in multivariable linear regression models, there was a strong inverse association between WC, BMI, and NT-proBNP in females and a weaker inverse association in males, with a significant difference between the sexes (P interaction <0.001). After adjusting for the effects of WC and BMI on each other, abdominal obesity was associated with lower NT-proBNP levels in females but not males (P interaction <0.001). CONCLUSIONS: In this large sample of young and healthy Asians, younger age, male sex, and increases in obesity-related parameters were related to lower levels of NT-proBNP. Further comprehensive studies are needed to understand the factors affecting NT-proBNP levels in different populations.

Relationship between alcohol consumption and insulin resistance measured using the homeostatic model assessment for insulin resistance: A retrospective cohort study of 280,194 people.

BACKGROUND AND AIM: Alcohol consumption causes metabolic disorders and is a known risk factor for cardiovascular disease. However, some studies suggested that low level alcohol consumption improves insulin resistance. We evaluated the effects of alcohol consumption on insulin resistance using the homeostatic model assessment for insulin resistance (HOMA-IR). METHODS AND RESULTS: This study included 280,194 people without diabetes who underwent comprehensive health examinations more than twice between 2011 and 2018. The levels of alcohol intake were obtained through a self-questionnaire. All subjects were divided into two groups based on the Korean standard cut-off value of HOMA-IR, 2.2. Cox proportional hazard analysis was used to assess the risk of insulin resistance according to alcohol consumption. The mean age of the study subjects was 38.2 years and 55.7% were men. During the follow-up period (median 4.13 years), HOMA-IR progressed from <2.2 to ≥2.2 in 64,443 subjects (23.0%) and improved from ≥2.2 to <2.2 in 21,673 subjects (7.7%). In the parametric survival analysis, alcohol consumption was associated with improvement of HOMA-IR (HR [95% CI], 1.09[1.03-1.14], 1.11[1.06-1.17] and 1.20[1.13-1.26], respectively). In the analysis classified according to changes in alcohol consumption amounts, increased alcohol consumption tended to prevent the progression of HOMA-IR (0.97[0.96-0.99]; p = 0.004). However, the association between the changes in alcohol consumption amounts and improvement of HOMA-IR was not statistically significant. CONCLUSION: This retrospective observational study has shown that alcohol consumption can improve insulin resistance and increased alcohol consumption amounts may have preventive effects on the progression of HOMA-IR compared to the baseline level.

Defining Early Life Stress as a Precursor for Autoimmune Disease.

Childhood exposure to traumatic events, termed early life stress (ELS), is now widely recognized for causing long-term negative health effects that may not manifest until adulthood. Allostatic load (AL) describes the cumulative "wear-and-tear" effects of chronic stress on the body that may adversely affect human health by accelerating other disease processes. Recent epidemiological studies have reported higher stress levels in industrialized countries and trends of increasing prevalence in autoimmune diseases during recent decades. To elucidate mechanisms of stress-related immune dysregulation, most animal studies up to now have focused on AL and stress-triggered events occurring in adults but have not explored ELS in the context of autoimmune disorders. We have identified a current gap in understanding the impact of ELS on immune system ontogeny and its potential for priming genetically susceptible individuals who are at increased risk for autoimmune diseases later in life, through mechanisms involving neuroendocrine-immune cross talk. In this review, we highlight the intersection between stress and immune function, with a focus on ELS as consequential for increased autoimmune disorder risks later in life.

Association of Self-Reported and Cotinine-Verified Smoking Status with Atrial Arrhythmia.

BACKGROUND: The relationship between self-reported and urinary cotinine-verified smoking status and atrial arrhythmia (AA) is unclear. The aim of this study was to evaluate the association of self-reported and urine cotinine-verified smoking status with AA. METHOD: A total of 201,788 participants (106,375 men, mean age 37 years) who had both a urinary cotinine measurement and electrocardiogram were included. Cotinine-verified current smoking was defined as a urinary cotinine level above 50 ng/mL. Individuals were divided into three groups based on self-reported smoking and two groups based on cotinine-verified smoking status. RESULTS: Among overall subjects, 505 had documented AA (0.3%) and 135 had atrial fibrillation (AF) (0.1%). Self-reported current smoking was associated with an increased risk of AA (odds ratio [OR], 1.42; 95% confidence interval [CI], 1.06-1.91; P = 0.019) and AF (OR, 2.20; 95% CI, 1.24-3.90; P = 0.007), whereas self-reported former smoking had no significant association with AA (OR, 1.30; 95% CI, 0.97-1.73; P = 0.078) and AF (OR, 1.74; 95% CI, 1.00-3.04; P = 0.051). Cotinine-verified current smoking showed no significant association with AA (OR, 1.24; 95% CI, 0.98-1.58; P = 0.080) and AF (OR, 1.20; 95% CI, 0.79-1.83; P = 0.391). CONCLUSION: Self-reported current smoking was associated with AA and AF, while self-reported former smoking and cotinine-verified current smoking showed no significant association with AA and AF.

Relationship Between Cotinine-Verified Smoking Status and Incidence of Hypertension in 74,743 Korean Adults.

BACKGROUND: The relationship between chronic smoking and hypertension (HTN) is inconclusive in previous studies, which were mainly based on self-reported smoking status. The aim of this study was to evaluate the association of cotinine-verified smoking status with incident HTN.Methods and Results:A total of 74,743 participants (43,104 men; age 38±5.4 years) were included in the study, with a mean follow-up period of 29 months. Individuals were divided into 4 groups on the basis of their cotinine-verified smoking status at baseline and at follow-up (never-smoking, new-smoking, former-smoking, and sustained-smoking). The incidence rate of HTN in the never-smoking, new-smoking, former-smoking, and sustained-smoking groups was 8.2%, 7.6%, 10.1%, and 8.7% for men and 1.8%, 2.5%, 1.5%, and 2.2% for women, respectively. In a multivariate Cox-hazard regression analysis adjusted for the variables with a univariate relationship, new-smoking and sustained-smoking had decreased relative risks (RRs) for incident HTN compared with never-smoking (RR [95% CI], 0.75 [0.58, 0.96] for new-smoking and 0.82 [0.74, 0.90] for sustained-smoking). Cotinine-verified current smoking at baseline was also inversely associated with incident HTN compared with cotinine-verified never-smoking at baseline (0.91 [0.84, 0.98]). These results remained significant only in men, although there was no sex interaction. CONCLUSIONS: This longitudinal study showed that cotinine-verified new-smoking and sustained-smoking decreased the risk for incident HTN, especially in men, compared with never-smoking.

The Role of c-Jun N-Terminal Kinase (JNK) in Retinal Degeneration and Vision Loss.

c-Jun N-terminal kinase (JNK), a member of stress-induced mitogen-activated protein (MAP) kinase family, has been shown to modulate a variety of biological processes associated with neurodegenerative pathology of the retina. In particular, various retinal cell culture and animal models related to glaucoma, age-related macular degeneration (AMD), and retinitis pigmentosa indicate that JNK signaling may contribute to disease pathogenesis. This mini-review discusses the impact of JNK signaling in retinal disease, with a focus on retinal ganglion cells (RGCs), photoreceptor cells, retinal pigment epithelial (RPE) cells, and animal studies, with particular attention to modulation of JNK signaling as a potential therapeutic target for the treatment of retinal disease.

Rapid repeatable in vivo detection of retinal reactive oxygen species.

Oxidative injuries, such as those related to reactive oxygen species (ROS), have been implicated in various retinal and optic nerve disorders. Many ROS detection methods have been developed. Although widely utilized, many of these methods are useful only in post mortem tissues, or require relatively expensive equipment, or involve intraocular injection. In the present study, we demonstrated and characterized a chemiluminescent probe L-012 as a noninvasive, in vivo ROS detection agent in the mouse retina. Using optic nerve crush (ONC) and retinal ischemia/reperfusion (I/R) as injury models, we show that L-012 produced intensive luminescent signals specifically in the injured eyes. Histological examination showed that L-012 administration was safe to the retina. Additionally, compounds that reduce tissue superoxide levels, apocynin and TEMPOL, decreased injury-induced L-012 chemiluminescence. The decrease in L-012 signals correlated with their protective effects against retinal I/R-induced morphological and functional changes in the retina. Together, these data demonstrate the feasibility of a fast, simple, reproducible, and non-invasive detection method to monitor in vivo ROS in the retina. Furthermore, the results also show that reduction of ROS is a potential therapeutic approach for protection from these retinal injuries.

Association between cotinine-verified smoking status and hypertension in 167,868 Korean adults.

PURPOSE: Previous studies showed inconsistent results concerning the relationship between chronic smoking and blood pressure. Most of the studies involved self-reported smoking status. This study was performed to evaluate the association of urinary cotinine or self-reported smoking status with hypertension and blood pressure in Korean adults. MATERIALS AND METHODS: Among individuals enrolled in the Kangbuk Samsung Health Study and Kangbuk Samsung Cohort Study, 167,868 participants (men, 55.7%; age, 37.5 ± 6.9 years) between 2011 and 2013 who had urinary cotinine measurements were included. Individuals with urinary cotinine levels ≥50 ng/mL were defined as cotinine-verified current smokers. RESULTS: The prevalence of hypertension and cotinine-verified current smokers in the overall population was 6.8% and 22.7%, respectively (10.0% in men and 2.8% in women for hypertension: 37.7% in men and 3.9% in women for cotinine-verified current smokers). In a multivariate regression analysis adjusted for age, sex, body mass index, waist circumference, alcohol drinking, vigorous exercise, and diabetes, cotinine-verified current smoking was associated with lower prevalence of hypertension compared with cotinine-verified never smoking (OR[95% CI], 0.79 [0.75, 0.84]). Log-transformed cotinine levels and unobserved smoking were negatively associated with hypertension, respectively (0.96 [0.96, 0.97] and 0.55 [0.39, 0.79]). In a multivariate linear regression analysis, the cotinine-verified current smoking was inversely associated with systolic and diastolic blood pressure (BP) (regression coefficient[95% CI], -1.23[-1.39, -1.07] for systolic BP and -0.71 [-0.84, -0.58] for diastolic BP). In subgroup analyses according to sex, the inverse associations between cotinine-verified current smoking and hypertension were observed only in men. CONCLUSIONS: This large observational study showed that cotinine-verified current smoking and unobserved smoking were inversely associated with hypertension in Korean adults, especially only in men.

Association between brachial-ankle pulse wave velocity and progression of coronary artery calcium: a prospective cohort study.

BACKGROUND: Few studies have investigated the association between coronary artery calcium (CAC) progression and arterial stiffness measured by brachial-ankle pulse wave velocity (baPWV). We examined the influence of the severity of baseline baPWV on CAC progression in a large prospective cohort. METHODS: A total of 1600 subjects who voluntarily participated in a comprehensive health-screening program between March 2010 and December 2013 and had baseline baPWV as well as CAC on baseline and serial follow-up computed tomography performed approximately 2.7 ± 0.5 years apart were enrolled in the study. RESULTS: A total of 1124 subjects were included in the analysis (1067 men; mean age, 43.6 ± 5.1 years). An increased CAC score was found in 318 subjects (28.3%) during the follow-up period. Baseline higher baPWV was significantly correlated with CAC progression, especially in subjects with third- and fourth-quartile values (adjusted odds ratio [OR] 2.04; 95% confidence interval [CI] 1.33-3.15 and OR 2.14; 95% CI 1.34-3.41, respectively) compared with the lowest-quartile values (P for trend <0.001). A similar effect was observed in diabetic subjects. Among the 835 subjects with a baseline CAC score = 0, progression to CAC score >0 was associated with male sex, diabetes, and higher baPWV. However, among the 289 individuals with a baseline CAC score >0, only the presence of CAC itself was predictive of CAC progression. CONCLUSIONS: Higher arterial stiffness measured by baPWV could be significantly associated with CAC progression.

Echocardiographic epicardial fat thickness is associated with coronary artery calcification - results from the CAESAR study.

BACKGROUND: Few studies have addressed the relationship between echocardiographic epicardial fat thickness (EFT) and coronary artery calcification in an apparently healthy Asian population, and those that have, are inconsistent. METHODS AND RESULTS: A total of 2,299 individuals (1,871 men; mean age, 45±8.9 years) were enrolled in the CArdiometabolic risk, Epicardial fat, and Subclinical Atherosclerosis Registry (CAESAR) study and underwent CT for measurement of coronary artery calcium score (CACS) and echocardiography for EFT. According to EFT quartiles, the prevalence of CAC >0 was 8.3%, 16.8%, 24.6%, and 28.3% in the lowest, second, third, and highest EFT quartiles, respectively (P<0.001). On multivariate logistic regression after adjusting for variables with a univariate relationship (P<0.05), the second, third, and highest quartile groups of EFT had higher odds ratios (OR) for the presence of CAC compared with those of the lowest quartile (OR, 1.634; 95% confidence interval (CI): 0.940-2.839; 1.762, 1.019-3.048; and 1.924, 1.107-3.342, respectively), and the increase in absolute EFT was also independently associated with higher OR for the presence of CAC (1.842; 95% CI: 1.057-3.208, P=0.031). Moreover, increasing absolute EFT was associated with increasing CACS on multivariate linear regression (standardized ß=0.081, P=0.005). CONCLUSIONS: There was an independent relationship between EFT and coronary artery calcification in Korean adults, suggesting that echocardiographic EFT might be an easily accessible tool for early detection of subclinical coronary atherosclerosis.

The association between serum ferritin level, microalbuminuria and non-alcoholic fatty liver disease in non-diabetic, non-hypertensive men.

BACKGROUND: Iron-mediated cell injury may cause glomerular endothelial dysfunction, which precedes microalbumuria. However, there have been no reports on the relationship between serum ferritin level and microalbuminuria. The aim of this study is to assess the relationship between serum ferritin level and microalbuminuria in apparently healthy men and to evaluate how non-alcoholic fatty liver disease (NAFLD) affects this association. METHODS: Microalbuminuria and serum ferritin level were measured, and hepatic ultrasound was performed in a sample of 2489 non-diabetic, non-hypertensive men. The patients were classified into two groups according to urinary albumin-creatinine ratio (UACR) in morning urine specimens: normoalbuminuria (<30 µg/mg) and microalbuminuria (30-300 µg/mg). RESULTS: The overall prevalence of microalbuminuria and NAFLD based on ultrasound findings were 4.5% (113 subjects) and 41.9% (1042 subjects), respectively. The microalbuminuric group had significantly higher levels of serum ferritin than the normoalbuminuric group (255.4 pmol/L versus 207.5 pmol/L, p<0.001). In the multivariate regression analysis, serum ferritin level was independently associated with microalbuminuria irrespective of multiple covariates (OR [95% CI] 1.746 [1.221-2.497]). Subgroup analyses according to NAFLD revealed that the NAFLD group had higher serum ferritin level and a higher prevalence of microalbuminuria compared with the non-NAFLD group (233.8 pmol/L versus 194.3 pmol/L, p<0.001) (6.3% versus 3.2%, p<0.001). However, in the multivariate regression analysis, there was a significant association between serum ferritin level and microalbuminuria in both the non-NAFLD and the NAFLD group. CONCLUSIONS: Our results indicate that serum ferritin level is associated with microalbuminuria in non-hypertensive, non-diabetic men, irrespective of NAFLD.

Emotion regulation from a virtue perspective.

BACKGROUND: The ability to regulate one's emotional state is an important predictor of several behaviors such as reframing a challenging situation to reduce anger or anxiety, concealing visible signs of sadness or fear, or focusing on reasons to feel happy or calm. This capacity is referred to as emotion regulation. Deficits in this ability can adversely affect one's adaptive coping, thus are associated with a variety of other psychopathological symptoms, including but not limited to depression, borderline personality disorder, substance use disorders, eating disorders, and somatoform disorders. METHODS: The present study examined emotion regulation in relation to the virtue-based psychosocial adaptation model (V-PAM). 595 participants were clustered based on their Difficulties in Emotion Regulation Scale (DERS) score, producing two clusters (i.e., high functioning vs. low functioning). Then, emotion regulation group membership was discriminated by using five V-PAM virtue constructs, including courage, integrity, practical wisdom, committed action, and emotional transcendence. RESULTS: Results show that five virtues contribute to differentiating group membership. Practical wisdom was the strongest contributor, followed by integrity, emotional transcendence, committed action, and courage. Predictive discriminant analysis was conducted and 71% of cases were correctly classified. A discussion of the relationship between emotion regulation and virtues was elaborated. CONCLUSION: The concept of virtue holds significant importance in the comprehension of an individual's capacity to regulate their emotions, meriting future study.

Association Between ECG Abnormalities and Mortality in a Low-Risk Population.

BACKGROUND: The ECG is a simple, noninvasive screening method for cardiovascular disease and arrhythmia. The impact of ECG abnormality on mortality is not certain in low-risk populations. To address this, we evaluated the association between ECG abnormality and mortality. METHODS AND RESULTS: We retrospectively assessed baseline ECG and all-cause mortality and cardiovascular mortality in 660 383 patients presenting for medical check-ups. Baseline ECG abnormalities were classified according to the Minnesota Code. Among the total 660 383 participants, 23 609 (3.6%) had major and 110 038 (16.7%) had minor ECG abnormalities. All-cause mortality occurred in 7751 patients (1.1%) and cardiovascular mortality in 1180 (0.18%) over a median follow-up period of 8.8 years. Major ECG abnormalities were associated with all-cause mortality (hazard ratio [HR], 1.11 [95%, 1.03-1.2]) and cardiovascular mortality (HR, 1.92 [95% CI, 1.63-2.27]) compared with no ECG abnormalities. All-cause mortality was associated with right atrial enlargement (HR, 2.11 [95% CI, 1.1-4.07]), left atrial enlargement (HR, 1.76 [95% CI, 1.1-2.84]), sinus tachycardia (HR, 1.52 [95% CI, 1.15-2.01]), complete atrioventricular block (HR, 2.1 [95% CI, 1.05-4.2]), atrial fibrillation (HR, 1.52 [95% CI, 1.26-1.84]), and left ventricular hypertrophy (HR, 1.15 [95% CI, 1.02-1.3]). Cardiovascular mortality was associated with left atrial enlargement (HR, 4.52 [95% CI, 2.15-9.5]), atrial fibrillation (HR, 3.22 [95% CI, 2.33-4.46]), left ventricular hypertrophy (HR, 1.72 [95% CI, 1.35-2.19]), major Q-wave abnormality (HR, 1.6 [95% CI, 1.08-2.39]), and major ST-T abnormality (HR, 1.76 [95% CI, 1.01-3.04]). CONCLUSIONS: ECG abnormalities, including left atrial enlargement, left ventricular hypertrophy, atrial fibrillation, and major Q-wave and ST-T abnormalities, were associated with cardiovascular mortality in a low-risk population.

The effect of postmortem time on the RNA quality of human ocular tissues.

PURPOSE: Profiling gene expression in human ocular tissues provides invaluable information for understanding ocular biology and investigating numerous ocular diseases. Accurate measurement of gene expression requires high-quality RNA, which often is a challenge with postmortem ocular tissues. METHODS: We examined the effect of various death to preservation (DP) times on the RNA quality of ten different ocular tissues. We used 16 eyes from eight different human donors. The eyes were preserved immediately in RNAlater or preserved after initial storage at 4 °C to create a range of DP times from 2 to 48 h. Ten ocular tissues were dissected from each eye. After total RNA was extracted from each dissected ocular tissue, the RNA integrity number (RIN) was determined using an Agilent Bioanalyzer. RESULTS: The RIN values from corneal and trabecular meshwork tissues were significantly (p<0.05) higher than those from the ciliary body at an earlier DP time (<6 h), but were not different among all tissues after 8 h. Interestingly, the RIN values from non-vascularized tissues were significantly (p=0.0002) higher than those from vascularized ocular tissues at early DP times (<6 h). The RIN value from the cornea was significantly (p<0.05) higher at short DP times compared to longer DP times. The RIN values from corneal tissues were significantly correlated to DP time according to regression analysis (p<0.05). CONCLUSIONS: In this study, we determined RNA quality from postmortem ocular tissues with various DP times. Our results emphasize the need for rapid preservation and processing of postmortem human donor eye tissues, especially for vascularized ocular tissues.

Arterial stiffness, fatty liver and the presence of coronary artery calcium in a large population cohort.

BACKGROUND: We tested whether fatty liver, brachial-ankle pulse wave velocity (baPWV) and conventional cardiovascular risk factors were associated with a coronary artery calcium (CAC) score > 0 (as a marker of the presence of early atherosclerosis) in a cohort of healthy Korean adults. METHOD: The study population consisted of individuals who underwent a comprehensive health examination in 2010 at Kangbuk Samsung Hospital, College of Medicine, Sungkyunkwan University in South Korea. The 6009 subjects of total 7371 participants who had an assigned CAC score following coronary computed tomography (CT) scanning and baPWV were analyzed. RESULTS: Among the study subjects, 39.2% of the population had evidence of fatty liver by ultrasound and 4.6% of the population had evidence of CAC score > 0. Among individuals with a CAC score = 0, 38% of the individuals had fatty liver compared with 58% of the individuals with a CAC score > 0. The individuals with a CAC score > 0 also had higher blood pressure and had more metabolic abnormalities. The prevalence of CAC score > 0 was increased according to baPWV quartiles and was higher in the fatty liver group in comparison with those without fatty liver. The odds ratio for CAC score > 0, after adjusting for clinical risk factors, showed a significant elevation with increasing quartiles of baPWV and the presence of fatty liver. CONCLUSION: We showed that both fatty liver and baPWV are independently associated with the presence of CAC, a marker of preclinical atherosclerosis. These associations are independent of conventional risk factors and medical history.

Interleukin-23 (IL-23) deficiency disrupts Th17 and Th1-related defenses against Streptococcus pneumoniae infection.

Resolution of acute of infection caused by capsular Streptococcus pneumoniae infection in the absence of effective antibiotic therapy requires tight regulation of immune and inflammatory responses. To provide new mechanistic insight of the requirements needed for innate host defenses against acute S. pneumoniae infection, we examined how IL-23 deficiency mediated acute pulmonary resistance. We found that IL-23 deficient mice were more susceptible to bacterial colonization in the lungs corresponding with greater bacterial dissemination. The lack of IL-23 was found to decrease IL-6 and IL-12p70 cytokine levels in bronchiolar lavage within the initial day after infection. Pulmonary leukocytes isolated from infected IL-23 deficient mice demonstrated a dramatic decrease in IL-17A and IFN-γ in response to heat-killed organisms. These findings corresponded with significant abrogation of neutrophilic infiltrate in the lungs compared to IL-23 competent mice. Whereas previous studies have shown opposing influences of IL-12/IL-23 regulation, our findings suggest a concordant dependency of IL-23 expression on Th1 and Th17-related responses.

Lipoprotein(a)-related cardiovascular and all-cause mortalities in Korean adults.

AIMS: There are inconsistent results on the association between lipoprotein(a) and mortality-related outcomes due to a lack of evidence from large-scale observational studies of Asians. This study aims to evaluate the effects of lipoprotein(a) on mortality-related outcomes in the Korean population. METHODS AND RESULTS: This cohort study included 275 430 individuals (mean age: 38 years; 50.1% men) enrolled in the Kangbuk Samsung Health Study between 2003 and 2016. The median follow-up period was 6.6 years. Cox proportional hazards analysis was used to estimate the adjusted hazard ratios (HRs) for evaluating mortality risk based on lipoprotein(a) levels and specific lipoprotein(a) categories. The median lipoprotein(a) value was 18.5 mg/dL, and the proportion of lipoprotein(a) ≥50 mg/dL was 12.8%. Multivariable Cox regression analysis showed that the group with lipoprotein(a) ≥50 mg/dL had a significantly increased risk of cardiovascular mortality (HR[95% CI]: 1.83[1.26, 2.64]) and all-cause mortality (1.20[1.03, 1.41]) than the group with lipoprotein(a) < 50 mg/dL without increased risk of cancer mortality (1.05[0.81, 1.34]). The relationship between lipoprotein(a) and cardiovascular mortality was significant regardless of low-density lipoprotein cholesterol. Specifically, lipoprotein(a) ≥100 mg/dL was associated with more than twice as increased a risk of cardiovascular mortality (2.45[1.12, 5.34]) than lipoprotein(a) < 10 mg/dL. In subgroup analyses, there was an interaction in the relationships between the two lipoprotein(a) categories and cardiovascular mortality for only high-density lipoprotein cholesterol. CONCLUSIONS: High lipoprotein(a) concentration is an independent predictor of cardiovascular mortality in the Korean population, regardless of low-density lipoprotein cholesterol levels.