A Data-Driven Approach to Support the Understanding and Improvement of Patients' Journeys: A Case Study Using Electronic Health Records of an Emergency Department.

OBJECTIVES: Given the increasing availability of electronic health records, it has become increasingly feasible to adopt data-driven approaches to capture a deep understanding of the patient journeys. Nevertheless, simply using data-driven techniques to depict the patient journeys without an integrated modeling and analysis approach is proving to be of little benefit for improving patients' experiences. Indeed, a model of the journey patterns is necessary to support the improvement process. METHODS: We presented a 3-phase methodology that integrates a process mining-based understanding of patient journeys with a stochastic graphical modeling approach to derive and analyze the analytical expressions of some important performance indicators of an emergency department including mean and variance of patients' length of stay (LOS). RESULTS: Analytical expressions were derived and discussed for mean and variance of LOS times and discharge and admission probabilities. LOS differed significantly depending on whether a patient was admitted to the hospital or discharged. Moreover, multiparameter sensitivity equations are obtained to identify which activities contribute the most in reducing the LOS at given operating conditions so decision makers can prioritize their improvement initiatives. CONCLUSIONS: Data-driven based approaches for understanding the patient journeys coupled with appropriate modeling techniques yield a promising tool to support improving patients' experiences. The modeling techniques should be easy to implement and not only should be capable of deriving some key performance indicators of interest but also guide decision makers in their improvement initiatives.

Folate deficiency is associated with increased radiographic severity of osteoarthritis in knee joints but not in hand joints.

OBJECTIVES: No previous studies have explored the effect of folate deficiency on the severity of osteoarthritis (OA). Therefore, we investigated the relationship between folate level and features on knee and hand radiographs in a large, population-based OA cohort. METHODS: Among 9,260 subjects enrolled in the Dong-gu study, 2,489 who had knee and hand joint radiographs were included. Of these, subjects with a history of amputation or total knee replacement were excluded. Serum folate levels were measured using blood samples collected at the time of enrolment and stored. A semi-quantitative system was used to grade the severity of hand and knee x-ray changes. Linear regression was performed to assess relationships between serum folate levels and knee and hand radiographic scores after adjusting for age, sex, body mass index, smoking, alcohol consumption, education, physical activity, occupation, vitamin D, and ferritin. RESULTS: A total of 2,322 subjects were recruited. After adjusting for confounders, participants with folate deficiency (<4 ng/mL) had higher total (p<0.001), osteophyte (p<0.001), joint space narrowing (p=0.002), tibial attrition (p<0.001), and sclerosis (p=0.005) scores for knee joint radiographs compared to participants with a normal folate level. After adjusting for confounders, the radiographic scores for hand joints did not differ between the groups. CONCLUSIONS: Folate deficiency is associated with increased radiographic severity of OA in knee joints, but not in hand joints. Further studies are needed to explore the differential effects of folate on the severity of knee and hand OA.

Understanding of the Lower Extremity Motor Recovery After First-Ever Ischemic Stroke.

BACKGROUND: We aimed to verify the validity of the proportional recovery model for the lower extremity. METHODS: We reviewed clinical data of patients enrolled in the Korean Stroke Cohort for Functioning and Rehabilitation between August 2012 and May 2015. Recovery proportion was calculated as the amount of motor recovery over initial motor impairment, measured as the Fugl-Meyer Assessment of Lower Extremity score. We used the logistic regression method to model the probability of achieving the full Fugl-Meyer Assessment of Lower Extremity score, whereby we considered the ceiling effect of the score. To show the difference in the prevalence of achieving the full Fugl-Meyer Assessment of Lower Extremity score between 3 and 6 months poststroke, we constructed a marginal model through the generalized estimating equation method. We also performed the propensity score matching analysis to show the dependency of recovery proportion on the initial motor deficit at 3 and 6 months poststroke. RESULTS: We evaluated 1085 patients. The recovery proportions at 3 and 6 months poststroke were 0.67±0.42 and 0.75±0.39, respectively. A 1-unit decrease in the initial neurological impairment and the age at stroke onset increased the probability of achieving the full Fugl-Meyer Assessment of Lower Extremity score, which occurred at both 3 and 6 months poststroke. The prevalence of those who reach full lower limb motor recovery differs significantly between 3 and 6 months poststroke. We also found out that the recovery proportion at both 3 and 6 months poststroke is determined by the initial motor deficits of the lower limb. These results are not consistent with the proportional recovery model. CONCLUSIONS: Our results demonstrated that the proportional recovery model for the lower limb is invalid.

Association between alcohol and bone mineral density in a Mendelian randomization study: the Dong-gu study.

INTRODUCTION: Many previous studies have reported a positive relationship between alcohol and bone mineral density (BMD). However, the causality between alcohol and BMD has not been fully evaluated. MATERIALS AND METHODS: This study enrolled 8892 participants from the Dong-gu study. Mendelian randomization (MR) using two-stage least-squared regression was used to evaluate the association between the genetically predicted amount of alcohol consumption per day and BMD. The aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism was used as instrumental variables for alcohol consumption. Age, smoking history, and BMI were adjusted in the multivariate model. RESULTS: Self-reported alcohol consumption was positively related to total hip and lumbar spine BMD in both sexes. In multivariate Mendelian randomization analysis, the genetically predicted amount of alcohol consumption was positively associated with both total hip and lumbar spine BMD in men. Total hip BMD and lumbar spine BMD increased by 0.004 g/cm2 (95% confidence interval [CI] 0.002-0.007) and 0.007 g/cm2 (95% CI 0.004-0.011) with doubling of alcohol consumption. However, in women, genetically predicted alcohol consumption was not significantly associated with BMD. CONCLUSION: In our MR study, genetically predicted alcohol consumption was positively associated with BMD in men. This result suggests that the association between alcohol consumption and BMD is causal.

Health-related quality of life using WHODAS 2.0 and associated factors 1 year after stroke in Korea: a multi-centre and cross-sectional study.

BACKGROUND: Little is known about the self-perceived level of disability of stroke survivors in the community. We aimed to characterise Health-related quality of life (HRQoL) 1 year after stroke and investigate how sociodemographic and stroke-related factors and medical adherence explain the self-perceived level of disability in a Korean stroke population. METHODS: This was a multicentre cross-sectional study. A total of 382 ischaemic stroke survivors at 1 year after onset from 11 university hospitals underwent a one-session assessment, including socioeconomic variables, the modified Rankin Scale (mRS), various neurological sequelae, the Morisky, Green and Levin-Medication Adherence Questionnaire (MGL), and the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) 36-items. The relationship between disability and different variables was analysed using ordinal logistic regression. RESULTS: The prevalence of disability based on global WHODAS 2.0 was 62.6% (mild, 41.6%; moderate, 16.0%; severe, 5.0%). The prevalence of severe disability was higher in participation in society (16.8%) and getting around (11.8%) than in other domains. Low MGL- motivation was the only factor determining a significant association between all six domains of disability after adjustment. Different predictors for specific domains were age, mRS, dysarthria, trouble seeing, cognition problems, and MGL-motivation for understanding and communicating; age, recurrent stroke, mRS, hemiplegia, facial palsy, general weakness, and MGL-motivation for getting around; age, education, mRS, hemiplegia, and MGL-motivation for self-care; education, recurrent stroke, hemiplegia, dysarthria, and MGL-motivation for getting along with people; age, education, income, mRS, hemiplegia, dysarthria, MGL-knowledge, and MGL-motivation for life activities; living without a spouse, mRS, hemiplegia, dysarthria, trouble seeing, cognition problems, general weakness, and MGL-motivation for participation in society. CONCLUSIONS: Self-perceived disability according to the WHODAS 2.0 at 1 year after stroke was highly prevalent. Each disability domain showed a different prevalence and associated factors. Interventions promoting medical adherence to motivation seemed to help achieve high HRQoL in all domains.

The longitudinal associations between trajectory of and quantity of alcohol consumption and subsequent changes in blood pressure levels among non-hypertensive adults.

Given the dynamic characteristic of an individual's drinking behaviours, comprehensive consideration of alcohol consumption variation using repeated measures may improve insight into the nature of its association with blood pressure (BP) change. We examined the association between longitudinal alcohol consumption (trajectory and quantity) and changes in BP and pulse pressure (PP) among Korean aged ≥ 40 years living in rural areas. Totally, 1682 hypertension-free participants who completed all three health examinations (median, 5·3 years) were included. All three visits were used to determine the cumulative trajectory of and quantity of alcohol consumption and the latest two visits and the last visit were used for the recent trajectory and the most recent quantity of alcohol consumption, respectively. Changes in BP and PP from the baseline to the third visit were used as outcome. In men, ≥30 ml/d cumulative average alcohol consumption was associated with the greatest increase in systolic BP (SBP) in both baseline outcome-unadjusted (2·9 mmHg, P = 0·032) and -adjusted models (3·6 mmHg, P = 0·001), and the given association for the most recent alcohol consumption was observed in the baseline outcome-adjusted model (3·9 mmHg, P = 0·003). For PP, similar associations were observed only in the baseline outcome-adjusted model. No meaningful associations in diastolic BP in men and any BP or PP in women existed. The quantity of alcohol consumption rather than the trajectory may be significantly related to raised SBP, and a possible short-term influence of the most recent alcohol consumption may exist when baseline SBP is adjusted in men.

Dietary iodine, seaweed consumption, and incidence risk of metabolic syndrome among postmenopausal women: a prospective analysis of the Korean Multi-Rural Communities Cohort Study (MRCohort).

PURPOSE: Despite a beneficial role of iodine and seaweed consumption against metabolic syndrome (MetS), which is high in postmenopausal women, few studies investigated such associations in a prospective study. This study aimed to investigate the association of dietary iodine and seaweed consumption with the incidence of MetS and its components in postmenopausal women. METHODS: A total of 2588 postmenopausal women aged ≥ 40 years were recruited between 2005 and 2011 in the Multi-Rural Communities Cohort (MRCohort). A validated semiquantitative food frequency questionnaire was used to collect dietary intake data. MetS was defined as three of five components [abdominal obesity, elevated blood pressure, glucose, triglyceride, and low-high density lipoprotein cholesterol (HDL-C)] and the incidence of MetS was checked every 2-4 years. The incidence rate ratio (IRR) was estimated using a modified Poisson regression model with a robust error estimator. RESULTS: During the mean follow-up period (3.4 ± 2.1 years), MetS occurred in 481 participants. The median cumulative average iodine intake was 108.9 µg/day (interquartile range, 60.8-190.2 µg/day). In multivariable analyses, average iodine and seaweed consumption were inversely associated with MetS (IRR = 0.61, 95% CI 0.47-0.78 in the highest quartile of iodine intake, P for trend = 0.0018; IRR = 0.52, 95% CI 0.39-0.69 in the highest quartile of seaweed consumption, P for trend = 0.0004). Among MetS components, blood glucose (> 100 mg/dL), blood pressure (≥ 130/85 mmHg), and lipid profiles (triglyceride, ≥ 150 mg/dL and HDL-C, < 50 mg/dL) were significantly inversely associated with dietary iodine and seaweed consumption, but there was no clear association for waist circumference (≥ 85 cm). CONCLUSION: Dietary iodine and seaweed consumption may be inversely associated with MetS incidence and its individual abnormalities in postmenopausal women.

Status Of Dysphagia After Ischemic Stroke: A Korean Nationwide Study.

OBJECTIVE: To identify the incidence of dysphagia after ischemic stroke and determine factors affecting the presence of dysphagia. DESIGN: Retrospective case-control study. This was an interim analysis of a prospective multicenter Korean stroke cohort. SETTING: Acute care university hospitals. PARTICIPANTS: Patients (N=6000) with first-ever acute ischemic stroke. Patients were divided into 2 groups according to the presence or absence of dysphagia confirmed at 7 days after onset using the American Speech-Language-Hearing Association National Outcomes Measurement System (ASHA-NOMS) scale, which was determined after conducting screening or standardized tests. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Age at stroke onset, body mass index (BMI), premorbid modified Rankin Scale (mRS), brainstem lesions, National Institutes of Health Stroke Scale (NIHSS), poststroke mRS, and ASHA-NOMS swallowing level at poststroke day 7 were evaluated. RESULTS: Among patients with ischemic stroke, 32.3% (n=1940) had dysphagia at 7 days after stroke onset. At discharge, 80.5% (n=1561) still had dysphagia. The prediction model for the presence of dysphagia identified age at onset, underweight (BMI <18.5 kg/m2), premorbid mRS, brainstem lesions, and NIHSS as independent predictors. The odds ratio (OR) for the presence of dysphagia significantly increased with underweight (OR, 1.6684; 95% confidence interval [CI], 1.27-2.20), increased age at onset (OR, 1.0318; 95% CI, 1.03-1.04), premorbid mRS (OR, 1.1832; 95% CI, 1.13-1.24), brainstem lesions (OR, 1.6494; 95% CI, 1.39-1.96), and NIHSS (OR, 1.2073; 95% CI, 1.19-1.23). CONCLUSIONS: The incidence of dysphagia after ischemic stroke was 32.3%. The prediction model for the presence of dysphagia identified age, low BMI, premorbid disabilities, brainstem lesions, and NIHSS as predictive factors.

Association between Alcohol Consumption and Serum Cortisol Levels: a Mendelian Randomization Study.

BACKGROUND: Several studies have reported conflicting results regarding the relationship between alcohol consumption and cortisol levels. However, the causality between alcohol consumption and cortisol levels has not been evaluated. METHODS: This study examined 8,922 participants from the Dong-gu Study. The aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism was used as an instrumental variable for alcohol consumption. The association between the genetically predicted alcohol consumption and cortisol level was evaluated with Mendelian randomization (MR) using two-stage least squares regression. RESULTS: Alcohol consumption was positively associated with the serum cortisol level in both sexes in the observational analysis. In the MR analysis, the genetically predicted alcohol consumption was positively related to the cortisol level in men, with cortisol levels increasing by 0.18 µg/dL per drink per day. However, there was no relationship in women in the MR analysis. CONCLUSION: The predicted alcohol consumption according to the ALDH2 rs671 polymorphism was positively related to the cortisol levels, suggesting a causal relationship between alcohol consumption and cortisol levels.

Optimal cost adjustment for a selfish routing healthcare network.

South Korea's large hospitals are severely burdened by patient congestion because patients throng to these places expecting to get treated better given their higher-quality healthcare. Effective cost management of the healthcare system is one way to reduce patient congestion in a large hospital. This study proposes methods that can help direct patient flows in a desirable direction and suggests ways to effectively manage the cost of healthcare. The study also discusses how selfish patients act in ways that maximize their benefits by choosing a specific hospital and in turn forcing the hospital and the healthcare network to bear more costs than is necessary. The study proposes a model describing the need for intervention from the government to control the cost escalation resulting from selfish routing. The study proposes two heuristic algorithms to solve the suggested model. The flow-based algorithm addresses the target quantum of flows, and the utility-based algorithm targets the value of cost functions. Performances of heuristics are evaluated through numerical experiments. The utility-based algorithm yields higher values for objectives, while the flow-based algorithm controls the extent of investment. A case study based on data from the Seoul city database is also analyzed. The cost adjustment policy is compared with simple, uniformly improved network policies, and findings show that such policies have the strength needed to improve the cost-effectiveness of the healthcare system if implemented fully and effectively.

Protection of Alcohol Dehydrogenase against Freeze-Thaw Stress by Ice-Binding Proteins Is Proportional to Their Ice Recrystallization Inhibition Property.

Ice-binding proteins (IBPs) have ice recrystallization inhibition (IRI) activity. IRI property has been extensively utilized for the cryopreservation of different types of cells and tissues. Recent reports demonstrated that IRI can also play a significant role in protecting proteins from freezing damage during freeze-thaw cycles. In this study, we hypothesized that the protective capability of IBPs on proteins against freeze-thaw damage is proportional to their IRI activity. Hence we used two IBPs: one with higher IRI activity (LeIBP) and the other with lower activity (FfIBP). Yeast alcohol dehydrogenase (ADH) was used as a freeze-labile model protein. IBPs and ADH were mixed, frozen at -20 °C, and thawed repeatedly. The structure of ADH was assessed using fluorescence emission spectra probed by 1-anilinonaphthalene-8-sulfonate over the repeated freeze-thaw cycles. The activity was monitored at 340 nm spectrophotometrically. Fluorescence data and activity clearly indicated that ADH without IBP was freeze-labile. However, ADH maintained about 70% residual activity after five repeated cycles at a minimal concentration of 0.1 mg mL-1 of high IRI-active LeIBP, but only 50% activity at 4 mg mL-1 of low active FfIBP. These results showed that the protection of proteins from freeze-thaw stress by IBPs is proportional to their IRI activity.

Effect Modification of Acetaldehyde Dehydrogenase 2 rs671 Polymorphism on the Association between Alcohol Intake and Blood Pressure: the Dong-gu Study.

BACKGROUND: Elevated blood pressure is a major preventable cause of cardiovascular diseases. Alcohol consumption is a well-known risk factor of elevated blood pressure. The aldehyde dehydrogenase 2 (ALDH2) polymorphism is common in Eastern Asians, and inactive ALDH2 genotypes are associated with both avoiding alcohol consumption and aldehyde accumulation. Therefore, this study assessed the associations between alcohol consumption and hypertension and blood pressure according to the ALDH2 genotypes. METHODS: This study consists of 8,526 participants in the Dong-gu Study. Multivariate logistic regression was used to calculate the odds ratio (OR) according to alcohol consumption after stratifying by gender and ALDH2 genotypes. Multivariate linear regression was performed to estimate the systolic blood pressure (SBP) and diastolic blood pressure (DBP) according to the amount of alcohol consumed. RESULTS: In men, alcohol consumption was positively associated with both SBP and DBP in active ALDH2 carriers, but not in inactive ALDH2 carriers. In active ALDH2 carriers, compared to non-drinkers, the OR of hypertension was 1.16 (95% confidence interval [CI], 0.91-1.49) for < 1 drink/day, and 1.44 (95% CI, 1.15-1.80) for ≥ 1 drink/day in men. With each 1 drink/day increase, SBP and DBP increased by 3 and 1 mmHg in men, respectively. There was no significant association between ALDH2 genotypes and hypertension and blood pressure in women. CONCLUSION: ALDH2 genotype modified the association between alcohol consumption and blood pressure in men. There was a positive relationship between alcohol consumption and blood pressure in active ALDH2 carriers, but no significant relationship in inactive ALDH2 carriers.

Can natural killer cell activity help screen patients requiring a biopsy for the diagnosis of prostate cancer?

PURPOSE: To evaluate the usefulness of natural killer cell activity (NKA) in diagnosing prostate cancer (PC). MATERIALS AND METHODS: The medical records of patients who underwent transrectal prostate biopsy (TRBx) at Korea University Ansan Hospital between May 2017 and December 2017 were retrospectively reviewed. NKA levels were measured using NK VueR Tubes (ATgen, Sungnam, Korea). All blood samples were obtained at 8 AM on the day of biopsy. Patients with other malignancies, chronic inflammatory conditions, high prostate-specifi c antigen (PSA) level (>20ng/mL), or history of taking 5-alphareductase inhibitor or testosterone replacement therapy were excluded. RESULTS: A total of 102 patients who underwent TRBx for PC diagnosis were enrolled. Among them, 50 were diagnosed with PC. Significant differences in age and NKA level were observed between the PC and no-PC groups. Receiver operating characteristic (ROC) curve analysis showed that the optimal cut-off of NKA level for the prediction of PC was 500pg/dL, with a sensitivity of 68.0% and a specifi city of 73.1%. In addition, NKA level (0.630) had the greatest area under the ROC curve compared to those for the ratio of total PSA to free PSA (0.597) and PSA density (0.578). CONCLUSIONS: The results of this pilot study revealed that low NKA and high PSA levels were likely to be associated with a positive TRBx outcome. NKA detection was easy and improved the diagnostic accuracy of PC.

Serum level vitamin D and parathyroid hormone, and mortality, with or without chronic kidney disease.

Levels of vitamin D and parathyroid hormone (PTH) are closely associated with renal function. We evaluated the associations among 25-hydroxyvitamin D (25OHD) levels, PTH levels, and mortality, and whether these associations varied by renal function. We used data from the Dong-gu Study, a population-based cohort in Korean adults. We analyzed the associations among intact PTH, 25OHD levels and mortality in 8580 participants. Hazard ratios (HRs) for mortality were calculated using Cox proportional hazards regression after adjusting for age, sex, month of sampling, lifestyle, and comorbidities. We also evaluated the effects of chronic kidney disease (CKD). A total of 860 deaths occurred during the follow-up period of 7.6 years. Compared to the first 25OHD quartile, the HRs of the second, third, and fourth quartiles were 0.96 [95% confidence interval (CI) 0.79-1.16], 0.84 (95% CI 0.68-1.02), and 0.71 (95% CI 0.57-0.89), respectively. The association between intact PTH levels and mortality varied by renal function, and was both nonlinear and significant only in subjects with CKD. Compared to the second intact PTH quartile in such subjects, the HRs for the first, third, and fourth quartiles were 1.61 (95% CI 0.92-2.81), 1.97 (95% CI 1.17-3.31), and 2.19 (95% CI 1.33-3.59), respectively. In conclusion, we demonstrated that low serum levels of 25OHD are associated with an increased risk of mortality. Serum levels of intact PTH are nonlinearly associated with mortality only in subjects with CKD, with the lowest risk for mortality being evident in the second quartile.

High sodium intake and sodium to potassium ratio may be linked to subsequent increase in vascular damage in adults aged 40 years and older: the Korean multi-rural communities cohort (MRCohort).

PURPOSE: Subclinical vascular damage is a chronic intermediate process in cardiovascular disease (CVD) and high sodium (Na) has been regarded as an adverse factor in subclinical vascular health; however, the longitudinal relationship between Na intake and subclinical vascular damage has not been studied. We aimed to evaluate the longitudinal relationship of dietary Na intake and sodium to potassium ratio (Na:K) with brachial-ankle pulse wave velocity (baPWV) and carotid intima media thickness (cIMT) in healthy adults aged 40 years and older in Korea. METHODS: The present study was based on participants (n = 2145 for baPWV analysis and n = 2494 for cIMT analysis) who visited three times during 2005-2013 (median 5.3 years of follow-up). We used both dietary Na intake and Na:K at baseline and its average (baseline, 2nd, 3rd), which was obtained from food frequency questionnaire (FFQ) as exposure at every visit. baPWV and cIMT levels at the third visit and change from baseline to the third visit were used to represent the level of subclinical vascular damage. RESULTS: After adjustment for potential confounders, significant positive relationships between dietary Na intake and both baPWV3rd and cIMT3rd were observed (baPWV: p for trend ≤ 0.0001 for Naaverage; cIMT: p for trend = 0.013 for Naaverage). Compared with Na:Ks less than 1.0, the levels of both baPWV and cIMT were higher for participants with Na:Ks over 1.0 (baPWV: p for trend = 0.0002 for Na:Kaverage; cIMT: p for trend = 0.005 for Na:Kaverage). Similar significant trends were shown in relationships between dietary Na intake and Na:K and changes in baPWV and cIMT levels. CONCLUSIONS: In conclusion, dietary Na intake and Na:K may be positively linked to subsequent baPWV and cIMT levels in adults aged 40 years and older in Korea. Our findings may provide informative evidence on subclinical vascular damage, particularly for populations with relatively high dietary Na intake and low dietary K intake.

Habitual consumption of soy protein and isoflavones and risk of metabolic syndrome in adults ≥ 40 years old: a prospective analysis of the Korean Multi-Rural Communities Cohort Study (MRCohort).

PURPOSE: Although considerable attention has been paid to the potential benefits of soy protein and isoflavones for preventing metabolic syndrome (MetS) and its components, findings linking habitual consumption of these factors to MetS are limited. This study aimed to evaluate the association of MetS incidence with habitual intake of soy protein/isoflavones among Korean men and women aged ≥ 40 years old who did not have MetS at baseline (n = 5509; 2204 men and 3305 women). METHODS: Dietary intake of soy protein/isoflavones at baseline and average consumption during follow-up were used. RESULTS: A significant inverse association between dietary intake and incidence of MetS was found in women (incidence rate ratios, IRR = 0.60, 95% CI = 0.46-0.78, P for trend = 0.0094 for the highest quintile of average soy protein intake compared with the lowest quintile; IRR = 0.57, 95% CI = 0.44-0.74, P for trend = 0.0048 for the highest quintile of average isoflavones intake compared with the lowest quintile). A tendency towards an inverse association was also found in men, although it was not significant for the highest quintile (IRR = 0.80, 95% CI = 0.58-1.11, P for trend = 0.9759, comparing the lowest to the highest quintile of average soy protein intake; IRR = 0.73, 95% CI = 0.53-1.01, P for trend = 0.8956, comparing the lowest to the highest quintile of average isoflavones intake). In terms of individual abnormalities, a significant inverse association was found between soy protein and isoflavones and the incidence of low-high-density lipoprotein cholesterol in both men and women. Abdominal obesity and elevated blood pressure were inversely related to soy protein/isoflavones only in women, and an inverse association of elevated triglyceride appeared only in men. CONCLUSION: Our findings suggest that habitual intake of soy protein and isoflavones is inversely associated with the risk of MetS and its components. There is likely to be a reverse J-shaped association of average intake with MetS.

The Association between the Apolipoprotein E Gene Polymorphism and All-cause Mortality in the Korean Population.

BACKGROUND: Apolipoprotein E (APOE) gene polymorphism is associated with neurodegenerative and cardiovascular diseases. Although the effects of the gene differ by ethnic group, few studies have examined Asians. Therefore, the association between APOE polymorphism and mortality in Koreans was evaluated in this study. METHODS: This study population included participants from the Dong-gu and Namwon Studies. APOE genotypes were categorized as E2 (E2/E2 and E2/E3), E3 (E3/E3), and E4 (E3/E4 and E4/E4). Multivariate Cox proportional hazard models were constructed using the E3 allele as a reference. RESULTS: In the model adjusting for study site, age, gender, and lifestyle, the hazard ratio (HR) of mortality for those with the E4 allele was 1.08 (95% confidence interval [CI], 0.97-1.20), while that for those with the E2 allele was 0.84 (95% CI, 0.74-0.96). After adjusting for blood lipids to evaluate their mediating effects, the HRs of mortality for those with E4 and E2 alleles were 1.08 (95% CI, 0.97-1.20) and 0.80 (95% CI, 0.70-0.92), respectively. These associations were more evident in younger groups, with HRs of 0.70 (95% CI, 0.52-0.92) for the E2 allele and 1.25 (95% CI, 1.03-1.53) for the E4 allele. CONCLUSION: In two large population-based cohort studies, the E2 allele was associated with a lower risk of mortality compared with the E3 allele, whereas the E4 genotype was not associated with mortality in Koreans.

NAADP-mediated Ca2+ signaling promotes autophagy and protects against LPS-induced liver injury.

LPS has been shown to induce hepatocyte autophagy, but little is known about how LPS is able to do this during acute toxic liver injury. Our aim was to determine the existence of any selective Ca2+ signaling coupling to hepatocyte autophagy in response to LPS. LPS increased the autophagic process in hepatocytes, and CD38 knockdown prevented this response. Ned19, a specific inhibitor for nicotinic acid adenine dinucleotide phosphate (NAADP), prevented LPS-mediated Ca2+ signaling and autophagosome formation in hepatocytes. CD38 overexpression protected the liver from LPS/d-galactosamine (GalN)-induced injury, and NAADP administration promoted autophagosome formation and protected hepatocytes from injury induced by LPS/GalN. Autophagy was promoted by the up-regulation of autophagy-related gene expression via NAADP-mediated Ca2+ signaling in response to LPS. However, CD38-knockout mice displayed down-regulation in hepatocyte gene expression. Ned19 also inhibited the NAADP-stimulated induction of gene expression by inhibiting the LPS-induced nuclear translocation of transcription factor EB (TFEB). Hepatocyte autophagy protects against LPS-induced liver injury via the CD38/NAADP/Ca2+/TFEB pathway. The role of NAADP-mediated Ca2+ signaling in the autophagic process will help elucidate the complexities of autophagy regulation, which is essential toward the discovery of new therapeutic tools against acute liver injury.-Rah, S.-Y., Lee, Y.-H., Kim, U.-H. NAADP-mediated Ca2+ signaling promotes autophagy and protects against LPS-induced liver injury.

Relationships among medication adherence, lifestyle modification, and health-related quality of life in patients with acute myocardial infarction: a cross-sectional study.

BACKGROUND: The healthy adherer effect is a phenomenon in which patients who adhere to medical therapies tend to pursue health-seeking behaviors. Although the healthy adherer effect is supposed to affect health outcomes in patients with coronary artery disease, evaluation of its presence and extent is not easy. This study aimed to assess the relationship between medication adherence and lifestyle modifications and health-related quality of life among post-acute myocardial infarction (AMI) patients. METHODS: A cross-sectional study was conducted in 417 post-AMI patients who underwent percutaneous coronary intervention (PCI). Patients were recruited from 11 university hospitals from December 2015 to March 2016 in South Korea. Details regarding socio-demographic factors, six health behaviors (low-salt intake, low-fat diet and/or weight-loss diet, regular exercise, stress reduction in daily life, drinking in moderation, and smoking cessation), medication adherence using the Modified Morisky Scale (MMS), and HRQoL using the Coronary Revascularization Outcome Questionnaire (CROQ) were surveyed in a one-on-one interview. RESULTS: In the univariate logistic analysis, sex (female), age (≥70 years), MMS score (≥5), and CROQ score were associated with adherence to lifestyle modification. In the multiple logistic analysis, a high MMS score (≥5) was associated with adherence to lifestyle modification after adjusting for sex, age, marital status, education, and family income (adjusted odds ratio [OR] = 11.7, 95% confidence interval [CI] = 1.5-91.3). After further adjusting for the CROQ score, the association between high MMS score and adherence to lifestyle modification was significant (adjusted OR = 11.5, 95% CI = 1.4-93.3). CONCLUSIONS: Adherence to medication was associated with adherence to lifestyle modification, suggesting the possible presence of the healthy adherer effect in post-AMI patients. After further adjusting for HRQoL, the association remained. To improve health outcome in post-AMI patients, early detection of patients with poor adherence to medication and lifestyle modification and motivational education programs to improve adherence are important. In addition, the healthy adherer effect should be considered in clinical research, in particular, in studies evaluating the effects of therapies on health outcomes.

Structural features of influenza A virus panhandle RNA enabling the activation of RIG-I independently of 5'-triphosphate.

Retinoic acid-inducible gene I (RIG-I) recognizes specific molecular patterns of viral RNAs for inducing type I interferon. The C-terminal domain (CTD) of RIG-I binds to double-stranded RNA (dsRNA) with the 5'-triphosphate (5'-PPP), which induces a conformational change in RIG-I to an active form. It has been suggested that RIG-I detects infection of influenza A virus by recognizing the 5'-triphosphorylated panhandle structure of the viral RNA genome. Influenza panhandle RNA has a unique structure with a sharp helical bending. In spite of extensive studies of how viral RNAs activate RIG-I, whether the structural elements of the influenza panhandle RNA confer the ability to activate RIG-I signaling has been poorly explored. Here, we investigated the dynamics of the influenza panhandle RNA in complex with RIG-I CTD using NMR spectroscopy and showed that the bending structure of the panhandle RNA negates the requirement of a 5'-PPP moiety for RIG-I activation.