Fruits and the Risk of Type 2 Diabetes: The Korean Genome and Epidemiology Study Cohort.

BACKGROUND: To determine the association between type 2 diabetes mellitus and the consumption of various fruits. METHODS: The Korean Genome And Epidemiology Study is an ongoing prospective longitudinal cohort study of community dwellers and participants (men and women, aged 40-69 years) recruited from the national health examinee registry of Korea. Their individual consumption habits for 12 different fruit types were recorded using food frequency questionnaires. The fruits were then divided into three groups according to their glycemic indexes and glycemic loads. Participants with extreme caloric intakes, pre-existing type 2 diabetes mellitus, chronic kidney diseases, chronic liver diseases, and ongoing cancer treatments were excluded. The incidence of type 2 diabetes in the cohort was identified through self-reporting and supplemented by glycated hemoglobin and fasting blood glucose levels. RESULTS: A total of 2,549 cases of type 2 diabetes were documented during 283,033.8 person-years of follow-up. After adjusting for personal, lifestyle, and dietary risk factors for diabetes, the pooled hazard ratio of type 2 diabetes for every serving per week of total whole fruit consumption was 1.02 (95% confidence interval [CI], 0.99-1.06; P=0.2). With mutual adjustment of individual fruits, the pooled hazard ratios of type 2 diabetes for every serving per week were 0.94 (95% CI, 0.88-1.00; P=0.039) for bananas, and 0.90 (95% CI, 0.84-0.96; P<0.001) for grapes. CONCLUSION: Our findings suggest associations between the consumption of certain fruits and the risk of developing type 2 diabetes. A greater consumption of grapes was significantly associated with a lower risk of type 2 diabetes in our cohort, but the total amount of fruit consumption was not associated with a reduced risk.

Targeting extracellular matrix glycation to attenuate fibroblast activation.

The extracellular matrix (ECM) of the tumor microenvironment undergoes constant remodeling that alters its biochemical and mechano-physical properties. Non-enzymatic glycation can induce the formation of advanced glycation end-products (AGEs), which may cause abnormal ECM turnover with excessively cross-linked collagen fibers. However, the subsequent effects of AGE-mediated matrix remodeling on the characteristics of stromal cells in tumor microenvironments remain unclear. Here, we demonstrate that AGEs accumulated in the ECM alter the fibroblast phenotype within a three-dimensional collagen matrix. Both the AGE interaction with its receptor (RAGE) and integrin-mediated mechanotransduction signaling were up-regulated in glycated collagen matrix, leading to fibroblast activation to acquire a cancer-associated fibroblast (CAF)-like phenotype. These effects were blocked with neutralizing antibodies against RAGE or the inhibition of focal adhesion (FA) signaling. An AGE cross-link breaker, phenyl-4,5-dimethylthiazolium bromide (ALT 711), also reduced the transformation of fibroblasts into the CAF-like phenotype because of its dual inhibitory role in the AGE-modified matrix. Apart from targeting the AGE-RAGE interaction directly, the decreased matrix stiffness attenuated fibroblast activation by inhibiting the downstream cellular response to matrix stiffness. Our results suggest that indirect/direct targeting of accumulated AGEs in the ECM has potential for targeting the tumor stroma to improve cancer therapy. STATEMENT OF SIGNIFICANCE: Advanced glycated end-products (AGEs)-modified extracellular matrix (ECM) is closely associated with pathological states and is recognized as a critical factor that precedes tumorigenesis. While increased matrix stiffness is known to induce fibroblast activation, less is known about how both biochemical and mechano-physical changes in AGE-mediated matrix-remodeling cooperate to produce a myofibroblastic cancer-associated fibroblast (CAF)-like phenotype. For the first time, we found that both the AGE interaction with its receptor (RAGE) and integrin-mediated mechanotransduction were up-regulated in glycated collagen matrix, leading to fibroblast activation. We further demonstrated that an AGE cross-link breaker, ALT-711, reduced the CAF-like transformation because of its dual inhibitory role in the AGE-modified matrix. Our findings offer promising extracellular-reversion strategies targeting the non-enzymatic ECM glycation, to regulate fibroblast activation.

Behavioral therapy and pharmacotherapy for relapse prevention in abstinent smokers: a rapid review and meta-analysis for the Korea Preventive Service Task Force.

OBJECTIVE: This study aimed to assess the effectiveness of relapse prevention interventions involving behavioral and pharmacological treatment among abstinent smokers. METHODS: This rapid review was conducted using MEDLINE, Cochrane CENTRAL, CINAHL, Embase, KMbase, and KoreaMed to identify studies published until June 20, 2020. The participants were abstinent smokers who quit smoking on their own, due to pregnancy, hospitalization, or by participating in a smoking cessation program. We found a systematic review that fit the objective of this study and included 81 randomized controlled trials (RCTs). Studies that did not present information on smoking cessation status, had no control group, or used reward-based interventions were excluded. Random effect and fixed effect meta-analyses were used to estimate the relative risk (RR) and 95% confidence interval (CI). In subgroup analyses, differences between subgroups were verified based on the participant setting, characteristics, intervention type, and intensity. RESULTS: Following screening, 44 RCTs were included in the meta-analysis. The review reported no differences in the success rate of relapse prevention between the behavioral interventions. Pharmacotherapy interventions showed higher success rates (RR, 1.15; 95% CI, 1.05-1.26; I2=40.71%), depending on prior abstinence duration and the drug type. CONCLUSIO: The results indicated that pharmacotherapy has a significant effect on preventing relapse among abstinent smokers.

A Health Information Quality Assessment Tool for Korean Online Newspaper Articles: Development Study.

BACKGROUND: Concern regarding the reliability and accuracy of the health-related information provided by online newspaper articles has increased. Numerous criteria and items have been proposed and published regarding the quality assessment of online information, but there is no standard quality assessment tool available for online newspapers. OBJECTIVE: This study aimed to develop the Health Information Quality Assessment Tool (HIQUAL) for online newspaper articles. METHODS: We reviewed previous health information quality assessment tools and related studies and accordingly developed and customized new criteria. The interrater agreement for the new assessment tool was assessed for 3 newspaper articles on different subjects (colorectal cancer, obesity genetic testing, and hypertension diagnostic criteria) using the Fleiss κ and Gwet agreement coefficient. To compare the quality scores generated by each pair of tools, convergent validity was measured using the Kendall τ ranked correlation. RESULTS: Overall, the HIQUAL for newspaper articles comprised 10 items across 5 domains: reliability, usefulness, understandability, sufficiency, and transparency. The interrater agreement for the article on colorectal cancer was in the moderate to substantial range (Fleiss κ=0.48, SE 0.11; Gwet agreement coefficient=0.74, SE 0.13), while for the article introducing obesity genetic testing it was in the substantial range, with values of 0.63 (SE 0.28) and 0.86 (SE 0.10) for the two measures, respectively. There was relatively low agreement for the article on hypertension diagnostic criteria at 0.20 (SE 0.10) and 0.75 (SE 0.13), respectively. Validity of the correlation assessed with the Kendall τ showed good correlation between tools (HIQUAL vs DISCERN=0.72, HIQUAL vs QUEST [Quality Evaluation Scoring Tool]=0.69). CONCLUSIONS: We developed a new assessment tool to evaluate the quality of health information in online newspaper articles, to help consumers discern accurate sources of health information. The HIQUAL can help increase the accuracy and quality of online health information in Korea.

Behavioral interventions for smoking cessation among adolescents: a rapid review and meta-analysis for the Korea Preventive Services Task Force.

OBJECTIVE: The aim of this study was to evaluate the effectiveness of behavioral smoking cessation interventions among adolescents. METHODS: MEDLINE, CENTRAL, Embase, CINAHL, KoreaMed, and KMbase were searched from inception to June 2020. Systematic reviews (SRs) or meta-analyses of randomized controlled trials (RCTs) were initially searched to perform a rapid SR. After selecting the final SR, RCTs after the publication year of the selected SR were searched. The primary outcome was smoking status after at least 6 months of follow-up, and the secondary outcome was smoking status at 4 weeks. Two reviewers independently assessed the selected studies' quality using the Cochrane risk of bias tool. The meta-analysis utilized a Mantel-Haenszel fixed-effect model reporting the relative risk (RR) and 95% confidence interval (CI). The subgroup analysis utilized Cochrane's Q. RESULTS: Thirty-two RCTs (11,637 participants) from a single SR were meta-analyzed. After 6 months of follow-up, the intervention group had significantly higher abstinence rates (RR, 1.30; 95% CI, 1.20-1.41; I2=26.46%). At 4 weeks of follow-up, the intervention group also had significantly higher abstinence rates (RR, 1.92; 95% CI, 1.49-2.47; I2=0.00%). The subgroup analysis indicated a significant difference in the abstinence rate according to the study setting and the period between intervention completion and follow-up. CONCLUSION: This review showed that adolescent behavioral smoking cessation intervention programs significantly increased abstinence rates compared to the usual care.

Matrix stiffness epigenetically regulates the oncogenic activation of the Yes-associated protein in gastric cancer.

In many cancers, tumour progression is associated with increased tissue stiffness. Yet, the mechanisms associating tissue stiffness with tumorigenesis and malignant transformation are unclear. Here we show that in gastric cancer cells, the stiffness of the extracellular matrix reversibly regulates the DNA methylation of the promoter region of the mechanosensitive Yes-associated protein (YAP). Reciprocal interactions between YAP and the DNA methylation inhibitors GRHL2, TET2 and KMT2A can cause hypomethylation of the YAP promoter and stiffness-induced oncogenic activation of YAP. Direct alteration of extracellular cues via in situ matrix softening reversed YAP activity and the epigenetic program. Our findings suggest that epigenetic reprogramming of the mechanophysical properties of the extracellular microenvironment of solid tumours may represent a therapeutic strategy for the inhibition of cancer progression.

Re-engineered cell-derived extracellular matrix as a new approach to clarify the role of native ECM.

An extracellular matrix (ECM) has both biochemical and mechanophysical characteristics obtained from multiple components, which provides cells a dynamic microenvironment. During reciprocal interactions with ECM, the cells actively remodel the matrix, including synthesis, degradation, and chemical modification, which play a pivotal role in various biological events such as disease progression or tissue developmental processes. Since a cell-derived decellularized ECM (cdECM) holds in vivo-like compositional heterogeneity and interconnected fibrillary architecture, it has received much attention as a promising tool for developing more physiological in vitro model systems. Despite these advantages, the cdECM has obvious limitations to mimic versatile ECMs precisely, suggesting the need for improved in vitro modeling to clarify the functions of native ECM. Recent studies propose to tailor the cdECM via biochemically, biomechanically, or incorporation with other systems as a new approach to address the limitations. In this chapter, we summarize the studies that re-engineered the cdECM to examine the features of native ECM in-depth and to increase physiological relevancy.

Impact of number of medications and age on adherence to antihypertensive medications: A nationwide population-based study.

This study tried to investigate the effects of number of medications and age on antihypertensive medication adherence in a real-world setting using a nationwide representative cohort.We obtained data from the National Health Insurance Service-National Sample Cohort (NHIS-NSC) of Korea, which is a sample of 2.2% (N = 1,048,061) of total population (N = 46,605,433). Patients aged 20 years or older (N = 150,550) who took antihypertensive medications for at least 1 year were selected. Medication possession ratio (MPR) was used for measuring adherence. The subjects were divided into 5 subgroups according to total number of medications: 1-2, 3-4, 5-6, 7-8, and 9 or more. The mean age and the mean number of medications were 60.3 ±â€Š12.6 years and 4.1 ±â€Š2.2, respectively. The mean MPR was 80.4 ±â€Š23.9%, and 66.9% (N = 100,645) of total subjects were adherent (MPR ≥ 80%). The overall tendency of antihypertensive medication adherence according to the total number of medications displayed an inverted U-shape with a peak at 3-4 drugs. Adherence consistently increased as the age increased until age 69 and started to decrease from age 70. The proportion of adherent patients (MPR ≥ 80%) according to the total number of medications also showed an inverted U-shape with a peak at 3-4 drugs. When the same number of drugs was taken, the proportion of adherent patients according to age featured an inverted U- shape with a peak at 60 to 69 years. Patients taking 9 or more total drugs had the overall odds ratio (95% CI) of non-adherence (MPR < 80%) with 1.17 (1.11-1.24) compared with those taking 1 to 8 total drugs and the odds ratios in the age subgroups of 40 to 49, 50 to 59, 60 to 69 years were 1.57 (1.31-1.87), 1.21 (1.08-1.36), and 1.14 (1.04-1.25), respectively (P < .05).Association between age, total number of medications, and antihypertensive adherence displayed an inverted U-shape with a peak at 3 to 4 total medications and at age 60 to 69 years. When the total number of drugs was 9 or more, adherence decreased prominently, regardless of age.

Nonarteritic anterior ischemic optic neuropathy is associated with cerebral small vessel disease.

We investigated the presence of cerebral small vessel disease (SVD) in patients with nonarteritic anterior ischemic optic neuropathy (NAION) compared to control subjects without NAION to identify the association between NAION and cerebral SVD. We retrospectively reviewed the cases of 63 patients with NAION and 2749 control subjects without any neurologic and ocular diseases including NAION who underwent careful medical interviews, ophthalmic examinations, and magnetic resonance imaging (MRI) studies of the brain. We assessed and compared the degree of cerebral SVD on the MRIs. The patients with NAION presented with cerebral SVD more frequently than controls (68% versus 37%, respectively, p<0.001), which was also observed after adjusting for age, sex, comorbid conditions including hypertension, diabetes, and dyslipidemia, and smoking using the standardized mortality ratio (68% vs. 37%, p<0.001). A multivariate logistic regression analysis showed that the odds of cerebral SVD were 4.86 (95% CI, 2.10 to 11.24, p<0.001) times higher in patients with NAION than in the controls. We found that there was an association between cerebral SVD and NAION even after adjusting for age, sex, and medical histories. Clinicians should consider brain MRI scans in patients with NAION to prevent neurological impairment after cerebral SVD.

The Relationship between Electronic Cigarette Use with or without Cigarette Smoking and Alcohol Use among Adolescents: Finding from the 11th Korea Youth Risk Behavior Web-based Survey.

BACKGROUND: Electronic cigarette (EC) consumption ('vaping') is rapidly increasing, not only in adults but also in adolescents. Little is known about the association between vaping and problem behaviors such as drinking. METHODS: We used data from the 11th Korea Youth Risk Behavior Web-based Survey, which was conducted in 2015 and included 68,043 participants who were Korean middle and high school students. The survey assessed EC, cigarette, and alcohol use. Multiple regression analysis was used to examine risk of current drinking and problem drinking across the following categories of users: never user (never used either product), former user (use of EC or cigarettes in the past, but not currently), vaping only, smoking only, and dual user (current use of both products). RESULTS: EC only users were 1.2% in males, and 0.3% in females. Dual user of both conventional cigarettes and ECs were 5.1% in males, and 1.2% in females. Drinking frequency, drinking quantity per once, and problem drinking were higher among vapers than non-vapers and former-vapers, moreover, were higher among daily vapers than intermittent vapers. Compared to never users, EC only users were higher on risk of current drink and problem drink. The dual users were highest on risk of current drink. CONCLUSION: Vaping is independently associated with alcohol use problems in Korean students, even those not currently smoking. Moreover, dual use of cigarettes and ECs is strongly associated with alcohol use problems. Therefore, vaping students should be concerned about their hidden alcohol use problems.

Metabolic Syndrome Prediction Using Machine Learning Models with Genetic and Clinical Information from a Nonobese Healthy Population.

The prevalence of metabolic syndrome (MS) in the nonobese population is not low. However, the identification and risk mitigation of MS are not easy in this population. We aimed to develop an MS prediction model using genetic and clinical factors of nonobese Koreans through machine learning methods. A prediction model for MS was designed for a nonobese population using clinical and genetic polymorphism information with five machine learning algorithms, including naïve Bayes classification (NB). The analysis was performed in two stages (training and test sets). Model A was designed with only clinical information (age, sex, body mass index, smoking status, alcohol consumption status, and exercise status), and for model B, genetic information (for 10 polymorphisms) was added to model A. Of the 7,502 nonobese participants, 647 (8.6%) had MS. In the test set analysis, for the maximum sensitivity criterion, NB showed the highest sensitivity: 0.38 for model A and 0.42 for model B. The specificity of NB was 0.79 for model A and 0.80 for model B. In a comparison of the performances of models A and B by NB, model B (area under the receiver operating characteristic curve [AUC] = 0.69, clinical and genetic information input) showed better performance than model A (AUC = 0.65, clinical information only input). We designed a prediction model for MS in a nonobese population using clinical and genetic information. With this model, we might convince nonobese MS individuals to undergo health checks and adopt behaviors associated with a preventive lifestyle.

Invasive Micropapillary Carcinoma in Axillary Ectopic Breast and Synchronous Ductal Carcinoma In Situ in the Contralateral Breast.

The development of ectopic breast tissue is attributable to the failure of primitive mammary tissue to regress after the development of the mammary ridge, except at pectoral breast sites, and is most often evident in the axillae. Several benign and malignant breast diseases have been reported in ectopic axillary breast tissues. The most common cancerous pathology of ectopic breast tissue is invasive ductal carcinoma. Ectopic breast cancer presenting with simultaneous primary cancer of the pectoral breast is extremely rare. Herein, we report an invasive micropapillary carcinoma of an axillary ectopic breast, combined with a synchronous ductal carcinoma in situ in the contralateral pectoral breast of a 61-year-old woman.

Association between Body Mass Index and Quality of Life in Elderly People over 60 Years of Age.

BACKGROUND: The Korean population is aging rapidly and the number of health threats is increasing. The elderly obese population is also increasing and this study aimed to evaluate the association between body mass index (BMI) and health-related quality of life in the elderly Korean population. METHODS: The Korean version Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) was administered to elderly subjects (≥60 years) selected from welfare and health centers, and university hospitals. Sociodemographic information and subjects' height and weight were also recorded. RESULTS: The study population's mean age was 74.2±7.1 years, and the average BMI was 24.5±3.2 kg/m2. The 542 participants were segregated based on BMI quartiles. The SF-36 scores were compared among the sex-stratified quartile groups after adjusting for age, education level, income, smoking, alcohol, and arthritis diagnosis. The SF-36 scores were compared for four BMI quartiles stratified by sex, after adjusting for age, education level, income, smoking, alcohol consumption, and arthritis diagnosis. Men in the Q3 and Q4 groups had higher mental health scores than men in Q2 group. Additionally, men in the Q3 group had higher social function scores than those in the Q2 and Q4 groups. No differences were observed for the remaining six domains; no significant score differences were observed in any of the survey domains for the female subjects. CONCLUSION: There was no significant association between a high BMI and a low quality of life in the elderly Korean population selected from hospitals and welfare centers, as assessed using the SF-36 scores.

MR imaging characteristics of breast cancer diagnosed during lactation.

OBJECTIVES: To describe the MR imaging characteristics of breast cancer diagnosed during lactation and evaluate the usefulness of MR imaging. METHODS: The MR images of nine patients (age range, 29-37 years) with pathologically confirmed breast carcinoma during lactation were evaluated retrospectively. Background parenchymal enhancement of the lactating mammary tissue was determined. The images were reviewed for evaluation of lesion detection, enhancement type (mass/non-mass), shape, margin, contrast enhancement and time-intensity curve pattern in the dynamic study. The breast MR images after neoadjuvant chemotherapy were also reviewed. RESULTS: Although the breasts showed marked (n = 7) or moderate (n = 2) background parenchymal enhancement, MR imaging depicted breast cancer in all patients. All nine tumours were visible as masses. The most common shape and margin of the masses were an irregular mass (n = 5) with an irregular margin (n = 9). Contrast enhancement was heterogeneous or rim enhancement. The predominant kinetic pattern was rapid increase (n = 9) in the initial phase and washout (n = 5) in the delayed phase. Additional sites of cancer other than the index lesion were detected with MR imaging in three patients (33.3%). MR imaging demonstrated partial response in five of six patients who were evaluated for response to chemotherapy. CONCLUSION: All breast cancers in lactating females in this study were observed on breast MR imaging despite the moderate-to-marked background parenchymal enhancement of lactating mammary tissue. Advances in knowledge: MR imaging can be used in the evaluation of disease extent and assessment of therapeutic response after neoadjuvant chemotherapy of breast cancer diagnosed during lactation.

Retinal Vein Occlusion as the Surrogate Marker for Premature Brain Aging in Young Patients.

Purpose: We investigated cerebral small vessel disease (SVD) in patients with incidental retinal vein occlusion (RVO). Methods: This retrospective, case-control, observational trial included 125 patients with RVO who underwent brain magnetic resonance imaging (MRI) and 1105 age-matched controls who underwent comprehensive medical interviews and MRI. Underlying cardiovascular diseases and MRI findings were investigated in the patients with RVO according to age (<60 or ≥60 years) and RVO occlusion level (central or branch). The characteristics of underlying cardiovascular disease and MRI findings were compared between the younger patients with RVO and age-matched controls. The cerebrovascular burden also was assessed in the younger patients with RVO. Results: The mean age of the patients with RVO was 63.9 ± 12.1 years and the predominant underlying disease was hypertension (72/125, 58%). The older RVO group had a longer history of hypertension and less smoking history. The prevalence of cerebral SVD in the RVO group was 54% (68/125), and was significantly higher in older than in younger patients with RVO (62% [53/86] vs. 38% [15/39], P = 0.016). However, the latter had a significantly higher prevalence of cerebral SVD than their age-matched controls (38% [15/39] vs. 4% [47/1105], P < 0.001). There was no difference in prevalence of cerebral SVD between the central and branch RVO groups (P = 0.478). Conclusions: Cerebral SVD presented frequently in patients with RVO and was magnified in young patients, suggesting that RVO is a surrogate marker for cerebral SVD.

Association between dietary fat intake and colorectal adenoma in korean adults: A cross-sectional study.

The incidence of colorectal cancer is rapidly increasing in South Korea. It is important to clarify the association between colorectal cancer and diet, being one of the main modifiable risk factors, as such studies in the Korean population are lacking.A cross-sectional study was performed using data from participants who had undergone a screening colonoscopy and a nutritional assessment during a routine health check-up from January 2008 to December 2011. Dietary intake data were derived from 1-day food records; colorectal adenoma was histopathologically confirmed by biopsy during colonoscopy. Eventually, 2604 participants were included in the analysis. The risk of colorectal adenoma by quintile of dietary fat intake was analyzed using logistic regression. Subgroup analyses by degree of risk and by location of colorectal adenoma were additionally performed.In men, total fat intake was not associated with risk of colorectal adenoma. However, risk of colorectal adenoma increased with higher saturated fatty acid (SFA) intake. The adjusted odds ratio in the highest quintile was 1.71 (95% confidence interval, 1.01-2.91) compared with that in the lowest quintile. There was no significant association between fat intake and risk of colorectal adenoma characterized by subsite. In female participants, total fat and specific fatty acid intake were not associated with risk of colorectal adenoma.These data support that high SFA intake is associated with risk of colorectal adenoma in Korean men.