In Situ-Crosslinked Zippersomes Enhance Cardiac Repair by Increasing Accumulation and Retention.

Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) are a promising treatment for myocardial infarction, but their therapeutic efficacy is limited by inefficient accumulation at the target site. A non-invasive MSC EV therapy that enhances EV accumulation at the disease site and extends EV retention could significantly improve post-infarct cardiac regeneration. Here we show that EVs decorated with the next-generation of high-affinity heterodimerizing leucine zippers, termed high-affinity (HiA) Zippersomes, amplify targetable surface areas through in situ crosslinking and exhibited ∼7-fold enhanced accumulation within the infarcted myocardium in mice after three days and continued to be retained up to day 21, surpassing the performance of unmodified EVs. After myocardial infarction in mice, high-affinity Zippersomes increase the ejection fraction by 53% and 100% compared with unmodified EVs and PBS, respectively. This notable improvement in cardiac function played a crucial role in restoring healthy heart performance. High-affinity Zippersomes also robustly decrease infarct size by 52% and 60% compared with unmodified EVs and PBS, respectively, thus representing a promising platform for non-invasive vesicle delivery to the infarcted heart. Translational Impact Statement: Therapeutic delivery to the heart remains inefficient and poses a bottleneck in modern drug delivery. Surgical application and intramyocardial injection of therapeutics carry high risks for most heart attack patients. To address these limitations, we have developed a non-invasive strategy for efficient cardiac accumulation of therapeutics using in situ crosslinking. Our approach achieves high cardiac deposition of therapeutics without invasive intramyocardial injections. Patients admitted with myocardial infarction typically receive intravenous access, which would allow painless administration of Zippersomes alongside standard of care.

Associations of early-life and adult anthropometric measures with the expression of stem cell markers CD44, CD24, and ALDH1A1 in women with benign breast biopsies.

BACKGROUND: According to the stem cell hypothesis, breast carcinogenesis may be related to the breast stem cell pool size. However, little is known about associations of breast cancer risk factors, such as anthropometric measures, with the expression of stem cell markers in non-cancerous breast tissue. METHODS: The analysis included 414 women with biopsy-confirmed benign breast disease (BBD) in the Nurses' Health Study (NHS) and NHSII. Birthweight, weight at age 18, current weight, and current height were reported via self-administered questionnaire. Immunohistochemical staining of stem cell markers (CD44, CD24, ALDH1A1) in histopathologically normal epithelial and stromal breast tissue was quantified with an automated computational image analysis system. Linear regression was used to examine the associations of early-life and adult anthropometric measures with log-transformed stem cell marker expression, adjusting for potential confounders. RESULTS: Birthweight (≥10.0 vs. <5.5 lbs: ß [95% CI]=4.29 [1.02, 7.56]; p-trend=0.001 in stroma) and adult height (≥67.0 vs. <63.0 inch: 0.86 [0.14, 1.58]; p-trend=0.02 in epithelium and stroma combined) were positively associated with CD44 expression. Childhood body fatness was inversely (p-trend=0.03) and adult height was positively associated with CD24 expression in combined stroma and epithelium (p-trend=0.03). CONCLUSION: Our data suggest that anthropometric measures, such as birthweight, adult height, and childhood body fatness, may be associated with the stem cell expression among women with BBD. IMPACT: Anthropometric measures, such as birthweight, height, and childhood body fatness, may have long-term impacts on stem cell population in the breast.

Bioresorbable Multilayer Organic-Inorganic Films for Bioelectronic Systems.

Bioresorbable electronic devices as temporary biomedical implants represent an emerging class of technology relevant to a range of patient conditions currently addressed with technologies that require surgical explantation after a desired period of use. Obtaining reliable performance and favorable degradation behavior demands materials that can serve as biofluid barriers in encapsulating structures that avoid premature degradation of active electronic components. Here, this work presents a materials design that addresses this need, with properties in water impermeability, mechanical flexibility, and processability that are superior to alternatives. The approach uses multilayer assemblies of alternating films of polyanhydride and silicon oxynitride formed by spin-coating and plasma-enhanced chemical vapor deposition , respectively. Experimental and theoretical studies investigate the effects of material composition and multilayer structure on water barrier performance, water distribution, and degradation behavior. Demonstrations with inductor-capacitor circuits, wireless power transfer systems, and wireless optoelectronic devices illustrate the performance of this materials system as a bioresorbable encapsulating structure.

Distress, multimorbidity, and complex multimorbidity among Chinese and Korean American older adults.

BACKGROUND: Studies suggest that distress is associated with various health conditions such as hypertension, asthma, diabetes, and coronary heart disease. However, only few studies focused on Asian Americans and little is known about the association with multiple comorbidity. METHODS: We conducted a cross-sectional analysis among 400 Chinese and Korean American participants (aged 50-75 years) of the STOP CRC randomized controlled trial. Perceived distress was assessed using the distress thermometer scale (range 0-10). Disease diagnosis was self-reported by the participants. Multimorbidity (MM) was defined as having ≥2 chronic conditions. Complex multimorbidity (CMM) was defined as having ≥3 of the following body system disorders: circulation disorder, endocrine-metabolic disorder, cancer, anxiety or depression, breathing problem, and other health problems. We performed logistic regression for CMM and Poisson regression with robust error variance for MM to estimate associations with distress, adjusting for potential confounders. RESULTS: The mean age was 58.4 years and mean distress score was 3.65. One-unit increase in distress score was associated with a 1.22-fold increase in the odds of having CMM (95% CI: 1.04-1.42). The magnitude of association slightly increased after additional adjustment for socioeconomic factors and health insurance status (OR: 1.29; 95% CI: 1.10-1.52). Higher distress score was positively associated with MM but the association was only marginally significant (PR: 1.04; 95% CI: 0.99-1.10), adjusting for socioeconomic factors and health insurance status. CONCLUSION: Our data suggest that higher perceived distress may be associated with simultaneous dysfunction of multiple distinct body systems among Chinese and Korean American older adults.

Ultra-processed Food Intake and Risk of Type 2 Diabetes in Korean Adults.

BACKGROUND: Several studies from the United States and European countries reported a positive association between ultra-processed food intake and diabetes risk. However, little is known about the association in Asian populations. It is also unknown about the individual ultra-processed food items that are most unfavorably associated with diabetes risk. OBJECTIVE: We examined the associations of ultra-processed food intake (combined, as well as individual ultra-processed food items) with the risk of type 2 diabetes. METHODS: This prospective analysis included 7438 participants aged 40-69 y from the Korean Genome and Epidemiology Study Ansan-Ansung cohort. Dietary intake was assessed at baseline using a 103-item semiquantitative food-frequency questionnaire. Ultra-processed foods were classified using the Nova definition. Incident type 2 diabetes cases were identified via follow-up interviews and health examination. Multivariable Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for potential confounders. RESULTS: During the follow-up (2001-2019; median: 15 y), a total of 1187 type 2 diabetes cases were identified. Compared with the lowest quartile of ultra-processed food intake, the highest quartile was positively associated with diabetes risk [HR (95% CI) = 1.34 (1.13, 1.59), P-trend = 0.002]. The association did not change after additional adjustment for diet quality or BMI. Among individual ultra-processed food items, a higher consumption of ham/sausage [per 1% increase in the weight ratio: HR (95% CI) = 1.40 (1.05, 1.86)], instant noodles [1.07 (1.02, 1.11)], ice cream [1.08 (1.03, 1.13)], and carbonated beverages [1.02 (1.00, 1.04)] were associated with an increased risk of type 2 diabetes, whereas a higher intake of candy/chocolate was associated with a decreased risk [0.78 (0.62, 0.99)]. CONCLUSIONS: Our data suggest that the high intake of ultra-processed foods, particularly ham/sausage, instant noodles, ice cream, and carbonated beverages, is associated with an increased risk of type 2 diabetes in Korean adults.

Understanding individuals with spinal cord injury's self-care practices: a technology probe study to promote pressure relief adherence.

Pressure reliefs (PRs) are self-care practices essential for individuals with spinal cord injury (SCI) to prevent life-threatening pressure injuries (PIs). Despite the benefits, individuals often do not do these exercises at home, leading to increased patient morbidity and mortality. To examine how digital technology could improve this population's adherence to PR exercises, we conducted a technology probe study with five individuals with SCI over ten consecutive business days. A chat-based intervention was created to send user-scheduled PR reminders, which were personalized with visual elements and progress trackers. Participants were interviewed before and after interacting with the probe to better understand their experiences with PIs and PR practices. Results shed light on specific factors that may impact individuals with SCI's behaviours towards PRs and four considerations to design a customisable reminder intervention: (1) easy to use and friendly technology, (2) design-your-own- schedule feature, (3) communication style feature, and (4) dialogue support features. Personalisation supported with gamified visual progress tracking and motivational messages emerged as a strong strategy to increase PR adherence. Both sets of findings expand upon the human-computer interaction (HCI) literature for mobile health tools that encourage self-care practices; in particular, to the specific needs of individuals with SCI and the use of visual elements to increase engagement.

Digital technology, such as chat-based reminders personalized with visual elements and progress trackers, has the potential to improve adherence to pressure reliefs among individuals with spinal cord injury (SCI).Human-centered design is essential for creating effective digital interventions for this population, and four key features of a customizable reminder intervention include easy-to-use technology, a design-your-own schedule feature, communication style options, and dialogue support features.Gamified visual progress trackers and motivational messages may be useful strategies to increase adherence to pressure reliefs and make these exercises more enjoyable for individuals with SCI.This study contributes to the growing body of research on gamification, mHealth, and human-computer interaction, and highlights the potential for digital interventions to improve self-care practices among individuals with disabilities.

Small Area Geographic Estimates of Cardiovascular Disease Risk Factors in India.

Importance: With an aging population, India is facing a growing burden of cardiovascular diseases (CVDs). Existing programs on CVD risk factors are mostly based on state and district data, which overlook health disparities within macro units. Objective: To quantify and geovisualize the extent of small area variability within districts in CVD risk factors (hypertension, diabetes, and obesity) in India. Design, Setting, and Participants: This cross-sectional study analyzed nationally representative data from the National Family Health Survey 2019-2021, encompassing individuals aged 15 years or older, for hypertension (n = 1 715 895), diabetes (n = 1 807 566), and obesity (n = 776 023). Data analyses were conducted from July 1, 2022, through August 1, 2023. Exposures: Geographic units consisting of more than 30 000 small areas, 707 districts, and 36 states or Union Territories across India. Main Outcomes and Measures: For primary outcomes, CVD risk factors, including hypertension, diabetes, and obesity, were considered. Four-level logistic regression models were used to partition the geographic variability in each outcome by state or Union Territory (level 4), district (level 3), and small area (level 2) and compute precision-weighted small area estimates. Spatial distribution of district-wide means, within-district small area variability, and their correlation were estimated. Results: The final analytic sample consisted of 1 715 895 individuals analyzed for hypertension (mean [SD] age, 39.8 [17.3] years; 921 779 [53.7%] female), 1 807 566 for diabetes (mean [SD] age, 39.5 [17.2] years; 961 977 [53.2%] female), and 776 023 for obesity (mean [SD] age, 30.9 [10.2] years; 678 782 [87.5%] women). Overall, 21.2% of female and 24.1% of male participants had hypertension, 5.0% of female and 5.4% of men had diabetes, and 6.3% of female and 4.0% of male participants had obesity. For female participants, small areas (32.0% for diabetes, 34.5% for obesity, and 56.2% for hypertension) and states (30.0% for hypertension, 46.6% for obesity, and 52.8% for diabetes) accounted for the majority of the total geographic variability, while districts accounted for the least (13.8% for hypertension, 15.2% for diabetes, and 18.9% for obesity). There were moderate to strong positive correlations between district-wide mean and within-district variability (r = 0.66 for hypertension, 0.94 for obesity, and 0.96 for diabetes). For hypertension, a significant discordance between district-wide mean and within-district small area variability was found. Results were largely similar for male participants across all categories. Conclusions and Relevance: This cross-sectional study found a substantial small area variability, suggesting the necessity of precise policy attention specifically to small areas in program formulation and intervention to prevent and manage CVD risk factors. Targeted action on policy-priority districts with high prevalence and substantial inequality is required for accelerating India's efforts to reduce the burden of noncommunicable diseases.

Aerobic, muscle-strengthening, and flexibility physical activity and risks of all-cause and cause-specific mortality: a population-based prospective cohort of Korean adults.

BACKGROUND: Studies have shown that aerobic and muscle-strengthening physical activities reduce mortality risk. However, little is known about the joint associations of the two activity types and whether other type of physical activity, such as flexibility activity, can provide similar mortality risk reduction. OBJECTIVES: We examined the independent associations of aerobic, muscle-strengthening, and flexibility physical activities with all-cause and cause-specific mortality in a population-based prospective cohort of Korean men and women. We also examined the joint associations of aerobic and muscle-strengthening activities, the two physical activity types that are recommended by the current World Health Organization physical activity guidelines. DESIGN: This analysis included 34,379 Korea National Health and Nutrition Examination Survey 2007-2013 participants (aged 20-79 years) with mortality data linkage through December 31, 2019. Engagement in walking, aerobic, muscle-strengthening, and flexibility physical activities was self-reported at baseline. Cox proportional hazards model was performed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for potential confounders. RESULTS: Flexibility physical activity (≥ 5 vs. 0 d/wk) was inversely associated with all-cause (HR [95% CI] = 0.80 [0.70-0.92]; P-trend < 0.001) and cardiovascular mortality (0.75 [0.55-1.03], P-trend = 0.02). Moderate- to vigorous-intensity aerobic physical activity (≥ 50.0 vs. 0 MET-h/wk) was also associated with lower all-cause (HR [95% CI] = 0.82 [0.70-0.95]; P-trend < 0.001) and cardiovascular mortality (0.55 [0.37-0.80]; P-trend < 0.001). Similar inverse associations were observed with total aerobic physical activity, including walking. Muscle-strengthening activity (≥ 5 vs. 0 d/wk) was inversely associated with all-cause mortality (HR [95% CI] = 0.83 [0.68-1.02]; P-trend = 0.01) but was not associated with cancer or cardiovascular mortality. Compared to participants meeting the highest guidelines for both moderate- to vigorous-intensity aerobic and muscle-strengthening physical activities, those not meeting in any guideline were associated with higher all-cause (1.34 [1.09-1.64]) and cardiovascular mortality (1.68 [1.00-2.82]). CONCLUSIONS: Our data suggest that aerobic, muscle-strengthening, and flexibility activities are associated with lower risk of mortality.

Overall and abdominal obesity and risks of all-cause and cause-specific mortality in Korean adults: a pooled analysis of three population-based prospective cohorts.

BACKGROUND: Studies found a J-shaped association between body mass index (BMI) and mortality. However, it is unclear whether the association is driven by biases, particularly confounding by fat-free mass. METHODS: We conducted an individual-level pooled analysis of three cohorts of Korean adults (aged ≥ 40 years; n = 153 248). Mortality was followed up through December 2019. Anthropometric data were directly measured at baseline. Fat and fat-free mass were predicted using validated prediction models. Using Cox proportional hazards models, we estimated the associations of BMI and waist circumference (WC) with all-cause and cause-specific mortality. To account for biases, we excluded participants aged ≥ 70 years, deaths that occurred within 5 years of follow-up and ever smokers, and adjusted for fat-free mass index (FFMI). RESULTS: During the follow-up of up to 18 years, 6061 deaths were identified. We observed J-shaped association of BMI (nadir at 22-26) and monotonically positive association of WC with all-cause, cardiovascular, and cancer mortality among Korean adults without a history of cancer or cardiovascular disease. In the BMI analysis, excluding ever smokers and adjusting for FFMI attenuated the excess mortality in underweight participants and transformed the J-shaped association into a monotonically positive shape, suggesting an increased mortality at BMI > 22.0. Excluding participants aged ≥ 70 years and deaths that occurred within 5 years of follow-up did not change the results. In the WC analysis, the monotonic positive associations did not change after the control. Similar results were observed among participants with a history of cancer or cardiovascular disease. CONCLUSIONS: Our data suggest that both overall and abdominal body fat are associated with increased mortality in Korean adults.

ZipperCells Exhibit Enhanced Accumulation and Retention at the Site of Myocardial Infarction.

There has been extensive interest in cellular therapies for the treatment of myocardial infarction, but bottlenecks concerning cellular accumulation and retention remain. Here, a novel system of in situ crosslinking mesenchymal stem cells (MSCs) for the formation of a living depot at the infarct site is reported. Bone marrow-derived mesenchymal stem cells that are surface decorated with heterodimerizing leucine zippers, termed ZipperCells, are engineered. When delivered intravenously in sequential doses, it is demonstrated that ZipperCells can migrate to the infarct site, crosslink, and show ≈500% enhanced accumulation and ≈600% improvement in prolonged retention at 10 days after injection compared to unmodified MSCs. This study introduces an advanced approach to creating noninvasive therapeutics depots using cellular crosslinking and provides the framework for future scaffold-free delivery methods for cardiac repair.

High-speed, scanned laser structuring of multi-layered eco/bioresorbable materials for advanced electronic systems.

Physically transient forms of electronics enable unique classes of technologies, ranging from biomedical implants that disappear through processes of bioresorption after serving a clinical need to internet-of-things devices that harmlessly dissolve into the environment following a relevant period of use. Here, we develop a sustainable manufacturing pathway, based on ultrafast pulsed laser ablation, that can support high-volume, cost-effective manipulation of a diverse collection of organic and inorganic materials, each designed to degrade by hydrolysis or enzymatic activity, into patterned, multi-layered architectures with high resolution and accurate overlay registration. The technology can operate in patterning, thinning and/or cutting modes with (ultra)thin eco/bioresorbable materials of different types of semiconductors, dielectrics, and conductors on flexible substrates. Component-level demonstrations span passive and active devices, including diodes and field-effect transistors. Patterning these devices into interconnected layouts yields functional systems, as illustrated in examples that range from wireless implants as monitors of neural and cardiac activity, to thermal probes of microvascular flow, and multi-electrode arrays for biopotential sensing. These advances create important processing options for eco/bioresorbable materials and associated electronic systems, with immediate applicability across nearly all types of bioelectronic studies.

Trends in Diet Quality and Cardiometabolic Risk Factors Among Korean Adults, 2007-2018.

Importance: Few studies have examined the dietary trends in Korea beyond evaluating selected food groups. To help prevent cardiometabolic disease burdens, a comprehensive investigation of the trends in overall diet quality and identification of possible contributing factors would be useful. Objective: To investigate the trends and independent associations of age, period, and birth cohort with diet quality and cardiometabolic risk factors among Korean adults. Design, Setting, and Participants: Serial cross-sectional and age-period-cohort analyses were conducted of nationally representative 24-hour dietary recall data from the Korea National Health and Nutrition Examination Survey 2007-2018. The study population included 65 416 Korean adults aged 19 to 79 years. Data analyses were conducted from March 1, 2020, through April 30, 2021. Exposures: Age, calendar year, birth cohort, and population sociodemographic characteristics. Main Outcomes and Measures: Korean Healthy Eating Index (KHEI), a validated diet quality score (range, 0-90, with higher scores indicating greater diet quality), and 8 cardiometabolic risk factors (waist circumference and systolic blood pressure, diastolic blood pressure, serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, and fasting blood glucose levels). Results: Among 65 416 participants, mean age (SD) was 44.5 (0.1) years and 36 631 were women (55.8%). In 2007-2018, the age-standardized mean (SE) KHEI score increased from 51.0 (0.4) to 52.1 (0.5), which was associated with reduced sodium intake and increased whole grain, dairy, and protein-rich food intakes. The mean (SE) KHEI score was lowest at age 39 years (50.1 [0.3]) and increased at older ages (58.0 [0.3] at 79 years). Controlling for age and period effects, the highest KHEI score was observed among the birth cohorts of 1960-1964 (53.6 [0.9]) and decreased in subsequent cohorts (45.5 [1.2] in the 1990-1999 birth cohort). Similar cohort effects in cardiometabolic risk factors were observed, showing the lowest waist circumference, blood pressure, and total cholesterol levels among the birth cohorts of the 1960s and 1970s and higher levels among more recent birth cohorts (1990-1999 vs 1960-1964: waist circumference, 83.8 [0.5] vs 81.4 [0.4] cm; systolic blood pressure, 118.7 [0.7] vs 116.4 [0.4] mm Hg; total cholesterol, 200.2 [0.9] vs 198.9 [0.7] mg/dL). At most ages, periods, and birth cohorts, the mean KHEI score was consistently higher in adults living in urban areas (at age 45 years: 50.5 [1.0] vs 49.7 [0.9] rural) and among high-income (at age 45 years: 50.7 [1.1] vs 49.3 [0.9] low income) and educational levels (at age 45 years: 53.1 [0.9] vs 49.1 [1.0] low educational level). Conclusions and Relevance: The findings of this study suggest that, from 2007 to 2018, the diet quality of Korean adults modestly improved. Despite the improvement, inequalities in diet among age, birth cohort, and socioeconomic subgroups persisted, suggesting that more intense interventions may be needed to target the susceptible groups.

Smartphone Usage Patterns and Dietary Risk Factors in Adolescents.

BACKGROUND: Whereas earlier studies have shown that traditional screen time such as TV watching influences dietary behaviors in adolescents, little is known about the effects of modern screen time such as smartphone use. OBJECTIVES: We examined the associations of smartphone usage duration and content type with dietary risk factors among adolescents. METHODS: We conducted a cross-sectional analysis using a nationally representative sample of 54,601 middle- and high-school students (aged 12-18 y; 26,928 boys and 27,673 girls) in the Korea Youth Risk Behavior Web-Based Survey 2017. Smartphone use (average duration and most frequently used content type) and dietary intakes [frequent breakfast skipping; less frequent intakes of fruits and vegetables; more frequent intakes of instant noodles, fast food, chips/crackers, and sugar-sweetened beverages (SSBs)] were self-reported via an online-based questionnaire. Multivariable logistic regression was performed to estimate ORs and 95% CIs for the associations of smartphone usage duration and content type with prevalence of dietary risk factors, adjusting for potential confounders. All analyses accounted for complex survey sampling. RESULTS: Prolonged smartphone use (≥300 compared with 1-59 min/d) was associated with (OR; 95% CI) higher prevalence of frequent breakfast skipping (1.60; 1.45, 1.76); frequent intakes of instant noodles (1.65; 1.47, 1.84), fast food (1.36; 1.20, 1.53), and SSBs (1.92; 1.75, 2.11); and less frequent intakes of fruits (1.44; 1.30, 1.59) and vegetables (1.32; 1.18, 1.47). Adjusting for usage duration, using smartphones mainly for messenger/e-mail, social networking service (SNS)/forum, and games were associated with less frequent intakes of fruits (OR: 1.21; 95% CI: 1.12, 1.31; OR: 1.28; 95% CI: 1.17, 1.40; and OR: 1.20; 95% CI: 1.10, 1.32, respectively) and vegetables (OR: 1.24; 95% CI: 1.12, 1.37; OR: 1.26; 95% CI: 1.13, 1.40; and OR: 1.25; 95% CI: 1.12, 1.40, respectively) than was using smartphones for education/information search. Using smartphones mainly for messenger/e-mail (OR: 1.24; 95% CI: 1.14, 1.35) and SNS/forum (OR: 1.18; 95% CI: 1.08, 1.29) were also associated with more frequent intake of SSBs. CONCLUSIONS: Our data suggest that both duration and content type of smartphone use are independently associated with dietary risk factors among adolescents.

Association of Smartphone Use With Body Image Distortion and Weight Loss Behaviors in Korean Adolescents.

Importance: Despite high use of smartphones among adolescents, little is known about the association of smartphone use with body image and related behaviors. Objective: To examine the associations of duration of smartphone use and types of content most frequently accessed via smartphone with body image distortion and weight loss behaviors in adolescents. Design, Setting, and Participants: This cross-sectional study used data from the population-based Korea Youth Risk Behavior Web-Based Survey 2017. Participants comprised a nationally representative sample of 53 133 Korean adolescents aged 12 to 18 years. Data were collected from June 1 to July 18, 2017. The analysis was performed from February 7, 2020, to March 30, 2022. Exposures: Self-reported duration of smartphone use (min/d) and types of content (educational or informational searches; chatting, messaging, or email; social networking services or forums; games; videos, movies, or music; webtoons or web novels; and shopping or other activities) most frequently accessed during smartphone use. Main Outcomes and Measures: Body image distortion (overperception of body weight), weight loss attempt, use of inappropriate weight loss strategies (skipping meals, eating only 1 food at a time, vomiting, or using laxatives), and healthy weight loss behaviors (muscle-strengthening and aerobic physical activity). Multivariable logistic regression analysis was performed to estimate odds ratios (ORs) and 95% CIs, accounting for survey sampling and adjusting for potential confounders. Results: Among 53 133 participants, the mean (SD) age was 15.0 (1.8) years; 50.7% of participants were female, and 49.3% were male. After adjusting for types of content accessed, prolonged smartphone use (≥301 min/d) was positively associated with body image distortion (boys: OR, 1.17; 95% CI, 1.07-1.28; girls: OR, 1.20; 95% CI, 1.10-1.30) and inappropriate weight loss strategies (boys: OR, 1.54; 95% CI, 1.25-1.90; girls: OR, 2.45; 95% CI, 2.14-2.79) in both sexes compared with minimal smartphone use (1-120 min/d). After adjusting for duration of smartphone use, the use of smartphones mainly for videos, movies, or music (OR, 1.15; 95% CI, 1.02-1.29), webtoons or web novels (OR, 1.28; 95% CI, 1.10-1.48), and games (OR, 1.17; 95% CI, 1.03-1.32) was positively associated with body image distortion in boys compared with the use of smartphones mainly for educational or informational content. Among boys, the use of smartphones mainly for chatting, messaging, or email was positively associated with muscle-strengthening activity (OR, 1.31; 95% CI, 1.18-1.44) and aerobic physical activity (OR, 1.41; 95% CI, 1.29-1.55), as was the use of smartphones mainly for social networking services or forums (muscle-strengthening activity: OR, 1.27; 95% CI, 1.13-1.42; aerobic physical activity: OR, 1.28; 95% CI, 1.15-1.43). Among girls, the use of smartphones mainly for chatting, messaging, or email was positively associated with weight loss attempts (OR, 1.34; 95% CI, 1.19-1.51) and the use of inappropriate weight loss strategies (OR, 1.57; 95% CI, 1.25-1.99), as was the use of smartphones mainly for social networking services or forums (weight loss attempts: OR, 1.20; 95% CI, 1.07-1.36; use of inappropriate weight loss strategies: OR, 1.37; 95% CI, 1.08-1.73). Conclusions and Relevance: In this cross-sectional study, both the duration of smartphone use and the types of content most frequently accessed via smartphone were associated with body image distortion and weight loss behaviors in adolescents. These findings suggest a need for the identification of strategies to help adolescents develop healthy smartphone use behaviors.

Association of periodontitis, missing teeth, and oral hygiene behaviors with the incidence of hypertension in middle-aged and older adults in Korea: A 10-year follow-up study.

BACKGROUND: The relationship between periodontitis and hypertension remains controversial. This study aimed to investigate the association of periodontitis, missing teeth, and oral hygiene behaviors with the incidence of hypertension. METHODS: A total of 104,349 participants were selected from the National Health Insurance System-Health Screening (NHIS-HEALS) cohort. Incident hypertension and periodontitis were diagnosed based on the patients' clinical records and health examinations. A multivariable Cox proportional hazards regression analysis was performed after adjusting for socioeconomic factors, coexisting disease, and health behaviors. RESULTS: The mean age of the participants was 51.1 years (range, 40-79 years) at baseline, and 55.1% were men. A total of 52,855 incident hypertension cases were identified during the median follow-up period of 9.6 years. Among the participants, periodontitis (hazard ratio [HR]: 1.02; 95% confidence interval [95% CI]: 1.00-1.04), number of missing teeth (for ≥15 group, HR: 1.40; 95% CI: 1.29-1.52), dental scaling (HR: 0.93; 95% CI: 0.91-0.95), and toothbrushing frequency (for ≥3 group, HR: 0.85; 95% CI: 0.83-0.88) were significantly associated with incident hypertension after full adjustments for covariates. While periodontitis was significantly associated with incident hypertension (HR: 1.04; 95% CI: 1.02-1.06) in the middle-aged group (40-64 years), the effect was insignificant in the older group (≥65 years). CONCLUSIONS: Oral inflammation could contribute to the incidence of hypertension; thus, efforts to reduce oral inflammation should be encouraged. Future intervention studies are warranted to determine whether oral health care could be beneficial in the management of hypertension.

Gender and tobacco epidemic in South Korea: implications from age-period-cohort analysis and the DPSEEA framework.

OBJECTIVES: To understand a 20-year trend of gender-specific smoking prevalence among adults in South Korea. DESIGN: Age-period-cohort analysis using the intrinsic estimator method was applied to examine the separate contribution of age, period and cohort effect on smoking prevalence. The Driving Force-Pressure-State-Exposure-Effect-Action (DPSEEA) framework was used to explain the observed smoking trends by mapping potential determinants and to address policy implications. SETTING: General adult population in South Korea. PARTICIPANTS: 34 828 men and 43 632 women who aged 19-78 years, were not currently pregnant and were without a prior diagnosis of cardiovascular disease or cancer. OUTCOME MEASURES: Gender-specific current smoking prevalence using the 1998-2017 Korea National Health and Nutrition Examination Survey. RESULTS: Our results showed gender-specific age and birth cohort effects. More specifically, the smoking prevalence peaked at their mid-20s (prevalence rate ratio (PRR): 1.54, 95% CI: 1.49 to 1.59) and cohort born in 1959-1963 (PRR: 1.63, 95% CI: 1.57 to 1.70) and then decreased in men. On the other hand, in women, the smoking prevalence consistently increased until their mid-40s (PRR: 1.53, 95% CI: 1.27 to 1.84) and in recent birth cohort groups (PRR in 1994-1998 cohort: 1.55, 95% CI: 1.13 to 2.13). The period effects declined from 1998-2002 to 2003-2007, following increasing fluctuations in both genders. The smoking-DPSEEA framework showed the absence of policy actions to target female smokers and emphasised a proactive approach that tackles the upstream causes for smoking in women. CONCLUSIONS: Men and women are clearly in different phases of the smoking epidemic in Korean population, and gender-tailored policies should be implemented.

Validity evaluation of indirect adjustment method for multiple unmeasured confounders: A simulation and empirical study.

BACKGROUND: An indirect adjustment method was developed to control for unmeasured confounders in a large administrative cohort study. A previous study that proposed the indirect adjustment method assessed the validity of the method by simulations but did not consider the direction of bias and scenarios with multiple missing confounders. In this study, we evaluated the direction and the magnitude of bias of the indirect adjustment method with multiple correlated unmeasured confounders using simulation and empirical datasets. METHODS: A simulation study was conducted to compare the bias of the indirect adjustment by varying the number of confounders, magnitude of correlation between confounders, and the number of adjustment variables. An empirical study was conducted by applying the indirect adjustment method to the association between PM10 and mortality using the Korea National Health and Nutrition Examination Survey linked Cause of Death data for 2007-2016. RESULTS: The simulations of the present study demonstrated that 1) when a confounder is positively associated with both exposure and outcome, indirect adjustment might bias the effect size downward; 2) the magnitude of bias might depend on the correlation between unmeasured confounders; and 3) indirect adjustment for multiple missing confounders at once could result in a higher bias than that for some of the missing confounders. Empirical analyses also showed consistent results, but the bias of indirectly adjusted effect estimates was sometimes larger than that of unadjusted effect estimates. CONCLUSIONS: The indirect adjustment method is a promising technique to reduce the bias from unmeasured confounding; however, it should be implemented carefully, particularly when there are multiple correlated unmeasured confounders of the same direction.

Early-life body mass index and risks of breast, endometrial, and ovarian cancers: a dose-response meta-analysis of prospective studies.

BACKGROUND: The evidence for the associations between early-life adiposity and female cancer risks is mixed. Little is known about the exact shape of the relationships and whether the associations are independent of adult adiposity. METHODS: We conducted dose-response meta-analyses of prospective studies to summarise the relationships of early-life body mass index (BMI) with breast, endometrial, and ovarian cancer risks. Pubmed and Embase were searched through June 2020 to identify relevant studies. Using random-effects models, the summary relative risks (RRs) and 95% confidence intervals (CIs) were estimated per 5-kg/m2 increase in BMI at ages ≤ 25 years. A nonlinear dose-response meta-analysis was conducted using restricted cubic spline analysis. RESULTS: After screening 33,948 publications, 37 prospective studies were included in this analysis. The summary RRs associated with every 5-kg/m2 increase in early-life BMI were 0.84 (95% CI = 0.81-0.87) for breast, 1.40 (95% CI = 1.25-1.57) for endometrial, and 1.15 (95% CI = 1.07-1.23) for ovarian cancers. For breast cancer, the association remained statistically significant after adjustment for adult BMI (RR = 0.80, 95% CI = 0.73-0.87). For premenopausal breast, endometrial, and ovarian cancers, the dose-response curves suggested evidence of nonlinearity. CONCLUSIONS: With early-life adiposity, our data support an inverse association with breast cancer and positive associations with ovarian and endometrial cancer risks.

Recreational Physical Activity, Sitting, and Androgen Metabolism among Postmenopausal Women in the Women's Health Initiative Observational Study.

BACKGROUND: Prolonged sitting and physical inactivity are associated with higher circulating levels of estrogens. It is unknown whether these risk factors are associated with circulating androgens/androgen metabolites, another set of hormones implicated in the etiology of cancers in postmenopausal women. METHODS: We conducted a cross-sectional analysis of 1,782 postmenopausal women in the Women's Health Initiative Observational Study. Serum concentrations of 12 androgens/androgen metabolites were quantified using liquid chromatography-tandem mass spectrometry. Physical activity and sitting time were self-reported at baseline. We performed linear regression to estimate geometric means (GM) of androgen/androgen metabolite concentrations (pmol/L) according to physical activity and sitting time, adjusting for potential confounders and stratified by menopausal hormone therapy (MHT) use. RESULTS: Physical activity (≥15 vs. 0 MET-h/wk) was inversely associated with estrogen-to-androgen ratios among never/former MHT users (adj-GM = 37.5 vs. 49.6 unconjugated estrone:androstenedione; 20.2 vs. 30.3 unconjugated estradiol:testosterone; all P trend ≤ 0.03) but was not associated among current MHT users. Prolonged sitting (≥10 vs. ≤5 h/d) was positively associated with these ratios among both never/former (adj-GM = 44.2 vs. 38.3, P trend = 0.10; adj-GM = 23.4 vs. 20.2, P trend = 0.17; respectively) and current MHT users (adj-GM = 197 vs. 147; 105 vs. 75.5; respectively; all P trend ≤0.02), but the associations were statistically significant among current MHT users only. The associations persisted after adjustment for BMI. After adjustment for adrenal androgens, physical activity and sitting were not associated with androgen metabolites. CONCLUSIONS: Physical activity and sitting were associated with serum estrogen-to-androgen ratios but not androgen metabolites. IMPACT: This study contributes to our understanding of the link between physical activity, sitting, and cancer risk in postmenopausal women.

Obesity, Height, and Serum Androgen Metabolism among Postmenopausal Women in the Women's Health Initiative Observational Study.

BACKGROUND: Anthropometric measures, including obesity, are important risk factors for breast and endometrial cancers in postmenopausal women. It is unknown whether these risk factors are associated with androgen metabolism, another risk factor for these cancers. METHODS: Using baseline data from 1,765 postmenopausal women in the Women's Health Initiative Observational Study, we conducted a cross-sectional analysis examining associations between anthropometric measures [current body mass index (BMI), waist-to-hip ratio (WHR), height, and recalled BMI at age 18) and serum androgen metabolites. Twelve androgens/androgen metabolites were quantified using LC-MS/MS. Geometric means of androgen/androgen metabolite concentrations were estimated using linear regression, adjusting for potential confounders and stratified by hormone therapy (HT) use. RESULTS: Regardless of HT use, higher current BMI (≥30 vs. <25 kg/m2) was associated with higher serum concentrations of dehydroepiandrosterone sulfate (DHEAS), 5α-reduced glucuronide metabolites [androsterone-glucuronide (ADT-G), 5α-androstane-3α,17ß diol-3-glucuronide (3α-diol-3G), 3α-diol-17-glucuronide (3α-diol-17G)], and DHEAS:DHEA ratio (all P trend ≤ 0.02). BMI was also positively associated with unconjugated estrone:androstenedione and unconjugated estradiol:testosterone ratios among never/former HT users (all P trend < 0.001) but not among current users (P-int < 0.001). WHR was positively associated with adrenal androgens and 5α-reduced glucuronide metabolites in obese women only (BMI ≥ 30 kg/m2; all P-trend ≤ 0.01). BMI at age 18 was inversely associated with adrenal androgens (DHEA, DHEAS, androstenedione, testosterone) and 5α-reduced glucuronide metabolites in never/former HT users (all P trend < 0.06). Height was not associated with androgen metabolites. CONCLUSIONS: Current BMI is associated with androgen metabolism among postmenopausal women. IMPACT: This study contributes to our understanding of the link between obesity and cancer risk in postmenopausal women.