Development of Lipid Nanoparticle Formulation for the Repeated Administration of mRNA Therapeutics.

During the COVID-19 pandemic, mRNA vaccines emerged as a rapid and effective solution for global immunization. The success of COVID-19 mRNA vaccines has increased interest in the use of lipid nanoparticles (LNPs) for the in vivo delivery of mRNA therapeutics. Although mRNA exhibits robust expression profiles, transient protein expression is often observed, raising uncertainty regarding the frequency of its administration. Additionally, various RNA therapeutics may necessitate repeated dosing to achieve optimal therapeutic outcomes. Nevertheless, the impact of repeated administrations of mRNA/LNP on immune responses and protein expression efficacy remains unclear. In this study, we investigated the influence of the formulation parameters, specifically ionizable lipids and polyethylene glycol (PEG) lipids, on the repeat administration of mRNA/LNP. Our findings revealed that ionizable lipids had no discernible impact on the dose-responsive efficacy of repeat administrations, whereas the lipid structure and molar ratio of PEG lipids were primary factors that affected mRNA/LNP performance. The optimization of the LNP formulation with PEG lipid confirmed the sustained dose-responsive efficacy of mRNA after repeated administrations. This study highlights the critical importance of optimizing LNP formulations for mRNA therapeutics requiring repeated administrations.

Real-world effectiveness of CDK4/6 inhibitors on patients with HR+/HER2- advanced breast cancer in South Korea, focusing on underrepresented patients.

OBJECTIVE: We assessed the real-world effectiveness of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors as first-line treatments in postmenopausal patients with HR+/HER2- advanced breast cancer, focusing on younger (<45 years) and older (>78 years) populations not considered in clinical trials. METHODS: We analyzed nationwide claims data from the Health Insurance Review and Assessment Service between November 2016 and February 2021. In this retrospective cohort study, patients using CDK4/6 inhibitors and aromatase inhibitors were selected and grouped by age as follows: 45-78 years (trial-enrolled), <45 years (younger), and >78 years (older). We estimated the median real-world progression-free survival (rwPFS) and overall survival (OS) using the Kaplan-Meier method. We conducted Cox regression analysis using a sub-distribution hazard model to evaluate risk factors (age, history of prior systemic treatment, presence of metastasis, comorbidity index, and type of provider) and estimated hazard ratios (HR). RESULTS: Among the 2,830 patients who received CDK4/6 inhibitors as first-line therapy, we identified 358 (12.65%) younger and 148 (5.23%) older underrepresented patients. The younger patient group (50.84%) had the highest rate of prior systemic therapy, followed by the trial-enrolled (25.39%) and older patient groups (8.11%). The median rwPFS was shorter in the older group (19.30 months) than those in the younger and the trial-enrolled age groups (30.33 and 34.53 months, respectively; p = .002). The HR of older age for death was 1.59 (95% confidence interval (CI) = 1.24-2.03). For rwPFS, the HR of prior systemic therapy was 1.19 (95% CI = 1.04-1.37). CONCLUSIONS: The younger age group, which was underrepresented in the trial, did not show a significant difference in risk compared with the enrolled age group. However, the older age group, which was also underrepresented in the trial, faces a risk of mortality but not progression. Patients who fall outside the specified age groups for the clinical trial can still expect the same level of effectiveness in terms of progression.

Association of hypertension with noodle consumption among Korean adults based on the Health Examinees (HEXA) study.

BACKGROUND/OBJECTIVES: The prevalence of hypertension is increasing, and noodles have a high sodium content, so noodle consumption might be associated with a higher prevalence of hypertension. This study aimed to analyze the association between total and types of noodle intake and the risk of hypertension among Korean adults. Subjects aged 40-69 years were selected for this study. SUBJECTS/METHODS: This study included 56,580 participants (18,246 men and 38,334 women) aged 40-69 years old from the Health Examinees study. Noodle and nutrient intakes were assessed using the food frequency questionnaire. Hypertension was diagnosed as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg or antihypertensive medication use. Cox proportional hazard models were used to calculate the hazard ratio (HR) and 95% confidence interval (CI) for hypertension. RESULTS: Higher noodle consumption was associated with increased hypertension among men (HR, 1.273; 95% CI, 1.166-1.390) and women (HR, 1.116; 95% CI, 1.038-1.199). CONCLUSION: We recommended reducing noodle intake and consuming vegetables and fruits to increase potassium intake, which can prevent vascular diseases.

Integration of risk factor polygenic risk score with disease polygenic risk score for disease prediction.

Polygenic risk score (PRS) is useful for capturing an individual's genetic susceptibility. However, previous studies have not fully exploited the potential of the risk factor PRS (RFPRS) for disease prediction. We explored the potential of integrating disease-related RFPRSs with disease PRS to enhance disease prediction performance. We constructed 112 RFPRSs and analyzed the association of RFPRSs with diseases to identify disease-related RFPRSs in 700 diseases, using the UK Biobank dataset. We uncovered 6157 statistically significant associations between 247 diseases and 109 RFPRSs. We estimated the disease PRSs of 70 diseases that exhibited statistically significant heritability, to generate RFDiseasemetaPRS-a combined PRS integrating RFPRSs and disease PRS-and compare the prediction performance metrics between RFDiseasemetaPRS and disease PRS. RFDiseasemetaPRS showed better performance for Nagelkerke's pseudo-R2, odds ratio (OR) per 1 SD, net reclassification improvement (NRI) values and difference of R2 considered by variance of R2 in 31 out of 70 diseases. Additionally, we assessed risk classification between two models by examining OR between the top 10% and remaining 90% individuals for the 31 diseases; RFDiseasemetaPRS exhibited better R2, NRI and OR than disease PRS. These findings highlight the importance of utilizing RFDiseasemetaPRS, which can provide personalized healthcare and tailored prevention strategies.

Association between kimchi consumption and obesity based on BMI and abdominal obesity in Korean adults: a cross-sectional analysis of the Health Examinees study.

OBJECTIVE: Previous animal studies have shown the anti-obesity effect of kimchi-derived probiotic lactic acid bacteria. However, only a few epidemiological studies have investigated the association between kimchi consumption and obesity. Therefore, we aim to assess this relationship in Korean adults. DESIGN: Cross-sectional study. SETTING: The Health Examinees study was conducted from 2004 to 2013. PARTICIPANTS: This study analysed 115 726 participants aged 40-69 years enrolled in the Health Examinees study in Korea. PRIMARY AND SECONDARY OUTCOME MEASURES: Obesity was defined as body mass index ≥25 kg/m2, and abdominal obesity was defined as waist circumference ≥90 cm in men and ≥85 cm in women. Kimchi consumption was assessed by the validated food frequency questionnaire. RESULTS: In men, total kimchi consumption of 1-3 servings/day was related to a lower prevalence of obesity (OR: 0.875 in 1-2 servings/day and OR: 0.893 in 2-3 servings/day) compared with total kimchi consumption of <1 serving/day. Also, men with the highest baechu kimchi (cabbage kimchi) consumption had 10% lower odds of obesity and abdominal obesity. Participants who consumed kkakdugi (radish kimchi) ≥median were inversely associated with 8% in men and 11% in women with lower odds of abdominal obesity compared with non-consumers, respectively. CONCLUSIONS AND RELEVANCE: Consumption of 1-3 servings/day of total kimchi was associated with a lower risk of obesity in men. Baechu kimchi was associated with a lower prevalence of obesity in men, and kkakdugi was associated with a lower prevalence of abdominal obesity in both men and women. However, since all results showed a 'J-shaped' association, it is recommended to limit excessive kimchi intake.

Real Time Observation of Halide Segregation in Mixed Halide Perovskite Solar Cells.

In this work, a novel real-time current-voltage (J-V) absorbance spectroscopy (RTJAS) setup is introduced for directly observing halide segregation in mixed halide perovskite solar cells under broadband light illumination, simulating solar exposure. The setup incorporates a broadband light source calibrated to one sun irradiation and a CMOS camera for simultaneous capture of all diffracted wavelengths. J-V measurements are performed concurrently with absorbance spectra collection, enabling in situ analysis of light-induced degradation due to halide segregation, including bandgap shifts and cell performance data. Comparison of photoluminescence measurements with RTJAS data reveals differing rates of bandgap decrease, underscoring the advantages of real-time measurement techniques. The work highlights the importance of accounting for experimental conditions, such as humidity and voltage injection, which can accelerate halide segregation, ultimately emphasizing the need for careful consideration of experimental conditions to accurately characterize perovskite solar cell behavior under realistic conditions.

Novel piperazine-based ionizable lipid nanoparticles allow the repeated dose of mRNA to fibrotic lungs with improved potency and safety.

mRNA-based protein replacement therapy has received much attention as a novel intervention in clinical disease treatment. Lipid nanoparticles (LNPs) are widely used for their therapeutic potential to efficiently deliver mRNA. However, clinical translation has been hampered by the immunogenicity of LNPs that may aggravate underlying disease states. Here, we report a novel ionizable LNP with enhanced potency and safety. The piperazine-based biodegradable ionizable lipid (244cis) was developed for LNP formulation and its level of protein expression and immunogenicity in the target tissue was evaluated. It was found that 244cis LNP enabled substantial expression of the target protein (human erythropoietin), while it minimally induced the secretion of monocyte chemoattractant protein 1 (MCP-1) as compared to other conventional LNPs. Selective lung targeting of 244cis LNP was further investigated in tdTomato transgenic mice with bleomycin-induced pulmonary fibrosis (PF). The repeated administration of 244cis LNP with Cre recombinase mRNA achieved complete transfection of lung endothelial cells (~80%) and over 40% transfection of Sca-1-positive fibroblasts. It was shown that 244cis LNP allows the repeated dose of mRNA without the loss of activity due to its low immunogenicity. Our results demonstrate that 244cis LNP has great potential for the treatment of chronic diseases in the lungs with improved potency and safety.

Identification of asthma-related genes using asthmatic blood eQTLs of Korean patients.

BACKGROUND: More than 200 asthma-associated genetic variants have been identified in genome-wide association studies (GWASs). Expression quantitative trait loci (eQTL) data resources can help identify causal genes of the GWAS signals, but it can be difficult to find an eQTL that reflects the disease state because most eQTL data are obtained from normal healthy subjects. METHODS: We performed a blood eQTL analysis using transcriptomic and genotypic data from 433 Korean asthma patients. To identify asthma-related genes, we carried out colocalization, Summary-based Mendelian Randomization (SMR) analysis, and Transcriptome-Wide Association Study (TWAS) using the results of asthma GWASs and eQTL data. In addition, we compared the results of disease eQTL data and asthma-related genes with two normal blood eQTL data from Genotype-Tissue Expression (GTEx) project and a Japanese study. RESULTS: We identified 340,274 cis-eQTL and 2,875 eGenes from asthmatic eQTL analysis. We compared the disease eQTL results with GTEx and a Japanese study and found that 64.1% of the 2,875 eGenes overlapped with the GTEx eGenes and 39.0% with the Japanese eGenes. Following the integrated analysis of the asthmatic eQTL data with asthma GWASs, using colocalization and SMR methods, we identified 15 asthma-related genes specific to the Korean asthmatic eQTL data. CONCLUSIONS: We provided Korean asthmatic cis-eQTL data and identified asthma-related genes by integrating them with GWAS data. In addition, we suggested these asthma-related genes as therapeutic targets for asthma. We envisage that our findings will contribute to understanding the etiological mechanisms of asthma and provide novel therapeutic targets.

Immunogenicity of lipid nanoparticles and its impact on the efficacy of mRNA vaccines and therapeutics.

Several studies have utilized a lipid nanoparticle delivery system to enhance the effectiveness of mRNA therapeutics and vaccines. However, these nanoparticles are recognized as foreign materials by the body and stimulate innate immunity, which in turn impacts adaptive immunity. Therefore, it is crucial to understand the specific type of innate immune response triggered by lipid nanoparticles. This article provides an overview of the immunological response in the body, explores how lipid nanoparticles activate the innate immune system, and examines the adverse effects and immunogenicity-related development pathways associated with these nanoparticles. Finally, we highlight and explore strategies for regulating the immunogenicity of lipid nanoparticles.

PRID: Prediction Model Using RWR for Interactions between Drugs.

Drug-drug interactions (DDI) occur because of the unexpected pharmacological effects of drug pairs. Although drug efficacy can be improved by taking two or more drugs in the short term, this may cause inevitable side effects. Currently, multiple drugs are prescribed based on the experience or knowledge of the clinician, and there is no standard database that can be referred to as safe co-prescriptions. Thus, accurately identifying DDI is critical for patient safety and treatment modalities. Many computational methods have been developed to predict DDIs based on chemical structures or biological features, such as target genes or functional mechanisms. However, some features are only available for certain drugs, and their pathological mechanisms cannot be fully employed to predict DDIs by considering the direct overlap of target genes. In this study, we propose a novel deep learning model to predict DDIs by utilizing chemical structure similarity and protein-protein interaction (PPI) information among drug-binding proteins, such as carriers, transporters, enzymes, and targets (CTET) proteins. We applied the random walk with restart (RWR) algorithm to propagate drug CTET proteins across a PPI network derived from the STRING database, which will lead to the successful incorporation of the hidden biological mechanisms between CTET proteins and disease-associated genes. We confirmed that the RWR propagation of CTET proteins helps predict DDIs by utilizing indirectly co-regulated biological mechanisms. Our method identified the known DDIs between clinically proven epilepsy drugs. Our results demonstrated the effectiveness of PRID in predicting DDIs in known drug combinations as well as unknown drug pairs. PRID could be helpful in identifying novel DDIs and associated pharmacological mechanisms to cause the DDIs.

Edible mushroom intake and risk of all-cause and cause-specific mortality: results from the Korean Genome and Epidemiology Study (KoGES) Cohort.

Mushroom is rich in protein, fiber, vitamins, and essential amino acids. A relationship between mushroom consumption and a lower all-cause mortality risk has been reported. This study aimed to examine the association of mushroom consumption with all-cause and cause-specific mortality. Data were extracted from the Korean Genome and Epidemiology Study cohort. Mortality outcomes were confirmed from 2001-2020 death records provided by the Korea National Statistical Office. Mushroom intake was assessed using food frequency questionnaires and categorized into four groups: none, <1 serving per week, 1-3 servings per week, and ≥3 servings per week. Cox proportional hazard regression was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality. The 152 828 participants ≥40 years had a mean age of 53.7 years. Over a mean 11.6-year follow-up, 7085 deaths were recorded. In men, consuming <1 and 1-3 servings per week of mushroom was associated with lower risks of all-cause (HR = 0.858, 95% CI = 0.793-0.929; HR = 0.902, 95% CI = 0.819-0.993) and cardiovascular disease (CVD) (HR = 0.767, 95% CI = 0.632-0.930; HR = 0.762, 95% CI = 0.601-0.967) mortality than non-consumption. In women, consuming <1 and 1-3 servings per week of mushrooms was associated with a lower risk of all-cause mortality (HR = 0.864, 95% CI = 0.784-0.952; HR = 0.869, 95% CI = 0.771-0.980) than non-consumption. This prospective cohort study demonstrated that low and medium mushroom consumption is associated with a lower risk of all-cause mortality in men and women. However, only men who consumed <1 and 1-3 servings per week of mushrooms exhibited a lower risk of CVD mortality.

Non-alcoholic fatty liver disease is associated with hyperandrogenism in women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a highly complex reproductive metabolic disorder and women with PCOS have high prevalence of non-alcoholic fatty liver disease (NAFLD). Despite both hyperandrogenism and insulin resistance are common pathophysiologies in NAFLD and PCOS, this association is still controversial. Therefore, the aim of this study is to evaluate the relationship between hyperandrogenism and NAFLD in females diagnosed with PCOS. We recruited 667 women diagnosed with PCOS and 289 women with regular menstrual cycles as control. The PCOS diagnosis was made using National Institute of Child Health and Human Disease criteria. Total and free testosterone levels (TT and TF, respectively), and free androgen index (FAI) were used as measures of hyperandrogenism. Fatty liver index and liver fat score (FLI and LFS, respectively), and hepatic steatosis index (HSI) were used to assess NAFLD. The prevalence of NAFLD in PCOS women evaluated by LFS, FLI, and HIS were 19.9, 10.3, and 32.2%, respectively. In the control group, the incidence was 2.1, 0.7, and 4.2%, respectively. Both FT and FAI levels showed significant association with increased NAFLD-related indices, after adjusting for insulin resistance and other factors (LFS (OR 3.18 (95% CI 1.53-6.63) in FT; 1.12 (1.04-1.22) in FAI), FLI (OR 2.68 (95% CI 1.43-5.03) in FT; 1.13 (1.06-1.20) in FAI), and HSI (OR 3.29 (95% CI 2.08-5.21) in FT; 1.5 (1.09-1.21) in FAI). TT did not exhibit association with any NAFLD index. In women with PCOS, significantly higher rate of NAFLD was observed compared to the control women. The FT and FAI were independently associated with NAFLD in women with PCOS. The findings suggest the possibility of hyperandrogenism contributing to the progression and/or development of NAFLD in PCOS.

Concomitant Use of Proton Pump Inhibitors and Palbociclib Among Patients With Breast Cancer.

Importance: Proton pump inhibitors (PPIs) are commonly used drugs to relieve gastrointestinal tract symptoms, but their acid-inhibitory action negatively affects the bioavailability and clinical outcomes of orally administered concomitant drugs. Objective: To identify the clinical outcomes of patients with advanced breast cancer who concomitantly use PPIs and palbociclib. Design, Setting, and Participants: This retrospective cohort study used nationwide claims data between November 1, 2016, and July 31, 2021, in South Korea. Patients with breast cancer receiving palbociclib between November 1, 2017, and July 31, 2020, were identified. Patients whose prescriptions for palbociclib and PPI overlapped by at least 33% were classified into a concomitant PPI group. Patients who never received PPI during the palbociclib treatment period were classified into a nonconcomitant PPI group. Patients were selected through 1:3 propensity score matching for analyses. Exposures: Concomitant use of PPIs with palbociclib. Main Outcomes and Measures: Time to progression and death. These outcomes were presented as progression-free survival (PFS) and overall survival (OS) and were analyzed using the Kaplan-Meier method and log-rank test. Cox proportional hazards regression was used to estimate the hazard ratio (HR) of concomitant PPI use associated with clinical PFS and/or OS. Results: A total of 344 women were included in the concomitant PPI group and 966 in the nonconcomitant PPI group. Among 1310 patients identified after matching, 1108 (84.6%) were older than 50 years; 1111 (84.8%) were treated with letrozole and anastrozole (endocrine sensitive); and 199 (15.2%) were treated with fulvestrant (endocrine resistant). The median clinical PFS in the concomitant PPI group was shorter than that of the nonconcomitant PPI group (25.3 [95% CI, 19.6-33.0] vs 39.8 [95% CI, 34.9 to not applicable] months; P < .001), and the HR was 1.76 (95% CI, 1.46-2.13). Concomitant use of PPI was also associated with shorter OS (HR, 2.71 [95% CI, 2.07-3.53]). Both clinical PFS and OS in the concomitant PPI group were consistently poor in patients receiving endocrine-sensitive and endocrine-resistant treatment. Conclusions and Relevance: These findings suggest that concomitant use of PPIs with palbociclib may hinder the complete therapeutic benefits of palbociclib in patients with breast cancer.

Lipid nanoparticles (LNPs) for in vivo RNA delivery and their breakthrough technology for future applications.

RNA therapeutics show a significant breakthrough for the treatment of otherwise incurable diseases and genetic disorders by regulating disease-related gene expression. The successful development of COVID-19 mRNA vaccines further emphasizes the potential of RNA therapeutics in the prevention of infectious diseases as well as in the treatment of chronic diseases. However, the efficient delivery of RNA into cells remains a challenge, and nanoparticle delivery systems such as lipid nanoparticles (LNPs) are necessary to fully realize the potential of RNA therapeutics. While LNPs provide a highly efficient platform for the in vivo delivery of RNA by overcoming various biological barriers, several challenges remain to be resolved for further development and regulatory approval. These include a lack of targeted delivery to extrahepatic organs and a gradual loss of therapeutic potency with repeated doses. In this review, we highlight the fundamental aspects of LNPs and their uses in the development of novel RNA therapeutics. Recent advances in LNP-based therapeutics and preclinical/clinical studies are overviewed. Lastly, we discuss the current limitations of LNPs and introduce breakthrough technologies that might overcome these challenges in future applications.

Investigation of heteroscedasticity in polygenic risk scores across 15 quantitative traits.

The polygenic risk score (PRS) could be used to stratify individuals with high risk of diseases and predict complex trait of individual in a population. Previous studies developed a PRS-based prediction model using linear regression and evaluated the predictive performance of the model using the R 2 value. One of the key assumptions of linear regression is that the variance of the residual should be constant at each level of the predictor variables, called homoscedasticity. However, some studies show that PRS models exhibit heteroscedasticity between PRS and traits. This study analyzes whether heteroscedasticity exists in PRS models of diverse disease-related traits and, if any, it affects the accuracy of PRS-based prediction in 354,761 Europeans from the UK Biobank. We constructed PRSs for 15 quantitative traits using LDpred2 and estimated the existence of heteroscedasticity between PRSs and 15 traits using three different tests of the Breusch-Pagan (BP) test, score test, and F test. Thirteen out of fifteen traits show significant heteroscedasticity. Further replication using new PRSs from the PGS catalog and independent samples (N = 23,620) from the UK Biobank confirmed the heteroscedasticity in ten traits. As a result, ten out of fifteen quantitative traits show statistically significant heteroscedasticity between the PRS and each trait. There was a greater variance of residuals as PRS increased, and the prediction accuracy at each level of PRS tended to decrease as the variance of residuals increased. In conclusion, heteroscedasticity was frequently observed in the PRS-based prediction models of quantitative traits, and the accuracy of the predictive model may differ according to PRS values. Therefore, prediction models using the PRS should be constructed by considering heteroscedasticity.

Association of smoking and dietary polycyclic aromatic hydrocarbon exposure on the prevalence of metabolic syndrome in Korean adults.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants that are potentially hazardous to human health. Dietary exposure is recognized as one of the major pathways of exposure to PAHs among humans. While some PAH exposures have been associated with metabolic syndrome (MetS) in the general population, most epidemiological studies are based on urinary metabolites of a few noncarcinogenic PAHs. OBJECTIVE: To investigate the association between estimates of dietary exposure to major carcinogenic PAHs and MetS in Korean adults. METHODS: Multi-cycle Korean National Health and Nutrition Examination Survey (KNHANES) database (n = 16,015) and PAH measurement data from the total diet survey were employed to estimate daily PAH intake for each participating adult. After adjusting for potential confounders, multinomial logistic regression analysis was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) between PAHs and MetS of the participating adults. RESULTS: Benzo(a)pyrene exposure was associated with an increased risk of MetS in men (OR = 1.30; 95% Cl: 1.03-1.63; P-trend = 0.03). In women, however, only chrysene and low high-density lipoprotein (HDL-c) were positively associated with an increased risk of MetS (OR = 1.24; 95% CI: 1.03-1.48; P-trend = 0.0172). Among men, smokers were at an increased risk for MetS, regardless of whether they were exposed to low or high total PAHs and benzo(a)pyrene levels. SIGNIFICANCE: Our findings suggested that PAHs are associated with the risk of MetS and MetS components in Korean adults. In particular, it was confirmed that smoking may influence the relationship between PAH exposure and MetS.Further prospective cohort studies are required to confirm the causal relationship between PAHs and MetS. IMPACT STATEMENT: Epidemiological studies on PAH exposure are often hampered by a lack of reliable exposure estimates, as biomonitoring of urine does not capture exposure to more toxic PAHs. Using multi-cycle KNHANES data and the measurement data from a total diet survey of Korea, we could develop a personalized PAH intake estimate for each participating adult and assessed the association with MetS.

Relationship between age at menarche and metabolic diseases in Korean postmenopausal women: The Korea National Health and Nutrition Examination Survey 2016-2018.

BACKGROUND: Cardiovascular disease is the leading cause of morbidity and mortality in postmenopausal women. Early menarche may be associated with an increased risk of metabolic diseases such as diabetes and cardiovascular disease. This study aimed to investigate the effect of menarche age and the risk of diabetes and metabolic syndrome in Korean postmenopausal women. METHODS: We analyzed 4,933 postmenopausal women (mean age: 64.7 years) using the Korean National Health and Nutritional Examination Survey 2016-2018. Subjects were divided into three groups according to menarche age (early menarche: ≤ 12 years (n = 451), reference: 13-16 years (n = 3,421), and late menarche: ≥ 17 years (n = 1,061)). Logistic regression analysis was used to estimate the odds ratio (OR) for diabetes and metabolic syndrome. RESULTS: Women with an early menarche age were younger, more educated, and had higher income than the other groups (p-value < 0.001). There were no differences in body mass index, blood pressure, fasting glucose, HbA1c, and cholesterol levels among the three groups. After adjusting for potential confounding factors, early menarche age was significantly associated with the risk of diabetes (OR 1.435, 95% confidence interval (CI): 1.069-1.928). The prevalence of metabolic syndrome in all subjects was 41.1%. After adjusting for potential confounding factors, the OR of metabolic syndrome in the early menarche group was 1.213 (95% CI: 0.971-1.515). CONCLUSION: The risk of diabetes was 1.43 times higher in postmenopausal Korean women with early menarche. Although the risk of metabolic syndrome was not statistically significant, it showed a tendency to increase in the early menarche group. Our results suggest that age at menarche may be helpful in diabetes risk stratification and early interventions for postmenopausal women.

Association between Tomato and Lycopene Consumption and Risk of All-Cause and Cause-Specific Mortality: Korean Genome and Epidemiology Study Cohort.

SCOPE: Tomato has well-known beneficial health effects and is an important source of lycopene. The study aims to clarify the evidence for the association between tomato and lycopene consumption and all-cause and cause-specific mortality in Korean adults. METHODS AND RESULTS: Data analyzed in the current study are obtained from the Korean Genome and Epidemiology Study Cohort. Mortality outcomes are determined based on death records from 2001 to 2020. Tomato and lycopene consumption is assessed using food frequency questionnaires and antioxidant databases and divided into quintiles. Over a mean follow-up of 11.5 years, 5863 deaths are recorded among 139913 participants aged over 40 years. Tomato consumption is not associated with the risk of all-cause and cancer mortality. However, the highest tomato consumption group has a lower risk of cardiovascular disease (CVD) mortality (HR = 0.779; 95% CI = 0.633, 0.957). Lycopene consumption is inversely associated with all-cause (HR = 0.872; 95% CI = 0.801, 0.950), and CVD (HR = 0.680; 95% CI = 0.548, 0.845) mortality. CONCLUSION: A higher intake of tomatoes and lycopene is inversely related to the risk of CVD mortality, and lycopene consumption is associated with a lower risk of all-cause mortality.

Association of milk consumption with management and incidence of hypertension among South Korean adults: A prospective analysis of the health examinees study cohort.

BACKGROUND AND AIMS: Studies have revealed a positive relationship between milk consumption and hypertension. However, few researchers have investigated the association between milk consumption and changes in blood pressure (BP) in South Korean adults. Therefore, we examined the association between milk intake and the management and risk of hypertension in South Korean adults. METHODS AND RESULTS: Participants were selected from the Health Examinees study. The definition of hypertension was based on the guidelines of the Korean Society of Hypertension. The participants were divided into three groups according to changes between baseline and follow-up BP data. Milk consumption was assessed using food frequency questionnaires. In both men and women, the higher milk consumption group had increased odds of trends of BP improvement (OR: 1.249, 95% CI: 1.043-1.496, p for trend: 0.2271 in men; OR: 1.147, 95% CI: 1.014-1.297, p for trend: 0.0293 in women) and decreased odds of trends of worsening (OR: 0.861, 95% CI: 0.756-0.980, p for trend: <0.0001 in men, OR: 0.866, 95% CI: 0.794-0.943, p for trend: 0.0010 in women) compared to those of the non-consumption group. In the prospective study, milk intake was inversely associated with hypertension risk (HR: 0.900, 95% CI: 0.811-0.999, p for trend: 0.0076 in men; HR: 0.879, 95% CI: 0.814-0.949, p for trend: 0.0002 in women). CONCLUSION: Increased intake of milk was inversely related to the risk of increased BP, with a decreased risk of hypertension events.

Lack of association between feline AB blood groups and retroviral status: a multicenter, multicountry study.

OBJECTIVES: The relationship between blood group antigens and disease has been studied in humans. Blood types have been associated with both decreased and increased rates of various infections. In addition, blood group expression has been shown to vary with some cancers and gastrointestinal diseases. The objective of this study was to explore whether there is a relationship between blood type and retroviral infections in cats. METHODS: Case records from a veterinary research laboratory, veterinary teaching hospitals and veterinary blood banks were retrospectively searched for cats where both blood type and retroviral status (feline leukemia [FeLV], feline immunodeficiency virus [FIV] or both) were listed (part 1). In addition, a sample of 33 cats with confirmed FIV infection was genotyped to determine blood groups (part 2). RESULTS: In part 1, 709 cats were identified, 119 of which were positive for retroviral infection. Among all cases, 621 were type A (87.6%), 68 were type B (9.6%) and 20 were type AB (2.8%). There was no relationship between overall retroviral status (positive/negative) and blood type (P = 0.43), between FeLV status and blood type (P = 0.86) or between FIV status and blood type (P = 0.94). There was no difference in the distribution of blood types between cats that were healthy and typed as possible blood donors vs sick cats that were typed prior to a possible transfusion (P = 0.13). In part 2, of the 33 FIV-infected cats, all blood group genotypes were identified, although this test did not discriminate type A from type AB. CONCLUSIONS AND RELEVANCE: No relationship was identified between feline retroviral status and blood type in this study. The relationship between blood type and other disease states requires further study in veterinary patients.